Cancer-associated thromboembolism: antithrombotic management of hospitalized patients

  • 102 Accesses


Cancer increases risk for venous thromboembolism. Incident thrombocytopenia increases hemorrhagic risk. Hospitalized adults with a cancer diagnosis who received subcutaneous dalteparin in doses adjusted according to platelet count were retrospectively evaluated. Outcomes of interest included nadir platelet counts, transfusions, thromboembolism, and hemorrhage. During a 2-year period of observation, 1854 cancer patients received individualized inpatient treatment with dalteparin. Transfusion was required in 38 of 77 (49.4%) patients with nadir platelet counts < 25 × 109 cells/L as compared with 16 of 75 (21.3%) patients whose nadir platelet counts were 25–50 × 109 cells/L [risk ratio (RR) 2.31; 95% CI 1.42 to 3.78, p < 0.001] and 45 of 1657 (2.7%) patients with platelet counts > 50 × 109 cells/L (RR − 8.07; 95% CI − 4.79 to − 13.59, p < 0.001). Transfusions were administered primarily as supportive therapy. Among transfusion recipients, new or recurrent venous thromboembolism was documented in 2.6%, 0%, and 2.2% of patients with nadir platelet counts of < 25, 25–50, or > 50 × 109 cells/L, respectively (p > 0.9 for all comparisons). Acute blood loss or major bleeding was documented in 10.5%, 12.5%, and 15.6% of patients with platelet counts of < 25, 25–50, or > 50 × 109 cells/L, respectively (p > 0.9 for all comparisons). Among hospitalized cancer patients who received individualized dalteparin treatment, transfusion requirements varied inversely with platelet count. Irrespective of platelet counts, occurrence rates for venous thromboembolism and acute hemorrhage were similar across all treatment groups. Individualized dalteparin treatment provided a consistent pattern of safety and effectiveness.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1


  1. 1.

    Blom JW, Doggen CJM, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293:715–722.

  2. 2.

    Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R, Rimm AA (1999) Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Medicine (Baltimore) 78:285–291

  3. 3.

    Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy [letter]. J Thromb Haemost 5:632–634.

  4. 4.

    Vergati M, Della-Morte D, Ferroni P, Cereda V, Tosetto L, La Farina F, Guadagni F, Roselli M (2013) Increased risk of chemotherapy-associated venous thromboembolism in elderly patients with cancer. Rejuvenation Res 16:224–231.

  5. 5.

    Khorana AA, Dalal M, Lin J, Connolly GC (2013) Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 119:648–655.

  6. 6.

    Anaissie EJ, Coleman EA, Goodwin JA, Kennedy RL, Lockhart KD, Stewart CB, Coon SK, Bailey C, Barlogie B (2012) Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis. Cancer 118:549–557.

  7. 7.

    Khorana AA, Dalal MR, Lin J, Connolly GC (2013) Health care costs associated with venous thromboembolism in selected high-risk ambulatory patients with solid tumors undergoing chemotherapy in the United States. Clinicoecon Outcomes Res 5:101–108.

  8. 8.

    James TN, Monto RW, Rebuck JW (1953) Thrombocytopenia and abnormal bleeding in multiple myeloma. Ann Intern Med 39:1281–1287

  9. 9.

    Rosenthal MC, Niemetz J, Wisch N (1963) Hemorrhage and thromboses associated with neoplastic diseases. J Chron Dis 16:667–675

  10. 10.

    Nieto JA, Solano R, Ruiz-Ribó MD, Ruiz-Gimenez N, Prandoni P, Kearon C, Monreal M (2010) Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE Registry. J Thromb Haemost 8:1216–1222.

  11. 11.

    Akl EA, Vasireddi SR, Gunukula S, Barba M, Sperati F, Terrenato I, Muti P, Schünemann H (2011) Anticoagulation for the initial treatment of thromboembolism in patients with cancer. Cochrane Database Syst Rev.

  12. 12.

    Akl EA, Labedi N, Barba M, Terrenato I, Sperati F, Muti P, Schünemann H (2011) Anticoagulation for the long-term treatment of thromboembolism in patients with cancer. Cochrane Database Syst Rev.

  13. 13.

    Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisto M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang T-F, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR (2018) Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624.

  14. 14.

