Comparison of laboratory characteristics between acute promyelocytic leukemia and other subtypes of acute myeloid leukemia with disseminated intravascular coagulation

Background Acute promyelocytic leukemia (APL) is an acute myeloid leukemia (AML) subtype with distinctive cell morphology, molecular presentation, clinical course, and treatment. About 90% of APL patients present with hemorrhagic complications due to disseminated intravascular coagulation (DIC). When APL is suspected, all-trans retinoic acid (ATRA) treatment is recommended even before confirmation by molecular tests. Specific criteria for differentiating unconfirmed APL from other AML subtypes with DIC are currently lacking. We aimed to achieve the early diagnosis of APL from other AML types with DIC by restricting the DIC criteria. Methods We retrospectively analyzed 29 patients newly diagnosed with AML accompanied by DIC from January 2005 to January 2013. Results Fibrin degradation products (FDP) (77.7 µg/mL vs. 23.7 µg/mL, p=0.026), D-dimer (7,376.2 ng/mL vs. 1,315.2 ng/mL, p=0.018), and TIBC (264.4 µg/dL vs. 206.8 µg/dL, P=0.046) were higher, while fibrinogen (133.8 mg/dL vs. 373.2 mg/dL, p<0.001), WBC (14.988×109/L vs. 70.755×109/L, p=0.015), and ESR (7.1 mm/h vs. 50.0 mm/h, p <0.001) were lower in APL patients than in the patients with other AML subtypes. FDP ≥27 µg/mL, D-dimer ≥2,071 ng/mL, and fibrinogen ≤279 mg/dL were our threshold values. These markers may be characteristic to APL and helpful in presumptive diagnosis. Conclusion APL may be differentiated from other AML subtypes by core markers of DIC (FDP, D-dimer, and fibrinogen). We suggest that clinicians set new diagnostic thresholds by restricting the DIC criteria. These findings support the early initiation of ATRA, prior to confirmation by PML-RARA molecular testing.

[1]  H. Wada,et al.  Diagnostic criteria and laboratory tests for disseminated intravascular coagulation. , 2011, Journal of clinical and experimental hematopathology : JCEH.

[2]  M. Höglund,et al.  Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry , 2011, Leukemia.

[3]  F. Santolaria,et al.  Prognostic value of inflammatory markers (notably cytokines and procalcitonin), nutritional assessment, and organ function in patients with sepsis. , 2010, European cytokine network.

[4]  M. Tallman,et al.  How I treat acute promyelocytic leukemia. , 2009, Blood.

[5]  J. Esteve,et al.  Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. , 2008, Blood.

[6]  Zhen-yi Wang,et al.  Acute promyelocytic leukemia: from highly fatal to highly curable. , 2008, Blood.

[7]  R. Ribeiro,et al.  Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines , 2007, Haematologica.

[8]  T. Naoe,et al.  Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome , 2007, European journal of haematology.

[9]  M. Yoshioka,et al.  Current research on acute phase proteins in veterinary diagnosis: an overview. , 2004, Veterinary journal.

[10]  J. Siegel,et al.  The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis , 2004, Amino Acids.

[11]  L. Boggio,et al.  Abnormalities in hemostasis in acute promyelocytic leukemia , 2002, Hematological oncology.

[12]  F B Taylor,et al.  Towards Definition, Clinical and Laboratory Criteria, and a Scoring System for Disseminated Intravascular Coagulation , 2001, Thrombosis and Haemostasis.

[13]  C. Bloomfield,et al.  All-trans-Retinoic Acid in Acute Promyelocytic Leukemia , 2000 .

[14]  J. Miguel,et al.  A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. , 1999, Blood.

[15]  Y. Miura,et al.  Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management. , 1997, International journal of hematology.

[16]  T. Barbui,et al.  Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients. , 1990, Blood.

[17]  B. Clarkson,et al.  Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. , 1989, Blood.