ABSTRACT
Current guidelines for venous thromboembolism (VTE) primary prophylaxis are based
on randomized clinical trials that exclude subjects at a potentially high bleeding
risk. Thus no specific recommendation/algorithm for pharmacological prophylaxis in
patients with thrombocytopenia and/or platelet dysfunction is available. Because at
least 25% of subjects admitted to medical departments exhibit these conditions, information
on this subject is provided here to optimize their VTE prophylaxis. Low platelet number/function
and clotting abnormalities are common in patients with liver cirrhosis. However, these
patients have a high incidence of portal and idiopathic venous thromboses, implying
that cirrhotic coagulopathy does not protect against thrombosis. At variance with
severe thrombocytopenia (< 50,000/μL), mild/moderate thrombocytopenia (> 50,000/μL)
should not interfere with VTE prevention decisions. In severe thrombocytopenia, prophylaxis
should be considered on an individual basis, however. In patients with antiphospholipid
antibodies and thrombocytopenia, a thrombotic tendency is usually associated rather
than a bleeding risk. VTE prophylaxis in high-risk conditions is thus suggested in
these patients. Except in cases with contraindications to anticoagulation, antithrombotic
prophylaxis should be always considered in hospitalized cancer patients with thrombocytopenia,
especially in those with hematologic malignancies and multiple VTE risk factors. Aspirin
treatment is not as effective as heparins in lowering the risk of VTE. Studies in
stroke suggest that thromboprophylaxis with heparins is safe in patients with ischemic
stroke undergoing aspirin treatment. The need for VTE prophylaxis in patients on chronic
treatment with aspirin and/or clopidogrel should be evaluated after assessing the
individual risk-benefit ratio.
KEYWORDS
Venous thromboembolism - primary prophylaxis - medical patients - thrombocytopenia
- antiplatelet agents
REFERENCES
- 1
Anderson Jr F A, Wheeler H B, Goldberg R J et al..
A population-based perspective of the hospital incidence and case-fatality rates of
deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.
Arch Intern Med.
1991;
151
(5)
933-938
- 2
Rubinstein I, Murray D, Hoffstein V.
Fatal pulmonary emboli in hospitalized patients. An autopsy study.
Arch Intern Med.
1988;
148
(6)
1425-1426
- 3
Di Minno G, Mannucci P M, Tufano A First Ambulatory Screening On Thromboembolism (fast)
Study Group et al.
The first ambulatory screening on thromboembolism: a multicentre, cross-sectional,
observational study on risk factors for venous thromboembolism.
J Thromb Haemost.
2005;
3
(7)
1459-1466
- 4
Samama M M, Cohen A T, Darmon J-Y et al..
A comparison of enoxaparin with placebo for the prevention of VTE in acutely ill medical
patients. Prophylaxis in Medical Patients Study Group.
N Engl J Med.
1999;
341
(11)
793-800
- 5
Leizorovicz A, Cohen A T, Turpie A G, Olsson C G, Vaitkus P T, Goldhaber S Z. PREVENT
Medical Thromboprophylaxis Study Group .
Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism
in acutely ill medical patients.
Circulation.
2004;
110
(7)
874-879
- 6
Cohen A T, Davidson B L, Gallus A S ARTEMIS Investigators et al.
Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in
older acute medical patients: randomised placebo controlled trial.
BMJ.
2006;
332
(7537)
325-329
- 7
Geerts W H, Bergkvist D, Pineo G F et al..
Prevention of venous thromboembolism: ACCP Evidence-Based Clinical Practice Guidelines
(8th Edition).
Chest.
2008;
133
(6, Suppl)
381S-453S
- 8
Tapson V F, Decousus H, Pini M IMPROVE Investigators et al.
Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings
from the International Medical Prevention Registry on Venous Thromboembolism.
Chest.
2007;
132
(3)
936-945
- 9
Monreal M, Kakkar A K, Caprini J A RIETE Investigators et al.
The outcome after treatment of venous thromboembolism is different in surgical and
acutely ill medical patients. Findings from the RIETE registry.
J Thromb Haemost.
2004;
2
(11)
1892-1898
- 10
Cohen A T, Tapson V F, Bergmann J F ENDORSE Investigators et al.
Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE
study): a multinational cross-sectional study.
Lancet.
