Von Willebrand Factor-GP1bα Interactions in Venoarterial Extracorporeal Membrane Oxygenation Patients.

OBJECTIVE

Evaluate extracorporeal membrane oxygenation (ECMO) patients' platelet adhesion and aggregation under shear stress and determine whether addition of von Willebrand factor (VWF) concentrate improves platelet function. Also, explore whether reduced platelet adhesion and aggregation is associated with clinical bleeding during ECMO.

DESIGN

Prospective observational cohort study with translational component.

SETTING

Academic medical center.

PARTICIPANTS

Consecutive venoarterial (VA) ECMO patients were screened and 20 patients enrolled.

INTERVENTIONS

VWF multimers, VWF antigen, ristocetin cofactor activity, and plasma glycocalicin levels were measured and values were compared at study points: ECMO day 1 or 2, day 3, and day 5. Platelet adhesion and aggregation were measured in vitro using the total thrombus analysis system. Platelet function was expressed as area under the flow-pressure curve (AUC). VWF concentrate was added in vitro and the AUC after VWF supplementation (VWF AUC) was compared with baseline AUC. Further, baseline AUCs and VWF AUCs were compared between patients who experienced bleeding during ECMO and those who did not.

MEASUREMENTS AND MAIN RESULTS

ECMO patients had high VWF antigen levels, high ristocetin cofactor activity, and large VWF multimer loss. Platelet counts fell over the first 5 days on ECMO, and plasma glycocalicin levels were elevated mildly. ECMO patients had severely low platelet adhesion and aggregation in vitro: median AUC = 5.8 (3.5-9.7) ECMO day 1 or 2, median AUC = 6.3 (5.3-11.1) day 3, and median AUC = 5.5 (4.1-8.1) day 5. There was no significant change in AUC over time (p = 0.47). Addition of VWF concentrate increased the AUC compared to baseline at each point (all p < 0.05), but VWF AUC values remained low. Patients with bleeding during ECMO had a low VWF AUC at all points, whereas those without bleeding had a higher VWF AUC on ECMO day 3.

CONCLUSIONS

VA ECMO patients have severely impaired platelet function, which improved but did not normalize with VWF concentrate. The data suggest that GP1bα receptor loss of dysfunction also contributes to impaired platelet adhesion and aggregation during ECMO. Based on these findings, clinical bleeding in ECMO patients is unlikely to be correctable with VWF supplementation alone.