PDF herunterladen
Semin Thromb Hemost 2019; 45(06): 612-621
DOI: 10.1055/s-0039-1693478
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Hau C. Kwaan
1   Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
,
Ivy Weiss
1   Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
,
Martin S. Tallman
2   Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
01. August 2019 (online)

    Lizenzen und Reprints

Abstract

Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.

Keywords

acute promyelocytic leukemia - coagulation - fibrinolysis - intracranial hemorrhage - all-trans retinoic acid arsenic trioxide
 

  • References

  • 1 Golomb HM, Rowley JD, Vardiman JW, Testa JR, Butler A. “Microgranular” acute promyelocytic leukemia: a distinct clinical, ultrastructural, and cytogenetic entity. Blood 1980; 55 (02) 253-259
    CrossrefPubMedGoogle Scholar
  • 2 Sainty D, Liso V, Cantù-Rajnoldi A. , et al; Groupe Français d'Hématologie Cellulaire; Groupe Français de Cytogénétique Hématologique; UK Cancer Cytogenetics Group; BIOMED 1 European Community-Concerted Action “Molecular Cytogenetic Diagnosis in Haematological Malignancies ” A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood 2000; 96 (04) 1287-1296
    PubMedGoogle Scholar
  • 3 Hillestad LK. Acute promyelocytic leukemia. Acta Med Scand 1957; 159 (03) 189-194
    CrossrefPubMedGoogle Scholar
  • 4 Lo-Coco F, Ammatuna E. The biology of acute promyelocytic leukemia and its impact on diagnosis and treatment. Hematology (Am Soc Hematol Educ Program) 2006; 514: 156-161
    PubMedGoogle Scholar
  • 5 Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111 (05) 2505-2515
    CrossrefPubMedGoogle Scholar
  • 6 Grimwade D, Lo Coco F. Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia 2002; 16 (10) 1959-1973
    CrossrefPubMedGoogle Scholar
  • 7 De Botton S, Chevret S, Sanz M. , et al; European APL Group. Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial. Br J Haematol 2000; 111 (03) 801-806
    PubMedGoogle Scholar
  • 8 Grimwade D, Biondi A, Mozziconacci MJ. , et al. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Français de Cytogénétique Hématologique, Groupe de Français d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action “Molecular Cytogenetic Diagnosis in Haematological Malignancies”. Blood 2000; 96 (04) 1297-1308
    PubMedGoogle Scholar
  • 9 Tallman MS, Abutalib SA, Altman JK. The double hazard of thrombophilia and bleeding in acute promyelocytic leukemia. Semin Thromb Hemost 2007; 33 (04) 330-338
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 10 Dombret H, Scrobohaci ML, Ghorra P. , et al. Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. Leukemia 1993; 7 (01) 2-9
    PubMedGoogle Scholar
  • 11 Breen KA, Grimwade D, Hunt BJ. The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia. Br J Haematol 2012; 156 (01) 24-36
    CrossrefPubMedGoogle Scholar
  • 12 Kwaan HC, Cull EH. The coagulopathy in acute promyelocytic leukaemia--what have we learned in the past twenty years. Best Pract Res Clin Haematol 2014; 27 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 13 Choudhry A, DeLoughery TG. Bleeding and thrombosis in acute promyelocytic leukemia. Am J Hematol 2012; 87 (06) 596-603
    CrossrefPubMedGoogle Scholar
  • 14 Falanga A, Rickles FR. Management of Thrombohemorrhagic Syndromes (THS) in hematologic malignancies. Hematology Am Soc Hematol Educ Program 2007; 165-171
    PubMedGoogle Scholar
  • 15 Kwaan HC. Double hazard of thrombophilia and bleeding in leukemia. Hematology (Am Soc Hematol Educ Program) 2007; 2007: 151-157
    CrossrefPubMedGoogle Scholar
  • 16 Breccia M, Lo Coco F. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia. Thromb Res 2014; 133 (Suppl. 02) S112-S116