2008;
371
(9610)
387-394
- 11
Lippi G, Favaloro E J, Cervellin G.
Prevention of venous thromboembolism: focus on mechanical prophylaxis.
Semin Thromb Hemost.
2011;
37
(3)
237-251
- 12
Prandoni P, Samama M M.
Risk stratification and venous thromboprophylaxis in hospitalized medical and cancer
patients.
Br J Haematol.
2008;
141
(5)
587-597
- 13
Maynard G A, Morris T A, Jenkins I H et al..
Optimizing prevention of hospital-acquired venous thromboembolism (VTE): prospective
validation of a VTE risk assessment model.
J Hosp Med.
2010;
5
(1)
10-18
- 14
Senzolo M, Sartori M T, Lisman T.
Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy?.
HPB (Oxford).
2009;
11
(6)
459-464
- 15
Northup P G, Caldwell S H.
New concepts of coagulation and bleeding in liver disease.
Intern Emerg Med.
2010;
5
(1)
3-6
- 16
Tripodi A, Primignani M, Mannucci P M.
Abnormalities of hemostasis and bleeding in chronic liver disease: the paradigm is
challenged.
Intern Emerg Med.
2010;
5
(1)
7-12
- 17
Northup P G, McMahon M M, Ruhl A P et al..
Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral
venous thromboembolism.
Am J Gastroenterol.
2006;
101
(7)
1524-1528
quiz 1680
- 18
Oka K, Tanaka K.
Intravascular coagulation in autopsy cases with liver diseases.
Thromb Haemost.
1979;
42
(2)
564-570
- 19
Wanless I R, Wong F, Blendis L M, Greig P, Heathcote E J, Levy G.
Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal
extinction and portal hypertension.
Hepatology.
1995;
21
(5)
1238-1247
- 20
Amitrano L, Guardascione M A, Ames P R.
Coagulation abnormalities in cirrhotic patients with portal vein thrombosis.
Clin Lab.
2007;
53
(9–12)
583-589
- 21
Søgaard K K, Horváth-Puhó E, Grønbaek H, Jepsen P, Vilstrup H, Sørensen H T.
Risk of venous thromboembolism in patients with liver disease: a nationwide population-based
case-control study.
Am J Gastroenterol.
2009;
104
(1)
96-101
- 22
Tripodi A, Primignani M, Chantarangkul V et al..
An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis.
Gastroenterology.
2009;
137
(6)
2105-2111
- 23
Kaushansky K.
Thrombopoietin.
N Engl J Med.
1998;
339
(11)
746-754
- 24
Adinolfi L E, Giordano M G, Andreana A et al..
Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients
with chronic viral hepatitis.
Br J Haematol.
2001;
113
(3)
590-595
- 25
Giannini E, Borro P, Botta F et al..
Serum thrombopoietin levels are linked to liver function in untreated patients with
hepatitis C virus-related chronic hepatitis.
J Hepatol.
2002;
37
(5)
572-577
- 26
Wang C S, Yao W J, Wang S T, Chang T T, Chou P.
Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications
from a survey of a community with hyperendemic HCV infection.
Clin Infect Dis.
2004;
39
(6)
790-796
- 27
Lisman T, Bongers T N, Adelmeijer J et al..
Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite
reduced functional capacity.
Hepatology.
2006;
44
(1)
53-61
- 28
Afdhal N, McHutchison J, Brown R et al..
Thrombocytopenia associated with chronic liver disease.
J Hepatol.
2008;
48
(6)
1000-1007
- 29
Amitrano L, Guardascione M A, Menchise A et al..
Safety and efficacy of anticoagulation therapy with low molecular weight heparin for
portal vein thrombosis in patients with liver cirrhosis.
J Clin Gastroenterol.
2010;
44
(6)
448-451
- 30
Lyman G H, Khorana A A, Falanga A American Society of Clinical Oncology et al.
American Society of Clinical Oncology guideline: recommendations for venous thromboembolism
prophylaxis and treatment in patients with cancer.
J Clin Oncol.
2007;
25
(34)
5490-5505
- 31
Tosetto A, Balduini C L, Cattaneo M Italian Society for Haemostasis and Thrombosis
et al.
Management of bleeding and of invasive procedures in patients with platelet disorders
and/or thrombocytopenia: Guidelines of the Italian Society for Haemostasis and Thrombosis
(SISET).
