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. 2022 Jul 28;20(1):42.
doi: 10.1186/s12959-022-00401-2.

Evaluation of clinical outcomes in patients treated with heparin or direct thrombin inhibitors during extracorporeal membrane oxygenation: a systematic review and meta-analysis

René M'Pembele  1 , Sebastian Roth  2 , Aljoscha Metzger  2 , Anthony Nucaro  2 , Alexandra Stroda  2 , Amin Polzin  3 , Markus W Hollmann  4 , Giovanna Lurati Buse  2 , Ragnar Huhn  2   5
Affiliations

Evaluation of clinical outcomes in patients treated with heparin or direct thrombin inhibitors during extracorporeal membrane oxygenation: a systematic review and meta-analysis

René M'Pembele et al. Thromb J. .

Abstract

Background: The number of patients treated with extracorporeal membrane oxygenation (ECMO) devices is increasing. Anticoagulation therapy is crucial to prevent thrombosis during ECMO therapy. Predominantly, heparin has been used as primary anticoagulant but direct thrombin inhibitors (DTI) have been established as alternatives. The aim of this systematic review and meta-analysis was to evaluate clinical outcomes in patients treated with heparin compared to different DTI during ECMO.

Methods: A systematic search was conducted. Full scientific articles were sought for inclusion if heparin anticoagulation was compared to DTI (argatroban/bivalirudin) in ECMO patients. Risk of bias was assessed by Newcastle Ottawa scale. Primary endpoint was in-hospital mortality. Bleeding events, thrombotic events, hours of ECMO support, days of hospital stay, percentage of time within therapeutic range and time to therapeutic range were extracted from full texts as secondary endpoints. Results were presented as Forrest-plots. GRADE was used for confidence assessment in outcomes.

Results: Systematic search identified 4.385 records, thereof 18 retrospective studies for a total of 1942 patients, complied with the predefined eligibility criteria:15 studies investigated bivalirudin and 3 studies investigated argatroban versus heparin. Risk of bias was high for most studies. In-hospital mortality, major bleeding events and pump-related thrombosis were less frequent in DTI group as compared to heparin [mortality-OR 0.69, 95% CI 0.54-0.86; major bleeding-OR 0.48, 95% CI 0.29-0.81; pump thrombosis-OR 0.55, 95% CI 0.40-0.76]. Additionally, percentage of time within therapeutic range was higher for DTI [SMD 0.54, 95% CI 0.14-0.94]. GRADE approach revealed a very low level of certainty for each outcome.

Conclusion: In this meta-analysis, DTI and especially bivalirudin showed beneficial effects on clinical outcomes in ECMO patients as compared to heparin. However, due to the lack of randomized trials, certainty of evidence is low.

Trial registration: This systematic review and meta-analysis was prospectively registered at PROSPERO data base (reference number CRD42021237252 ).

Keywords: Anticoagulation; Argatroban; Bivalirudin; Bleeding; Mechanical circulatory support; Thrombosis.

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Conflict of interest statement

The authors declare no competing interests.

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow-chart of study selection process
Fig. 2
Fig. 2
Risk of bias assessment. Legend: The figure shows risk of bias for included studies using the Newcastle Ottawa scale. Overall risk of bias is presented as low (green), intermediate (yellow) or high (red)
Fig. 3
Fig. 3
Mortality. Legend: The figure shows results of data synthesis for mortality. Pooled estimates are presented as Odds ratios for direct thrombin inhibitors versus heparin as well as for bivalirudin and argatroban subgroups
Fig. 4
Fig. 4
Major bleeding events. Legend: The figure shows results of data synthesis for major bleeding events. Pooled estimates are presented as Odds ratios for direct thrombin inhibitors versus heparin as well as for bivalirudin and argatroban subgroups
Fig. 5
Fig. 5
Minor bleeding events. Legend: The figure shows results of data synthesis for minor bleeding events. Pooled estimates are presented as Odds ratios for direct thrombin inhibitors versus heparin as well as for bivalirudin and argatroban subgroups
Fig. 6
Fig. 6
Patient-related thrombosis. Legend: The figure shows results of data synthesis for patient-related thrombotic events. Pooled estimates are presented as Odds ratios for direct thrombin inhibitors versus heparin as well as for bivalirudin and argatroban subgroups
Fig. 7
Fig. 7
Pump-related thrombosis. Legend: The figure shows results of data synthesis for pump-related thrombotic events. Pooled estimates are presented as Odds ratios for direct thrombin inhibitors versus heparin as well as for bivalirudin and argatroban subgroups
Fig. 8
Fig. 8
Length of extracorporeal membrane oxygenation therapy. Legend: The figure shows results of data synthesis for length of extracorporeal membrane oxygenation therapy. Pooled estimates are presented as standardized mean difference for direct thrombin inhibitors versus heparin as well as for bivalirudin and argatroban subgroups
See this image and copyright information in PMC

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