    Fanola CL, Ruff CT, Murphy SA, Jin J, Duggal A, Babilonia NA, Sritara P, Mercuri MF, Kamphuisen PW, Antman EM, Braunwald E, Giugliano RP (2018) Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation: analysis of the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc 7:e008987.

  15. 15.

    Young AM, Marshall A, Thirwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallu P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M (2018) Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 36:2017–2023.

  16. 16.

    Prins MH, Lensing AW, Brighton TA, Myons RM, Rehm J, Trajanovic M, Davidson BI, Beyer-Westendorf J, Pap AF, Berkowitz SD, Cohen AT, Kovacs MJ, Prandoni P (2014) Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol 1:e37–e46.

  17. 17.

    Agnelli G, Buller HR, Cohen A, Gallus AS, Lee TC, Pak R, Raskob GE, Weitz JI, Yamabe T (2015) Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost 13:2187–2191.

  18. 18.

    Agnelli G, Becattini C, Bauersachs R, Brenner B, Campani M, Cohen A, Connors JM, Fontanella A, Gussoni G, Huisman MV, Lambert C, Meyer G, Muñoz A, Abreu de Sousa J, Torbicki A, Verso M, Vescovo G (2018) Apixaban versus dalteparin for the treatment of acute venous thromboembolism in patients with cancer: the Caravaggio study. Thromb Haemost 118:1668–1678.

  19. 19.

    Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers DR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol 33:654–656.

  20. 20.

    Kearon C, Ornelas J, Blaivas A, Jimenez D, Bounbmeaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L (2016) Antithrombotic therapy for VTE disease: Chest guideline and expert panel report. Chest 149:315–352.

  21. 21.

    Streiff MB, Holmstrom B, Angelini D, Ashrani A, Bockenstedt PL, Chesney C, Fanikos J, Fenninger RB, Fogerty AE, Gao S, Goldhaber SZ, Gundabolu K, Hendrie P, Lee AI, Lee JT, Mann J, McMahon B, Millenson MM, Morton C, Ortel TL, Ozair S, Paschal R, Shattil S, Siddiqi T, Smock KJ, Soff G, Wang T-F, Williams E, Zakarija A, Hammond L, Dwyer MA, Engh AM (2018) NCCN Guidelines Insights: cancer-associated venous thromboembolic disease, version 2.2018. J Natl Compr Cancer Netw 16:1289–1303.

  22. 22.

    Carrier M, Blais N, Crowther M, Kavan P, Le Gal G, Moodley O, Shivakumar S, Tagalakis V, Wu C, Lee AYY (2018) Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus. Curr Oncol 25:329–337.

  23. 23.

    Siragusa S, Armani U, Carpenedo M, Falanga A, Fulfaro F, Imberti D, Laurora R, Molinari AC, Prisco D, Silingardi M, Verso M, Visoná A (2012) Prevention of venous thromboembolism in patients with cancer: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res 129:e171–e176.

  24. 24.

    Nicolaides A, Fareed J, Kakkar AK, Comerota AJ, Goldhaber SZ, Hull R, Myers K, Samama M, Fletcher J, Kalodiki E, Bergqvist D, Bonnar J, Caprini JA, Carter C, Conard J, Eklof B, Elalamy I, Gerotziafas G, Geroulakos G, Giannoukas A, Greer I, Griffin M, Kakkos S, Lassen MR, Lowe GDO, Markel A, Prandoni P, Raskob G, Spyropoulos AC, Turpie AG, Walenga JM, Warwick D (2013) Prevention and treatment of venous thromboembolism. International consensus statement: treatment for patients with cancer. Clin Appl Thromb Hemost 19:206–208.

  25. 25.

    Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Büller HR (2013) International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 11:56–70.

  26. 26.

    Farge D, Bounameaux H, Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A (2016) International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 17:e452–e466.

  27. 27.

    Prisco D, Tufano A, Cencci C, Pignatelli P, Santilli F, Di Minno G, Perticone F (2019) Position paper of the Italian Society of Internal Medicine (SIMI) on prophylaxis and treatment of venous thromboembolism in patients with cancer. Intern Emerg Med 14:21–38.

  28. 28.

    Watson HG, Keeling DM, Laffan M, Tait RC, Makris M (2015) Guideline on aspects of cancer-related venous thrombosis. Br J Haematol 170:540–548.

