Blood Disorders

Blood Disorders, General Health & Wellness

The platelet, of growing practical clinical importance in hemostatic considerations and a variety of medical/surgical processes is also fundamental to etiologic considerations of arteriosclerotic3and malignant disease.4Careful estimate of platelet number from stained peripheral blood smear can provide useful information. A variety of factors affect the distribution of platelets on a peripheral blood smear, and thus platelet estimates lack precision. Capillary blood platelet counts (c.f. to venous blood counts) may be significantly underestimated. Platelets are often clumped on smears obtained from capillary blood, contributing to imprecision. A small whole blood clot or very small fibrin clots in the EDTA anticoagulated specimen will usually be associated with clumping of platelets on the slide, and with a false low platelet count.Quantitative platelet disorders have varied etiology. Thrombocytopenia may have an immunologic basis, the result of production deficiency due to the effect of drugs or physical agents, abnormal platelet pooling or increased destruction (eg, sequestration by large vascular tumor), or result from a variety of probably nonimmunologic mechanisms (eg, hypersplenism). Decreases may occur after bleeding, transfusion, infections, or relating to defective production of or regulation by thrombopoietin.Drugs and chemicals associated with thrombocytopenia, often on an immune mediated basis5or as the result of marrow suppression, include quinidine, quinine, heparin, gold salts, sulfas, rifampicin, ASA, digitoxin, apronal, chlorothiazides, chlorpropamide, meprobamate, antihistamines, chloramphenicol, penicillin, DDT, benzol, a variety of other industrial organic chemicals, diphenylhydantoin, PAS, hydrochlorothiazide, phenylbutazone, and a variety of antineoplastic chemotherapeutic agents. ASA acts by acetylating cyclo-oxygenase.Thrombocytosis is less common, but likewise varied in etiology: physiologic (eg, postpartum, or after exercise); myeloproliferative syndromes (eg, thrombocythemia, some cases of chronic myelogenous leukemia, myelofibrosis with myeloid metaplasia); rebound following thrombocytopenia, marrow regenerative activity after bleeding episode, hemophilia, iron deficiency; asplenism, infections, inflammatory or malignant disease, especially carcinomatosis. Oral contraceptives may cause slight increase.Congenital causes of thrombocytopenia include Wiskott-Aldrich syndrome, May-Hegglin anomaly, thrombocytopenia with absent radius, and Bernard-Soulier syndrome. See table.Inherited Abnormalities of Platelet Production (Characterized by Thrombocytopenia)ConditionInheritanceAbnormalityTherapyAdapted from Penner J.Blood Coagulation Laboratory Manual.University of Michigan Medical School; Sep, 1979.May-HegglinAutosomal DominantSevere thrombocytopeniaPlatelet replacementWiskott-AldrichSex-linkedSevere thrombocytopenia with small plateletsPossibly splenectomyCongenital thrombopoietin deficiency? AutorecessiveSevere thrombocytopeniaPlasma transfusionThrombocytopenia with absent radiusAutorecessiveModerate thrombocytopeniaPlatelet replacementAbnormalities of Platelet Function, Familial Transmission, AutorecessiveThrombastheniaAbsent clot retraction, absent aggregation, mild thrombocytopeniaPlatelet replacement, steroidsBernard-Soulier syndromeGiant platelets, absent Ristocetin® aggregationPlatelet replacementPlatelet storage pool diseaseAbsent aggregation with collagen, mild thrombocytopenia, absent dense granules with decreased platelet serotoninSplenectomy, platelet replacementHermansky-Pudlak syndromeAggregation abnormal with epinephrine and collagen, decreased dense granules and absent ADP storesPlatelet replacementRelease reaction abnormalitiesAbsent second wave aggregation with epinephrine and collagen, absent PF-3 release, varied inheritancePlatelet replacement

Blood Disorders, General Health & Wellness

Offered as part of multiple lab tests

Blood Disorders, Nutrition & Vitamins

Offered as part of multiple lab tests

Heart Health & Cardiovascular, Blood Disorders

The thromboplastin reagent used by LabCorp consists of recombinant tissue factor mixed with synthetic phospholipid. Recombinant tissue factor is free from contamination with coagulation factors that can be found in tissue factor extracted from other sources. This serves to increase the PT assay's sensitivity for factor efficiencies. Prothrombin time results are reported in seconds and are also converted to international normalized ratio (INR) values. The INR serves to normalize results obtained from different laboratories for the variable responsiveness of different thromboplastin reagents. Each thromboplastin is assigned an activity Index (ISI) based on comparison to an international reference thromboplastin from the World Health Organization. The formula for calculating the INR isINR = [patient's results / normal patient average](ISI)The ISI of the thromboplastin used in the LabCorp assay is near 1.0. The use of low ISI thromboplastin serves to improve the precision of therapeutic monitoring by enhancing sensitivity of the prothrombin assay.The PT is sensitive to deficiencies of extrinsic and common pathway factors X, VII, V, II, and fibrinogen.6-8The PT is more responsive to deficiencies of factors X and V than is the aPTT. Congenital deficiencies of these factors are relatively rare and cause bleeding disorders of varying severity. Refer to individual test descriptions for more information. Acquired deficiencies of the vitamin K-dependent factors II and VII may occur during warfarin therapy and in patients with vitamin K deficiency. Diminished levels of all the factors of the extrinsic pathway can also occur in consumptive coagulopathies, such as disseminated intravascular coagulation (DIC), and as the result of decreased factor production as can be seen with severe liver disease or malnutrition. Specific inhibitors of extrinsic pathway factors are extremely rare, but may produce a prolonged PT.6-8Lupus anticoagulants (LA) may cause a prolonged PT due to nonspecific factor inhibition. Some individuals with LA can develop antibodies that bind to and increase the rate of clearance of prothrombin (factor II). These patients typically have an extended PT due to reduced factor II level and an increased risk of bleeding.Coumarins, a family of compounds that inhibit the vitamin K-dependent carboxylation of several coagulation factors, are commonly used to limit fibrin clot formation in individuals with increased risk of venous or arterial thrombosis.10-12Warfarin, also referred to as Coumadin®, is the most commonly used coumarin in North America.11Overdosing with warfarin can increase the risk of hemorrhage and inadequate dosing decreases the efficacy of anticoagulation. Unfortunately, a large number of factors can affect the pharmacological potency of these oral anticoagulants. These factors are reviewed in considerable detail in the American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy.12Therapeutic monitoring is essential to maintain the dosage within the appropriate range range. Because the PT is sensitive to deficiencies of vitamin K-dependent factors II and VII, it is used to monitor warfarin therapy.Coumarins inhibit the carboxylation of procoagulant factors II, VII, IX, X, and anticoagulants proteins C and S to a similar extent. Steady-state levels of these proteins are all reduced to a similar degree, based on the dose and effectiveness of the oral anticoagulant given; however, during the initial days of treatment, the rate of decline of factor levels is dependent on their half-life. Since factor VII has a short half-life relative to other vitamin K-dependent factors, the levels of this factor drop much more precipitously than the others.11Superwarfarins, such as brodifacoum, are often found in rat poison and may cause prolongation of the PT. Patients suffering brodifacoum poisoning respond to vitamin K often bringing their PT into the normal range briefly, but since the drug is stored for long periods of time in fat, the PT rises again over time.

Blood Disorders, General Health & Wellness

Offered as part of multiple lab tests

Blood Disorders, Nutrition & Vitamins

Ferritin is found in virtually all cells of the body and serves as the cellular storage repository for iron.2,3Ferritin is a macromolecule with an average molecular weight of near 440 kD that varies depending on the iron content. Ferritin consists of a protein shell (apoferritin) of 24 subunits surrounding an iron core consisting of up to 4000 ferric iron ions. The majority of ferritin iron stores are found in the liver, spleen, and bone marrow. Ferritin is present in small concentration correlates with total-body iron stores, making its measurement valuable for the assessment of disorders of iron metabolism.Low levels of ferritin can be found when iron stores are exhausted, well before the serum iron level has become affected. In the setting of anemia, low serum ferritin is a very specific biomarker for iron deficiency anemia. In fact, there is no clinical situation other than iron deficiency in which extremely low values of serum ferritin are seen; however, some clinical states involving infection or inflammation can cause the ferritin level in the serum of patients with iron deficiency to increase into the normal range. Ferritin is an acute-phase reactant that is thought to play a role in the body's defense against oxidative stress and inflammation. Increased ferritin values can also be observed in malignant disease, including acute leukemia; Hodgkin's disease; and carcinoma of the lung, colon, liver, and prostate. Consequently, serum ferritin in the normal range reflects iron sufficiency only in the absence of these conditions.Patients with a serum ferritin concentration below the lower limit of the reference interval have a very high probability of being iron deficient; however, given the low sensitivity of a low ferritin level (below the lower limit of normal), a higher ferritin cutoff may be more appropriate for screening for potential iron deficiency in some populations.4-7It is exceedingly uncommon for ferritin levels to exceed 100 ng/mL in patients with iron deficiency.6,7An elevated ferritin level can result from iron overload due, in part, to increased hepatic ferritin synthesis.8Iron overload can occur in hemochromatosis, other excess iron storage disorders, and in individuals who have received multiple blood transfusions. Ferritin can also become markedly elevated secondary to obesity, chronic alcohol consumption, steatohepatitis, chronic inflammation, viral hepatitis, and malignancy. The increased prevalence of obesity has likely resulted in the increased incidence of ferritin elevations, as fatty liver may be the most common cause of an elevated serum ferritin.8Clinical assessment is required to determine whether the serum ferritin elevation is related to hemochromatosis or another underlying liver disease.9To confirm the diagnosis of hemochromatosis, other iron tests (iron, TIBC), and genetic testing may be performed.

General Health & Wellness, Blood Disorders

Using advanced flow-cytometric technology, our sophisticated instruments will analyze the specimen based upon a complex set of flags and middleware rules. These rules help separate relatively normal results with nonspecific abnormalities from patients with hemolysis, hematological malignancies and/or the presence of microorganisms. Normal CBCs with differentials and CBCs with nonspecific abnormalities (i.e. nonspecific neutrophilia, anemia, thrombocytopenia) will be reported without smear review. The absence of additional report comments indicates that a smear review was not medically necessary. If specific morphologic abnormalities are detected, a peripheral smear will be prepared for review by a medical laboratory scientist. Depending on the abnormality, the medical laboratory scientist may perform a manual differential and/or assess for red cell morphology (abnormalities such as basophilic stippling, Howell-Jolly bodies, target cells, spherocytes and schistocytes), white cell abnormalities (neutrophil hypersegmentation, hypogranularity, toxic granulation, Dohle bodies or abnormal cells), or platelet abnormalities (i.e., hypogranular, large or giant platelets). If there are abnormal cells such as blasts, or lymphoma cells, microorganisms or evidence of hemolysis, the smear will be examined by a pathologist. The pathologist's comments will appear in a footnote to the CBC or in a separate report and will detail the hematologic disease. Life-threatening hematologic disorders (i.e., acute leukemia, chronic myeloproliferative disorders, microangiopathic hemolytic anemia, bacteremia) also will be called to the physician as a critical value.The CBC with differential cascade will be performed as follows: 1) Run CBC through analyzer. 2) Apply flags and rules to generate smear. 3) Medical laboratory scientist reviews smear. 4) If criteria met, pathologist reviews smear.Please note that many CBC abnormalities are nonspecific and not definitively related to a hematologic disorder. Please refer to the CBC Guide for the differential diagnosis of these CBCs.A six-part differential reported in some lab locations includes IG% and IG absolute counts. IG (immature granulocytes) includes metamyelocytes and myelocytes. It does not include bands or blast cells. Promyelocytes and blasts are reported separately to denote the degree of left shift. An elevated percentage of IG has not been found to be clinically significant as a sole clinical predictor of disease. IGs are associated with infections, a variety of inflammatory disorders, cytokine therapy, neoplasia, hemolysis, tissue damage, seizures, metabolic abnormalities, myeloproliferative neoplasms and with the use of certain medications such as steroids.