    PubMedGoogle Scholar
  • 17 Croizat P, Favre-Gilly J. Les aspects du syndrome hemorrhagiue des leucemias. Sang (Paris) 1949; 20: 417-421
    PubMedGoogle Scholar
  • 18 Kwaan HC, Wang J, Boggio LN. Abnormalities in hemostasis in acute promyelocytic leukemia. Hematol Oncol 2002; 20 (01) 33-41
    CrossrefPubMedGoogle Scholar
  • 19 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
  • 20 Di Bona E, Avvisati G, Castaman G. , et al. Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. Br J Haematol 2000; 108 (04) 689-695
    CrossrefPubMedGoogle Scholar
  • 21 Ziegler S, Sperr WR, Knöbl P. , et al. Symptomatic venous thromboembolism in acute leukemia. incidence, risk factors, and impact on prognosis. Thromb Res 2005; 115 (1-2): 59-64
    CrossrefPubMedGoogle Scholar
  • 22 Breccia M, Avvisati G, Latagliata R. , et al. Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features. Leukemia 2007; 21 (01) 79-83
    CrossrefPubMedGoogle Scholar
  • 23 De Stefano V, Sorà F, Rossi E. , et al. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 2005; 3 (09) 1985-1992
    CrossrefPubMedGoogle Scholar
  • 24 Montesinos P, de la Serna J, Vellenga E. , et al. Incidence and risk factors for thrombosis in patients with acute promyelocytic leukemia. experience of the PETHEMA LPA96 and LPA99 Protocols. Blood 2011; 108 (Suppl. 11) 1503
    PubMedGoogle Scholar
  • 25 Lengfelder E, Hanfstein B, Haferlach C. , et al; German Acute Myeloid Leukemia Cooperative Group (AMLCG). Outcome of elderly patients with acute promyelocytic leukemia: results of the German Acute Myeloid Leukemia Cooperative Group. Ann Hematol 2013; 92 (01) 41-52
    CrossrefPubMedGoogle Scholar
  • 26 Dally N, Hoffman R, Haddad N, Sarig G, Rowe JM, Brenner B. Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia-a single center experience in 34 patients. Thromb Res 2005; 116 (02) 109-114
    CrossrefPubMedGoogle Scholar
  • 27 Tallman MS, Brenner B, Serna JdeL. , et al. Meeting report. acute promyelocytic leukemia-associated coagulopathy, 21 January 2004, London, United Kingdom. Leuk Res 2005; 29 (03) 347-351
    CrossrefPubMedGoogle Scholar
  • 28 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 (03) 213-219
    CrossrefPubMedGoogle Scholar
  • 29 Matarraz S, Leoz P, Fernández C. , et al. Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy. Mod Pathol 2018; 31 (08) 1318-1331
    PubMedGoogle Scholar
  • 30 Barbui T, Finazzi G, Falanga A. The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood 1998; 91 (09) 3093-3102
    CrossrefPubMedGoogle Scholar
  • 31 Karim F, Shaikh U, Adil SN, Khurshid M. Clinical characteristics, outcome and early induction deaths in patients with acute promyelocytic leukaemia: a five-year experience at a tertiary care centre. Singapore Med J 2014; 55 (08) 443-447
    CrossrefPubMedGoogle Scholar
  • 32 Sanz MA, Martín G, González M. , et al; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood 2004; 103 (04) 1237-1243
    PubMedGoogle Scholar
  • 33 Rego EM, Kim HT, Ruiz-Argüelles GJ. , et al. Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL. Blood 2013; 121 (11) 1935-1943
    CrossrefPubMedGoogle Scholar
  • 34 Kario K, Matsuo T, Kodama K, Katayama S, Kobayashi H. Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia. Thromb Res 1992; 66 (04) 435-444
    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 Tallman MS, Lefèbvre P, Baine RM. , et al. Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost 2004; 2 (08) 1341-1350
    CrossrefPubMedGoogle Scholar
  • 38 Myers TJ, Rickles FR, Barb C, Cronlund M. Fibrinopeptide A in acute leukemia: relationship of activation of blood coagulation to disease activity. Blood 1981; 57 (03) 518-525
