Labhorizons a Newsletter for Clients

Acute Myelocytic Leukemia (AML) Profile, Chromosome Analysis With Reflex to FLT3, CEBPA, and NPM1 . . . . . 511972 CPT Contact CPT coding department at 800-222-7566, ext. 6-8400. Synonyms AML Use Diagnostic and prognostic test for acute myeloid leukemia Limitations Molecular mutations not targeted by the probes included in this profile will not be detected. This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration. Methodology Short-term cell culture; synchronization; chromosome harvest; G-banding; analysis (20 metaphases) and karyotyping; polymerase chain reaction (PCR); capillary electrophoresis; Sanger sequencing Additional Information NPM1 (nucleophosmin) mutation is one of the most common recurring genetic lesions in acute myeloid leukemia (AML). This AML type frequently has myelomonocytic or monocytic features and typically presents de novo in older adults with a normal karyotype. Prevalence increases with age, occurring in 2% to 8% of childhood AML and 27% to 35% of adult AML. The most common mutation, insertion at nucleotide position c.863 (exon 11), accounts for 90% to 95% of NPM1 mutations. NPM1 mutations in absence of FLT3-ITD identify a prognostically favorable subgroup. The CEBPA (CCAAT/enhancer binding protein alpha) gene encodes a transcription factor important for granulocyte differentiation. CEBPA mutations are found in 6% to 15% of de novo acute myeloid leukemia (AML) and in 15% to 18% of AML with normal karyotypes. CEBPA mutations are associated with favorable prognosis in the absence of associated cytogenetic abnormalities and FLT3 internal duplication (FLT-ITD). Germline mutations are a cause of nonsyndromic, familial AML. The FLT3 ITD mutation is an adverse prognostic marker in patients with cytogenetically normal acute myeloid leukemia. A patient without a detectable FLT3 ITD mutation generally has a more favorable prognosis than patients with a FLT3 ITD mutation. A patient without a detectable FLT3 TKD (tyrosine kinase domain) mutation generally has a more favorable prognosis than patients with a FLT3 TKD mutation. Specimen Bone marrow, blood (5% to 10% blasts required) See Collection. Volume One tube of 5 mL blood (adult); one tube of 3 mL blood (pediatric); or one tube of 1-3 mL bone marrow Minimum Volume One tube of 5 mL blood (adult); one tube of 3 mL blood (pediatric); or one tube of 1-3 mL bone marrow Container Green-top (heparin) tube is required for chromosome testing; pediatric Vacutainer® is optimal and lavender-top (EDTA) tube is required for molecular testing. Collection The requirement of 5% to 10% blasts does not apply to cases of CCL, hairy cell leukemia and some cases of SCLL (small cell lymphocytic leukemia) which can be beta-mitogen stimulated. Specimens should arrive in the laboratory within 48 hours of collection. Indicate date and time of collection on the test request form. Storage Instructions Maintain specimen at room temperature. Causes for Rejection Broken Vacutainer®; frozen specimen; clotted blood specimen; quantity not sufficient for analysis Factor VIII Chromogenic Activity . . . . . . . . . . . . . . . . . . 500192 CPT 85240 Synonyms Antihemophilic Factor (AHF) Use Used in the diagnosis of nonsevere hemophilia A.6,7,13 Useful in the accurate determination of factor VIII (FVIII) activity in the presence of a lupus anticoagulant or when certain modified recombinant FVIII replacement products are present. This assay can also be used in place of the one-stage (standard) FVIII activity assay for any indication. Limitations Factor VIII is an acute phase reactant and can be elevated in a number of clinical conditions. This can affect the accuracy of the test in diagnosing hemophilia. Factor VIII levels should not be used to determine the carrier status of females. Genetic testing should be used for this purpose. Factor VIII inhibitors (both autoantibodies that develop after replacement therapy and autoantibodies that develop spontaneously) can result in low factor VIII levels. A lupus anticoagulant may cause factor VIII activity to appear spuriously low and a chromogenic factor VIII activity is recommended in this circumstance. Direct Xa inhibitor therapy may cause factitiously low results. Methodology Factor VIII activity is determined by a two-stage chromogenic substrate assay where the amount of activated factor X generated is proportional to the amount of functional FVIII present in the test plasma in the presence of excess activated FIX. The amount of activated factor X generated is read with a chromogenic substrate and the activity is determined from a standard curve. Additional Information 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.8,9 Factor VIII circulates in the plasma bound to von Willebrand factor (vWF) at a concentration of approximately 0.1 mg/mL.9 The plasma half-life of factor VIII is short at about 8 to 10 hours.9 Factor 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.8,10 Clinical features of hemophilia A are the same as for hemophilia B, which is caused by factor IX deficiency (see Factor 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.8,10 Hemophilia A accounts for approximately 85% of all hemophilia cases.10 This condition is transmitted as an X chromosome-linked hereditary disorder.10 The 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.8,10 The prevalence of hemophilia A is equal in all ethnic New Procedures