Blood Disorders, Nutrition & Vitamins

Reticulocytes stained with a fluorescent reagent can be differentiated from mature red cells and other cell populations by light scatter, direct measurements, and opacity characteristics when using an automated hematology analyzer equipped with reticulocyte counting technology.

Blood Disorders, Nutrition & Vitamins

Serum iron is increasedin hemosiderosis, hemolytic anemias especially thalassemia, sideroachrestic anemias, hepatitis, acute hepatic necrosis, hemochromatosis, and with inappropriate iron therapy. Iron may reach high levels with iron poisoning. Some patients who receive multiple transfusions (eg, some hemolytic anemias, thalassemia, renal dialysis patients) will have increased serum iron levels.Serum iron is decreasedwith insufficient dietary iron, chronic blood loss (including the hemolytic anemias paroxysmal nocturnal hemoglobinuria), inadequate absorption of iron and impaired release of iron stores as in inflammation, infection and chronic diseases. The combination of low iron, high TIBC and/or transferrin and low saturation indicates iron deficiency. Without all of these findings together, iron deficiency is unproven.2Low ferritin supports the diagnosis of iron deficiency.Detection of iron deficiency may lead to detection of adenocarcinoma of gastrointestinal tract, a point which cannot be overemphasized.In recovery from pernicious anemia, especially just after B12dose, iron levels are low. In fact, the drop in serum iron 1 to several days after the Schilling test flushing dose of vitamin B12may be more useful in diagnosis than the radioactivity of the 24-hour urine collection. Serum iron is reported to drop with acute infarct of myocardium.TIBC is increasedin iron-deficiency, use of oral contraceptives, and in pregnancy.TIBC is decreasedin hypoproteinemia due to many causes, and is decreased in a number of inflammatory states.Increased saturationoccurs with HLA-related (classical) hemochromatosis before ferritin is greatly increased, and also with iron overload (eg, cirrhosis and portacaval shunt), in hemolytic anemias and with iron therapy. Saturation >70% in females, >80% in males is described as prerequisite for parenchymal loading; however, sample contamination and the vagaries of fluctuation in serum iron levels can make such criteria misleading on occasion.2The serum ferritin is a more sensitive test than the serum iron or TIBC for iron deficiency and for iron overload.2When all these tests are used together, as is often necessary, they usually can distinguish between iron deficiency anemia and the anemia of chronic disease. The best and most reliable evaluation of total body iron stores is by bone marrow aspiration and biopsy. The best evaluation of iron deficiency in childhood (unless lead toxicity is suspected) is free erythrocyte porphyrins.With recombinant erythropoietin therapy serum iron, transferrin saturation, and ferritin levels decline due to rapid utilization by stimulated erythropoiesis with resultant decrease in storage iron.3,5While iron is usually considered in relation to hematopoiesis and oxygen transport functions of red cells, it is also of prime import to the lymphomyeloid systems.6

Blood Disorders

The aPTT is often ordered, along with the prothrombin time, to diagnose the cause of patient bleeding or as part of a presurgical screen to rule out coagulation defects.9-11The aPTT can be prolonged when the activities of any of the factors of the intrinsic pathway are significantly diminished. Deficiencies or inhibition of high molecular weight kininogen (HMWK), prekallikrein, or factors XII, XI, IX, and VIII can result in an extended aPTT with a normal protime (PT) since these factors are not part of the extrinsic pathway. Significant deficiencies of factors that are common to both the intrinsic and extrinsic pathways (factors X, V, prothrombin, or fibrinogen) can extend both the aPTT and PT.An extended aPTT can be seen in acquired deficiencies of factors II, IX, and X that result from vitamin K deficiency or the use of anticoagulants that block vitamin K-dependent production of procoagulant factors. These conditions also affect the level of factor VII, an extrinsic pathway factor. Since factor VII has a short half-life relative to the vitamin K-dependent factors of the intrinsic pathway, nutritional or therapeutic vitamin K-dependent factor deficiency can sometimes result in an extended PT with a normal aPTT. Consumption coagulopathies, such as disseminated intravascular coagulation (DIC), can produce an extended aPTT due to depletion of intrinsic factors. The aPTT can also be extended in conditions that reduce the production of procoagulant factors (ie, severe liver disease or malnutrition). Inhibitors, both factor specific and nonspecific, can also prolong the aPTT. A description of the many potential causes of an extended aPTT is described in more detail in the online Coagulation Appendix: Lupus Anticoagulants.Unfractionated heparin is commonly used to limit fibrin clot formation in individuals with increased risk of venous or arterial thrombosis.12Overdosing with heparin can increase the risk of hemorrhage and inadequate dosing decreases the efficacy of anticoagulation. Heparin works as an anticoagulant by enhancing the ability of plasma antithrombin to bind and inactivate the serine proteases XII, XI, IX, X, and thrombin. Therapeutic monitoring with the aPTT is commonly used because of the wide interindividual variation in response to this therapy; however, this application of the aPTT test can be less than optimal in a number of clinical circumstances (see Limitations).

Blood Disorders

Distinction between Hb S β-thalassemia and sickle cell anemia is not always possible on clinical, hematologic, or electrophoretic grounds. Thalassemia heterozygotes have hypochromia and microcytosis, but overlap values exist. Differentiation can best be made by family or molecular pathology methods. Regional prevalence in the midwest area of Hb S β-thalassemia is estimated to be 1:23,000 of the black population. It is recommended that positive sickle cell patients be further evaluated with Hb fractionation (HPLC), Hb F studies, and family studies. Complete characterization may require sophisticated laboratory studies with DNA amplification.2

Blood Disorders

Offered as part of multiple lab tests

Heart Health & Cardiovascular, Blood Disorders

Fibrinogen, also referred to as factor I, is a 340-kilodalton glycoprotein that is produced by the liver.6Fibrinogen has a plasma half-life of about four days. Proteolytic conversion of fibrinogen to fibrin occurs through both the extrinsic and intrinsic pathways.6Severe fibrinogen deficiency should be considered when a patient with bleeding history has both extended protime (PT) and activated partial thromboplastin time (aPTT).7,8Mild deficiency may not produce prolongation of either the aPTT or PT and, therefore, fibrinogen activity should be measured in individuals with a bleeding tendency even when the aPTT and PT are in the normal reference interval.Congenital afibrinogenemia, a condition associated with the complete absence of fibrinogen, is rare with only about 150 cases reported in the literature.6,7Fibrinogen deficiency is inherited as an autosomal recessive trait.7,8Afibrinogenemia occurs in individuals who are homozygous or doubly heterozygous for mutations. These individuals have infinite protime and aPTT results due to the inability to produce fibrin. Approximately 25% of patients with afibrinogenemia have mild thrombocytopenia.7Individuals who are heterozygous for congenital fibrinogen deficiency are usually asymptomatic unless their fibrinogen levels fall to <50 mg/dL.7Both functional (activity) and antigenic levels are diminished in these individuals.7Fibrinogen deficiency affects both males and females with a prevalence that is equal in all ethnic groups.7Acquired deficiencies occur in individuals with significant hepatic dysfunction, renal disease, and after L-asparaginase therapy.6Diminished levels can also be seen in patients with disseminated intravascular coagulation (DIC) or who are undergoing thrombolytic therapy.6Fibrinogen is one of the major determinants of the erythrocyte sedimentation rate and individuals with afibrinogenemia typically have greatly extended sedimentation rates.7Individuals with dysfibrinogenemia have fibrinogen that is qualitatively defective with low functional fibrinogen levels (activity) and normal or decreased antigenic levels.6Congenital dysfibrinogenemia is inherited as an autosomal dominant mutation.6A number of disfibrinogenemic defects have been identified with a variety of manifestations including abnormal fibrin polymerization, impaired fibrinopeptide release, abnormal fibrin stabilization, and abnormal fibrin clot lysis.6,7Fibrinogen activity and antigen levels are useful in the diagnosis of dysfibrinogenemia since these individuals often have diminished activity relative to antigen levels.8Typically, dysfibrinogenemia is associated with an elevated thrombin time and greatly elevated reptilase time.Individuals with afibrinogenemia have a bleeding tendency of varying severity.7Symptoms often start in early infancy with umbilical cord bleeding, intracerebral hemorrhage, or bleeding at circumcision.6-8Individuals with afibrinogenemia also suffer from deep muscle and joint bleeding and other mucous membrane bleeding throughout life.6Women with afibrinogenemia typically do not experience menorrhagia.8Patients with heterozygous hypofibrinogenemia usually have a minimal history of bleeding with symptoms only observed after major surgery or trauma.6,7Approximately 50% of individuals with dysfibrinogenemia are asymptomatic suffering neither bleeding nor thrombosis.6,7These individuals are usually detected when prolonged clotting times are discovered as a result of routine laboratory testing. About one in four will suffer prolonged bleeding after surgery and approximately 20% will have an increased tendency toward thrombosis.6A number of clinical and epidemiological studies have revealed a consistent association between elevated fibrinogen levels and increased risk for atherosclerotic vascular disease;11however, it remains to be determined whether increased fibrinogen acts as a mediator of arterial thrombosis or simply reflects the inflammation associated with atherosclerosis.11

Nutrition & Vitamins, Blood Disorders

Vitamin B12, or cyanocobalamin, is a complex corrinoid compound containing four pyrrole rings that surround a single cobalt atom.2Humans obtain vitamin B12exclusively from animal dietary sources, such as meat, eggs, and milk. Vitamin B12requires intrinsic factor, a protein secreted by the parietal cells in the gastric mucosa, for absorption. Vitamin B12and intrinsic factor form a complex that attaches to receptors in the ileal mucosa, where proteins known as transcobalamins transport the vitamin B12from the mucosal cells to the blood and tissue.3,4Most vitamin B12is stored in the liver as well as in the bone marrow and other tissues.Vitamin B12and folate are critical to normal DNA synthesis, which in turn affects erythrocyte maturation.3,5,6Vitamin B12is also necessary for myelin sheath formation and maintenance.7The body uses its B12stores very economically, reabsorbing vitamin B12from the ileum and returning it to the liver so that very little is excreted.4,8Clinical and laboratory findings for B12deficiency include neurological abnormalities, decreased serum B12levels, and increased excretion of methylmalonic acid.4,8,9The impaired synthesis associated with vitamin B12deficiency causes macrocytic anemias. These anemias are characterized by abnormal maturation of erythrocyte precursors in the bone marrow, which results in the presence of megaloblasts and in decreased erythrocyte survival.3,10Pernicious anemia is a macrocytic anemia caused by vitamin B12deficiency that is due to lack of intrinsic factor.5,6Low vitamin B12intake, gastrectomy, diseases of the small intestine, malabsorption, and transcobalamin deficiency can also cause vitamin B12deficiency.3Pregnant women need increased amounts of folate for proper fetal development.11If a woman has a folate deficiency prior to pregnancy, it will be intensified during gestation and may lead to premature birth and neural tube birth defects, such as spina bifida, in the child.11

Blood Disorders, Nutrition & Vitamins

Serum measurements are useful in the diagnosis of iron deficiency and hemochromatosis.