    CrossrefPubMedGoogle Scholar
  • 39 Falanga A, Barbui T. Coagulopathy of acute promyelocytic leukemia. Acta Haematol 2001; 106 (1-2): 43-51
    CrossrefPubMedGoogle Scholar
  • 40 Bauer KA, Rosenberg RD. Thrombin generation in acute promyelocytic leukemia. Blood 1984; 64 (04) 791-796
    CrossrefPubMedGoogle Scholar
  • 41 Sakata Y, Murakami T, Noro A, Mori K, Matsuda M. The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia. Blood 1991; 77 (09) 1949-1957
    CrossrefPubMedGoogle Scholar
  • 42 Kwaan HC. The unique hemostatic dysfunction in acute promyelocytic leukemia. Semin Thromb Hemost 2014; 40 (03) 332-336
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 43 Stein E, McMahon B, Kwaan H, Altman JK, Frankfurt O, Tallman MS. The coagulopathy of acute promyelocytic leukaemia revisited. Best Pract Res Clin Haematol 2009; 22 (01) 153-163
    CrossrefPubMedGoogle Scholar
  • 44 Bennett B, Booth NA, Croll A, Dawson AA. The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination. Br J Haematol 1989; 71 (04) 511-517
    CrossrefPubMedGoogle Scholar
  • 45 Avvisati G, ten Cate JW, Sturk A, Lamping R, Petti MG, Mandelli F. Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia. Br J Haematol 1988; 70 (01) 43-48
    CrossrefPubMedGoogle Scholar
  • 46 Falanga A, Iacoviello L, Evangelista V. , et al. 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 (03) 1072-1081
    CrossrefPubMedGoogle Scholar
  • 47 Falanga A, Russo L, Tartari CJ. Pathogenesis and treatment of thrombohemorrhagic diathesis in acute promyelocytic leukemia. Mediterr J Hematol Infect Dis 2011; 3 (01) e2011068
    CrossrefPubMedGoogle Scholar
  • 48 Booth NA, Bennett B. Plasmin-alpha 2-antiplasmin complexes in bleeding disorders characterized by primary or secondary fibrinolysis. Br J Haematol 1984; 56 (04) 545-556
    CrossrefPubMedGoogle Scholar
  • 49 Tapiovaara H, Alitalo R, Stephens R, Myöhänen H, Ruutu T, Vaheri A. Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients. Blood 1993; 82 (03) 914-919
    CrossrefPubMedGoogle Scholar
  • 50 Tapiovaara H, Matikainen S, Hurme M, Vaheri A. Induction of differentiation of promyelocytic NB4 cells by retinoic acid is associated with rapid increase in urokinase activity subsequently downregulated by production of inhibitors. Blood 1994; 83 (07) 1883-1891
    CrossrefPubMedGoogle Scholar
  • 51 Meijers JC, Oudijk EJ, Mosnier LO. , et al. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia. Br J Haematol 2000; 108 (03) 518-523
    CrossrefPubMedGoogle Scholar
  • 52 Vallier L, Cointe S, Lacroix R. , et al. Microparticles and Fibrinolysis. Semin Thromb Hemost 2017; 43 (02) 129-134
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 53 Tallman MS, Altman JK. Curative strategies in acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program 2008; 391-399
    PubMedGoogle Scholar
  • 54 Jillella AP, Kota VK. The global problem of early deaths in acute promyelocytic leukemia: a strategy to decrease induction mortality in the most curable leukemia. Blood Rev 2018; 32 (02) 89-95
    CrossrefPubMedGoogle Scholar
  • 55 Park JH, Qiao B, Panageas KS. , et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011; 118 (05) 1248-1254
    PubMedGoogle Scholar
  • 56 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 (07) 1128-1134
    CrossrefPubMedGoogle Scholar
  • 57 Rahmé R, Thomas X, Recher C. , et al. Early death in acute promyelocytic leukemia (APL) in French centers: a multicenter study in 399 patients. Leukemia 2014; 28 (12) 2422-2424
    CrossrefPubMedGoogle Scholar
  • 58 Zhu J, Guo WM, Yao YY. , et al. Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents. Leukemia 1999; 13 (07) 1062-1070
    CrossrefPubMedGoogle Scholar
