Acute promyelocytic leukemia laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Laboratory Findings

• Anemia: Anemia refers to decreased red blood cell production, which results in low hemoglobin content in the peripheral blood. Hemoglobin values are typically less than 10 g/dl in most patients with acute promyelocytic leukemia. The degree of anemia corresponds with the amount of bone marrow infiltration by leukemic cells. Patients with severe or advanced leukemia will usually have severe anemia. Severe anemia can result in profound fatigue, pallor, and shortness of breath.
• Thrombocytopenia: Thrombocytopenia refers to low platelet count. The platelet count is usually less than 150,000 cells per microliter. Low platelet count in patients with acute promyelocytic leukemia is typically due to two reasons. Firstly, leukemic cell infiltration in the bone marrow results in disruption of normal megakaryocyte production with decreased platelet production. Secondly, coagulopathy (disseminated intravascular coagulation) results in platelet consumption and therefore a low platelet count. This latter reason is unique to acute promyelocytic leukemia compared to other types of leukemia. The degree of thrombocytopenia also confers prognostic value in acute promyelocytic leukemia: platelet counts lower than 40,000 cells per microliter carries a worse prognosis than platelet counts greater than 40,000 cells per microliter.
• Leukopenia: Leukopenia refers to white blood cell count below 4,000 cells per microliter. Leukopenia is common in patients with acute promyelocytic leukemia, unlike most other types of leukemia. In some cases, however, patients can have high white blood cell counts, which confers a worse prognosis. White blood cell count above 10,000 cells per microliter defines high-risk disease.
• Hypofibrinogenemia: Hypofibrinogenemia, or fibrinogen level below 100 mg/dl, is commonly found in patients with acute promyelocytic leukemia. Hypofibrinogenemia is a key component of disseminated intravascular coagulation, which is characterized by widespread clot formation and breakdown. Fibrinogen, also known as factor I of the coagulation cascade, is broken down in patients with acute promyelocytic leukemia, resulting in bleeding complications. Values of less than 100 mg/dl require treatment with cryoprecipitate, which restores fibrinogen levels towards normal range.
• Elevated prothrombin time (PT): High PT values, typically above 15 seconds, are common in patients with acute promyelocytic leukemia. This is due to disseminated intravascular coagulation, which results in consumption of coagulation factors of the intrinsic and extrinsic coagulation pathways. High INR reflects consumption of factors from the extrinsic pathway, such as factor VII.
• Elevated partial thromboplastin time (PTT): High PTT values, typically above 40 second, are common in patients with acute promyelocytic leukemia. This is due to disseminated intravascular coagulation, which results in consumption of coagulation factors of the intrinsic and extrinsic coagulation pathways. High PTT reflects consumption of factors from the intrinsic pathway, such as factors XII, XI, IX, and VIII.
• Elevated thrombin time: Thrombin time measures the conversion of fibrinogen to fibrin, and therefore a high thrombin time is seen in patients with coagulopathy from acute promyelocytic leukemia. Thrombin is also known as factor II of the coagulation cascade and is immediate upstream of fibrinogen.
• Elevated reptilase time: Reptilase time also measures the conversion of fibrinogen to fibrin, but this test uses a different enzyme, known as reptilase, which is derived from snake venom. The unique feature of the reptilase time is that it can be used to differentiate high PTT caused by heparin effect: the reptilase time is not sensitive to heparin. Reptilase time is high in patients with coagulopathy from acute promyelocytic leukemia.
• Elevated D-dimer: D-dimer measures simulataneous clot formation and breakdown. Elevated D-dimer is not specific to acute promyelocytic leukemia, as it can be found in patients with obstetric complications (eclampsia and amniotic fluid embolism) or sepsis from Neisseria meningitides. Elevated D-dimer is very sensitive for an underlying coagulopathy and is an excellent test for ruling out a hematologic condition is the pre-test probability is low. D-dimer is elevated in the majority of cases of acute promyelocytic leukemia.