General Health & Wellness, Blood Disorders

A complete blood count is used as a screening test for various disease states to include: anemia, leukemia and inflammatory processes.

Blood Disorders

G6PD hemolysis is associated with formation of Heinz bodies in peripheral red blood cells. It is the older erythrocytes that are most G6PD-deficient in affected individuals. These cells are first eliminated in a hemolytic crisis. The younger cells and reticulocytes contain more G6PD. For these reasons, after a hemolytic crisis, when only younger erythrocytes and reticulocytes are present, the G6PD values may be spuriously normal.These "false-negative" (ie, spuriously normal or high) results are a potential concern because the most severely deficient red cells have already been removed from the circulation via hemolysis.This problem is usually not important when testing male Caucasians but is a concern in some Caucasian females and blacks of both sexes, especially during the reticulocytosis following acute hemolysis. When a false-negative test is suspected, the best approach is to reëvaluate the patient three months after the hemolytic episode, a time at which the red cell mass will have been repopulated with red cells of all ages.To prevent future hemolytic episodes, subjects with G6PD deficiency should avoid drugs and chemicals with oxidant potential. A partial list of safe and unsafe drugs is given in following table.Partial List of Drugs and Chemicals in Glucose-6-Phosphate Dehydrogenase Deficiency*Unsafe for Class I, II, and III VariantsSafe for Class II and III Variants*Note:This is a partial list only.Source: Beutler E. G6PD deficiency.Blood.1994 Dec 1; 84(11):3613-3636.AcetanilidAcetaminophenDapsoneAminopyrineFurazolidoneAscorbic acid (except in very high doses)Methylene blueAspirinNalidixic acidChloramphenicolNaphthalene (mothballs, henna)ChloroquineNiridazoleColchicineNitrofurantoinDiphenhydraminePhenazopyridineIsoniazidPhenylhydrazineL-DopaPrimaquineMenadioneSulfacetamidePara-aminobenzoic acidSulfamethoxazole (Δ)PhenacetinSulfanilamidePhenytoinSulfapyridineProbenecidThiazolesulfoneProcainamideToluidine bluePyrimethamineTrinitrotolueneQuinidineUricase (rasburicase, pegloticase)QuinineStreptomycinSulfamethoxypyridazineSulfisoxazoleTrimethoprimTripelennamineVitamin K

Heart Health & Cardiovascular, Blood Disorders

Screening test for abnormalities of coagulation factors that are involved in the extrinsic pathway. Also used to monitor effects of Warfarin therapy and to study patients with hereditary and acquired clotting disorders.

Blood Disorders, Nutrition & Vitamins

Useful in the diagnosis of hypochromic, microcytic anemias. Decreased in iron deficiency anemia and increased in iron overload.

Blood Disorders, Nutrition & Vitamins

Serum iron quantification is useful in confirming the diagnosis of iron-deficiency anemia or hemochromatosis. The measurement of total iron binding in the same specimen may facilitate the clinician's ability to distinguish between low serum iron levels caused by iron deficiency from those related to inflammatory neoplastic disorders. The assay for iron measures the amount of iron which is bound to transferrin. The total iron binding capacity (TIBC) measures the amount of iron that would appear in blood if all the transferrin were saturated with iron. It is an indirect measurement of transferrin concentrations but expressed as an iron measurement. To obtain the percent saturation, the serum iron is divided by the TIBC which gives the actual amount of saturated transferrin. The percent saturation is low in iron deficiency and high in iron storage diseases.

Nutrition & Vitamins, Blood Disorders

Folic acid deficiency is common in pregnant women, alcoholics, in patients whose diets do not include raw fruits and vegetables, and in people with structural damage to the small intestine. The most reliable and direct method of diagnosing folate deficiency is the determination of folate levels in both erythrocytes and serum. Low folic acid levels, however, can also be the result of a primary vitamin B12deficiency that decreases the ability of cells to take up folic acid.

Nutrition & Vitamins, Blood Disorders

Offered as part of multiple lab tests

Blood Disorders

Toxocaral disease (visceral larva migrans) is a typical parasitic disease in which eosinophil counts (eosinophils >30% on differential) are usually elevated. Taylor et al1point out, however, that up to 27% of children with toxocariasis have normal eosinophil counts. Thus, normal eosinophil counts do not rule out toxocaral disease or other parasitic infestations. The cytokine interleukin 5 appears to induce eosinophilia in patients with certain parasitic diseases.2An important although rare cause of increased eosinophils in the peripheral blood is the acute hypereosinophilic syndrome (HES). Reported mortalities ranged from 81% to 95% in one to three years. The HES syndrome includes high peripheral WBC count, circulating early eosinophilic forms without blast cells, mental confusion, delusions, near coma, and severe cardiac symptoms. Consistently associated with a poor prognosis are WBC count ≥90,000/mm3, blast forms in blood, heart failure, and severe CNS symptoms (confusion, organic psychosis and coma). This condition may not be a true leukemic myeloproliferative disease, although concepts of HES are controversial.Infiltrative lung diseases, in which peripheral blood eosinophils may be increased, include eosinophilic pneumonia, Löffler syndrome (often related toAscarisinfestation), and tropical eosinophilia (usually related to filariasis).3Eosinophilic gastroenteritis may occur with blood eosinophilia.4Eosinophilia myalgia syndrome (EMS) characterized by an eosinophil count of 2000 cells/mm3or more and severe often incapacitating myalgia is possibly associated with the use of L-tryptophan-containing products (LTCPs). Further definition of this syndrome, causal association between LTCPs and EMS, and modifying etiologic factors/cofactors has been recommended and is being pursued by CDC.5,6EMS is potentially fatal (Guillain-Barré like ascending polyneuropathy) with a clinical course resembling the toxic oil syndrome that was epidemic in Spain in 1981.7

Blood Disorders

Offered as part of multiple lab tests

Nutrition & Vitamins, Blood Disorders

Folic acid deficiency is common in pregnant women, alcoholics, patients with diets that do not include raw fruits and vegetables, and people with structural damage to the small intestine. The most reliable and direct method of diagnosing folate deficiency is the determination of folate levels in both erythrocytes and serum. Low folic acid levels, however, can also be the result of a primary Vitamin B12 deficiency that decreases the ability of cells to take up folic acid.B12 is decreased in pernicious anemia, total or partial gastrectomy, malabsorption and certain congenital biochemical disorders.

Blood Disorders

The aPTT is a screening test that will detect deficiencies or inhibitors to the intrinsic (Factors VIII, IX, XI and XII) and common (Factors II, V, X and fibrinogen) pathway coagulation factors.

Nutrition & Vitamins, Blood Disorders

B12 is decreased in pernicious anemia, total or partial gastrectomy, malabsorption and certain congenital and biochemical disorders.

Blood Disorders, General Health & Wellness

ABO type and Rh are needed to identify candidates for Rh immune globulin and to assess the risk of hemolytic disease of the newborn.

Blood Disorders, Nutrition & Vitamins

This serum iron study panel may help diagnose iron deficiency or overload. Because ferritin level can be affected by clinical conditions other than iron disorders, the measurement of transferrin saturation-calculated from serum iron level and total iron binding capacity (TIBC)-in the same serum specimen may facilitate the diagnosis of iron deficiency or overload [1-3].Serum ferritin level generally reflects body iron storage and can be used in the diagnosis of iron deficiency and overload. Transferrin saturation is the percentage of iron bound to transferrin. In patients with anemia, ferritin levels are most frequently used to determine whether iron deficiency is the cause [1]. However, as an acute phase protein, ferritin levels can be increased independently of iron status in inflammatory conditions, kidney disease, liver disease, and malignancy. In these clinical scenarios, the combination of ferritin level with other tests, such as transferrin saturation, may aid in the evaluation of iron deficiency [1,3].In patients with suspected hemochromatosis, transferrin saturation and serum ferritin may be included in the initial evaluation of iron overload [2]. The combination of a transferrin saturation under 45% and a normal serum ferritin level may help exclude iron overload. A transferrin saturation equal or over 45% alone or with an elevated ferritin level may suggest further testing. Serum ferritin level is also a predictor of advanced fibrosis [2].Note that reference intervals of serum iron, TIBC, transferrin saturation, and ferritin depend upon age and sex.The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Ko CW, et al.Gastroenterology. 2020;159(3):1085-1094.2. Kowdley KV, et al.Am J Gastroenterol. 2019;114(8):1202-1218.3. Lopez A, et al.Lancet. 2016;387(10021):907-916.

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders, Nutrition & Vitamins

Use in evaluating erythropoietic activity.

Blood Disorders, Nutrition & Vitamins

Transferrin is a direct measure of the iron binding capacity. Transferrin is thus useful in assessing iron balance. Iron deficiency and overload are often evaluated with complementary laboratory tests.

Heart Health & Cardiovascular, Blood Disorders

PT/INR:Screening test for abnormalities of coagulation factors that are involved in the extrinsic pathway. Also used to monitor effects of Warfarin therapy and to study patients with hereditary and acquired clotting disorders.aPTT:The aPTT is a screening test that will detect deficiencies or inhibitors to the intrinsic (Factors VIII, IX, XI and XII) and common (Factors II, V, X and Fibrinogen) pathway coagulation factors.

Heart Health & Cardiovascular, Blood Disorders

SeeAntithrombin (AT) Deficiency Profile [015594]for more clinical information.

Blood Disorders

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world, affecting an estimated 400 million people worldwide [1]. It is more common in people of African, Mediterranean, and Asian descent. G6PD deficiency is an X-linked genetic disorder and, in general, affects males more than females. Severity ranges from mild to severe subtypes. Newborns with G6PD deficiency may have prolonged and more pronounced neonatal jaundice than other newborns. Adults with G6PD deficiency may have episodes of acute hemolytic anemia, and symptoms may include jaundice, fatigue, splenomegaly, and dark urine. Episodes may be induced by illness (infections), certain foods (fava beans), and particular medications (for example some sulfonamides and antimalarial drugs)[2]; therefore, some precautions may be recommended to avoid offending triggers.Quantitative Glucose-6-Phosphate Dehydrogenase is an assay that measures the G6PD enzyme level. A low value may indicate G6PD deficiency (as opposed to values either within or above the reference range). [Perkins[3]] has found that some females with G-6-PD deficiency have difficulty in carrying a pregnancy to term. Erythrocytic G-6-PD appears to be sensitive to the endocrine changes associated with pregnancy. [Vergnes and Clerc [4]] found that 65% of their patients showed a significant fall in the G-6-PD activity in the later months of pregnancy with return to normal after delivery. Of note, as reticulocytes have higher G6PD activity than mature erythrocytes, if the blood sample is collected just after an acute hemolytic episode, G6PD activity levels can be falsely normal [5]. Therefore, if G6PD deficiency is suspected, consider repeating the test. Molecular genetic testing may also be indicated in cases where the disorder is suspected, or where there is a family history of G6PD deficiency, as enzyme activity may be normal in heterozygous females.References1.https://www.who.int/malaria/mpac/mpac-october2019- session7-updating-G6PD-classification.pdf2. Luzzatto L, Nannelli C, Notaro R. Glucose-6-Phosphate Dehydrogenase Deficiency. Hematol Oncol Clin North Am. 2016 Apr;30(2):373-93.3. Perkins, R. The significance of glucose-6-phosphate dehydrogenase deficiency in pregnancy. Amer. J Obstetr. And Gynec. 1976. May;125(2):215-223.4. Vergnes, H and Clerc, A. Erythrocyte Enzyme Activity in Pregnancy. Lancet 1968 Oct;292(7572):834.5. Frank J. Diagnosis and Management of G6PD Deficiency. Am Fam Physician. 2005 Oct;72(7):1277-82.

