Abstract
It is well recognized that thrombosis and bleeding are two major complications seen in cancer patients. Recent advances in both basic and clinical observations have enhanced our understanding of the pathogenesis of both phenomena. In this article, the significance of thrombotic complications is reviewed first. This is followed by a detailed discussion of the present day concept of thrombogenesis in cancer based on Virchow’s original triad of aberrant blood flow, loss of vascular integrity and altered blood components. While most cancer patients experience bleeding at some time during the course of their illness, there are special situations that increase bleeding diathesis. These include thrombocytopenia, endothelial injury, acquired hemophilia and adverse effects of drugs.
Recognition of these factors will assit in the adoption of appropriate preventive and therapeutic measures.
Similar content being viewed by others
References
Virchow R. Phlogose und Thrombose in gefabsystem. In: Virchow R (ed) Gesammelte Abdhandlunhen zur Wissenschaftlicgen Medicin. Von Meidinger Sohn, Frankfurt 1856:458
Trousseau A (1865) Phlegmasia Alba Dolens. Clinique Médicale de l’Hôtel Dieu de Paris. Baillière, Paris 659–712
Costantini V, De Monte P, Cazzato AO et al (1998) Systemic thrombin generation in cancer patients is correlated with extrinsic pathway activation. Blood Coagul Fibrinolysis 9:79–84
Goldenberg N, Kahn SR, Solymoss S (2003) Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism. J Clin Oncol 21:4194–4199
Johnson MJ, Walker ID, Sproule MW et al (1999) Abnormal coagulation and deep venous thrombosis in patients with advanced cancer. Clin Lab Haematol 21:51–54
Ozyilkan O, Baltali E, Ozdemir O et al (1998) Haemostatic changes; plasma levels of alpha2-antiplasmin-plasmin complex and thrombin-antithrombin III complex in female breast cancer. Tumori 84:364–367
Rickles FR, Levine MN (2001) Epidemiology of thrombosis in cancer. Acta Haematol 106:6–12
White RH, Chew HK, Zhou H et al (2005) Incidence of venous thromboembolism in the year before the diagnosis of cancer in adults. Arch Intern Med 165:1782–1787
Murchison JT, Wylie L, Stockton DL (2004) Excess risk of cancer in patients with primary venous thromboembolism: a national, population-based cohort study. Br J Cancer 91:92–95
Khorana AA, Francis CW, Culakova E et al (2006) Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 24:484–490
Otten HM, Mathijssen J, Ten Cate H et al (2004) Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med 164:190–194
Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005). Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293:715–722
Mohren M, Markmann I, Jentsch-Ullrich K et al (2005) Increased risk of thromboembolism in patients with malignant lymphoma: a single-centre analysis. Br J Cancer 92:1349–1351
Goldschmidt N, Linetsky E, Shalom E et al (2003) High incidence of thromboembolism in patients with central nervous system lymphoma. Cancer 98:1239–1242
Komrokji RS, Uppal NP, Khorana AA et al (2006) Venous thromboembolism in patients with diffuse large B-cell lymphoma. Leuk Lymphoma 47:1029–1033
Mohren M, Markmann I, Jentsch-Ullrich K et al (2006) Increased risk of venous thromboembolism in patients with acute leukaemia. Br J Cancer 4:200–202
Ziegler S, Sperr WR, Knobl P et al (2005) Symptomatic venous thromboembolism in acute leukemia. Incidence, risk factors, and impact on prognosis. Thromb Res 115:59–64
Hugo JZ, Jeanet DM (2006) Acquired activated protein C resistance and thrombosis in multiple myeloma patients. Thrombos J 4:11
