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Thromb Haemost 2000; 83(06): 906-908
DOI: 10.1055/s-0037-1613942
Commentary
Schattauer GmbH

Elastase Mediated Fibrinolysis in Acute Promyelocytic Leukemia

Erik-Jan D. Oudijk
1   From the Department of Haematology, University Medical Centre, Utrecht, the Netherlands
,
H. Karel Nieuwenhuis
1   From the Department of Haematology, University Medical Centre, Utrecht, the Netherlands
2   The Institute of Biomembranes, Utrecht University, the Netherlands
,
Rogier Bos
3   TNO-Prevention and Health, Leiden, The Netherlands
,
Rob Fijnheer
1   From the Department of Haematology, University Medical Centre, Utrecht, the Netherlands
› Author Affiliations
Further Information

Publication History

Received 05 November 1999

Accepted after revision 14 February 2000

Publication Date:
14 December 2017 (online)

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Summary

The bleeding syndrome of acute promyelocytic leukemia (APL) is complex and consists of disseminated intravascular coagulation (DIC) and hyperfibrinolysis. Elastase, derived from malignant promyelocytes, is believed to mediate the fibrinogeno- and fibrinolysis by aspecific proteolysis. In this study we measured the role of elastase in fifteen patients with APL by using an assay for elastase degraded fibrin(ogen) and the results were compared with those obtained in patients with sepsis induced DIC.

High levels of elastase were observed in sepsis and APL. The levels of fibrinogen and fibrin degradation products were significantly higher in APL patients compared to patients with sepsis induced DIC. Nevertheless, the level of elastase degraded fibrin(ogen) was higher in the sepsis group (635.3 ng/ml, compared to 144.3 ng/ml in APL; p <0.0001). So, the enormous increase in fibrin and fibrinogen degradation products in APL cannot be explained by elastase activity. This study suggests a minor role for elastase mediated proteolysis in the hemorrhagic diathesis in APL patients.

Key words

Acute promyelocytic leukemia - fibrinolysis - coagulation - sepsis - elastase
 

  • References

  • 1 Dombret H, Scrobohaci ML, Ghorra P, Zini JM, Daniel MT, Castaigne S, Degos L. Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. Leukemia 1993; 07: 2-9.
    PubMedGoogle Scholar
  • 2 De Stefano V, Teofili L, Sica S, Mastrangelo S, Di Mario A, Rutella S, Salutari P, Rumi C, d’Onofrio G, Leone G. Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia. Blood 1995; 86: 3535-41.
    PubMedGoogle Scholar
  • 3 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: 2112-7.
    PubMedGoogle Scholar
  • 4 Tallman MS, Kwaan HC. Reassessing the hemostatic disorder associated with acute promyelocytic leukemia. Blood 1992; 79: 543-53.
    PubMedGoogle Scholar
  • 5 Barbui T, Finazzi G, Falanga A. The Impact of All-trans-Retinoic Acid on the Coagulopathy of Acute Promyelocytic Leukemia. Blood 1998; 91: 3093-102.
    PubMedGoogle Scholar
  • 6 Kario K, Matsuo T, Kodam K, Matuso M, Yamamoto K, Kobayashi H. imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Haemostasis 1992; 22: 179-86.
    PubMedGoogle Scholar
  • 7 Bauer KA, Rosenberg RD. Thrombin generation in acute promyelocytic leukemia. Blood 1984; 64: 791-6.
    PubMedGoogle Scholar
  • 8 Booth NA, Bennett B. Plasmin-alpha-2-antiplasmin complexes in bleeding disorders characterised by primary or secondary fibrinolysis. Br J Haematol 1984; 56: 545.
    CrossrefPubMedGoogle Scholar
  • 9 Reddy VB, Kowas-Vern A, Hoppensteadt DA, Kumar A, Walenga JM, Fareed J, Shumacher HR. Global and hemostatic markers in acute myeloid leukemia. Am J Clin Pathol 1990; 94: 397.
    CrossrefPubMedGoogle Scholar
  • 10 Viljoen M, Roux LJ, Pretorius JP, Coetzee IH, Viljoen E. Hemostatic competency and elastase-α1-proteinase inhibitor levels in surgery, trauma, and sepsis. J Trauma:Injury, Infect and Crit care 1995; 39: 381-5.
    PubMedGoogle Scholar
  • 11 Samis JA, Garret M, Manuel RP, Nesheim ME, Giles AR. Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V. Blood 1997; 90: 1065-74.
    PubMedGoogle Scholar
  • 12 Gralnick HR, Abrell E. Studies of the procoagulant and fibrinolytic activity of promyelocytes in acute promyelocytic leukaemia. Br J Haematol 1973; 24: 89-99.
    CrossrefPubMedGoogle Scholar
  • 13 Falanga A, Iacoviello L, Evangelista V, Belotti D, Consonni R, D`Orazio A, Robba L, Donati MB, Barbui T. Loss of blast cell procoagulant activity and improvement of hemostatic variables in patients with acute promyelocytic leukemia administered all-trans-retinoic acid. Blood 1995; 86: 1072-81.
    PubMedGoogle Scholar
  • 14 Hoegee de Nobel E, Voskuilen M, Briet E, Brommer EJ, Nieuwenhuizen W. A monoclonal antibody-based quantitative enzyme immunoassay for the determination of plasma fibrinogen concentrations. Thromb Haemost 1988; 60: 415-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Bos R, Laterveer-Vreeswijk GH, Lockwood D, Szecwcyk K, Nieuwenhuizen W. A new enzyme immunoassay for soluble fibrin in plasma with a high discriminating power for thrombotic disorders. Thromb Haemost 1999; 81: 54-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Koppert PW, Kuipers W, Hoegee de Nobel B, Brommer EJ, Koopman J, Nieuwenhuizen W. A quantitative enzyme immunoassay for primary fibrinogenolysis products in plasma. Thromb Haemost 1987; 57: 25-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Koppert PW, Hoegee de Nobel E, Nieuwenhuizen W. A monoclonal antibody-based enzyme immunoassay for fibrin degradation products in plasma. Thromb Haemost 1988; 59: 310-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Bos R, van Leuven CJM, Stolk J, Hiemstra PS, Ronday HK, Nieuwenhuizen W. An enzyme immunoassay for polymorphonuclear leucocytemediated fibrinogenolysis. Eur J Clinic Invest 1997; 27: 148-56.
    PubMedGoogle Scholar
  • 19 Sterrenberg I, Blonk A, van Liempt GJ, Hermans J, Nieuwenhuizen W. Purification and properties of early (X-like) and late (D-like) fibrinogen fragments, produced by leukocyte elastase. In: Fibrinogen, Structure, Functional Aspects, Metabolism. Haverkate F, Henschen A, Nieuwenhuizen W, Straub PW. eds. Berlin: Walter de Gruyter; 1983: 235-53.
    Google Scholar
  • 20 Machovich R, Owen WG. The elastase-mediated pathway of fibrinolysis. Blood Coag Fibrinol 1990; 01: 79-90.
    CrossrefPubMedGoogle Scholar