Heart Health & Cardiovascular, Blood Disorders

Thrombin time will be extended when functional fibrinogen levels are <100 mg/dL.6,7This can occur due to congenital conditions including afibrinogenemia (complete lack of fibrinogen), hypofibrinogenemia, and in dysfibrinogenemia, a condition characterized by the presence of dysfunctional fibrinogen. Acquired conditions can lead to diminished fibrinogen levels and extended thrombin times include liver disease, renal disease, disseminated intravascular coagulation (DIC), amyloidosis, malignancy, and thrombolytic therapy.6Thrombin inhibitors including heparin, argatroban, and hirudin will cause an extended thrombin time.7

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders, Liver & Kidney Health

Offered as part of multiple lab tests

Blood Disorders, Nutrition & Vitamins

Offered as part of multiple lab tests

Blood Disorders, Genetic Testing

This is a screening test to determine the presence of sickling hemoglobins. (e.g. hemoglobin-s, hemoglobin c-Harlem). It is important to detect Hb-S in order to determine which individuals are at risk of crisis when exposed to prolonged anoxia such as may occur during surgery, athletic programs or high altitude conditions.

Genetic Testing, Blood Disorders

Acute attacks of acute intermittent porphyria are precipitated by drugs, including barbiturates, hydantoins, hormones, infection, and diet. The most common symptom of acute intermittent porphyria is abdominal pain. The most common sign is tachycardia.1Subjects with the porphyrias may pass urine the color of port wine. The term porphyria derives from the Greek “porphyria,” an expression for the color purple.1Quantitative porphobilinogen will pick up many but not all patients with acute intermittent porphyria in the latent period.

Nutrition & Vitamins, Blood Disorders

Folate levels have diagnostic significance in nutritional deficiencies, especially in cases of severe alcoholism, function damage to the upper third of small bowel, pregnancy and various forms of megoblastic anemia. Since serum folate levels are subject to rapid changes reflecting diet and absorption, RBC folate may be a better diagnostic tool since the levels remain fairly constant.

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders, Liver & Kidney Health

Elevated levels of serum erythropoietin (EPO) occur in patients with anemias due to increased red cell destruction in hemolytic anemia and also in secondary polycythemias associated with impaired oxygen delivery to the tissues, impaired pulmonary oxygen exchange, abnormal hemoglobins with increased oxygen affinity, constriction of the renal vasculature, and inappropriate EPO secretion caused by certain renal and extrarenal tumors. Normal or depressed levels may occur in anemias due to increased oxygen delivery to tissues, in hypophosphatemia, and in polycythemia vera.

Blood Disorders

SeeProtein S Deficiency Profile [117754]for more clinical information.

Genetic Testing, Blood Disorders

Offered as part of multiple lab tests

Blood Disorders

The detection and proper identification of hemoglobinopathies and thalassemias is an important aspect of the evaluation of patients with anemia, microcytosis and erythrocytosis.

Blood Disorders

Intrinsic Factor, produced by cells lining the stomach, binds Vitamin B12 (cyanocobalamin) to facilitate absorption of the vitamin. Blocking antibody impedes the action of Intrinsic Factor as observed in approximately half of the patients who develop pernicious anemia.

Nutrition & Vitamins, Blood Disorders

Vitamin K is a required co-factor for the synthesis of factors 2, 7, 9, and 10 and proteins C and S. Deficiencies of vitamin K lead to bleeding. Coumadin® (warfarin) acts as an anticoagulant because it is a vitamin K antagonist.

Nutrition & Vitamins, Blood Disorders

The Methylmalonic Acid (MMA) test is used in the diagnosis of acquired cobalamin (vitamin B12) deficiency in adults and to screen for inherited organic acidemia in neonates and infants. Elevated MMA in either blood or urine indicates vitamin B12 deficiency in adults, with MMA acting as a functional biomarker for vitamin B12 status. In neonates and infants, elevated MMA is associated with inborn errors of metabolism.Adults with signs and symptoms of cobalamin deficiency, including peripheral neuropathy, ataxia, memory impairment, depression, behavioral changes, and anemia, should be tested for MMA, especially if they are elderly or have experienced intestinal malabsorption or digestive disorders [1]. In the United States all newborns should be screened for MMA as part of the Department of Health and Human Services (HHS) Recommended Universal Newborn Screening Panel [1].MMA can be acquired due to underlying medical conditions that lead to B-vitamin deficiencies or inherited as an autosomal recessive inborn error of metabolism. If a neonate or infant has elevated MMA suggestive of an organic acidemia, the parents may elect to undergo carrier testing, or have their other children undergo genetic testing. Siblings of a child with MMA-related mutation have a 25% chance of being affected and a 50% chance of being a carrier [2].References1. Department of Health and Human Services. Recommended Uniform Screening Panel.https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html. Updated February 2019. Accessed July 2019.2. Manoli, et al. Isolated methylmalonic academia. Updated: December 1, 2016. In: Adam MP, Ardinger HH, Pagon RA, et al. editors. GeneReviews [Internet]. Seattle (WA)L University of Washington

Blood Disorders

Urinary Porphobilinogen is the first step in the diagnosis of acute porphyrias such as acute intermittent porphyria (AIP). AIP is an autosomal dominant disorder characterized by deficiency of porphobilinogen deaminase. An acute attack usually includes gatrointestinal disturbance and neuropsychiatric disorders.

Blood Disorders

Haptoglobin is a protein that binds free hemoglobin. Part of α2on serum protein electrophoresis, serum haptoglobin is a glycoprotein consisting of two pairs of nonidentical chains, α and β, made by the liver. The subunit structure is represented as α2β2. The haptoglobin-bound hemoglobin complex is removed rapidly by the reticuloendothelial system and metabolized to free amino acids and iron in just a few hours. This represents an efficient method for the conservation of iron. Low α2is commonly due to hemolysis and/or liver disease. Serum protein electrophoretic pattern showing low albumin, polyclonal increase in γ-globulin, and decrease in α2-globulin shown to be due to decreased haptoglobin has been correlated with poor prognosis in severe liver disease.2Haptoglobin is decreased for two to three days after only 25 mL of blood is lysed.1Thus, transfusions, which contain red blood cells which do not all survive in the recipient, can lower the level. The decrease in haptoglobin (after hemolysis) precedes any drop in hemopexin levels or the appearance of methemalbumin in serum or urine. Myoglobin, unlike hemoglobin, is not bound by haptoglobin.

Blood Disorders

Offered as part of multiple lab tests

Nutrition & Vitamins, Blood Disorders

Methylmalonic Acid (MMA) is useful to diagnose and monitor Vitamin B12(cobalamin) deficiency, and to diagnose and monitor patients with methylmalonic acidemia.

Blood Disorders

Decreased haptoglobin is found in hemolytic disease, hepatocellular disease and infectious mononucleosis. Increased level is found in inflammatory disease in the presence of tissue necrosis and in general acute inflammatory conditions.

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders

Bacterial sepsis constitutes one of the most serious infectious diseases. The detection of microorganisms in a patient's blood has importance in the diagnosis and prognosis of endocarditis, septicemia, or chronic bacteremia.

Blood Disorders, Heart Health & Cardiovascular

High serum viscosity may be most commonly observed in patients with Waldenström's macroglobulinemia and multiple myeloma. Patients with high viscosity may have capillary occlusion, stasis hypoxia, and acidosis.

Blood Disorders, Heart Health & Cardiovascular

Factor VII is a 48 kilodalton single-chain nonenzymatic cofactor that is synthesized in the liver.6Factor VII is a vitamin K-dependent protein with a plasma concentration of 0.5 mg/mL.6The plasma half-life of factor VII is short at about four to six hours.6Factor VII deficiency should be considered when a patient with excessive bleeding has an extended protime (PT) and a normal activated partial thromboplastin time (aPTT). Congenital factor VII deficiency is rare (less than one case per 500,000 individuals) and is inherited as an autosomal recessive trait.6,7This condition affects both males and females and the prevalence of factor VII deficiency is equal in all ethnic groups.6,7A few cases of combined congenital factor II, VII, IX, and X factor deficiencies have been reported.6Symptoms (homozygotes and double heterozygotes) can include mucosal bleeding, epistaxis, postsurgical and postpartum hemorrhage, menorrhagia, gastrointestinal bleeding, and umbilical cord hemorrhage.6-8Heterozygotes are usually asymptomatic.8Factor VII plasma activity <30% may result in excessive bleeding following a traumatic event.6Spontaneous bleeding similar to that observed in severe hemophilia may occur when the activity is <1%;6,7however, symptomatology does not always correlate with the degree of factor VII deficiency and some patients with low levels may have no bleeding symptoms at all.6,7Diminished factor VII levels can be seen in patients with significant hepatic dysfunction, with oral anticoagulant (coumarin) therapy, and in individuals with vitamin K deficiency.6,7Low levels can also be observed in patients with specific factor VII inhibitors and in association with homocystinuria and aplastic anemia.7High levels of factor VII activity were found to be associated with increased risk for ischemic heart disease events by the Northwick Park Heart Study in 1986;9however, more recent studies have failed to identify factor VII levels as an independent risk factor for thrombosis.10A recent consensus conference of the College of American Pathologists on diagnostic issues in thrombophilia did not recommend measurement of factor VII levels for the assessment of thrombotic risk.10