  • 59 Falanga A, Alessio MG, Donati MB, Barbui T. A new procoagulant in acute leukemia. Blood 1988; 71 (04) 870-875
    CrossrefPubMedGoogle Scholar
  • 60 Wang J, Weiss I, Svoboda K, Kwaan HC. Thrombogenic role of cells undergoing apoptosis. Br J Haematol 2001; 115 (02) 382-391
    CrossrefPubMedGoogle Scholar
  • 61 Dunoyer-Geindre S, Rivier-Cordey AS, Tsopra O, Lecompte T, Kruithof EKO. Effect of ATRA and ATO on the expression of tissue factor in NB4 acute promyelocytic leukemia cells and regulatory function of the inflammatory cytokines TNF and IL-1β. Ann Hematol 2017; 96 (06) 905-917
    CrossrefPubMedGoogle Scholar
  • 62 Watanabe R, Murata M, Takayama N. , et al; Keio Hematology-Oncology Cooperative Study Group (KHOCS). Long-term follow-up of hemostatic molecular markers during remission induction therapy with all-trans retinoic acid for acute promyelocytic leukemia. Thromb Haemost 1997; 77 (04) 641-645
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 63 Kwaan HC, Cull EH. The coagulopathy in acute promyelocytic leukaemia – what have we learned in the past twenty years. Best Pract Res Clin Haematol 2014; 27 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 64 Zhao W, Wang X, Guo W. , et al. Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment. Chin Med J (Engl) 2000; 113 (03) 236-240
    PubMedGoogle Scholar
  • 65 Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 1999; 340 (13) 994-1004
    CrossrefPubMedGoogle Scholar
  • 66 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
  • 67 O'Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-α oncoprotein. Blood 2011; 117 (15) 4095-4105
    CrossrefPubMedGoogle Scholar
  • 68 Madureira PA, O'Connell PA, Surette AP, Miller VA, Waisman DM. The biochemistry and regulation of S100A10: a multifunctional plasminogen receptor involved in oncogenesis. J Biomed Biotechnol 2012; 2012: 353687
    PubMedGoogle Scholar
  • 69 Miller VA, Madureira PA, Kamaludin AA. , et al. Mechanism of plasmin generation by S100A10. Thromb Haemost 2017; 117 (06) 1058-1071
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 70 Huang D, Yang Y, Sun J. , et al. Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia. Front Med 2017; 11 (03) 410-422
    CrossrefPubMedGoogle Scholar
  • 71 Wang P, Zhang Y, Yang H. , et al. Characteristics of fibrinolytic disorders in acute promyelocytic leukemia. Hematology 2018; 23 (10) 756-764
    CrossrefPubMedGoogle Scholar
  • 72 Wassenaar T, Black J, Kahl B. , et al. Acute promyelocytic leukaemia and acquired alpha-2-plasmin inhibitor deficiency: a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30 patients. Hematol Oncol 2008; 26 (04) 241-246
    CrossrefPubMedGoogle Scholar
  • 73 Kwaan HC, Rego EM. Role of microparticles in the hemostatic dysfunction in acute promyelocytic leukemia. Semin Thromb Hemost 2010; 36 (08) 917-924
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 74 Lacroix R, Dignat-George F. Microparticles as a circulating source of procoagulant and fibrinolytic activities in the circulation. Thromb Res 2012; 129 (Suppl. 02) S27-S29
    CrossrefPubMedGoogle Scholar
  • 75 Ma G, Liu F, Lv L, Gao Y, Su Y. Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia. Ann Hematol 2013; 92 (05) 645-652
    CrossrefPubMedGoogle Scholar
  • 76 Lavallée VP, Chagraoui J, MacRae T. , et al. Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin. Leukemia 2018; 32 (06) 1349-1357
    CrossrefPubMedGoogle Scholar
  • 77 Oudijk EJ, Nieuwenhuis HK, Bos R, Fijnheer R. Elastase mediated fibrinolysis in acute promyelocytic leukemia. Thromb Haemost 2000; 83 (06) 906-908
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 78 Federici AB, D'Amico EA. The role of von Willebrand factor in the hemostatic defect of acute promyelocytic leukemia. Leuk Lymphoma 1998; 31 (5-6): 491-499
