{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:18:28Z","timestamp":1787019508096,"version":"build-2736575974"},"reference-count":44,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The rate of venous thromboembolism (VTE) in patients with acute leukemia or lymphomas is comparable with that of other \u201chigh-risk\u201d cancer types. Chemotherapy and anti-angiogenic drugs increase the thrombotic risk in patients with lymphomas, acute leukemias and multiple myeloma (MM). Patients with hematologic malignancies often present with a hypercoagulable state or chronic disseminated intravascular coagulation (DIC) in the absence of active thrombosis and\/or bleeding. Malignant cell procoagulant properties, cytotoxic therapies, and concomitant infections are major determinants for clotting activation in hematologic malignancies. In acute leukemia, clinical manifestations range from localized venous or arterial thrombosis to a diffuse, life-threatening thrombohemorrhagic syndrome (THS). All-trans retinoic acid (ATRA) has greatly improved the management of acute promyelocytic leukemia (APL), but has not significantly changed the rate of early hemorrhagic deaths and may actually promote thrombosis. Randomized, controlled trials (RCTs) of different prophylactic regimens to prevent VTE or THS in hematologic malignancies are urgently needed, particularly in patients with lymphoma or MM during chemotherapy and in patients with APL. Anticoagulant therapy is a particular challenge in patients with hematologic malignancies, since these patients are at very high risk for hemorrhage. No guidelines are available for the prophylaxis or treatment of VTE; extrapolations can be made from existing guidelines for management of patients with other malignancies; prolonged periods of treatment-induced thrombocytopenia in patients with hematologic malignancies, however, require a more judicious application of standard anticoagulant approaches. Use of the newer anticoagulants will require careful assessment of hemorrhagic risk in this group of high-risk patients but may be justified under special circumstances.<\/jats:p>","DOI":"10.1182\/asheducation-2007.1.165","type":"journal-article","created":{"date-parts":[[2007,11,16]],"date-time":"2007-11-16T13:08:40Z","timestamp":1195218520000},"page":"165-171","source":"Crossref","is-referenced-by-count":44,"title":["Management of Thrombohemorrhagic Syndromes (THS) in Hematologic Malignancies"],"prefix":"10.1182","volume":"2007","author":[{"given":"Anna","family":"Falanga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick R.","family":"Rickles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019101007430423100_R1","unstructured":"Barbui T, Finazzi G, Falanga A. The management of bleeding and thrombosis in acute leukemia and chronic myeloproliferative disorders. In: Henderson ES, Lister TA, Greaves MF, eds. Leukemia, 7th ed. Philadelphia, PA: WB Saunders Company; 2001:363\u2013382."},{"key":"2019101007430423100_R2","doi-asserted-by":"crossref","unstructured":"Falanga A, Rickles FR. Pathogenesis and management of the bleeding diathesis in acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003;16:463\u2013482.","DOI":"10.1016\/S1521-6926(03)00059-8"},{"key":"2019101007430423100_R3","doi-asserted-by":"crossref","unstructured":"Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293:715\u2013722.","DOI":"10.1001\/jama.293.6.715"},{"key":"2019101007430423100_R4","doi-asserted-by":"crossref","unstructured":"White RH, Chew HK, Zhou H, et al. Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528,693 adults. Arch Intern Med. 2005;165:1782\u20131787.","DOI":"10.1001\/archinte.165.15.1782"},{"key":"2019101007430423100_R5","doi-asserted-by":"crossref","unstructured":"Khorana AA, Francis CW, Culakova E, et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer. 2005;104:2822\u20132829.","DOI":"10.1002\/cncr.21496"},{"key":"2019101007430423100_R6","doi-asserted-by":"crossref","unstructured":"Khorana AA, Francis CW, Culakova E, et al. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol. 2006;24:484\u2013490.","DOI":"10.1200\/JCO.2005.03.8877"},{"key":"2019101007430423100_R7","doi-asserted-by":"crossref","unstructured":"Barbui T, Falanga A. Thalidomide and thrombosis in multiple myeloma. J Thromb Haemost. 2003;1:421\u2013422.","DOI":"10.1046\/j.1538-7836.2003.00084.x"},{"key":"2019101007430423100_R8","doi-asserted-by":"crossref","unstructured":"Cavo M, Zamagni E, Cellini C, et al. Deep vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. Blood. 2002;100:2272\u20132273.","DOI":"10.1182\/blood-2002-06-1674"},{"key":"2019101007430423100_R9","doi-asserted-by":"crossref","unstructured":"Cortelezzi A, Moia M, Falanga A, et al. Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study. Br J Hematol. 