Blood Disorders, Heart Health & Cardiovascular

Factor VIII is a large glycoprotein cofactor (320 kilodaltons) that is produced mainly in hepatocytes, but also to some extent by liver macrophages, megakaryocytes, and endothelial cells.6,10Factor VIII circulates in the plasma bound to von Willebrand factor (vWF) at a concentration of approximately 0.1 mg/mL.10The plasma half-life of factor VIII is short at about 8 to 10 hours.10Factor VIII deficiency should be suspected when a patient with excessive bleeding has a normal protime (PT) and an extended activated partial thromboplastin time (aPTT).Hemophilia A, or classic hemophilia, occurs as the result of congenital deficiency of factor VIII.6,11Clinical features of hemophilia A are the same as for hemophilia B which is caused by factor IX deficiency (seeFactor IX Activity [086298]). Hemophilia A is the second most common inherited bleeding abnormality (second only to von Willebrand disease), occurring in approximately 1 of every 5000 live male births.6,11Hemophilia A accounts for approximately 85% of all hemophilia cases.11This condition is transmitted as an X chromosome-linked hereditary disorder.11The majority of cases occur in men whose mothers are carriers of the genetic defect. About 30% of factor VIII deficiencies arise in men as spontaneous mutations.6,11The prevalence of hemophilia A is equal in all ethnic groups.6,11Female carriers of hemophilia A may rarely present with excessive bleeding.6Hemophilia symptoms can also occur in female carriers who have a high degree of lyonization of the factor VIII alleles.11Females with Turner syndrome karyotype XO, can also be symptomatic.11The severity of hemophilia A can be defined by the level of factor VIII activity.7,11Severe hemophilia, which represents approximately half the cases, is associated with a factor VIII level <1%. About 10% of cases are moderate with factor VIII levels of 1% to 5% and the remaining 30% to 40% of hemophiliacs have the mild condition with factor VIII levels above >5%.Approximately 45% of cases of severe hemophilia A occur as the result of a genetic inversion of intron 22 of the factor VIII gene locus.7,11,12This genetic mutation results in the production of a protein that has no functional or immunologic factor VIII activity.11Numerous deletions, point mutations, and missense mutations have also been implicated in hemophilia A.7,11Family studies combined with genetic testing can determine if at-risk women are carriers for a hemophilia A mutation.11Factor VIII activity levels should not be used as the method of determining carrier status because a number of clinical conditions including pregnancy, infection, or inflammation can affect activity levels.11Patients with hemophilia A can present with any number of bleeding manifestations.6,11Often, infants with severe hemophilia are first diagnosed during the neonatal period because of excessive bleeding after circumcision or due to cord necrosis.11Hemophilic infants also frequently suffer from intracranial hemorrhage or scalp hematomas. Spontaneous hemarthroses, a common symptom of hemophilias, typically do not occur until the child starts walking.7,11Hematomas can often be observed at the sites of intramuscular injections for vaccination or medication. The most common sites of spontaneous bleeding in patients with severe hemophilia involve the joints and muscles. Recurrent bleeding leads to chronic muscle injury and degeneration of the joint tissue.6,11Gastrointestinal bleeding can occur in approximately 10% of hemophiliacs.11Males with mild-to-moderate hemophilia and female carries may have an increased bleeding tendency, especially following surgery or trauma.7Most individuals with von Willebrand disease will have decreased factor VIII levels because the von Willebrand factor (vWF) is the carrier protein for factor VIII in plasma.6,11Individuals with von Willebrand disease type 2 Normandy will have normal to slightly low vWF ristocetin cofactor activity and von Willebrand factor antigen and low factor VIII levels due to defective binding of factor VIII to the variant vWF molecule.11Factor VIII levels are elevated at birth and increase during pregnancy.6Factor VIII is an acute phase reactant with levels that rise during periods of acute stress, following surgery, and in inflammatory conditions.6Levels can also increase as the result of strenuous exercise or the administration of several drugs including epinephrine, DDAVP, or estrogen (for birth control or hormone replacement therapy). Factor VIII levels can be elevated in a number of clinical conditions including carcinoma, leukemia, liver disease, renal disease, hemolytic anemia, diabetes mellitus, deep vein thrombosis, and myocardial infarction.6Persistent elevation of factor VIII above 150% is associated with an increased risk for venous thrombosis of more than fivefold.10,13Elevated factor VIII is also associated with an increased risk for recurrence of venous thromboembolism. Risk is graded such that the higher the factor VIII activity, the higher the risk.14The basis for this increased risk is not well understood as genetic studies of the factor VIII and von Willebrand factor genes failed to identify a genetic basis for this increased risk.10Values >150% are observed in 20% to 25% of individuals with venous thrombosis or thromboembolism in the absence of other known causes of factor VIII elevation.13A syndrome of combined factor VIII and V deficiencies has been described in over 60 families in and around the Mediterranean basin.15Hemophilia A patients receiving replacement products can develop inhibitors to factor VIII due to the production of alloantibodies.6,8Acquired hemophilia caused by the development of autoantibodies to factor VIII can also occur.9This rare condition (1 in 1,000,000 individuals) can following pregnancy and in elderly individual with autoimmune disorders. In this life-threatening condition, patients have bleeding symptoms similar to those seen in severe congenital hemophilia A.

Blood Disorders, Liver & Kidney Health

A serum protein electrophoresis should be reviewed concurrently if one has not been recently studied. In nonselective glomerular proteinuria, the urine electrophoretic pattern is often a nonspecific one which may be called “mirror image” to that of the serum. Contamination of the urine with blood can give a similar pattern. With selective glomerular permeability, albumin, α1proteins, and transferrin are the predominant proteins identified on the urine protein electrophoresis, with a relative absence of heavier molecular weight proteins (ie, α2-macroglobulin and immunoglobulins). With tubular proteinuria, low molecular weight proteins (α2- and β2-microglobulins) are predominant, with trace amounts of albumin. So called “overflow proteinuria” occurs when low molecular weight proteins are filtered through the glomerulus in increased amounts.

Blood Disorders, Liver & Kidney Health

This test is used to analyze the protein content in urine. The proteins are separated into 5 major components: albumin, alpha-1, alpha-2, beta, and gamma. Interpretation of elevations, decreases, or visual changes in different components and/or associated patterns can provide information on various disease states, including inflammatory diseases, autoimmune diseases, different types of kidney injury, plasma cell disorders, and cancers [1,2].UPEP is used to evaluate an individual with symptoms associated with potential monoclonal gammopathy, or when an individual has abnormally high total protein, albumin, or immunoglobulin levels. This test can help with initial diagnosis, as well as monitoring disease progression and treatment effectiveness [1,2].Specifically, the use of 24-hour urine collection (vs random urine) is recommended by the National Comprehensive Cancer Network (NCCN) Panel as one of the tests for diagnosis for multiple myeloma and for monitoring response to treatment. The International Myeloma Working Group (IMWG) recommends ordering this test every 3 to 6 months, or as needed, for example, to establish baseline or if disease worsens [1].The advantage of analyzing urine that has been collected over a 24-hour period is that it provides insight into compositional changes in urine throughout the day. This allows for a more accurate assessment of urine composition, based on averages, making the test more sensitive than a random UPEP test (test code 8525).NOTE: The results of this test should not be used in isolation; these results alone are not enough to make a diagnosis or for monitoring. UPEP results should be evaluated along with other laboratory, clinical, and imaging findings as appropriate. Additional testing, such as bone marrow studies, serum protein electrophoresis (SPEP), and immunofixation (IFE), may be required for comprehensive evaluation [1,2].References1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Multiple myeloma. Version 2.2020; October 9, 2019.https://www.nccn.org2. Rajkumar SV, et al.Lancet Oncol. 2014;15:e538-e548.

Blood Disorders

Soluble Transferrin Receptor (sTFR) values can be within normal limits over a broad range of body iron stores and is elevated only when there is functional (i.e. cellular) iron deficiency. It is usually not affected by chronic disease states, sTFR levels are about 6% higher in people in high altitudes (above 5200 ft/1600 m) and in African-Americans. Reference value may not apply to pregnant females and recent or frequent blood donors.

Infectious Diseases, Blood Disorders

Parvovirus B19 is also known as Fifth Disease. It primarily affects children and causes a rash on the face, trunk, and limbs. Joint pain and swelling is more common in adults. Although one-fifth of those affected have only mild disease, patients with sickle cell anemia or similar types of chronic anemia can suffer from acute anemia. Infection during pregnancy can lead to complications.

Blood Disorders, Heart Health & Cardiovascular

To evaluate an isolated prolonged PT or to evaluate prolongation of both the APTT and PT and to document factor X deficiency.6-8Factor X is a 54.8 kilodalton vitamin K-dependent glycoprotein coagulation factor that is produced by the liver.6Normal factor X's plasma concentration is approximately 10 mg/mL and half-life is about 40 hours.6Factor X activation occurs by both the extrinsic and intrinsic pathways. Factor X deficiency should be considered when a patient with bleeding history has both extended protime (PT) and activated partial thromboplastin time (aPTT). The dilute Russell viper venom (dRVVT) measures the activation of factor X and will be prolonged in patients with deficiency.7,8Congenital factor X deficiency is rare and is inherited as an autosomal recessive trait.6This condition affects both males and females.6A few cases of combined congenital factor II, VII, IX, and X factor deficiencies have been reported.6Acquired deficiencies occur with significant hepatic dysfunction, with vitamin K antagonist (warfarin) therapy, and in individuals with vitamin K deficiency.6,7Factor X deficiency may be associated with primary systemic amyloidosis.6,8Isolated factor X deficiency may also occur in patients with respiratory infections, acute myeloid leukemia, amyloidosis, and with other malignancies.7Acquired specific factor X inhibitors are rare in patients without congenital deficiency.6,7Symptoms (homozygotes) include hematoma formation, postsurgical hemorrhage, menorrhagia, hematuria, and umbilical cord hemorrhage.6,7Factor X plasma activity <30% may result in excessive bleeding following a traumatic event.6Spontaneous bleeding similar to that observed in severe hemophilia may occur when the activity is <1%.6,7

Blood Disorders

Offered as part of multiple lab tests

Nutrition & Vitamins, Blood Disorders

B12 is essential for certain enzymatic reactions that are required for numerous physiologic functions including erythropoiesis and myelin synthesis.1,2Impaired DNA synthesis caused by B12 deficiency impacts nuclear maturation of rapidly dividing cells. This affects hematopoiesis and results in the presence of immature and ineffective red cells that are larger than normal (megaloblasts) in a context of severe anemia and pancytopenia. This megaloblastic anemia is characterized by the hypersegmented neutrophils that can be seen on peripheral smears and giant bands in bone marrow. Other rapidly dividing cells of the small-bowel epithelium can be affected resulting in malabsorption and diarrhea.3Glossitis is a frequent hallmark of megaloblastic anemia, with the patient experiencing a painful, smooth, red tongue. Ineffective erythropoiesis and associated increased red cell turnover can result in elevation in bilirubin levels, manifesting as jaundice.3B12 deficiency can also produce neurological manifestations including sensory and motor disturbances (symmetric paresthesias, numbness and gait problems), ataxia, cognitive decline leading to dementia and psychiatric disorders. These neurological symptoms often predominate and can frequently occur in the absence of hematological complications.3,7In fact, the majority of patients with suspected B12 deficiency do not have anemia.5-8Emerging evidence indicates that low (though not necessarily deficient) B12 is associated with increased risk of various chronic diseases of ageing including cognitive dysfunction, cardiovascular disease and osteoporosis.5,6Dietary vitamin B12 is normally bound to proteins in food and requires release by gastric acid and pepsin in the stomach.7In the small intestine, vitamin B12 binds to intrinsic factor (IF) produced by gastric parietal cells. In the ileum, the B12-IF complex binds to specific receptors, which facilitates absorption into the blood. Large amounts of absorbed vitamin B12 are stored in the liver such that any reduction in vitamin B12 intake/absorption may take many years to manifest clinically.8Low B12 status, especially in older adults, is rarely attributable to dietary insufficiency9and is more typically the result of malabsorption related to atrophic gastritis, inflammatory bowel disease or use of proton pump inhibitors or other gastric acid suppressant drugs.2,6,7,10-13The diagnosis of vitamin B12 deficiency requires consideration of both the clinical state of the patient and the results of laboratory tests. Screening average-risk adults for vitamin B12 deficiency is not recommended.2However, testing should be considered in patients with risk factors and/or clinical blood count and serum vitamin B12 level.2,5,7,14,15The World Health Organization16and the British Committee for Standards in Haematology14suggested using 200 pg/mL as a cut-off to define B12 deficiency. In practice, detectable disturbances in metabolic networks consistent with possible deficiency occur at B12 levels as high as 400 pg/mL.17A significant number of B12-deficient patients may be overlooked when serum B12 measurement is used in isolation.5,17Further investigation using a second-line test can be useful for serum B12 results that fall within the indeterminate range. The enzyme, methylmalonyl-CoA mutase requires vitamin B12 as a cofactor for the conversion of methylmalonyl-CoA to succinyl-CoA.5In vitamin B12 depletion, reduced activity of this enzyme leads to an accumulation of methylmalonyl-CoA which is, in turn, hydrolyzed to methylmalonic acid. Measurement of serum methylmalonic acid provides biochemical evidence of metabolic abnormalities consistent with B12 insufficiency.2,5,7,10,14,18,19In the United States and the United Kingdom, the prevalence of vitamin B12 deficiency has been estimated to be approximately 6% of persons younger than 60 years, and nearly 20% in those older than 60 years.10B12 status in the United States has been assessed in the National Health and Nutrition Examination Survey (NHANES).20Using NHANES data from 1999 to 2004, the prevalence of B12 status defined as low was estimated to be 2.9%, 10.6% or 25.7% based on serum B12 cut-off values of 200, 300 and 400 pg/mL, respectively.20Using these cut-off values, the prevalence of low B12 status increased with age from young adults (19-39 years of age) to older adults (greater than or equal to 60 years of age), and was generally higher in women than than in men (prevalence of 3.3% versus 2.4% with a serum B12 level of <200 pg/mL, respectively).20Using increased levels of MMA as a functional indicator of B12 status, the prevalence of low B12 status was 2.3% or 5.8% based on cut-off values of >376 and >271 nmol/L, respectively.20The prevalence of increased levels of MMA increased with age and was not different between men and women.20Notably, only 50-75% of participants in NHANES with low levels of serum B12 had increased levels of MMA.20It should also be noted that modest increases occur with renal failure.7Pernicious Anemia (PA) caused by autoimmune destruction of gastric parietal cells and atrophy of the gastric mucosa is the most common cause of vitamin B12 deficiency.3,6,7,21Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of mucosal atrophy by 10-20 years.22With disease progression, an increasing number of the parietal cells that produce hydrochloric acid and intrinisic factor are destroyed.22This may present initially as iron deficiency anemia due to loss of gastric acid, which is required for iron absorption.1,23Ultimately, diminished production of intrinsic factor together with development of neutralizing antibody against intrinsic factor itself leads to B12 malabsorption.2,3,10,24The autoimmune nature of PA is reflected by the presence of autoantibodies against the parietal cell proton pump protein (H/K ATPase) and to intrinsic factor.3,20,24,25This condition frequently coexists with other autoimmune disorders including Hashimoto's thyroiditis and type 1 diabetes mellitus.3,24,29Parietal Cell Antibodies (PCA) are present at a high frequency in PA (80%-90%), especially in early stages of the disease and are considered a predictive marker of subsequent gastric mucosa atrophy and its hematologic manifestations.3,24In the later stages of the disease, the incidence of PCA decreases due to the progression of autoimmune gastritis and a loss of gastric parietal cell mass, as a result of the decrease in antigenic rate.26PCA can precede the clinical symptoms of the gastric disease by several years.3PCA are found in 90% of patients with PA, but have low specificity and are seen in various autoimmune disorders.1Intrinsic Factor Antibodies (IFA) are less sensitive, but are considered highly specific for PA.3Studies have reported positivity for IFA in 40%-60% of patients with PA, which rises to 60%-80% with increasing duration of disease.3,27The combined assessment of both PCA and IFA increases diagnostic performance, with 73% sensitivity and 100% specificity.28Diminished acid secretion caused by gastric atrophy resulting from autoimmune disease or some other etiology elevates secretion of gastrin. Elevated gastrin levels can support the diagnosis of PA.24,29Hypergastrinaemia arising from loss gastric parietal cells drives development of antral enterochromaffin cell hyperplasia that can further develop into neoplasia and carcinoid syndrome.1,3,24,30,31

