Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Intensive Care Medicine
Published in: Intensive Care Medicine 7/2015

01-07-2015 | Systematic Review

Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis

Authors: Sigrid Beitland, Irene Sandven, Lill-Kristin Kjærvik, Per Morten Sandset, Kjetil Sunde, Torsten Eken

Published in: Intensive Care Medicine | Issue 7/2015

Login to get access

Abstract

Purpose

To compare benefits and harms of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as thromboprophylaxis in intensive care unit (ICU) patients.

Methods

We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised controlled trials (RCTs) comparing LMWH with UFH as thromboprophylaxis in adult ICU patients. We searched Ovid Medline, PubMed, Embase, Cochrane Library, UpToDate, Guidelines International Network, PROSPERO and the metaRegister of Controlled Trials through 3 December 2014. Random effects risk ratios (RR) and 95 % confidence intervals (CI) were derived for the endpoints deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, mortality and net clinical benefit (any DVT, any PE, major bleeding and/or mortality).

Results

Eight RCTs (5567 patients) were included, whereof two were considered to have overall low risk of bias. Pooled analyses showed that LMWH compared with UFH reduced the risk of any DVT (RR 0.84, 95 % CI 0.71–0.98, p = 0.03) and resulted in a net clinical benefit (RR 0.90, 95 % CI 0.83–0.97, p = 0.01). There was no statistically significant difference in the risk of any PE (RR 0.65, 95 % CI 0.41–1.03, p = 0.06), major bleeding (RR 0.99, 95 % CI 0.77–1.28, p = 0.96) or mortality (RR 0.93, 95 % CI 0.78–1.12, p = 0.43). TSA supported the results of the conventional analysis on the outcome net clinical benefit but not on risk of any DVT.