Srkalovic G, Cameron MG, Rybicki L et al (2004) Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer 101:558–566
Zangari M, Saghafifar F, Anaissie E et al (2002) Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications. Blood Coagul Fibrinolysis 13:187–192
Chew HK, Wun T, Harvey D et al (2006) Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 166:458–464
Tetsche MS, Norgaard M, Pedersen L et al (2006) Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study. BMC Cancer 6:189
Sorensen HT, Mellemkjaer L, Olsen JH et al (2000) Prognosis of cancers associated with venous thromboembolism. N Engl J Med 343:1846–1850
Alexy T, Pais E, Wenby RB et al (2005) Measurement of whole blood viscosity profiles via an automated viscometer: technical details and clinical relevance. Clin Lab 51:523–529
Philippe F, Lacombe C, Bucherer C et al (2001) Whole blood viscosity measurement in acute myocardial infarction: feasibility and significance. J Malad Vascul 26:243–247
Bell W (1973) Defibrinogenation with Arvin. In: Brinkhouse KM (ed) Thombosis: mechanism and control. FA Schattauer Verlag, Stuttgart pp. 371–375
Resch KL EE (1994) Fibrinogen and viscosity: risk factors for cardiovascular events. Compr Ther 20:170–173
Lowe GD (2005) Fibrin D-dimer and cardiovascular risk. Semin Vasc Med 5:387–398
Masuda H, Kurita Y, Fukuta K et al (1998) Significant prognostic factors for 5-year survival after curative resection of renal cell carcinoma. Int J Urol 5:418–422
Wojtukiewicz MZ, Zacharski LR, Memoli VA et al (1990) Fibrinogenfibrin transformation in situ in renal cell carcinoma. Anticancer Res 10:579–582
Koh SC, Khalil R, Lim FK et al (2006) The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer. Clin Appl Thromb Hemost 12:3–8
Ogata Y, Hepplmann CJ, Charlesworth MC et al (2006) Elevated levels of phosphorylated fibrinogen-alpha-isoforms and differential expression of other post-translationally modified proteins in the plasma of ovarian cancer patients. J Proteome Res 5:3318–3325
McGrath MA, Penny R (1976). Paraproteinemia: blood hyperviscosity and clinical manifestations. J Clin Invest; 58:1155–1162
Foester J (1998) Cryoglobulins and cryoglobulinemia. Lee GR FJ, Lukens J, Paraskevas F, et al (eds) Wintrobe’s Clinical Haematology. Williams & Wilkins, Baltimore pp 2725–2737
Wasserman LR, Balcerzak SP, Berk PD et al (1981) Influence of therapy on causes of death in polycythemia vera. Trans Assoc Am Physicians 94:30–38
Marchioli R, Finazzi G, Landolfi R et al (2005) Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23:2224–2232
Pearson TC, Wetherley-Mein G (1978) Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia. Lancet 2:1219–1222
Spivak JL (2002) Polycythemia vera: myths, mechanisms, and management. Blood 100:4272–4290
Schafer AI (2006) Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood 107:4214–4222
Berk PD WL, Fruchtman SM, Goldberg JD (1995) Treatment of polycythemia vera: a summary of clinical trials conducted by the Polycythemia Vera Study Group. In: Wasserman LR BP, Berlin NI (eds) Polycythemia vera and the myeloproliferative disorders. W.B. Sauders, Philadelphia, PA pp 166–194
Di Nisio M, Barbui T, Di Gennaro L et al (2007) The haematocrit and platelet target in polycythemia vera. Br J Haematol 136:249–259
Landolfi R, Ciabattoni G, Patrignani P et al (1992) Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo. Blood 80:1965–1971.
Kwaan HC, Bongu A (1999) The hyperviscosity syndromes. Semin Thromb Hemost 25:199–208
Cukierman T, Gatt ME, Libster D et al (2002) Chronic lymphocytic leukemia presenting with extreme hyperleukocytosis and thrombosis of the common femoral vein. Leuk Lymphoma 43:1865–1868.