    CrossrefPubMedGoogle Scholar
  • 79 Federici AB, Falanga A, Lattuada A, Di Rocco N, Barbui T, Mannucci PM. Proteolysis of von Willebrand factor is decreased in acute promyelocytic leukaemia by treatment with all-trans-retinoic acid. Br J Haematol 1996; 92 (03) 733-739
    CrossrefPubMedGoogle Scholar
  • 80 O'Connell PA, Waisman DM. Regulation of plasmin generation by the annexin A2 heterotetramer: a shift in perspective. Future Oncol 2012; 8 (07) 763-765
    CrossrefPubMedGoogle Scholar
  • 81 Whiteley WN, Emberson J, Lees KR. , et al; Stroke Thrombolysis Trialists' Collaboration. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol 2016; 15 (09) 925-933
    CrossrefPubMedGoogle Scholar
  • 82 Yepes M, Sandkvist M, Moore EG, Bugge TH, Strickland DK, Lawrence DA. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest 2003; 112 (10) 1533-1540
    CrossrefPubMedGoogle Scholar
  • 83 Su EJ, Fredriksson L, Geyer M. , et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med 2008; 14 (07) 731-737
    CrossrefPubMedGoogle Scholar
  • 84 Medcalf RL. The traumatic side of fibrinolysis. Blood 2015; 125 (16) 2457-2458
    CrossrefPubMedGoogle Scholar
  • 85 Medcalf RL. Fibrinolysis: from blood to the brain. J Thromb Haemost 2017; 15 (11) 2089-2098
    CrossrefPubMedGoogle Scholar
  • 86 Lewandowski SA, Fredriksson L, Lawrence DA, Eriksson U. Pharmacological targeting of the PDGF-CC signaling pathway for blood-brain barrier restoration in neurological disorders. Pharmacol Ther 2016; 167: 108-119
    CrossrefPubMedGoogle Scholar
  • 87 Song J, Wu C, Korpos E. , et al. Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration. Cell Reports 2015; 10 (07) 1040-1054
    CrossrefPubMedGoogle Scholar
  • 88 Lewandowski SA, Nilsson I, Fredriksson L. , et al. Presymptomatic activation of the PDGF-CC pathway accelerates onset of ALS neurodegeneration. Acta Neuropathol 2016; 131 (03) 453-464
    CrossrefPubMedGoogle Scholar
  • 89 Wahlgren N, Thorén M, Höjeberg B. , et al. Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis. J Intern Med 2017; 281 (03) 273-283
    CrossrefPubMedGoogle Scholar
  • 90 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
  • 91 Kwaan HC, Wang J, Weiss I. Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin. J Thromb Haemost 2004; 2 (02) 306-312
    CrossrefPubMedGoogle Scholar
  • 92 Altman JK, Rademaker A, Cull E. , et al. Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res 2013; 37 (09) 1004-1009
    CrossrefPubMedGoogle Scholar
  • 93 Sanz MA, Grimwade D, Tallman MS. , et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2009; 113 (09) 1875-1891
    CrossrefPubMedGoogle Scholar
  • 94 Zhang Y, Wu S, Luo D, Zhou J, Li D. Addition of arsenic trioxide into induction regimens could not accelerate recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia. PLoS One 2016; 11 (01) e0147545
    CrossrefPubMedGoogle Scholar
  • 95 Hashimoto S, Koike T, Tatewaki W. , et al. Fatal thromboembolism in acute promyelocytic leukemia during all-trans retinoic acid therapy combined with antifibrinolytic therapy for prophylaxis of hemorrhage. Leukemia 1994; 8 (07) 1113-1115
    PubMedGoogle Scholar
  • 96 Tsukada N, Wada K, Aoki S. , et al. Induction therapy with all-trans retinoic acid for acute promyelocytic leukemia: a clinical study of 10 cases, including a fatal [correction of fetal] case with thromboembolism. Intern Med 1996; 35 (01) 10-14
    CrossrefPubMedGoogle Scholar
  • 97 Levin MD, Betjes MG, , V d Kwast TH, Wenberg BL, Leebeek FW. Acute renal cortex necrosis caused by arterial thrombosis during treatment for acute promyelocytic leukemia. Haematologica 2003; 88 (06) ECR21