Conclusions

Evidence from this systematic review revealed a beneficial effect of LMWH compared with UFH when used as thromboprophylaxis in ICU patients.
Appendix
Available only for authorised users
Literature
1.
Cook D, Crowther M, Meade M et al (2005) Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med 33:1565–1571PubMedCrossRef
2.
Geerts WH, Pineo GF, Heit JA et al (2004) Prevention of venous thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 126:338S–400SPubMedCrossRef
3.
Ribic C, Lim W, Cook D et al (2009) Low-molecular-weight heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review. J Crit Care 24:197–205PubMedCrossRef
4.
Geerts WH, Bergqvist D, Pineo GF et al (2008) Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 133:381S–453SPubMedCrossRef
5.
Guyatt GH, Akl EA, Crowther M et al (2012) Executive summary: antithrombotic therapy and prevention of thrombosis, American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):7S–47SPubMedCentralPubMedCrossRef
6.
Alhazzani W, Lim W, Jaeschke RZ et al (2013) Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care Med 41:2088–2098PubMedCrossRef
7.
Dentali F, Douketis JD, Gianni M et al (2007) Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 146:278–288PubMedCrossRef
8.
Mismetti P, Laporte S, Darmon JY et al (2001) Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 88:913–930PubMedCrossRef
9.
Barrera LM, Perel P, Ker K et al (2013) Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev 3:1–79
10.
Kakkos SK, Caprini JA, Geroulakos G et al (2008) Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients. Cochrane Database Syst Rev 4:1–37
11.
Arnold DM, Donahoe L, Clarke FJ et al (2007) Bleeding during critical illness: a prospective cohort study using a new measurement tool. Clin Invest Med 30:E93–102PubMed
12.
Briegel J, Mohnle P (2013) International guidelines of the Surviving Sepsis Campaign: update 2012. Anaesthesist 62:304–309PubMedCrossRef
13.
14.
15.
Cohran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRef
16.
17.
Peduzzi P, Concato J, Kemper E et al (1996) A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 49:1373–1379PubMedCrossRef
18.
19.
Sterne JA, Sutton AJ, Ioannidis JP et al (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002PubMedCrossRef
20.
Pogue JM, Yusuf S (1997) Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta-analysis. Control Clin Trials 18:580–593PubMedCrossRef
21.
Pogue J, Yusuf S (1998) Overcoming the limitations of current meta-analysis of randomised controlled trials. Lancet 351:47–52PubMedCrossRef
22.
Wetterslev J, Thorlund K, Brok J et al (2008) Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol 61:64–75PubMedCrossRef
23.
Greenland S, Robins JM (1985) Estimation of a common effect parameter from sparse follow-up data. Biometrics 41:55–68PubMedCrossRef
24.
25.
Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62:1006–1012PubMedCrossRef
26.
Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–34PubMedCrossRef
27.
Cohn SA, Moller BA, Feinstein AJ et al (1999) Prospective trial of low-molecular-weight heparin versus unfractionated heparin in moderately injured patients. Vasc Surg 33:219–223CrossRef
28.
Cook D, Meade M, Guyatt G et al (2011) Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 364:1305–1314PubMedCrossRef
29.
De A, Roy P, Garg VK et al (2010) Low-molecular-weight heparin and unfractionated heparin in prophylaxis against deep vein thrombosis in critically ill patients undergoing major surgery. Blood Coagul Fibrinolysis 21:57–61PubMedCrossRef
30.
Geerts WH, Jay RM, Code KI et al (1996) A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 335:701–707PubMedCrossRef
31.
Goldhaber S, Kett D, Cusumano CJ et al (2000) Low molecular weight heparin versus minidose unfractionated heparin for prophylaxis against venous thromboembolism in medical intensive care unit patients: a randomized controlled trial. J Am Coll Cardiol 35(Suppl):A325
32.
Greenfield LJ, Proctor MC, Rodriguez JL et al (1997) Posttrauma thromboembolism prophylaxis. J Trauma 42:100–103PubMedCrossRef
33.
Roque T, Thompson J, Kuru T (2005) A clinical trial to compare thromboprophylaxis options in the medical ICU: challanges to treatment (conference abstract). Chest 128:296CrossRef
34.
Shorr AF, Williams MD (2009) Venous thromboembolism in critically ill patients. Observations from a randomized trial in sepsis. Thromb Haemost 101:139–144PubMed
35.
Baker SP, O’Neill B, Haddon W Jr et al (1974) The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187–196PubMedCrossRef
36.
37.
Marik PE, Andrews L, Maini B (1997) The incidence of deep venous thrombosis in ICU patients. Chest 111:661–664PubMedCrossRef
38.
Hirsch DR, Ingenito EP, Goldhaber SZ (1995) Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 274:335–337PubMedCrossRef
39.
Harris LM, Curl GR, Booth FV et al (1997) Screening for asymptomatic deep vein thrombosis in surgical intensive care patients. J Vasc Surg 26:764–769PubMedCrossRef
40.
Twigg SJ, McCrirrick A, Sanderson PM (2001) A comparison of post mortem findings with post hoc estimated clinical diagnoses of patients who die in a United Kingdom intensive care unit. Intensive Care Med 27:706–710PubMedCrossRef
41.
Wahl WL, Ahrns KS, Zajkowski PJ et al (2003) Normal d-dimer levels do not exclude thrombotic complications in trauma patients. Surgery 134:529–532PubMedCrossRef
42.