Khorana AA, Francis CW, Culakova E et al (2005) Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 104:2822–2829
Chang VT, Aviv H, Howard LM et al (2003) Acute myelogenous leukemia associated with extreme symptomatic thrombocytosis and chromosome 3q translocation: case report and review of literature. Am J Hematol 72:20–26
Otten TR, Stein PD, Patel KC et al (2003) Thromboembolic disease involving the superior vena cava and brachiocephalic veins. Chest 123:809–812
Mamede RC, Resende e Almeida KO, de Mello-Filho FV (2004) Neck mass due to thrombosis of the jugular vein in patients with cancer. Otolaryngol Head Neck Surg 131:968–972
Hiraiwa K, Morozumi K, Miyazaki H et al (2006) Isolated splenic vein thrombosis secondary to splenic metastasis: a case report. World J Gastroenterol 12:6561–6563
Inoue H, Yasu T, Kawahito K et al (2006) Successfully treated massive pulmonary thromboembolism and thrombus in the right atrium due to diffuse malignant lymphoma: a case report. J Cardiol 48:159–163
Bergqvist D (2006) Venous thromboembolism: a review of risk and prevention in colorectal surgery patients. Dis Colon Rectum 49:1620–1628
Mason DP, Quader MA, Blackstone EH et al (2006) Thromboembolism after pneumonectomy for malignancy: an independent marker of poor outcome. J Thorac Cardiovasc Surg 131:711–718
Andtbacka RH, Babiera G, Singletary SE et al (2006) Incidence and prevention of venous thromboembolism in patients undergoing breast cancer surgery and treated according to clinical pathways. Ann Surg 243:96–101.
Martino MA, Borges E, Williamson E et al (2006) Pulmonary embolism after major abdominal surgery in gynecologic oncology. Obstetrics Gynecol 107:666–671.
Smith SF, Simpson JM, Sekhon LH (2004) Prophylaxis for deep venous thrombosis in neurosurgical oncology: review of 2,779 admissions over a 9-year period. Neurosurg Focus 17:E4
Agnelli G, Bolis G, Capussotti L et al (2006) A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 243:89–95
Le Treut YP, Hardwigsen J, Ananian P et al (2006) Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series. J Gastrointest Surg 10:855–862
Chen XP, Qiu FZ, Wu ZD et al (2006) Effects of location and extension of portal vein tumor thrombus on long-term outcomes of surgical treatment for hepatocellular carcinoma. Ann Surg Oncol 13:940–946.
Ikai I, Hatano E, Hasegawa S et al (2006) Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein. J Am College Surgeons 202:431–438
Zini L, Haulon S, Leroy X et al (2006) Endoluminal occlusion of the inferior vena cava in renal cell carcinoma with retro-or suprahepatic caval thrombus. BJU international 97:1216–1220
Jiang H, Zhang ZG, Chen ZD et al (2006) Renal cell carcinoma with vena caval tumor thrombus extending into the right atrium. Chinese Med J 119:1934–1936
Sakuma M, Fukui S, Nakamura M et al (2006) Cancer and pulmonary embolism: thrombotic embolism, tumor embolism, and tumor invasion into a large vein. Circ J 70:744–749
Reyes MA, Ciancio G, Singal R et al (2006) Adrenocortical carcinoma with tumor thrombus in the right hepatic vein. Int J Urol 13:1233–1235.