    PubMedGoogle Scholar
  • 98 Mahendra P, Keeling DM, Hood IM, Baglin TP, Marcus RE. Fatal thromboembolism in acute promyelocytic leukaemia treated with a combination of all-trans retinoic acid and aprotonin. Clin Lab Haematol 1996; 18 (01) 51-52
    CrossrefPubMedGoogle Scholar
  • 99 Brown JE, Olujohungbe A, Chang J. , et al. All-trans retinoic acid (ATRA) and tranexamic acid: a potentially fatal combination in acute promyelocytic leukaemia. Br J Haematol 2000; 110 (04) 1010-1012
    CrossrefPubMedGoogle Scholar
  • 100 Kawano N, Kuriyama T, Yoshida S. , et al. Clinical features and treatment outcomes of six patients with disseminated intravascular coagulation resulting from acute promyelocytic leukemia and treated with recombinant human soluble thrombomodulin at a single institution. Intern Med 2013; 52 (01) 55-62
    CrossrefPubMedGoogle Scholar
  • 101 Mitrovic M, Suvajdzic N, Elezovic I. , et al. Thrombotic events in acute promyelocytic leukemia. Thromb Res 2015; 135 (04) 588-593
    CrossrefPubMedGoogle Scholar
  • 102 Mitrovic M, Suvajdzic N, Bogdanovic A. , et al. International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥ 6: a new predictor of hemorrhagic early death in acute promyelocytic leukemia. Med Oncol 2013; 30 (01) 478
    CrossrefPubMedGoogle Scholar
  • 103 Rashidi A, Silverberg ML, Conkling PR, Fisher SI. Thrombosis in acute promyelocytic leukemia. Thromb Res 2013; 131 (04) 281-289
    CrossrefPubMedGoogle Scholar
  • 104 Goldschmidt N, Gural A, Ben Yehuda D. Extensive splenic infarction, deep vein thrombosis and pulmonary emboli complicating induction therapy with all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia. Leuk Lymphoma 2003; 44 (08) 1433-1437
    CrossrefPubMedGoogle Scholar
  • 105 Kutiyal AS, Dharmshaktu P, Kataria B, Garg A. A rare occurrence of simultaneous venous and arterial thromboembolic events - lower limb deep venous thrombosis and pulmonary thromboembolism as initial presentation in acute promyelocytic leukemia. Clin Med Insights Oncol 2016; 10: 1-4
    PubMedGoogle Scholar
  • 106 Trottier-Tellier F, Durand M, Kolan C, Wistaff R, Nguyen PV, Laskine M. Recurrent arterial and venous thromboemboli as initial presentation of acute promyelocytic leukemia. J Clin Med Res 2014; 6 (05) 388-391
    PubMedGoogle Scholar
  • 107 Escudier SM, Kantarjian HM, Estey EH. Thrombosis in patients with acute promyelocytic leukemia treated with and without all-trans retinoic acid. Leuk Lymphoma 1996; 20 (5-6): 435-439
    CrossrefPubMedGoogle Scholar
  • 108 Altwegg SC, Altwegg LA, Maier W. Intracoronary thrombus with tissue factor expression heralding acute promyelocytic leukaemia. Eur Heart J 2007; 28 (22) 2731
    CrossrefPubMedGoogle Scholar
  • 109 Cahill TJ, Chowdhury O, Myerson SG. , et al. Myocardial infarction with intracardiac thrombosis as the presentation of acute promyelocytic leukemia: diagnosis and follow-up by cardiac magnetic resonance imaging. Circulation 2011; 123 (10) e370-e372
    PubMedGoogle Scholar
  • 110 Li Y, Suo S, Mao L. , et al. Acute myocardial/cerebral infarction as first/relapse manifestation in one acute promyelocytic leukemia patient. Int J Clin Exp Med 2015; 8 (08) 14210-14213
    PubMedGoogle Scholar
  • 111 Torromeo C, Latagliata R, Avvisati G, Petti MC, Mandelli F. Intraventricular thrombosis during all-trans retinoic acid treatment in acute promyelocytic leukemia. Leukemia 2001; 15 (08) 1311-1313
    CrossrefPubMedGoogle Scholar
  • 112 Nicholas-Bublick S, Irlam JH, Tietjen G. A malignant case of acute promyelocytic leukemia with occlusion of carotid artery by tumor thrombus. J Stroke Cerebrovasc Dis 2012; 21 (04) 325-326
    CrossrefPubMedGoogle Scholar