Blood Disorders

Porphyria is a group of distinct disorders characterized by the abnormal accumulation of porphyrins or porphyrin precursors. Porphyrin fractionation of plasma is useful in diagnosing certain types of porphyrias and excluding porphyrias in patients with chronic renal failure suspected of having a porphyria.

Blood Disorders, Heart Health & Cardiovascular

Protein C (PC) is a vitamin K-dependent plasma protein that is synthesized by the liver as an inactive precursor.7-9This protein is then further transformed into activated PC by a complex of thrombin and the endothelial factor, thrombomodulin, that is bound to phospholipid membrane in a calcium-dependent manner. aPC regulates the coagulation process by inactivating factors Va and VIIIa. Protein S, another vitamin K-dependent protein, serves as an essential cofactor of aPC for the inactivation of factors Va and VIIIa. In inhibiting these factors, PC serves to limit thrombus extension, and thus acts as a major regulator of the coagulation process.Congenital protein C deficiency:Congenital PC deficiency has been estimated to occur in approximately 3 out of 1000 individuals.7,8Between 2% and 5% of cases of recurrent venous thrombosis are related to congenital PC deficiency.7Nearly 50% of individuals with heterozygous PC deficiency and 10% of their relatives experience thrombotic episodes by age 45. Initial thrombotic events frequently occur between 20 and 30 years of age. The probabilities of thrombosis or pulmonary emboli increase dramatically when PC activity levels fall to <50%.7Thrombosis can sometime occur at unusual sites, including mesenteric and axillary veins. Recurrent thrombotic events are common.7In the majority of cases, thrombosis can be linked to trauma, surgery, pregnancy oral contraceptive usage, or other risk factors. However, thrombosis can occur spontaneously with no precipitating events or other known risk factors in about 33% of cases.7Congenital PC deficiency can be classified as either type I or type II.9Type I deficiency results from a quantitative reduction in PC production, resulting in a simultaneous decrease of both the functional and antigenic levels of PC. In type II deficiency, PC antigen concentration is normal but its activity is diminished because the PC is dysfunctional due to genetic defect. This is reflected by a diminished PC activity in the context of normal PC antigen levels. Neonates born with homozygous or doubly heterozygous PC deficiency suffer from DIC or purpura fulminans of the newborn, devastating conditions requiring immediate treatment.8Acquired protein C deficiency:Acquired PC deficiency occurs more frequently than congenital deficiency.7PC levels can be transiently diminished after a thrombotic event or surgery. Oral anticoagulant therapy with warfarin will lower PC levels. Vitamin K deficiency, due to dietary insufficiency or malabsorption, will also lead to reduced PC levels. Acquired deficiency can be found in individuals with disseminated intravascular coagulation (DIC) and sepsis. Severe hepatic disorders (hepatitis, cirrhosis, etc), renal failure, malignancy, and inflammatory bowel disease can lead to diminished PC levels.7Drug therapy with L-asparaginase or fluorouracil can also reduce PC levels.In some cases, warfarin anticoagulation of thrombotic patients with heterozygous PC deficiency will induce skin necrosis due to the rapid drop in already low PC activity.7,9

Blood Disorders, Heart Health & Cardiovascular

Factor IX is a 72 kilodalton vitamin K-dependent glycoprotein proenzyme that is produced by the liver.6Factor IX's plasma concentration is 3-5 mg/mL and half-life is about 24 hours.6Factor IX deficiency should be suspected when a patient with excessive bleeding has a normal protime (PT) and an extended activated partial thromboplastin time (aPTT).Hemophilia B, or Christmas disease, occurs as the result of congenital deficiency of factor IX.6,7Clinical features of hemophilia B are the same as for hemophilia A which is caused by factor VIII deficiency (seeFactor VIII Activity [086264]). Hemophilia B is less common than hemophilia A, occurring in approximately 1 of every 30,000 live male births.7The prevalence is significantly higher in Amish and East Indian populations.8This condition is transmitted as an X chromosome-linked hereditary disorder.7The majority of cases occur in men whose mothers are carriers of the genetic defect. A subtype of hemophilia B, hemophilia B Leiden, is characterized by altered developmental expression of factor IX such that plasma factor IX levels may be <1% of normal during childhood, but after puberty may gradually rise to a maximum of 70% of normal.12Hemophilia B can also occur as the result of spontaneous mutations of the factor IX gene locus.7Female carriers of hemophilia B may rarely present with excessive bleeding.7Hemophilia symptoms can also occur in female carriers that have a high degree of lyonization of the factor X alleles.7Females with Turner syndrome, karyotype XO, can also be symptomatic.7The severity of hemophilia B can be defined by the level of factor IX activity.7,8Severe hemophilia is associated with a factor IX level of <1%. Moderate hemophilia B occurs with factor IX levels of 1% to 5% and mild hemophilia has factor IX levels >5%.Patients with hemophilia B can present with any of a number of bleeding manifestations.6,7Often, infants with severe hemophilia are first diagnosed during the neonatal period because of excessive bleeding after circumcision or due to cord necrosis.7Hemophilic infants also frequently suffer from intracranial hemorrhage or scalp hematomas. Spontaneous hemarthroses, a common symptom of hemophilias, typically do not occur until the child starts walking.7,8Hematomas can often be observed at the sites of intramuscular injections for vaccination or medication. The most common sites of spontaneous bleeding in patients with severe hemophilia are involve the joints and muscles. Recurrent bleeding leads to chronic muscle injury and degeneration of the joint tissue.6,7Gastrointestinal bleeding can occur in approximately 10% of hemophiliacs.7Males with mild to moderate hemophilia and female carriers may have an increased bleeding tendency, especially following surgery or trauma.8Acquired factor IX deficiency can occur as the result of oral anticoagulant therapy or with vitamin K deficiency.6,8Individuals with advance liver disease can have a generalized decrease in coagulation factors, including factor IX.Elevation of factor IX, if persistent, has been associated with approximately a twofold increased risk for venous thrombosis.9The basis for this increased risk is not well understood and the clinical cutoff for risk assessment has yet to be established.9Hemophilia B patients receiving replacement products can develop inhibitors to factor IX in approximately 3% of cases, due to the production of alloantibodies.6,10Acquired hemophilia caused by the development of autoantibodies to factor IX can also occur.11This rare condition can occurs most often in individuals with autoimmune disorders. These patients have bleeding symptoms similar to those seen in congenital hemophilia B.

Blood Disorders, Heart Health & Cardiovascular

Factor V is a large (330 kilodalton) single-chain nonenzymatic cofactor that is synthesized in hepatocytes, megakaryocytes, and endothelial cells.6,7,9Approximately 20% of the total factor V is carried in the α granules of platelets and is released when platelets are activated.6The structure of factor V is similar to that of factor VIII.9Factor V's plasma concentration is 7 mg/mL and half-life is about 15 to 36 hours. Factor V activation occurs by both the extrinsic and intrinsic pathways. Factor V deficiency should be considered when a patient with bleeding history has both extended protime (PT) and activated partial thromboplastin time (aPTT).Congenital factor V deficiency, sometimes referred to as parahemophilia, is rare (less than one case per million individuals) and is inherited as an autosomal recessive trait.6,7,9This condition affects both males and females and the prevalence of inherited factor V deficiency is equal in all ethnic groups.9Factor V levels are decreased both in plasma and platelets.6A syndrome of combined factor V and VIII deficiencies has been described in over 60 families in and around the Mediterranean basin.8Symptoms (homozygotes) can include hematoma formation, postsurgical and postpartum hemorrhage, menorrhagia, hematuria, and umbilical cord hemorrhage.6,9Factor V plasma activity <30% may result in excessive bleeding following a traumatic event.9Unlike individuals with severe hemophilia, patients with factor V levels <1% do not typically develop spontaneous joint hemarthroses.6Diminished factor V levels can be seen in liver disease, disseminated intravascular coagulation (DIC) syndromes, and in other consumption coagulopathies.9,10Specific factor V inhibitors can occur, especially after surgical procedures that involve multiple exposures to bovine topical thrombin.9Postoperative treatment with aminoglycosides and penicillin has also been associated with development of factor V inhibitors.6,7Inhibitors do not typically develop in individuals with factor V deficiency.6One study found that elevated factor V activity may be associated with increased risk for myocardial infarction;11however, a recent consensus conference of the College of American Pathologists on diagnostic issues in thrombophilia did not recommend measurement of factor V levels for the assessment of thrombotic risk.10