Aryana A, Esterbrooks DJ, Morris PC (2006) Nonbacterial thrombotic endocarditis with recurrent embolic events as manifestation of ovarian neoplasm. J Gen Intern Med 21:C12–C15
Buckendahl AC, Martens F, Scholman HJ et al (2006) Acute myocardial infarction caused by coronary tumor thromboembolism: a rare primary manifestation of malignant tumor disease. Human Pathol 37:236–238
Rickles FR, Falanga A (2001) Molecular basis for the relationship between thrombosis and cancer. Thromb Res 102:V21–V24
Brusselmans K, Bono F, Collen D et al (2005) A novel role for vascular endothelial growth factor as an autocrine survival factor for embryonic stem cells during hypoxia. J Biol Chem 280:3493–3499
Salgado R, Benoy I, Weytjens R et al (2002) Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer. Br J Cancer 87:1437–1444
Yan SF, Mackman N, Kisiel W et al (1999) Hypoxia/Hypoxemia-Induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis. Arterioscler Thromb Vasc Biol 19:2029–2035
Anderson KC (2003) The role of immunomodulatory drugs in multiple myeloma. Semin Hematol [Suppl 4] 40:23–32
Anderson KC (2003) Moving disease biology from the lab to the clinic. Cancer 97[Suppl 3]:796–801
Berenson JR, Jagannath S, Barlogie B et al (2005) Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. Cancer 104:2141–2148
Chauhan D, Uchiyama H, Akbarali Y et al (1996) Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood 87:1104–1112
Urashima M, Ogata A, Chauhan D et al (1996) Transforming growth factor-beta1: differential effects on multiple myeloma versus normal B cells. Blood 87:1928–1938
Podar K, Tai YT, Davies FE et al (2001) Vascular endothelial growth factor triggers signalling cascades mediating multiple myeloma cell growth and migration. Blood 98:428–435
Hideshima T, Chauhan D, Schlossman R et al (2001) The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene 20:4519–4527
Fibach E, Treves A, Korenberg A et al (1985) In vitro generation of procoagulant activity by leukemic promyelocytes in response to cytotoxic drugs. Am J Hematol 20:257–265
Prandoni P, Falanga A, Piccioli A (2005) Cancer and venous thromboembolism. Lancet Oncol 6:401–410
Grignani G, Maiolo A (2000) Cytokines and hemostasis. Haematologica 85:967–972
Leone G, Sica S, Chiusolo P et al (2001) Blood cell diseases and thrombosis. Haematologica 86:1236–1244
De Gaetano G, Cerletti C, Evangelista V (1999) Recent advances in platelet-polymorphonuclear leukocyte interaction. Haemostasis 29:41–49
Gale AJ, Gordon SG (2001) Update on tumor cell procoagulant factors. Acta Haematol 106:25–32
Falanga A (2005) Thrombophilia in cancer. Semin Thromb Haemost 31:104–110
Kwaan HC, Parmar S, Wang J (2003) Pathogenesis of increased risk of thrombosis in cancer. Semin Thromb Haemost 29:283–290
Negaard H, Dahm A, Sandset PM et al (2005) Angiogenesis and hemostasis in hematological neoplasias. Curr Drug Targets 6:683–699
Rickles FR, Shoji M, Abe K (2001) The role of the hemostatic system in tumor growth, metastasis, and angiogenesis: tissue factor is a bifunctional molecule capable of inducing both fibrin deposition and angiogenesis in cancer. Int J Hematol 73:145–150
Bach RR (2006) Tissue factor encryption. Arterioscler Thromb Vasc Biol 26:456–461
Bach R, Gentry R, Nemerson Y (1986) Factor VII binding to tissue factor in reconstituted phospholipid vesicles: induction of cooperativity by phosphatidylserine. Biochemistry 25:4007–4020
Kamikura Y, Wada H, Nobori T et al (2005) Elevated levels of leukocyte tissue factor mRNA in patients with venous thromboembolism. Thromb Res 116:307–312
Sase T, Wada H, Yamaguchi M et al (2005) Haemostatic abnormalities and thrombotic disorders in malignant lymphoma. Thromb Haemost 93:153–159
Kamikura Y, Wada H, Sase T et al (2006) Hemostatic abnormalities and leukocyte activation caused by infection in patients with malignant lymphoma during chemotherapy. Thromb Res 117:671–679
