Thrombosis in Acute Leukemia

1. Thrombosis in Acute Leukemia
Ade Wijaya, MD – August 2018

2. Outline:
 Introduction
 Pathophysiology
 Thrombosis in ALL & AML
 Management
 Summary

3. Introduction
 Thrombosis is the most frequent
complication in malignancy
 Thrombosis: 2nd leading cause of
death
 Thrombosis in cancer is 7 times
greater than in general population
 Thrombosis in haematological
malignancy such as acute leukemia is
as frequent as it is in solid tumors
Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res 2010; 125:490 – 493.
Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293:715 – 722.
Jasmijn F, Timp 1, Sigrid K, etal. Epidemiology of cancer-associated venousthrombosis. Blood 2013; 122:1712 – 1723.
Khorana AA, Francis CW, Culakova E, et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007; 110:2339 – 2346

4. Pathophysiology
Del Principe MI, Del Principe D, Venditti A. Thrombosis in adult patients with acute leukemia. Current opinion in oncology. 2017 Nov 1;29(6):448-54.

5. Thrombosis in ALL
 Therapy-related
 Induction phase
 L-ASP being the agent most
frequently associated with this
complication
De Stefano V, Sora F, Rossi E, et al. The risk of thrombosis in patients with acute leukaemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost
2005; 3:1985 – 1992.
Koprivnikar J, McCloskey J, Faderl S. Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia.
Onco Targets Ther 2017; 10:1413 – 1422.

6. Thrombosis in AML
 ATRA-related
 Risk factors: F, older age, comorbids
Demers M, Krause DS, Schatzberg D, et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci
USA 2012; 109:13076 – 13081.
Fang Y, Garnier D, Lee TH, et al. RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells. Angiogenesis 2016; 19:25 – 38
O’Donnell MR, Abboud CN, Altman J, etal. Acute myeloid leukaemia. J Natl Compr Canc Netw 2012; 10:984– 1021.

7. Management
 Lack of evidence for
thromboprophylaxis
 UFH / LMWH / NOAC
Geerts W. Central venous catheter-related thrombosis. Hematology Am Soc Hematol Educ Program 2014; 2014:306 – 311.
Kovacs MJ, Kahn SR, Rodger M, et al. A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without
catheter removal for the treatment of upper extremity deep vein thrombosis (the Catheter Study). J Thromb Haemost 2007; 5:1650– 1653.

8. Summary
 Procoagulant activity of malignant
cells, procoagulant platelets,
chemotherapy, infections and central
venous catheter contribute to
multifactorial process of thrombosis in
acute leukemia.
 Thrombosis can significantly affect
morbidity and mortality.
 Management with UFH/LMWH/NOAC

9. THANK YOU