Blood Disorders, Heart Health & Cardiovascular

Factor II is a 72-kilodalton vitamin K-dependent glycoprotein coagulation factor that is produced by the liver.6Normal factor II plasma concentration is approximately 100 mg/mL and half-life is about 60 hours.6Factor II activation occurs by both the extrinsic and intrinsic pathways. Factor II deficiency should be considered when a patient with bleeding history has both extended protime (PT) and activated partial thromboplastin time (aPTT). Inhibitors to factor II may develop in select patients with lupus anticoagulants and tends to occur more frequently in a pediatric population. These inhibitors bind factor II in plasma and clear the antibody-antigen complex resulting in a factor II deficiency and enhanced bleeding potential. A factor II Bethesda (inhibitor) assay is negative in this instance. The dilute Russell's viper venom time (dRVVT) will be prolonged in patients with factor II deficiency.7,8Congenital factor II deficiency is rare (fewer than 100 cases have been reported) and is inherited as an autosomal recessive trait.6,7This condition affects both males and females, and the prevalence of factor II deficiency is equal in all ethnic groups.6A few cases of combined congenital factor II, VII, IX, and X deficiencies have been reported.6Acquired deficiencies occur with significant hepatic dysfunction, with oral anticoagulant (coumarin) therapy, and in individuals with vitamin K deficiency.7,8Diminished levels that can be associated with bleeding can be observed in some patients with lupus anticoagulants due to enhanced clearance of prothrombin/antibody complexes.6,7Symptoms of factor II deficiency include easy bruising, hematoma formation, postsurgical hemorrhage, menorrhagia, epistaxis, and umbilical cord hemorrhage.6,7Heterozygous individuals typically have factor II activities near 50% and are asymptomatic or have minor bleeding complications associated with trauma or surgery.7Factor II plasma activity <30%, as can be observed in individuals with homozygous deficiency, may result in excessive bleeding following a traumatic event.6,8Spontaneous bleeding or hemarthroses are rare but may occur in homozygotes with very low activity.6-8Factor II activity in excess of 115% has been associated with an increased risk of thrombosis.6TheG20210Amutation in the prothrombin gene can be associated with increased plasma prothrombin levels.6,9This polymorphism can be identified in 1% to 2% of the US population, but is highly race-dependent. This mutation is relatively uncommon in African Americans, Asians, and native Americans.9A recent consensus conference of the College of American Pathologists on diagnostic issues in thrombophilia concluded that the prothrombinG20210Amutation is a significant risk factor of venous thromboembolism and should be considered in the initial evaluation of potential inherited thrombophilia.9

Blood Disorders, Heart Health & Cardiovascular

Factor XI is a 160 kilodalton glycoprotein proenzyme that is produced by the liver and megakaryocytes.6-8Factor XI's plasma concentration is 4-6 mg/mL and half-life is about 60 hours.6Hereditary factor XI deficiency, referred to as hemophilia C, is transmitted as an autosomal recessive mutation.6-8This condition affects both males and females and the majority of reported cases have been diagnosed in Ashkenazi Jews.6,7As many as 11% of Ashkenazi Jews will be heterozygous for factor XI deficiency and up to 0.3% will be homozygous.8Individuals who are heterozygous for factor XI deficiency mutation typically have levels between 30% to 60% and homozygotes have levels <20%.8The bleeding associated with factor XI deficiency is generally not as severe as that found with hemophilia A or B.7Severity of bleeding does not always correlate with the plasma level of factor XI.6,7Individuals with factor XI deficiency can suffer from easy bruising, epistaxis, hematuria, and menorrhagia.6,7Excessive bleeding postpartum and after oral cavity surgery can occur.7Acquired inhibitors of factor XI are very rare.6Spontaneous autoantibodies are more common and generally occur in patients with underlying autoimmune disorders or in patients treated with chlorpromazine.6

Blood Disorders, Heart Health & Cardiovascular

Factor XII along with prekallikrein and high molecular weight kininogen make up the contact activation system. These factors are necessary for clot formation in the activated partial thromboplastin (aPTT). In the test tube, factor XII is activated by contact with negatively-charged surfaces;8however, deficiencies of these factors have no hemorrhagic consequence because physiologic clotting is activated by alternate paths that bypass the contact system.6,7Factor XII is an 80 kilodalton single-chain proenzyme that is synthesized in the liver. Factor XII's plasma concentration is 30 mg/mL and half-life is about 50 hours. Factor XII deficiency is usually inherited in an autosomal recessive manner and heterozygous deficiency is relatively common, affecting somewhere between 1.5% and 3% of the population.6In fact, mild factor XII deficiency is the most common cause of extended aPTT in the nonbleeding patient in the absence of lupus anticoagulant.6Factor XII deficiency should be suspected whenever a patient has a normal protime (PT) and an extended aPTT and no history of bleeding. Factor XII levels are moderately diminished in heterozygous individuals with levels ranging between 20% and 60% of normal.7Homozygous individuals typically have levels <1%.6Severe factor XII deficiency is characterized by aPTT that can be longer than 100 seconds.7Typically, there is correction with a normal plasma mixing study.Factor XII can be affected, either increased and decreased in a number of conditions including septicemia, coronary artery disease, pharmacological thrombolysis, inflammatory bowel disease, pregnancy, lactic acidosis, hemodialysis, and angioedema.6,8Decreased factor XII levels can be seen in liver disease and renal disease.6A number of investigators have reported that congenital factor XII deficiency may be associated with an increased incidence of venous thrombosis;8however, a recent consensus conference of the College of American Pathologists on diagnostic issues in thrombophilia found no evidence to support hypercoagulability in patients homozygously deficient for factor XII or any of the other contact factors.8

Blood Disorders

A complete blood count is used as a screening test for various disease states to include: anemia, leukemia and inflammatory processes.

Blood Disorders, Cancer Screening

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) recommend the use of serum free light chain assays in the initial diagnostic work-up of multiple myeloma and related disorders."Use of free light chain (FLC) assay along with SPEP and SIFE yields high sensitivity while screening for MM and related plasma cell disorders. Therefore, this assay is now included as a part of the initial diagnostic work-up in the NCCN Multiple Myeloma Guidelines."1If screening for plasma cell dyscrasias, the International Myeloma Working Group recommends a screening panel consisting of serum free light chain assay, serum protein electrophoresis (SPEP), and serum immunofixation (IFE) to maximize sensitivity. (A 24-hour urine IFE can be added if AL amyloidosis is suspected.)2

Blood Disorders, Heart Health & Cardiovascular

Protein S (PS) is produced by the liver, megakaryocytes, and endothelial cells.6-8PS is synthesized as an inactive precursor that is activated by carboxylation of several glutamic acid residues by a vitamin K-dependent carboxylase. PS serves as an essential cofactor of activated protein C (aPC). In the presence of calcium, PS binds tightly to the phospholipid surfaces of endothelial cells and activated platelets. This serves to concentrate the PS/aPC complex at the site of thrombus formation where it regulates the coagulation process by enzymatically neutralizing activated factors Va and VIIIa. PS greatly potentiates the anticoagulant function of aPC. PS is enzymatically neutralized by thrombin. After thrombin proteolysis, PS retains its affinity for phospholipids, but loses its anticoagulant function as the cofactor for aPC.A portion of the PS in blood is bound to the protein, which binds the C4b region of complement (ie, the C4b-binding protein [C4b-BP]).7This C4b-BP forms a 1:1 complex with PS. In plasma, a dynamic equilibrium is reached between C4b-BP-bound and free PS. The free PS form represents about 40% of total PS in normal individuals. Only the free form can act as the cofactor for aPC and accelerate its anticoagulant activity. The PS that is bound to C4b-BP does not possess any anticoagulant activity because in cannot interact with aPC.A deficiency in PS, either congenital or acquired, increases the risk of thromboembolism because of a decrease in the anticoagulant capacity of the blood. Thrombotic episodes can occur when PS activity drops to <50% of normal.6Congenital protein S deficiency:The prevalence of congenital PS deficiency in the general population experiencing their first venous thrombosis is approximately 1%.7In patients with a family history of thrombophilia, the likelihood of congenital PS deficiency being the cause reaches as high as 10%.7This autosomal dominant defect occurs in the general population in approximately 1 in 700 individuals.6Nearly 50% of individuals with congenital PS deficiency will experience a thrombotic event before the age of 45.6Thrombosis can sometimes occur at unusual sites, including mesenteric and axillary veins. Recurrent thrombotic events are common.6Congenital PS deficiency can be further classified based on the measured levels of total and free PS antigen along with functional PS activity.7• Type I PS deficiency is the most common type, representing approximately 90% of cases.6This condition is characterized by a reduction in overall PS antigen levels. Levels of total PS in patients with type I deficiency are typically around 50% of normal while free PS and PS activity are often even lower.• Type II PS deficiency is characterized by a reduced PS activity but with normal antigen levels of both total and free PS.• Type III PS deficiency is characterized by a disproportionately reduced PS activity and free antigen levels in individuals with normal total PS levels.Acquired protein S deficiency:Acquired PS deficiency occurs more frequently than congenital deficiency.6-8Acquired deficiency can occur as the result of decreased PS synthesis or increased consumption. PS synthesis can be diminished in a number of conditions including oral anticoagulant therapy, vitamin K deficiency, liver disease, chemotherapy, and L-asparaginase therapy. PS consumption can occur during disseminated intravascular coagulation (DIC), acute thrombosis, polycythemia vera, sickle cell disease, and essential thrombocythemia. Protein S levels are also dependent, in part, on age, sex, and hormonal status, tending to be lower in the young and lower in women than in men. Levels may be further decreased in premenopausal women on oral contraceptive agents. Protein S values decrease with increasing gestational age. Free PS antigen and PS activities are also often diminished in nephrotic syndrome.7Warfarin-induced skin necrosis has been reported in some cases of PS deficiency.8Infants born with homozygous or doubly heterozygous PS deficiency are usually born with purpura fulminans of the newborn, a devastating condition requiring immediate treatment.8

Blood Disorders

Positive results suggest coccidioides infection.

Blood Disorders

Protein S (PS) deficiency may be congenital or acquired and is associated with venous thrombosis. Acquired PS deficiency may occur with vitamin K antagonists/deficiency, liver disease, malignancy, consumptive DIC, surgery, trauma, and hepatic immaturity of the newborn. In addition, PS deficiency is physiologic in pregnancy.Anticoagulant interference: Expected impact by therapeutic levels (potential interference depends upon drug concentration): Vitamin K Antagonists (eg. warfarin):decrease; Heparin (UFH or LMWH): no effect to falsely increased activity levels at higher levels; Dabigatran or Argatroban (Direct Thrombin Inhibitors): may falselyincrease activity; Rivaroxaban, Apixaban, Edoxaban (Factor Xa Inhibitors): may falsely increase activity.