Han LY, Landen CN Jr, Kamat AA et al (2006) Preoperative serum tissue factor levels are an independent prognostic factor in patients with ovarian carcinoma. J Clin Oncol 24:755–761
Uno K, Homma S, Satoh T et al (2007) Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer 96:290–295
Altomare DF, Rotelli MT, Pentimone A et al (2007) Tissue factor and vascular endothelial growth factor expression in colorectal cancer: relation with cancer recurrence. Colorectal Dis 9:133–138
Haas SL, Jesnowski R, Steiner M et al (2006) Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation. World J Gastroenterol 12:4843–4849
Yamashita H, Kitayama J, Ishikawa M et al (2007) Tissue factor expression is a clinical indicator of lymphatic metastasis and poor prognosis in gastric cancer with intestinal phenotype. J Surg Oncol 95:324–331
Nadir Y, Katz T, Sarig G et al (2005) Hemostatic balance on the surface of leukemic cells: the role of tissue factor and urokinase plasminogen activator receptor. Haematologica 90:1549–1556
Falanga A, Gordon SG (1985) Isolation and characterization of cancer procoagulant: a cysteine proteinase from malignant tissue. Biochemistry 24:5558–5567
Kazmierczak M, Lewandowski K, Wojtukiewicz MZ et al (2005) Cancer procoagulant in patients with adenocarcinomas. Blood Coagul Fibrinolysis 16:543–547
Falanga A, Consonni R, Marchetti M et al (1998) Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells. Blood 92:143–151
Olas B, Mielicki WP, Wachowicz B et al (1999) Cancer procoagulant stimulates platelet adhesion. Thromb Res 94:199–203
Kwaan HC (1992) The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev 11:291–311
_Kwaan HC, Wang J, Svoboda K et al (2000) Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis. Br J Cancer 82:1702–1708
Menell JS, Cesarman GM, Jacovina AT et al (1999) Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 340:994–1004
Soff GA, Sanderowitz J, Gately S et al (1995) Expression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model. J Clin Invest 96:2593–2600
Lisman T, de Groot PG, Meijers JC et al (2005) Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 105:1102–1105
Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol 106:1659–1665
Wilson EL, Jacobs P, Dowdle EB (1983) The secretion of plasminogen activators by human myeloid leukemic cells in vitro. Blood 61:568–574
Wilson EL, Jacobs P, Dowdle EB (1983) The effects of dexamethasone and tetradecanoyl phorbol acetate on plasminogen activator release by human acute myeloid leukemia cells. Blood 61:561–567
Martin SJ, Reutelingsperger CP, McGahon AJ et al (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182:1545–1556
Fadok VA, Voelker DR, Campbell PA et al (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216
Flynn PD, Byrne CD, Baglin TP et al (1997) Thrombin generation by apoptotic vascular smooth muscle cells. Blood 89:4378–4384
Casciola-Rosen L, Rosen A, Petri M et al (1996) Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. Proc Natl Acad Sci USA 93:1624–1629
Wang J, Weiss I, Svoboda K, Kwaan HC (2001) Thrombogenic role of cells undergoing apoptosis. Br J Haematol 115:382–391
Barbui T, Finazzi G, Falanga A (1998) The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood 91:3093–3102
Tallman MS, Lefebvre P, Baine RM et al (2004) 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 2:1341–1350
Beer JH, Haeberli A, Vogt A et al (2002) Coagulation markers predict survival in cancer patients. Thromb Haemost 88:745–749
Antoniou D, Pavlakou G, Stathopoulos GP et al (2006) Predictive value of D-dimer plasma levels in response and progressive disease in patients with lung cancer. Lung Cancer 53:205–210
Blann AD, Gurney D, Wadley M et al (2001) Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor. Blood Coagul Fibrinolysis 12:43–50
_Simak J, Gelderman MP (2006) Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus Med Rev 20:1–26
