PDF herunterladen
Hamostaseologie 2021; 41(02): 120-126
DOI: 10.1055/a-1393-8302
Review Article

Management of Disseminated Intravascular Coagulation in Acute Leukemias

Hugo ten Cate
1   Department of Internal Medicine and Thrombosis Expert Center, Maastricht University Medical Center, Maastricht, The Netherlands
2   CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands
,
Avi Leader
2   CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands
3   Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
4   Hematology Institute, Rabin Medical Center, Petah Tikva, Israel
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Disseminated intravascular coagulation (DIC) is characterized by the intravascular activation of coagulation with loss of localization arising from different causes, and is diagnosed using scoring systems which rely upon the presence of an underlying disorder compatible with DIC alongside hemostatic derangements such as low platelet count, prolonged prothrombin time, and elevated fibrinogen degradation products. DIC is common in patients with acute leukemia, with prevalence ranging from 17 to 100% in acute promyelocytic leukemia (APL) and 8.5 to 25% in acute lymphoblastic leukemia (ALL) and non-APL acute myeloid leukemia (AML). The pathophysiology is complex and varies between the leukemia subtypes, and is not fully reflected by the laboratory markers currently used to classify DIC. Similarly, the clinical consequence of DIC in acute leukemia also varies across the types of leukemia. DIC is primarily associated with bleeding in APL, while thrombosis is the dominant phenotype in ALL and non-APL AML. The cornerstone of managing DIC is the treatment of the underlying disease, as exemplified by the important role of early administration of all-trans retinoic acid in APL. Other aspects of management focus on supportive care aimed at minimizing the risk of bleeding, via transfusion of blood products. The use of blood products is more liberal in APL, due to the hemorrhagic phenotype and unacceptably high rates of early hemorrhagic death. This review will focus on the pathophysiology, risk factors, clinical implications, and the management of DIC in patients across the spectrum of acute leukemias.