Blood Disorders

Venous thromboembolism is a multifactorial disease influenced by genetic, environmental, and circumstantial risk factors. The c.1601G>A (p. Arg534Gln) variant in the F5 gene, commonly referred to as Factor V Leiden, is a genetic risk factor for venous thromboembolism. Heterozygous carriers of this variant have a 6- to 8-fold increased risk for venous thromboembolism. Individuals homozygous for this variant (ie, they have a copy of the variant on each chromosome) have an approximately 80-fold increased risk for venous thromboembolism. Individuals who carry both a *97G>A variant in the F2 gene and Factor V Leiden have an approximately 20-fold increased risk for venous thromboembolism. Risks are likely to be even higher in more complex genotype combinations involving theF2c.*97G>A variant and Factor V Leiden.1Additional risk factors include but are not limited to: deficiency of protein C, protein S, or antithrombin III, age, male sex, personal or family history of deep vein thromboembolism, smoking, surgery, prolonged immobilization, malignant neoplasm, tamoxifen treatment, raloxifene treatment, oral contraceptive use, hormone replacement therapy, and pregnancy. Management of thrombotic risk and thrombotic events should follow established guidelines and fit the clinical circumstance. This result cannot predict the occurrence or recurrence of a thrombotic event.Genetic coordinators are available for health care providers to discuss results and for information on how to order additional testing, if desired, at 1-800-345-GENE.

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders, Heart Health & Cardiovascular

This test is useful to evaluate a prolonged aPTT. The most common form of hemophilia is caused by a deficiency of Factor VIII. Hemophilia A is an X-linked disorder affecting between 1 in 5,000 to 10,000 males. Borderline low Factor VIII activity can be seen in female carriers of the defective Factor VIII gene. Typically this test is combined with other screening tests (eg. von Willebrand factor, Ristocetin Cofactor Activity) to evaluate for the presence von Willebrand disease.Anticoagulant interference: Expected impact by therapeutic levels (potential interference depends upon drug concentration): Warfarin: no effect; Heparin (UFH or LMWH): no effect to inhibitor pattern; Dabigatran or Argatroban (Thrombin Inhibitors): no effect to inhibitor pattern; Rivaroxaban, Apixaban, Edoxaban (Factor Xa Inhibitors): no effect to inhibitor pattern. Other limitations: Factor VIII levels may be falsely low due to Lupus anticoagulant. A chromogenic Factor VIII activity is suggested. The presence of factor VIII antibodies (autoantibodies or antibodies resulting from replacement therapy) can result in low factor VIII levels. This test is NOT recommended for patients receiving emicizumab (ie. Hemilbra) as this therapy will yield falsely elevated values. Factor VIII is a positive acute phase reactant and levels will increase in a variety of clinical scenerios.

Blood Disorders, Heart Health & Cardiovascular

Aids in characterization of Antithrombin deficiency (AT, previously referred to as Antithrombin III) which is associated with increased thrombotic risk. Type I deficiency is characterized by reduction in activity and antigen levels simultaneously. With type II deficiency, activity levels are lower in comparison to the antigen levels (dysfunctional protein). Acquired deficiency, more common than inherited defects, can occur due to: liver disease, nephrotic syndrome, heparin therapy, disseminated intravascular coagulation (DIC), sepsis, and L-asparaginase chemotherapy.Anticoagulant interference: heparin therapy may lower AT levels. Other anticoagulants do not impact testing (warfarin, target specific anticoagulants such as Dabigatran, Argatroban, Rivaroxaban, Apixaban, Edoxaban).

Blood Disorders

This test detects the factor V Leiden variant, the most common cause of inherited thrombophilia; it may be used to evaluate individuals with a strong personal or family history of venous thromboembolism (VTE) and inform treatment or preventive decisions [1].Factor V Leiden refers to the c.1691G>A variant in theFVgene, which encodes coagulation factor V. This variant results in resistance to factor V protein degradation by activated protein C and increases the risk of VTE 6 to 8 fold in heterozygous carriers and 80 fold in homozygous carriers [1]. The mean age of symptom onset is 31 to 44 years, but some heterozygous carriers can be asymptomatic [2]. In the United States, Factor V Leiden is most prevalent in White individuals, with an estimated frequency of 5% [1].Factor V Leiden testing may be indicated in clinical scenarios where results can help guide clinical decisions for the patient and family members. These clinical scenarios include first VTE developed under 50 years of age, VTE at an unusual site (eg, cerebral veins), recurrent VTE, a strong family history of VTE, and low activated protein C resistance activity [1].Routine testing for factor V Leiden is not recommended for prenatal carrier screening, newborn screening, or individuals taking an oral contraceptive [2]. A negative result of this test does not rule out inherited thrombophilia. Other than factor V Leiden, variants in the genes that encode coagulation factor II, protein C, protein S, and antithrombin can also cause inherited thrombophilia.The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Zhang S, et al.Genet Med.2018;20(12):1489-1498.2. Vnencak-Jones CL, et al. Genetics. In: Rifai R, et al, eds.Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier Inc; 2022.

Blood Disorders

Offered as part of multiple lab tests

Genetic Testing, Blood Disorders

Refer to individual assays for additional information.

Genetic Testing, Blood Disorders

Offered as part of multiple lab tests

Blood Disorders

Platelet antibodies can be autoimmune (directed against endogenous, i.e., the patient's own platelet antigens) or alloimmune (directed against antigens on exogenous platelets encountered through pregnancy or transfusion). Platelet antibodies may be directed to a number of antigenic “targets” carried on platelet cytoplasmic membranes.1-6This platelet antibody profile is designed to detect antibodies to HLA class I and platelet glycoprotein IV (CD36) antigens, and to polymorphic epitopes on the platelet GPs IIb/IIIa, Ib/IX, and Ia/IIa.4Platelet glycoprotein (GP) IV antigen deficiency is rare in Caucasians but frequent in Asians and Africans.4,7,8The IIb/IIIa glycoprotein complex plays a central role in platelet adhesion by binding fibrinogen, fibronectin, vitronectin, and von Willebrand factor.2Glycoprotein Ib/IX is the main receptor for von Willebrand factor and glycoprotein Ia/IIa is involved in collagen adhesion.2The congenital absence of IIb/IIIa results in Glanzmann thrombasthenia and the absence of Ib/IX causes Bernard-Soulier syndrome.Platelet antibodies may be involved in several clinical situations described below3,9:Immune Thrombocytopenic Purpura (ITP),formerly referred to as idiopathic thrombocytopenic purpura, occurs when platelet autoantibodies with broad reactivity against common epitopes on platelet glycoprotein complexes destroy an individual's platelets and result in a persistent thrombocytopenia.3,9-11Antiplatelet autoantibodies also are thought to impair platelet production by megakaryocytes.9,12,13ITP in children often can be associated to a transient viral infection. Approximately 15% of childhood ITP cases become chronic.2ITP in adults often has an insidious onset, resulting in chronic thrombocytopenia that rarely remits spontaneously.1,2This condition can be idiopathic, or in some cases, associated with another autoimmune condition (e.g., SLE) or malignancy.1The majority of autoantibodies identified in patients with ITP are directed against components of platelet glycoprotein IIb/IIIa. Antibodies to glycoprotein Ib/IX also are observed. Some authors have found that identification of platelet associated antibodies has prognostic significance in ITP and can help in understanding the underlying mechanism of thrombocytopenia.14-16According to the American Society for Hematology practice guideline, routine evaluation for platelet reactive antibodies in the evaluation of ITP is not recommended while testing for HIV and HCV should be considered in all patients with acute ITP.11Neonatal alloimmune thrombocytopenia (NAIT)typically occurs when fetal platelets have an antigen from the father that is absent in the mother.1,5,17In this condition, which can be considered to be the platelet equivalent of hemolytic disease of the newborn (HDN), maternal antibodies cross the placenta and destroy fetal platelets. This condition occurs in 1 in 1200 live births in the Caucasian population, and unlike HDN, frequently occurs during the first pregnancy.1,2Affected infants may have severe thrombocytopenia and are at increased risk for intracranial bleeding.1,18As a component of the work-up, diagnostic testing of the mother's blood is performed for the presence of platelet antibody. Evaluation should also include typing maternal and paternal platelet glycoproteins. In Caucasians, 80% of NAIT is caused by alloimmunization to HPA-1a (a component of platelet glycoprotein IIb/IIIa) in HPA-1a-negative mothers.5Other antigens, including HPA 2, 3, 4, 5, and 15, are less frequently implicated.18,19The majority of platelet reactive antibodies identified in patients with NAIT are directed against components of platelet glycoprotein IIb/IIIa, most commonly HPA-1a.1Antibodies to HPA-5b (detected as anti-Ia/IIa) are frequently observed in pregnancy but tend to be associated with milder thrombocytopenia.1Antibodies to HLA also have been associated with NAIT.1Platelet antigen incompatibility is necessary but not sufficient to cause NAIT.18Neonatal serum or plasma samples are less sensitive for circulating antibody detection than maternal samples since the antibodies may be attached to platelets or cleared.Post-transfusion purpura (PTP)is a rare condition where a patient suffers from an acute episode of severe immune-mediated thrombocytopenia that occurs 5 to 14 days after a platelet-containing transfusion.1,2,20,21The patient's own platelets also are destroyed along with transfused platelets, a phenomenon thought to be caused by panreactive platelet reactive antibodies.20,22Antigen sensitization can frequently be traced to exposure to exogenous platelet antigen either through pregnancy or previous transfusion. Like NAIT, the majority of autoantibodies identified in patients with PTP are directed against components of platelet glycoprotein IIb/IIIa, most commonly HPA-1a.1,2Platelet transfusion refractorinessis a condition characterized by the lack of expected platelet count increment after a platelet transfusion.1As many as 70% of patients receiving multiple platelet transfusions for thrombocytopenia will exhibit some degree of refractoriness.1,23This condition is most common in patients treated for malignant hematopoietic disorders.1While platelet antibody production can cause platelet refractoriness, other potential causes include sepsis, disseminated intravascular coagulation (DIC), or drug-induced thrombocytopenia. Immune-mediated platelet refractoriness is most commonly caused by antibodies to HLA antigens but has also been observed in association with antibodies to platelet-specific antigens.1,2,23-25

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders

Offered as part of multiple lab tests

Blood Disorders

Venous thromboembolism is a multifactorial disease influenced by genetic, environmental, and circumstantial risk factors. The c.*97G>A variant in the F2 gene is a genetic risk factor for venous thromboembolism. Heterozygous carriers have a 2- to 4-fold increased risk for venous thromboembolism. Homozygotes for the c.*97G>A variant are rare. The annual risk of VTE in homozygotes has been reported to be 1.1% per year. Individuals who carry both a *97G>A variant in the F2 gene and a c. 1601G>A (p.Arg534Gln) variant in the F5 gene (commonly referred to as Factor V Leiden) have an approximately 20-fold increased risk for venous thromboembolism. Risks are likely to be even higher in more complex genotype combinations involving theF2c.*97G>A variant and Factor V Leiden.1Additional risk factors include but are not limited to: deficiency of protein C, protein S, or antithrombin III-, age, male sex, personal or family history of deep vein thromboembolism, smoking, surgery, prolonged immobilization, malignant neoplasm, tamoxifen treatment, raloxifene treatment, oral contraceptive use, hormone replacement therapy, and pregnancy. Management of thrombotic risk and thrombotic events should follow established guidelines and fit the clinical circumstance. This result cannot predict the occurrence or recurrence of a thrombotic event. Genetic coordinators are available for health care providers to discuss results and for information on how to order additional testing, if desired, at 1-800-345-GENE.

Cancer Screening, Blood Disorders

Offered as part of multiple lab tests

Autoimmune & Inflammation, Blood Disorders

Monoclonal antibody-based therapies block available CD20-binding sites and, therefore, the antibody used for this flow cytometric assay cannot recognize the CD20 molecule on B cells. The concomitant use of the CD19 marker provides information on the extent of B-cell depletion when using this particular treatment strategy. This Flow Cytometry panel is also useful for confirming the complete absence of B cells in suspected primary humoral immunodeficiencies.