Shebuski RJ, Kilgore KS (2002) Role of inflammatory mediators in thrombogenesis. J Pharmacol Exp Ther 300:729–735
Horstman LL, Jy W, Jimenez JJ et al (2004) New horizons in the analysis of circulating cell-derived microparticles. Keio J Med 53:210–230
Hron G, Kollars M, Weber H et al (2007) Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 97:119–123
_Tesselaar ME, Romijn FP, van der Linden IK et al (2007) Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 5:520–527
Dixit A, Kannan M, Mahapatra M et al (2006) Roles of protein C, protein S, and antithrombin III in acute leukemia. Am J Hematol 81:171–174
Haim N, Lanir N, Hoffman R et al (2001) Acquired activated protein C resistance is common in cancer patients and is associated with venous thromboembolism. Am J Med 110:91–96
Sarig G, Michaeli Y, Lanir N et al (2005) Mechanisms for acquired activated protein C resistance in cancer patients. J Thromb Haemost 3:589–590
Green D, Maliekel K, Sushko E et al (1997) Activated-protein-C resistance in cancer patients. Haemostasis 27:112–118
Nojima J, Kuratsune H, Suehisa E et al (2002) Acquired activated protein C resistance is associated with the coexistence of anti-prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus. Br J Haematol 118:577–583
Gomez-Puerta JA, Cervera R, Espinosa G et al (2006) Antiphospholipid antibodies associated with malignancies: clinical and pathological characteristics of 120 patients. Semin Arthritis Rheum 35:322–332
Pusterla S, Previtali S, Marziali S et al (2004) Antiphospholipid antibodies in lymphoma: prevalence and clinical significance. Hematol J 5:341–346
Genvresse I, Luftner D, Spath-Schwalbe E et al (2002) Prevalence and clinical significance of anticardiolipin and anti-beta2-glycoprotein-I antibodies in patients with non-Hodgkin’s lymphoma. Eur J Haematol 68:84–90
Khan S, Dickerman JD (2006) Hereditary thrombophilia. Thromb J 4:15
Simioni P, Tormene D, Spiezia L et al (2006) Inherited thrombophilia and venous thromboembolism. Semin Thromb Hemost 32:700–708
Leroyer C, Mercier B, Oger E et al (1998) Prevalence of 20210 A allele of the prothrombin gene in venous thromboembolism patients. Thromb Haemost 80:49–51
Abramson N, Costantino JP, Garber JE et al (2006) Effect of Factor V Leiden and prothrombin G20210—>A mutations on thromboembolic risk in the national surgical adjuvant breast and bowel project breast cancer prevention trial. J Natl Cancer Inst 98:904–910
Elice F, Fink L, Tricot G et al (2006) Acquired resistance to activated protein C (aAPCR) in multiple myeloma is a transitory abnormality associated with an increased risk of venous thromboembolism. Br J Haematol 134:399–405
Di Micco P, Niglio A, De Renzo A et al (2004) Congenital and acquired thrombotic risk factors in lymphoma patients bearing upper extremities deep venous thrombosis: a preliminary report. J Transl Med 2:7
Agnelli G, Verso M (2006) Therapy Insight: venous-catheter-related thrombosis in cancer patients. Nature Clin Practice 3:214–222
Lokich JJ, Becker B (1983) Subclavian vein thrombosis in patients treated with infusion chemotherapy for advanced malignancy. Cancer 52:1586–1589
Verso M, Agnelli G (2003) Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. J Clin Oncol 21:3665–3675
Monreal M, Munoz FJ, Rosa V et al (2006) Upper extremity DVT in oncological patients: analysis of risk factors. Data from the RIETE registry. Exp Oncol 28:245–247
Lee AY, Levine MN, Butler G et al (2006) Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. J Clin Oncol 24:1404–1408
Cortelezzi A, Moia M, Falanga A et al (2005) Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study. Br J Haematol 129:811–817
Webert K, Cook RJ, Sigouin CS et al (2006) The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia. Haematologica 91:1530–1537
Spectre G, Libster D, Grisariu S et al (2006) Bleeding, obstruction, and perforation in a series of patients with aggressive gastric lymphoma treated with primary chemotherapy. Ann Surg Oncol 13:1372–1378