  • 113 Liu L, Yuan X. Transient ischemic attack as an unusual initial manifestation of acute promyelocytic leukemia. Int J Hematol 2016; 104 (01) 134-138
    CrossrefPubMedGoogle Scholar
  • 114 Rolston DD, Rubin S, Topolsky D, Styler M, Crilley P. Arterial occlusions as a presenting feature of acute promyelocytic leukemia. Am J Clin Oncol 1998; 21 (05) 436-437
    CrossrefPubMedGoogle Scholar
  • 115 Fass R, Haddad M, Zaizov R. , et al. Recurrent peripheral arterial occlusion by leukemic cells sedimentation in acute promyelocytic leukemia. J Pediatr Surg 1992; 27 (05) 665-667
    CrossrefPubMedGoogle Scholar
  • 116 Kalk E, Goede A, Rose P. Acute arterial thrombosis in acute promyelocytic leukaemia. Clin Lab Haematol 2003; 25 (04) 267-270
    CrossrefPubMedGoogle Scholar
  • 117 Chotai PN, Kasangana K, Chandra AB, Rao AS. Recurrent arterial thrombosis as a presenting feature of a variant M3-acute promyelocytic leukemia. Vasc Spec Int 2016; 32 (02) 65-71
    CrossrefPubMedGoogle Scholar
  • 118 Farah RA, Jalkh KS, Farhat HZ, Sayad PE, Kadri AM. Acquired protein C deficiency in a child with acute myelogenous leukemia, splenic, renal, and intestinal infarction. Blood Coagul Fibrinolysis 2011; 22 (02) 140-143
    CrossrefPubMedGoogle Scholar
  • 119 Sargsyan Z, Higgins C, Alexandrescu S, Ott DA, Jain SK. Acute promyelocytic leukemia as a cause of intracoronary drug-eluting-stent thrombosis. Tex Heart Inst J 2012; 39 (03) 416-419
    PubMedGoogle Scholar
  • 120 Fujita H, Takemura S, Hyo R. , et al. Pulmonary embolism and thrombotic thrombocytopenic purpura in acute promyelocytic leukemia treated with all-trans retinoic acid. Leuk Lymphoma 2003; 44 (09) 1627-1629
    PubMedGoogle Scholar
  • 121 Vaid AK, Batra S, Karanth SS, Gupta S. Acute promyelocytic leukemia presenting as pulmonary thromboembolism: Not all APLs bleed. Avicenna J Med 2015; 5 (04) 131-133
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 122 Ciccone M, Rigolin GM, Viglione GM, Borrelli M, Serino ML, Cuneo A. Thrombosis of the cerebral veins and sinuses in acute promyelocytic leukemia after all-trans retinoic acid treatment: a case report. Blood Coagul Fibrinolysis 2008; 19 (07) 721-723
    CrossrefPubMedGoogle Scholar
  • 123 Song LX, Lu HY, Chang CK, Li X, Zhang Z. Cerebral venous and sinus thrombosis in a patient with acute promyelocytic leukemia during all-trans retinoic acid induction treatment. Blood Coagul Fibrinolysis 2014; 25 (07) 773-776
    CrossrefPubMedGoogle Scholar
  • 124 Beslow LA, Abend NS, Smith SE. Cerebral sinus venous thrombosis complicated by cerebellar hemorrhage in a child with acute promyelocytic leukemia. J Child Neurol 2009; 24 (01) 110-114
    CrossrefPubMedGoogle Scholar
  • 125 Lee KR, Subrayan V, Win MM, Fadhilah Mohamad N, Patel D. ATRA-induced cerebral sinus thrombosis. J Thromb Thrombolysis 2014; 38 (01) 87-89
    CrossrefPubMedGoogle Scholar
  • 126 Hazani A, Weidenfeld Y, Tatarsky I, Bental E. Acute promyelocytic leukemia presenting as sudden blindness and sinus vein thrombosis. Am J Hematol 1988; 28 (01) 56-57
    CrossrefPubMedGoogle Scholar
  • 127 Kayal S, Singhal B, Thulkar S, Mishra J, Kumar R, Bakhshi S. Acute Budd-Chiari syndrome in pediatric acute promyelocytic leukemia. Leuk Lymphoma 2011; 52 (08) 1611-1614
    CrossrefPubMedGoogle Scholar
  • 128 Havelange V, Annet L, Poiré X, Lambert C, Vekemans MC. Budd-Chiari syndrome in a patient with acute promyelocytic leukaemia. Br J Haematol 2014; 166 (01) 1
    CrossrefPubMedGoogle Scholar
  • 129 Amitrano L, Guardascione MA, Schiavone EM. , et al. Hepatic vein thrombosis leading to fulminant hepatic failure in a case of acute non-promyelocytic myelogenous leukemia. Blood Coagul Fibrinolysis 2006; 17 (01) 59-61
