Blood Res.  2013 Dec;48(4):250-253. 10.5045/br.2013.48.4.250.

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

• Lee HJ
• Park HJ
• Kim HW
• Park SG

• KMID: 2172871
• DOI: http://doi.org/10.5045/br.2013.48.4.250

Abstract

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 microg/mL vs. 23.7 microg/mL, p=0.026), D-dimer (7,376.2 ng/mL vs. 1,315.2 ng/mL, p=0.018), and TIBC (264.4 microg/dL vs. 206.8 microg/dL, P=0.046) were higher, while fibrinogen (133.8 mg/dL vs. 373.2 mg/dL, p<0.001), WBC (14.988x109/L vs. 70.755x109/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 > or =27 microg/mL, D-dimer > or =2,071 ng/mL, and fibrinogen < or =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.

Keyword

Acute myeloid leukemia; Acute promyelocytic leukemia; Disseminated intravascular coagulation

MeSH Terms

Dacarbazine
Diagnosis
Disseminated Intravascular Coagulation*
Early Diagnosis
Fibrin Fibrinogen Degradation Products
Fibrinogen
Humans
Leukemia, Myeloid, Acute*
Leukemia, Promyelocytic, Acute*
Retrospective Studies
Tretinoin
Dacarbazine
Fibrin Fibrinogen Degradation Products
Fibrinogen
Tretinoin

Reference

1. Tallman MS, Altman JK. How I treat acute promyelocytic leukemia. Blood. 2009; 114:5126–5135. PMID: 19797519.

2. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008; 111:2505–2515. PMID: 18299451.

3. Kwaan HC, Wang J, Boggio LN. Abnormalities in hemostasis in acute promyelocytic leukemia. Hematol Oncol. 2002; 20:33–41. PMID: 11921015.

4. Fenaux P, Chastang C, Chevret S, et al. The European APL Group. 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. Blood. 1999; 94:1192–1200. PMID: 10438706.

5. NCCN Clinical practice guidelines in oncology: Acute myeloid leukemia, Version 2. Fort Washington, PA: National Comprehensive Cancer Network;2013. Accessed September 23, 2013. Available from: http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf.

6. Kaneko T, Wada H. Diagnostic criteria and laboratory tests for disseminated intravascular coagulation. J Clin Exp Hematop. 2011; 51:67–76. PMID: 22104305.

7. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86:1327–1330. PMID: 11816725.

8. Cunningham I, Gee TS, Reich LM, Kempin SJ, Naval AN, Clarkson BD. Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. Blood. 1989; 73:1116–1122. PMID: 2930837.

9. Rodeghiero F, Avvisati G, Castaman G, Barbui T, Mandelli F. Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients. Blood. 1990; 75:2112–2117. PMID: 2189506.

10. de la Serna J, Montesinos P, Vellenga E, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008; 111:3395–3402. PMID: 18195095.

11. Lehmann S, Ravn A, Carlsson L, et al. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia. 2011; 25:1128–1134. PMID: 21502956.

12. Yanada M, Matsushita T, Asou N, et al. Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome. Eur J Haematol. 2007; 78:213–219. PMID: 17241371.

13. Jácomo RH, Melo RA, Souto FR, et al. Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines. Haematologica. 2007; 92:1431–1432. PMID: 18024380.

14. Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997; 337:1021–1028. PMID: 9321529.

15. Hatake K, Uwai M, Ohtsuki T, et al. Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management. Int J Hematol. 1997; 66:13–19. PMID: 9220656.

16. Murata H, Shimada N, Yoshioka M. Current research on acute phase proteins in veterinary diagnosis: an overview. Vet J. 2004; 168:28–40. PMID: 15158206.

17. Chiarla C, Giovannini I, Siegel JH. The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis. Amino Acids. 2004; 27:97–100. PMID: 15309577.

18. Suárez-Santamaria M, Santolaria F, Perez-Ramirez A, et al. Prognostic value of inflammatory markers (notably cytokines and procalcitonin), nutritional assessment, and organ function in patients with sepsis. Eur Cytokine Netw. 2010; 21:19–26. PMID: 20146986.