Deshpande A, Storch I, Barkin J (2007) Diagnosis of lymphoma in overt obscure GI bleeding aided by capsule endoscopy. Gastrointest Endosc 65:159–160
Koornstra JJ, Schot BW, Dijkstra G (2007) Mantle cell lymphoma involving the appendiceal orifice as an unusual cause of lower gastrointestinal bleeding. Int J Colorectal Dis 22:99–100
Okajima K, Sakamoto Y, Uchiba M (2000) Heterogeneity in the incidence and clinical manifestations of disseminated intravascular coagulation: a study of 204 cases. Am J Hematol 65:215–222
Tapiovaara H, Matikainen S, Hurme M et al (1994) 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 83:1883–1891
Kwaan HC, Wang J, Weiss I (2004) Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin. J Thromb Haemost 2:306–312
Dally N, Hoffman R, Haddad N et al (2005) Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemiaa single center experience in 34 patients. Thromb Res 116:109–114
Boggio LN, Green D (2001) Acquired hemophilia. Rev Clin Exp Hematol 5:389–404
Collins PW, Hirsch S, Baglin TP et al (2006) Acquired haemophilia A in the UK: a two year national surveillance study by UK Haemophilia Centre Doctors’ Organisation. Blood 109:1870–1877
Sallah S, Wan JY (2001) Inhibitors against factor VIII in patients with cancer. Analysis of 41 patients. Cancer 91:1067–1074
Sallah S, Nguyen NP, Abdallah JM, Hanrahan LR (2000) Acquired hemophilia in patients with hematologic malignancies. Arch Pathol Lab Med 124:730–734
Kucuk O, Kwaan HC, Gunnar W et al (1985) Thromboembolic complications associated with L-asparaginase therapy. Etiologic role of low antithrombin III and plasminogen levels and therapeutic correction by fresh frozen plasma. Cancer 55:702–706
Mitchell LG, Sutor AH, Andrew M (1995) Hemostasis in childhood acute lymphoblastic leukemia: coagulopathy induced by disease and treatment. Semin Thromb Hemost 21:390–401
Mitchell L, Hoogendoorn H, Giles AR et al (1994) Increased endogenous thrombin generation in children with acute lymphoblastic leukemia: risk of thrombotic complications in L-Asparaginase-induced antithrombin III deficiency. Blood 83:386–391
Isacson S (1970) Effect of prednisolone on the coagulation and fibrinolytic systems. Scand J Haematol 7:212–216
Jorgensen KA, Sorensen P, Freund L (1982) Effect of glucocorticosteroids on some coagulation tests. Acta Haematol 68:39–42
Bennett CL, Schumock GT, Desai AA et al (2002). Thalidomide-associated deep vein thrombosis and pulmonary embolism. Am J Med 113:603–606
Singhal S, Mehta J (2002) Thalidomide in cancer. Biomed Pharmacother 56:4–12
Barlogie B, Desikan R, Eddlemon P et al (2001) Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 98:492–494
Osman K, Comenzo R, Rajkumar SV (2001) Deep venous thrombosis and thalidomide therapy for multiple myeloma. N Engl J Med 344:1951–1952
Cavo M, Zamagni E, Cellini C et al (2002) Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. Blood 100:2272–2273
Zangari M, Siegel E, Barlogie B et al (2002) Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 100:1168–1171
Rajkumar SV, Hayman SR, Lacy MQ et al (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106:4050–4053
Rajkumar SV, Blood E (2006) Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 354:2079–2080.
Zonder JA, Barlogie B, Durie BG et al (2006) Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. Blood 108:403
Baz R, Li L, Kottke-Marchant K et al (2005) The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma. Mayo Clin Proc 80:1568–1574
Zangari M, Barlogie B, Anaissie E et al (2004) Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation. Br J Haematol 126:715–721
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kwaan, H.C., Vicuna, B. Thrombosis and bleeding in cancer patients. Oncol Rev 1, 14–27 (2007). https://doi.org/10.1007/s12156-007-0003-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12156-007-0003-7