Keywords

leukemia - disseminated intravascular coagulation - management of disease


Publikationsverlauf

Eingereicht: 10. Dezember 2020

Angenommen: 15. Februar 2021

Artikel online veröffentlicht:
15. April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86 (05) 1327-1330
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 2 Mandernach MM, Kitchens CS. Disseminated intravascular coagulation. In: Kitchens CS, Kessler CM, Konkle BA, Streif MB, Garcia DA. Consultative Hemostasis and Thrombosis. 4th ed.. Elsevier; 2019: 207-226
    CrossrefGoogle Scholar
  • 3 Squizzato A, Gallo A, Levi M. et al. Underlying disorders of disseminated intravascular coagulation: communication from the ISTH SSC Subcommittees on Disseminated Intravascular Coagulation and Perioperative and Critical Care Thrombosis and Hemostasis. J Thromb Haemost 2020; 18 (09) 2400-2407
    CrossrefPubMedGoogle Scholar
  • 4 Levi M. Clinical characteristics of disseminated intravascular coagulation in patients with solid and hematological cancers. Thromb Res 2018; 164 (Suppl. 01) S77-S81
    CrossrefPubMedGoogle Scholar
  • 5 Thomas X. Acute promyelocytic leukemia: a history over 60 years—from the most malignant to the most curable form of acute leukemia. Oncol Ther 2019; 7 (01) 33-65
    CrossrefPubMedGoogle Scholar
  • 6 Iba T, Levy JH, Connors JM, Warkentin TE, Thachil J, Levi M. The unique characteristics of COVID-19 coagulopathy. Crit Care 2020; 24 (01) 360
    CrossrefPubMedGoogle Scholar
  • 7 Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood 2018; 131 (08) 845-854
    CrossrefPubMedGoogle Scholar
  • 8 Franchini M, Di Minno MN, Coppola A. Disseminated intravascular coagulation in hematologic malignancies. Semin Thromb Hemost 2010; 36 (04) 388-403
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 9 Guo Z, Chen X, Tan Y, Xu Z, Xu L. Coagulopathy in cytogenetically and molecularly distinct acute leukemias at diagnosis: comprehensive study. Blood Cells Mol Dis 2020; 81: 102393
    CrossrefPubMedGoogle Scholar
  • 10 Barbui T, Falanga A. Disseminated intravascular coagulation in acute leukemia. Semin Thromb Hemost 2001; 27 (06) 593-604
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 11 Uchiumi H, Matsushima T, Yamane A. et al. Prevalence and clinical characteristics of acute myeloid leukemia associated with disseminated intravascular coagulation. Int J Hematol 2007; 86 (02) 137-142
    CrossrefPubMedGoogle Scholar
  • 12 Libourel EJ, Klerk CPW, van Norden Y. et al. Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia. Blood 2016; 128 (14) 1854-1861
    CrossrefPubMedGoogle Scholar
  • 13 Kongstad C, Mikkelsen TS, Hvas AM. Disseminated intravascular coagulation in children with cancer: a systematic review. Pediatr Hematol Oncol 2020; 37 (05) 390-411
    CrossrefPubMedGoogle Scholar
  • 14 Del Principe MI, Del Principe D, Venditti A. Thrombosis in adult patients with acute leukemia. Curr Opin Oncol 2017; 29 (06) 448-454
    CrossrefPubMedGoogle Scholar
  • 15 Anderson DR, Leader A, Karrison TG, Stock A. D-dimer as a predictor of thrombotic events during early acute lymphoblastic leukemia therapy. Blood 2020; 136 (Suppl. 01) 5-6 DOI: 10.1182blood-2020-140324.
    CrossrefPubMedGoogle Scholar
  • 16 Rangaswamy C, Englert H, Deppermann C, Renné T. Polyanions in coagulation and thrombosis: focus on polyphosphate and NETs. Thromb Haemost 2020; ; ( epub ahead of print) DOI: 10.1055/a-1336-0526.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Harada-Shirado K, Wang X, Mori H. et al. Circulating intranuclear proteins may play a role in development of disseminated intravascular coagulation in individuals with acute leukemia. Int J Hematol 2020; 111 (03) 378-387
    CrossrefPubMedGoogle Scholar
  • 18 Kwaan HC, Weiss I, Tallman MS. The role of abnormal hemostasis and fibrinolysis in morbidity and mortality of acute promyelocytic leukemia. Semin Thromb Hemost 2019; 45 (06) 612-621
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 19 Naymagon L, Mascarenhas J. Hemorrhage in acute promyelocytic leukemia: Can it be predicted and prevented?. Leuk Res 2020; 94: 106356
    CrossrefPubMedGoogle Scholar
  • 20 Mantha S, Goldman DA, Devlin SM. et al. Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era. Blood 2017; 129 (13) 1763-1767
    CrossrefPubMedGoogle Scholar
  • 21 Mitrovic M, Suvajdzic N, Elezovic I. et al. Thrombotic events in acute promyelocytic leukemia. Thromb Res 2015; 135 (04) 588-593
    CrossrefPubMedGoogle Scholar
  • 22 de Albuquerque Antunes A, Breviglieri CNM, Celeste DM, Garanito MP, Cristofani LM, Carneiro JDA. Prevalence and outcomes of thrombotic and hemorrhagic complications in pediatric acute promyelocytic leukemia in a tertiary Brazilian center. Hematol Transfus Cell Ther 2020; ; (epub ahead of print) DOI: 10.1016/j.htct.2020.06.017.
    CrossrefPubMedGoogle Scholar
  • 23 Jiang H, Liu L, Guo T. et al. Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy. Ann Hematol 2019; 98 (07) 1721-1732