  29. 29.

    Mandalá M, Falanga A, Roila F (2011) Management of venous thromboembolism (VTE) in cancer patients: ESMO clinical practice guidelines. Ann Oncol 22(Suppl 6):vi85–vi92.

  30. 30.

    Wickham N, Gallus AS, Walters BNJ, Wilson A (2012) Prevention of venous thromboembolism in patients admitted to Australian hospitals: summary of National Health and Medical Research Council clinical practice guideline. Intern Med J 42:698–708.

  31. 31.

    Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A (2013) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Practice Guideline update. J Clin Oncol 31:2189–2204.

  32. 32.

    Carrier M, Lazo-Langner A, Shivakumar S, Tagalakis V, Gross PL, Blais N, Butts CA, Crowther M (2015) Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations. Curr Oncol 22:49–59.

  33. 33.

    Napolitano M, Saccullo G, Marietta M, Carpenedo M, Castaman G, Cerchiara E, Chistolini A, Contino L, De Stefano V, Falanga A, Federici AB, Rossi E, Santoro R, Siragusa S (2018) Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus. Blood Transfus 17:171–180.

  34. 34.

    Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY (2013) Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost 11:1760–1765.

  35. 35.

    Samuelson Bannow BT, Lee A, Khorana AA, Zwicker JI, Noble S, Ay C, Carrier M (2018) Management of cancer-associated thrombosis in patients with thrombocytopenia: guidance from the SSC of the ISTH. J Thromb Haemost 16:1246–1249.

  36. 36.

    Houghton DE, Key NS, Zakai NA, Laux JP, Shea TC, Moll S (2017) Analysis of anticoagulation strategies for venous thromboembolism during severe thrombocytopenia in patients with hematologic malignancies: a retrospective cohort. Leuk Lymphoma 58:2573–2581.

  37. 37.

    Samuelson Bannow BT, Walter RB, Gernsheimer TB, Garcia DA (2017) Patients treated for acute VTE during periods of treatment-related thrombocytopenia have high rates of recurrent thrombosis and transfusion-related adverse outcomes. J Thromb Thrombolysis 44:442–447.

  38. 38.

    Babilonia KM, Golightly LK, Gutman JA, Hassell KL, Kaiser JN, Kiser TH, Klem PM, Trujillo TC (2014) Antithrombotic therapy in patients with thrombocytopenic cancer: outcomes associated with reduced-dose low-molecular-weight heparin during hospitalization. Clin Appl Thromb Hemost 20:799–806.

  39. 39.

    Khanal N, Bociek RG, Chen B, Vose JM, Armitage JO, Bierman PJ, Maness LJ, Lunning MA, Gundabolu K, Bhatt VR (2016) Venous thromboembolism in patients with hematologic malignancy and thrombocytopenia. Am J Hematol 91:e468–e472.

  40. 40.

    Mantha S, Miao Y, Wills J, Parameswaran R, Soff GA (2017) Enoxaparin dose reduction for thrombocytopenia in patients with cancer: a quality assessment study. J Thromb Thrombolysis 43:514–518.

  41. 41.

    Khan M, Cox TM, Nassif M, Alzubaidi MA, Garg N, Qiao W, Aung FM, Oo TH, Rojas-Hernandez CM (2018) Comparative outcomes of thrombocytopenic acute leukemic patients with venous thromboembolism at a comprehensive cancer center. J Thromb Thrombolysis 45:377–435.

  42. 42.

    Htun KT, Ma MJY, Lee AYY (2018) Incidence and outcomes of catheter related thrombosis (CRT) in patients with leukemia using a platelet-adjusted low molecular weight heparin regimen. J Thromb Thrombolysis 46:386–392.

Download references

Author information

LKG contributed to data acquisition and recording. All authors contributed to data aggregation, data analysis, and manuscript development.

Correspondence to Larry K. Golightly.

Ethics declarations

Conflict of interest

All authors attest that they have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Golightly, L.K., Simendinger, B.A. & Kiser, T.H. Cancer-associated thromboembolism: antithrombotic management of hospitalized patients. J Thromb Thrombolysis 49, 59–66 (2020).

Download citation


  • Thromboembolism
  • Anticoagulation
  • Cancer
  • Dalteparin
  • Thrombocytopenia