Thromb Res.
2009;
124
(5)
e13-e18
- 32
Prandoni P, Falanga A, Piccioli A.
Cancer and venous thromboembolism.
Lancet Oncol.
2005;
6
(6)
401-410
- 33
Caine G J, Stonelake P S, Lip G YH, Kehoe S T.
The hypercoagulable state of malignancy: pathogenesis and current debate.
Neoplasia.
2002;
4
(6)
465-473
- 34
Lee A Y, Levine M N.
Venous thromboembolism and cancer: risks and outcomes.
Circulation.
2003;
107
(23, Suppl 1)
I17-I21
- 35
Caine G J, Stonelake P S, Rea D, Lip G YH.
Coagulopathic complications in breast cancer.
Cancer.
2003;
98
(8)
1578-1586
- 36
Heit J A, Silverstein M D, Mohr D N, Petterson T M, O'Fallon W M, Melton III L J.
Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control
study.
Arch Intern Med.
2000;
160
(6)
809-815
- 37
Falanga A, Donati M B.
Pathogenesis of thrombosis in patients with malignancy.
Int J Hematol.
2001;
73
(2)
137-144
- 38
Rickles F R, Falanga A.
Molecular basis for the relationship between thrombosis and cancer.
Thromb Res.
2001;
102
(6)
V215-V224
- 39
Baron J A, Gridley G, Weiderpass E, Nyrén O, Linet M.
Venous thromboembolism and cancer.
Lancet.
1998;
351
(9109)
1077-1080
- 40
Rickles F R, Falanga A, Montesinos P, Sanz M A, Brenner B, Barbui T.
Bleeding and thrombosis in acute leukemia: what does the future of therapy look like?.
Thromb Res.
2007;
120
(Suppl 2)
S99-S106
- 41
Herishanu Y, Misgav M, Kirgner I, Ben-Tal O, Eldor A, Naparstek E.
Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive
chemotherapy regimens.
Leuk Lymphoma.
2004;
45
(7)
1407-1411
- 42
Cortelezzi A, Moia M, Falanga A CATHEM Study Group et al.
Incidence of thrombotic complications in patients with haematological malignancies
with central venous catheters: a prospective multicentre study.
Br J Haematol.
2005;
129
(6)
811-817
- 43
Lim W.
Antiphospholipid antibody syndrome.
Hematology Am Soc Hematol Educ Program.
2009;
233-239
- 44
Metjian A, Lim W.
ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid
antibodies receive primary prophylaxis to prevent thrombosis?.
Hematology Am Soc Hematol Educ Program.
2009;
247-249
- 45
Kitchens C S.
Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC).
Hematology Am Soc Hematol Educ Program.
2009;
240-246
- 46
Antithrombotic Trialists' Collaboration .
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention
of death, myocardial infarction, and stroke in high risk patients.
BMJ.
2002;
324
(7329)
71-86
- 47
Douketis J D, Berger P B, Dunn A S American College of Chest Physicians et al.
The perioperative management of antithrombotic therapy. American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
Chest.
2008;
133
(6, Suppl)
299S-339S
- 48
Biondi-Zoccai G GL, Lotrionte M, Agostoni P et al..
A systematic review and meta-analysis on the hazards of discontinuing or not adhering
to aspirin among 50,279 patients at risk for coronary artery disease.
Eur Heart J.
2006;
27
(22)
2667-2674
- 49
Di Minno M ND, Prisco D, Ruocco A L, Mastronardi P, Massa S, Di Minno G.
Perioperative handling of patients on antiplatelet therapy with need for surgery.
Intern Emerg Med.
2009;
4
(4)
279-288
- 50
Kamphuisen P W, Agnelli G.
What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis
and pulmonary embolism in patients with acute ischemic stroke?.
Thromb Res.
2007;
119
(3)
265-274
- 51
Chassot P G, Delabays A, Spahn D R.
Perioperative antiplatelet therapy: the case for continuing therapy in patients at
risk of myocardial infarction.
Br J Anaesth.
2007;
99
(3)
316-328
Antonella TufanoM.D. Ph.D.
Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental
Medicine
“Federico II” University of Naples, Naples, Italy
eMail: aTufano@uninsc.it