Cook DJ, Donadini MP (2010) Pulmonary embolism in medical-surgical critically ill patients. Hematol Oncol Clin North Am 24:677–688PubMedCrossRef
43.
Cook D, Meade M, Guyatt G et al (2004) Clinically important deep vein thrombosis in the intensive care unit: a survey of intensivists. Crit Care 8:R145–R152PubMedCentralPubMedCrossRef
44.
Hinz P, Lubenow N, Wessel A et al (2009) Thrombosis prophylaxis in trauma surgery units in Germany: a survey. Unfallchirurg 112:1029–1033PubMedCrossRef
45.
Junqueira DR, Perini E, Penholati RR et al (2012) Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev 9:1–35
46.
Fareed J, Jeske W, Fareed D et al (2008) Are all low molecular weight heparins equivalent in the management of venous thromboembolism? Clin Appl Thromb Hemost 14:385–392PubMedCrossRef
47.
Nenci GG (2003) Low molecular weight heparins: are they interchangeable? No. J Thromb Haemost 1:12–13PubMedCrossRef
48.
Prandoni P (2003) Low molecular weight heparins: are they interchangeable? Yes. J Thromb Haemost 1:10–11PubMedCrossRef
49.
van der Heijden JF, Prins MH, Buller HR (2000) Low-molecular-weight heparins: are they interchangeable? Haemostasis 30(Suppl 2):148–157PubMed
50.
Limpus A, Chaboyer W, McDonald E et al (2006) Mechanical thromboprophylaxis in critically ill patients: a systematic review and meta-analysis. Am J Crit Care 15:402–410PubMed
51.
Huo MH, Muntz J (2009) Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: a review. Clin Ther 31:1129–1141PubMedCrossRef
52.
Garcia-Olivares P, Guerrero JE, Galdos P et al (2014) PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care units in Spain. Intensive Care Med 40:1698–1708PubMedCrossRef
53.
Schaden E, Metnitz PG, Pfanner G et al (2012) Coagulation day 2010: an Austrian survey on the routine of thromboprophylaxis in intensive care. Intensive Care Med 38:984–990PubMedCrossRef
54.
Wilbur K, Lynd LD, Sadatsafavi M (2011) Low-molecular-weight heparin versus unfractionated heparin for prophylaxis of venous thromboembolism in medicine patients—a pharmacoeconomic analysis. Clin Appl Thromb Hemost 17:454–465PubMedCrossRef
55.
Fowler RA, Mittmann N, Geerts W et al (2014) Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients. JAMA 312:2135–2145PubMedCrossRef
56.
Thorlund K, Imberger G, Walsh M et al (2011) The number of patients and events required to limit the risk of overestimation of intervention effects in meta-analysis—a simulation study. PLoS One 6:e25491PubMedCentralPubMedCrossRef
57.
Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines 6. Rating the quality of evidence—imprecision. J Clin Epidemiol 64:1283–1293PubMedCrossRef
58.
Schulz KF, Chalmers I, Hayes RJ et al (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1(273):408–412CrossRef
59.
Oxman AD, Guyatt GH (1992) A consumer’s guide to subgroup analyses. Ann Intern Med 16:78–84CrossRef
60.
Sun X, Briel M, Walter SD et al (2010) Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ 30(340):c11
61.
Egger M, Juni P, Bartlett C et al (2003) How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technol Assess 7:1–76PubMed
62.
Egger M, Smith GD, Altman DG (1995) Systematic reviews in health care: meta-analysis in context, 2nd edn. BMJ, London
63.
Raskob GE, Hirsh J (2003) Controversies in timing of the first dose of anticoagulant prophylaxis against venous thromboembolism after major orthopedic surgery. Chest 124(Suppl 6):379S–385SPubMedCrossRef
64.
Tribout B, Colin-Mercier F (2007) New versus established drugs in venous thromboprophylaxis: efficacy and safety considerations related to timing of administration. Am J Cardiovasc Drugs 7:1–15PubMedCrossRef
65.
Bottaro FJ, Elizondo MC, Doti C et al (2008) Efficacy of extended thrombo-prophylaxis in major abdominal surgery: what does the evidence show? A meta-analysis. Thromb Haemost 99:1104–1111PubMed
66.
67.
Cheng SS, Nordenholz K, Matero D et al (2012) Standard subcutaneous dosing of unfractionated heparin for venous thromboembolism prophylaxis in surgical ICU patients leads to subtherapeutic factor Xa inhibition. Intensive Care Med 38:642–648PubMedCrossRef
68.
Malinoski D, Jafari F, Ewing T et al (2010) Standard prophylactic enoxaparin dosing leads to inadequate anti-Xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients. J Trauma 68:874–880PubMedCrossRef
69.
Robinson S, Zincuk A, Strom T et al (2010) Enoxaparin, effective dosage for intensive care patients: double-blinded, randomised clinical trial. Crit Care 14:R41PubMedCentralPubMedCrossRef
Metadata
Title
Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis
Authors
Sigrid Beitland
Irene Sandven
Lill-Kristin Kjærvik
Per Morten Sandset
Kjetil Sunde
Torsten Eken
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 7/2015
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-015-3840-z

Other articles of this Issue 7/2015

Intensive Care Medicine 7/2015 Go to the issue

Imaging in Intensive Care Medicine

Uremic frost: a clinical symptom of severe azotemia

Correspondence

Neuroprotection and cardioprotection after cardiac arrest: how cool is cool enough?

Editorial

Feeding the kidneys in AKI: no appetite for a change in practice

Correspondence

Trials on stress ulcer prophylaxis: finding the balance between benefit and harm

Original

Prognostication of post-cardiac arrest coma: early clinical and electroencephalographic predictors of outcome

Editorial

Do we need a pharmacist in the ICU?