Prevalence and outcomes of patients developing heparin-induced thrombocytopenia during extracorporeal membrane oxygenation

Abstract

Objectives: Unfractionated heparin (UFH) is the commonly used anticoagulant to prevent clotting of the ECMO circuit and thrombosis of the cannulated vessels. A side effect of UFH is heparin-induced thrombocytopenia (HIT). Little is known about HIT during ECMO and the impact of changing anticoagulation in ECMO patients with newly diagnosed HIT. The aim of the study was to determine the prevalence, complications, impact of switching anticoagulation to argatroban and outcomes of patients developing heparin-induced thrombocytopenia (HIT) during either veno-venous (VV) or veno-arterial (VA) ECMO.

Methods: Retrospective observational single centre study of prospectively collected data of consecutive patients receiving VV ECMO therapy for severe respiratory failure and VA ECMO for circulatory failure from January 2006 to December 2016 of the Medical intensive care unit (ICU) of the University Hospital of Regensburg. Treatment of HIT on ECMO was done with argatroban.

Results: 507 patients requiring ECMO were included. Further HIT-diagnostic was conducted if HIT-4T-score was ≥4. The HIT-confirmed group had positive HIT-enzyme-linked-immunosorbent-assay (ELISA) and positive heparin-induced-platelet-activation (HIPA) test, the HIT-suspicion group a positive HIT-ELISA and missing HIPA but remained on alternative anticoagulation until discharge and the HIT-excluded group a negative or positive HIT-ELISA, however negative HIPA. These were compared to group ECMO-control without any HIT suspicion. The prevalence of HIT-confirmed was 3.2%, of HIT-suspicion 2.0% and HIT-excluded 10.8%. Confirmed HIT was trendwise more frequent in VV than in VA (3.9 vs. 1.7% p = 0.173). Compared to the ECMO control group, patients with confirmed HIT were longer on ECMO (median 13 vs. 8 days, p = 0.002). Different types of complications were higher in the HIT-confirmed than in the ECMO-control group, but in-hospital mortality was not different (31% vs. 41%, p = 0.804).

Conclusion: HIT is rare on ECMO, should be suspected, if platelets are decreasing, but seems not to increase mortality if treated promptly.

Fig 1. Flowchart of the study.

Flowchart of the observational study evaluating heparin-induced thrombocytopenia (HIT) of the prospective extracorporeal membrane oxygenation (ECMO) registry Regensburg. VA: veno-arterial; VV: veno-venous; ELISA: enzyme-linked immunosorbent assay; HIPA: heparin induced platelet aggregation.

Fig 2. Confirmed HIT probability during ECMO therapy according to VV and VA ECMO.

Kaplan-Meier plot of HIT probability during ECMO therapy according to VV ECMO and VA ECMO of group HIT-comfirmed. X-axis: Time to HIT = Time between ECMO initiation and switch to alternative anticoagulation (argatroban). Y-axis: Probability of confirmed HIT diagnosis 0–100%.

Fig 3. Platelet count on extracorporeal membrane oxygenation.

Trajectories of thrombocytes before and after suspicion of heparin-induced thrombocytopenia (HIT) according to the groups: HIT-confirmed, HIT-suspicion, HIT-excluded and ECMO-control. Data show median and interquartile range (q1-q3). Time axis in days from day x. x: day of HIT suspicion (change to alternative anticoagulation) or, for group ECMO-control day 7 of ECMO therapy (as median time to HIT on ECMO was 7,5 days). 35 patients were excluded because the extracorporeal membrane oxygenation (ECMO) was explanted within 3 days after changing of anticoagulation or they died within 3 days after changing of anticoagulation, to show the effect of the alternative anticoagulation on coagulation parameters. Occasional missings e.g. if ECMO duration was shorter than 7 days.