2005;129:811\u2013817.","DOI":"10.1111\/j.1365-2141.2005.05529.x"},{"key":"2019101007430423100_R10","doi-asserted-by":"crossref","unstructured":"Couban S, Goodyear M, Burnell M, et al. Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter\u2013associated thrombosis in patients with cancer. J Clin Oncol. 2005;23:4063\u20134069.","DOI":"10.1200\/JCO.2005.10.192"},{"key":"2019101007430423100_R11","unstructured":"Dvorak HF, Rickles FR. Malignancy and hemostasis. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, eds. Hemostasis and Thrombosis, Basic Principles and Clinical Practice. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:851\u2013873."},{"key":"2019101007430423100_R12","doi-asserted-by":"crossref","unstructured":"Rickles FR, Falanga A. Molecular basis for the relationship between thrombosis and cancer. Thromb Res. 2001;102:215\u2013224.","DOI":"10.1016\/S0049-3848(01)00285-7"},{"key":"2019101007430423100_R13","doi-asserted-by":"crossref","unstructured":"Zigler S, Sperr WR, Knobl P, et al. Symptomatic venous thromboembolism in acute leukemia. Incidence, risk factors, and impact on prognosis. Thromb Res. 2005;115:59\u201364.","DOI":"10.1016\/j.thromres.2004.07.016"},{"key":"2019101007430423100_R14","doi-asserted-by":"crossref","unstructured":"De Stefano V, Sora 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;3:1985\u20131992.","DOI":"10.1111\/j.1538-7836.2005.01467.x"},{"key":"2019101007430423100_R15","doi-asserted-by":"crossref","unstructured":"Bu\u0308ller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004;126:401S\u2013428S.","DOI":"10.1378\/chest.126.3_suppl.401S"},{"key":"2019101007430423100_R16","unstructured":"NCCN Practice Guidelines in Oncology. National Comprehensive Cancer Network, Inc. V2.2006, October 11, 2006."},{"key":"2019101007430423100_R17","doi-asserted-by":"crossref","unstructured":"Mandala M, Falanga A, Piccioli A, et al. Venous thromboembolism and cancer: guidelines of the Italian Society of Oncology (AIOM). Crit Reviews Oncol\/Hematol. 2006;59:194\u2013204.","DOI":"10.1016\/j.critrevonc.2006.05.001"},{"key":"2019101007430423100_R18","unstructured":"Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology Guideline: recommendations for venous thromboembolism prophylaxis in patients with cancer. J Clin Oncol. In Press."},{"key":"2019101007430423100_R19","doi-asserted-by":"crossref","unstructured":"Lee AYY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146\u2013153.","DOI":"10.1056\/NEJMoa025313"},{"key":"2019101007430423100_R20","doi-asserted-by":"crossref","unstructured":"Boccaccio C, Sabatino G, Medico E, et al. The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature. 2005;434:396\u2013400.","DOI":"10.1038\/nature03357"},{"key":"2019101007430423100_R21","doi-asserted-by":"crossref","unstructured":"Rong Y, Post DE, Pieper RO, et al. PTEN and hypoxia regulate tissue factor expression and plasma coagulation by glioblastoma. Cancer Res. 2005;65:1406\u20131413.","DOI":"10.1158\/0008-5472.CAN-04-3376"},{"key":"2019101007430423100_R22","doi-asserted-by":"crossref","unstructured":"Yu JL, May L, Lhotak V, et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood. 2005;105:1734\u20131741.","DOI":"10.1182\/blood-2004-05-2042"},{"key":"2019101007430423100_R23","doi-asserted-by":"crossref","unstructured":"Falanga A, Marchetti M, Vignoli A, et al. V617F JAK-2 mutation in patients iwth essential thrombocythemia: relation to platelet, granulocyte and plasma hemostatic and inflammatory molecules. Exp Hematol. 2007;35:702\u2013711.","DOI":"10.1016\/j.exphem.2007.01.053"},{"key":"2019101007430423100_R24","doi-asserted-by":"crossref","unstructured":"Zangari M, Saghafifar F, Mehta P, et al. The blood coagulation mechanism in multiple myeloma. Semin Thromb Hemost. 2003;29:275\u2013282.","DOI":"10.1055\/s-2003-40965"},{"key":"2019101007430423100_R25","doi-asserted-by":"crossref","unstructured":"Tallman MS, Lefebvre 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;2:1341\u20131350.","DOI":"10.1111\/j.1538-7836.2004.00787.x"},{"key":"2019101007430423100_R26","doi-asserted-by":"crossref","unstructured":"Falanga A, Vignoli A, Marchetti M, et al. Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells. Leukemia. 2003;17:1636\u20131642.","DOI":"10.1038\/sj.leu.2403004"},{"key":"2019101007430423100_R27","doi-asserted-by":"crossref","unstructured":"Ewenstein BM. Nonhemophilic inhibitors of coagulation. In: Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis. Philadelphia, PA: WB Saunders; 2007;81\u201395.","DOI":"10.1016\/B978-141602401-9.10006-9"},{"key":"2019101007430423100_R28","doi-asserted-by":"crossref","unstructured":"Rick ME. von Willebrand Disease. In: Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis. Philadelphia, PA: WB Saunders; 2007;97\u2013109.","DOI":"10.1016\/B978-141602401-9.10007-0"},{"key":"2019101007430423100_R29","doi-asserted-by":"crossref","unstructured":"Kumar S, Pruthi RK, Nichols WL. Acquired von Willebrand\u2019s syndrome: a single institution experience. Am J Hematol. 