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. 2017 Apr 21;4(4):CD007557.
doi: 10.1002/14651858.CD007557.pub3.

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients

Daniela R Junqueira  1 , Liliane M Zorzela  2 , Edson Perini  3
Affiliations

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients

Daniela R Junqueira et al. Cochrane Database Syst Rev. .

Abstract

Background: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012.

Objectives: The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH).

Search methods: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications.

Selection criteria: We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use the accepted definition of HIT. This was defined as a relative reduction in the platelet count of 50% or greater from the postoperative peak (even if the platelet count at its lowest remained greater than 150 x 109/L) occurring within five to 14 days after the surgery, with or without a thrombotic event occurring in this timeframe. Additionally, we required circulating antibodies associated with the syndrome to have been investigated through laboratory assays.

Data collection and analysis: Two review authors independently extracted data and assessed the risk of bias. Disagreements were resolved by consensus with participation of a third author.

Main results: In this update, we included three trials involving 1398 postoperative participants. Participants were submitted to general surgical procedures, minor and major, and the minimum mean age was 49 years. Pooled analysis showed a significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.07 to 0.73); low-quality evidence. The number needed to treat for an additional beneficial outcome (NNTB) was 59. The risk of HIT was consistently reduced comparing participants undergoing major surgical procedures exposed to LMWH or UFH (RR 0.22, 95% CI 0.06 to 0.75); low-quality evidence. The occurrence of HIT complicated by venous thromboembolism was significantly lower in participants receiving LMWH compared with UFH (RR 0.22, 95% CI 0.06 to 0.84); low-quality evidence. The NNTB was 75. Arterial thrombosis occurred in only one participant who received UFH. There were no amputations or deaths documented. Although limited evidence is available, it appears that HIT induced by both types of heparins is common in people undergoing major surgical procedures (incidence greater than 1% and less than 10%).

Authors' conclusions: This updated review demonstrated low-quality evidence of a lower incidence of HIT, and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. Similarily, the risk of HIT in people undergoing major surgical procedures was lower when treated with LMWH compared to UFH (low-quality evidence). The quality of the evidence was downgraded due to concerns about the risk of bias in the included studies and imprecision of the study results. These findings may support current clinical use of LMWH over UFH as front-line heparin therapy. However, our conclusions are limited and there was an unexpected paucity of RCTs including HIT as an outcome. To address the scarcity of clinically-relevant information on HIT, HIT must be included as a core harmful outcome in future RCTs of heparin.

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Conflict of interest statement

DJ: has declared that she received funds from the Minas Gerais State Research Foundation (Fapemig, Brazil) to prepare the first version of this review (published 2012). DJ received a scholarship from CAPES during her Master degree (2007 to 2008), when the review title was registered, and she was supported by CNPq with a PhD fellowship (2009 to 2012) when the first version of this review was developed and published. LZ: none known EP: has declared that he is employed as Professor by the Universidade Federal de Minas Gerais and has no known conflicts. EP has declared that the review authors received funds from the Minas Gerais State Research Foundation (Fapemig, Brazil) for their research. The first version of this review (published 2012) was completed as part of this research.

Figures

1
1
Flow diagram
2
2
Flowchart illustrating the recruitment of the participants included in and extracted from the study reported by Levine 1991 and Warkentin 2003
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1 Heparin‐induced thrombocytopenia (HIT).
1.2
1.2. Analysis
Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2 HIT in people undergoing major surgical procedures.
1.3
1.3. Analysis
Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3 HIT complicated by venous thromboembolism.
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