    CrossrefPubMedGoogle Scholar
  • 24 Wang Y, Qi K, Cheng H. et al. Coagulation disorders after chimeric antigen receptor T cell therapy: analysis of 100 patients with relapsed and refractory hematologic malignancies. Biol Blood Marrow Transplant 2020; 26 (05) 865-875
    CrossrefPubMedGoogle Scholar
  • 25 Wang TF, Makar RS, Antic D. et al. Management of hemostatic complications in acute leukemia: guidance from the SSC of the ISTH. J Thromb Haemost 2020; 18 (12) 3174-3183
    CrossrefPubMedGoogle Scholar
  • 26 Zakarija A, Kwaan HC. Adverse effects on hemostatic function of drugs used in hematologic malignancies. Semin Thromb Hemost 2007; 33 (04) 355-364
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 27 Goyal G, Bhatt VR. L-asparaginase and venous thromboembolism in acute lymphocytic leukemia. Future Oncol 2015; 11 (17) 2459-2470
    CrossrefPubMedGoogle Scholar
  • 28 Hua VM, Abeynaike L, Glaros E. et al. Necrotic platelets provide a procoagulant surface during thrombosis. Blood 2015; 126 (26) 2852-2862
    CrossrefPubMedGoogle Scholar
  • 29 Truelove E, Fielding AK, Hunt BJ. The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia. Leukemia 2013; 27 (03) 553-559
    CrossrefPubMedGoogle Scholar
  • 30 Zwicker JI, Wang TF, DeAngelo DJ. et al. The prevention and management of asparaginase-related venous thromboembolism in adults: guidance from the SSC on hemostasis and malignancy of the ISTH. J Thromb Haemost 2020; 18 (02) 278-284
    CrossrefPubMedGoogle Scholar
  • 31 David S, Mathews V. Mechanisms and management of coagulopathy in acute promyelocytic leukemia. Thromb Res 2018; 164 (Suppl. 01) S82-S88
    CrossrefPubMedGoogle Scholar
  • 32 Koyama T, Hirosawa S, Kawamata N, Tohda S, Aoki N. All-trans retinoic acid upregulates thrombomodulin and downregulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells. Blood 1994; 84 (09) 3001-3009
    CrossrefPubMedGoogle Scholar
  • 33 Saito T, Koyama T, Nagata K, Kamiyama R, Hirosawa S. Anticoagulant effects of retinoic acids on leukemia cells. Blood 1996; 87 (02) 657-665
    CrossrefPubMedGoogle Scholar
  • 34 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 (07) 3395-3402
    CrossrefPubMedGoogle Scholar
  • 35 Lo-Coco F, Avvisati G, Vignetti M. et al; Gruppo Italiano Malattie Ematologiche dell'Adulto, German-Austrian Acute Myeloid Leukemia Study Group, Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 2013; 369 (02) 111-121
    CrossrefPubMedGoogle Scholar
  • 36 Burnett AK, Russell NH, Hills RK. et al; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol 2015; 16 (13) 1295-1305
    CrossrefPubMedGoogle Scholar
  • 37 Sanz MA, Fenaux P, Tallman MS. et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood 2019; 133 (15) 1630-1643
    CrossrefPubMedGoogle Scholar
  • 38 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 (11) 2112-2117
    CrossrefPubMedGoogle Scholar
  • 39 Cao M, Li T, He Z. et al. Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia. Blood 2017; 129 (13) 1855-1864
    CrossrefPubMedGoogle Scholar
  • 40 Leader A, Ten Cate H, Spectre G, Beckers EAM, Falanga A. Antithrombotic medication in cancer-associated thrombocytopenia: current evidence and knowledge gaps. Crit Rev Oncol Hematol 2018; 132: 76-88
    CrossrefPubMedGoogle Scholar
  • 41 Feldman EJ, Arlin ZA, Ahmed T. et al. Acute promyelocytic leukemia: a 5-year experience with new antileukemic agents and a new approach to preventing fatal hemorrhage. Acta Haematol 1989; 82 (03) 117-121
    CrossrefPubMedGoogle Scholar
  • 42 Hambley BC, Norsworthy KJ, Jasem J. et al. Fibrinogen consumption and use of heparin are risk factors for delayed bleeding during acute promyelocytic leukemia induction. Leuk Res 2019; 83: 106174
    CrossrefPubMedGoogle Scholar
  • 43 Watanabe-Kusunoki K, Nakazawa D, Ishizu A, Atsumi T. Thrombomodulin as a physiological modulator of intravascular injury. Front Immunol 2020; 11: 575890
    CrossrefPubMedGoogle Scholar
  • 44 Matsushita T, Watanabe J, Honda G. et al. Thrombomodulin alfa treatment in patients with acute promyelocytic leukemia and disseminated intravascular coagulation: a retrospective analysis of an open-label, multicenter, post-marketing surveillance study cohort. Thromb Res 2014; 133 (05) 772-781
    CrossrefPubMedGoogle Scholar
  • 45 Martí-Carvajal AJ, Anand V, Solà I. Treatment for disseminated intravascular coagulation in patients with acute and chronic leukemia. Cochrane Database Syst Rev 2015; 2015 (06) CD008562
    PubMedGoogle Scholar
  • 46 Fredenburgh JC, Weitz JI. New anticoagulants: moving beyond the direct oral anticoagulants. J Thromb Haemost 2021; 19 (01) 20-29
    CrossrefPubMedGoogle Scholar
  • 47 Visser M, Heitmeier S, Ten Cate H, Spronk HMH. Role of factor XIa and plasma kallikrein in arterial and venous thrombosis. Thromb Haemost 2020; 120 (06) 883-993
    Artikel in Thieme ConnectPubMedGoogle Scholar