    CrossrefPubMedGoogle Scholar
  • 130 Assouline D, Negrier C, Coguard I. , et al. Successful systemic thrombolysis of hepatic vein thrombosis in a patient with promyelocytic leukemia treated with all-trans retinoic acid. Am J Hematol 1995; 48 (04) 291-292
    PubMedGoogle Scholar
  • 131 Colović M, Miljić P, Colović N, Janković G, Stojković M. Reversible portal vein thrombosis complicating induction therapy of acute promyelocytic leukemia. Thromb Res 2001; 101 (02) 101-103
    CrossrefPubMedGoogle Scholar
  • 132 Grisariu S, Spectre G, Kalish Y, Gatt ME. Increased risk of central venous catheter-associated thrombosis in acute promyelocytic leukemia: a single-institution experience. Eur J Haematol 2013; 90 (05) 397-403
    CrossrefPubMedGoogle Scholar
  • 133 Koçak U, Gürsel T, Oztürk G, Kantarci S. Thrombosis during all-trans-retinoic acid therapy in a child with acute promyelocytic leukemia and factor VQ 506 mutation. Pediatr Hematol Oncol 2000; 17 (02) 177-180
    CrossrefPubMedGoogle Scholar
  • 134 Rees D, Grimwade D, Langabeer S, Burnett A, Goldstone A. ; MRC Adult Leukaemia Working Party. Influence of genetic predisposition to thrombosis on natural history of acute promyelocytic leukaemia. Br J Haematol 1997; 96 (03) 490-492
    CrossrefPubMedGoogle Scholar
  • 135 Key NS, Mackman N. Tissue factor and its measurement in whole blood, plasma, and microparticles. Semin Thromb Hemost 2010; 36 (08) 865-875
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 136 Key NS, Chantrathammachart P, Moody PW, Chang JY. Membrane microparticles in VTE and cancer. Thromb Res 2010; 125 (Suppl. 02) S80-S83
    CrossrefPubMedGoogle Scholar
  • 137 Rak J. Microparticles in cancer. Semin Thromb Hemost 2010; 36 (08) 888-906
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 138 Silva MM, Thelwell C, Williams SC, Longstaff C. Regulation of fibrinolysis by C-terminal lysines operates through plasminogen and plasmin but not tissue-type plasminogen activator. J Thromb Haemost 2012; 10 (11) 2354-2360
    CrossrefPubMedGoogle Scholar
  • 139 Fenaux P, Le Deley MC, Castaigne S. , et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. results of a multicenter randomized trial. European APL 91 Group. Blood 1993; 82 (11) 3241-3249
    CrossrefPubMedGoogle Scholar
  • 140 Mandelli F, Diverio D, Avvisati G. , et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Blood 1997; 90 (03) 1014-1021
    PubMedGoogle Scholar
  • 141 Lengfelder E, Reichert A, Schoch C. , et al; German AML Cooperative Group. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. Leukemia 2000; 14 (08) 1362-1370
    CrossrefPubMedGoogle Scholar
  • 142 Paulson K, Serebrin A, Lambert P. , et al. Acute promyelocytic leukaemia is characterized by stable incidence and improved survival that is restricted to patients managed in leukaemia referral centres: a pan-Canadian epidemiological study. Br J Haematol 2014; 166 (05) 660-666
    CrossrefPubMedGoogle Scholar
  • 143 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 (10) 1431-1432
    CrossrefPubMedGoogle Scholar
  • 144 Serefhanoglu S, Buyukasik Y, Goker H. , et al. Clinical features and outcomes of 49 Turkish patients with acute promyelocytic leukemia who received ATRA and anthracyclines (PETHEMA protocol) therapy. Leuk Res 2010; 34 (12) e317-e319
    CrossrefPubMedGoogle Scholar
  • 145 Iland HJ, Bradstock K, Supple SG. , et al; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood 2012; 120 (08) 1570-1580 , quiz 1752
    PubMedGoogle Scholar
  • 146 Silva Jr WFD, Rosa LID, Marquez GL. , et al. Real-life outcomes on acute promyelocytic leukemia in brazil - early deaths are still a problem. Clin Lymphoma Myeloma Leuk 2019; 19 (02) e116-e122
    PubMedGoogle Scholar