2003;72:243\u2013247.","DOI":"10.1002\/ajh.10298"},{"key":"2019101007430423100_R30","doi-asserted-by":"crossref","unstructured":"Zangari M, Barlogie B, Anaissie E, et al. Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation. Br J Haematol. 2004;126:715\u2013721.","DOI":"10.1111\/j.1365-2141.2004.05078.x"},{"key":"2019101007430423100_R31","doi-asserted-by":"crossref","unstructured":"Minnema MC, Breitkreutz I, Auwerda JJ, et al. Prevention of venous thromboembolism with low molecular-weight heparin in patients with multiple myeloma treated with thalidomide and chemotherapy. Leukemia. 2004;18:2044\u20132046.","DOI":"10.1038\/sj.leu.2403533"},{"key":"2019101007430423100_R32","unstructured":"Cavo M, Zamagni E, Tosi P, et al. First-line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica. 2004;89:826\u2013831."},{"key":"2019101007430423100_R33","doi-asserted-by":"crossref","unstructured":"Baz R, Li L, Kottke-Marchant K, et al. The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma. Mayo Clin Proc. 2005;80:1568\u20131574.","DOI":"10.4065\/80.12.1568"},{"key":"2019101007430423100_R34","doi-asserted-by":"crossref","unstructured":"Rajkumar SV, Hayman S, Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev\/Dex) for newly diagnosed myeloma [abstract]. Blood. 2005;106:230a\u2013231a.","DOI":"10.1182\/blood-2005-07-2817"},{"key":"2019101007430423100_R35","doi-asserted-by":"crossref","unstructured":"Niesvizky R, Martinez-Banos DM, Gelbshtein UY, et al. Prophylactic low-dose aspirin is effective as antithrombotic therapy in patients receiving combination thalidomide or lenalidomide [abstract]. Blood. 2005;106:964a.","DOI":"10.1182\/blood.V106.11.3454.3454"},{"key":"2019101007430423100_R36","doi-asserted-by":"crossref","unstructured":"Palumbo A, Rus C, Zeldis JB, et al. Enoxaparin or aspirin for the prevention of recurrent thromboembolism in newly diagnosed myeloma patients treated with melphalan and prednisone plus thalidomide or lenalidomide. J Thromb Haemost. 2006;4:1842\u20131845.","DOI":"10.1111\/j.1538-7836.2006.02059.x"},{"key":"2019101007430423100_R37","doi-asserted-by":"crossref","unstructured":"Herishanu Y, Misgav M, Kirgner I, et al. Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens. Leuk Lymphoma. 2004;45:1407\u20131411.","DOI":"10.1080\/10428190410001663671"},{"key":"2019101007430423100_R38","doi-asserted-by":"crossref","unstructured":"Imberti D, Vallisa D, Anselmi E, et al. Safety and efficacy of enoxaparin treatment in venous thromboembolic disease during acute leukemia. Tumori. 2004;90:1\u20134.","DOI":"10.1177\/030089160409000405"},{"key":"2019101007430423100_R39","doi-asserted-by":"crossref","unstructured":"The PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism. The PREPIC (Prevention du Risque d\u2019Embolie Pulmonaire par Interruption Cave) randomized study. Circulation. 2005;112:416\u2013422.","DOI":"10.1161\/CIRCULATIONAHA.104.512834"},{"key":"2019101007430423100_R40","doi-asserted-by":"crossref","unstructured":"Montesinos P, Sanz MA. Incidence and prognostic factors for hemorrhagic death in patients with acute myeloid leukemia: a single-centre historical report. Thromb Res. 2007; in press.","DOI":"10.1182\/blood.V110.11.4300.4300"},{"key":"2019101007430423100_R41","doi-asserted-by":"crossref","unstructured":"Rodeghiero F, Avvisati G, Castaman G, et al. Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients. Blood. 1990;75:2112\u20132117.","DOI":"10.1182\/blood.V75.11.2112.2112"},{"key":"2019101007430423100_R42","doi-asserted-by":"crossref","unstructured":"Sanz MA, Martin G, Gonzalez M, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237\u20131243.","DOI":"10.1182\/blood-2003-07-2462"},{"key":"2019101007430423100_R43","doi-asserted-by":"crossref","unstructured":"Rickles FR, Mechanisms of cancer-induced thrombosis [review]. Pathophysiol Haemost Thromb. 2006;35:103\u2013110.","DOI":"10.1159\/000093551"},{"key":"2019101007430423100_R44","unstructured":"Falanga A, Marchetti M. Thromboembolism in hematologic malignancies. In: Khorana AA, Francis CW, eds. Cancer-Associated Thrombosis: New Findings in Translational Science, Prevention, and Treatment. New York, NY: Informa Healthcare; In press."}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2007\/1\/165\/646243\/165_171ash.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2007\/1\/165\/646243\/165_171ash.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T02:58:28Z","timestamp":1588042708000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2007\/1\/165\/19178\/Management-of-Thrombohemorrhagic-Syndromes-THS-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2007.1.165","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,1,1]]}}}