Abstract Number: PB0482
Meeting: ISTH 2022 Congress
Theme: Acquired Bleeding Disorders » Coagulopathy of Major Bleeding (Trauma, PPH, Vascular/surgical, ECMO, GI bleeding, etc.)
Background: Short-term cardiopulmonary extracorporeal life supports (ECLS) are invasive devices whose use has increased exponentially during the COVID-19 pandemic. Major bleeding is a main cause of morbi-mortality in ECLS patients and acquired von Willebrand disease (aVWD) could justify this complication.
Aims: We aim at investigating the primary hemostasis alterations profile in ECLS patients, and to propose a potential treatment if bleeding.
Methods: Patients in ECLS at our center since June 2021 were included (n=25). Primary hemostasis was evaluated by: von Willebrand Factor antigen (VWF:Ag) and activity (VWF:GPIbM) measurement (immunoturbidimetry), VWF multimeric analysis (agarose-gels and immunoblotting), platelet function analysis (PFA-200), and platelet activation (CD62P and CD63 expression by flow cytometry). Studies were performed 24h after implant, each 7 days, and in the first week after ECLS extraction. T-TAS® was used for hemostasis analysis in samples from bleeding patients, before and after in vitro addition of purified VWF. This study was approved by the Hospital Clinic’s Ethics Committee (HCB/2021/0200).
Results: After 24h of ECLS implant, increased VWF:Ag levels and prolonged PFA occlusion times. In 60% of patients, altered VWF:GPIbM/VWF:Ag ratio ( < 0.7) and loss of VWF high molecular weight multimers (HMWM) were observed. CD62P expression was slightly higher in ECLS patients platelets than in controls (MFI±SD of 4.34±2.2 vs. 3.27±0.6, respectively; p=0.3). Early after ECLS extraction, there was normalization of the VWF multimeric profile and PFA values. Interestingly, in samples from bleeding patients, addition of purified VWF reduced significantly the T-TAS occlusion times (776s±207s vs. 1161s±251s, Mean±SD, post vs. pre, respectively; p=0.033).
Conclusion(s): ECLS caused primary hemostasis alterations, leading to aVWD and platelet activation, solved early after support removal. Hemostatic efficiency in ECLS bleeding patients, with lack of HMWM, was corrected in vitro by providing functional purified VWF.
Figure 1
A. Multimeric analysis of Von Willebrand Factor -VWF- by agarose -1.2%- gel electrophoresis. Plasma sample dilutions were performed according to the VWF:Ag levels, in order to homogenize the VWF concentration to levels seen in plasma samples from healthy individuals. Control sample -C, healthy donor-; Samples from a patient after 1 -E1- and 7 days -E7- of ECLS; and 7 days after ECLS was removed. E1 and E7 show loss of VWF HMWM and A7 shows the recovery of a normal VWF multimeric pattern, early after ECLS removal. B. Platelet activation measurement by P-Selectin and Lisosomal antigen analysis by flow cytometry -Mean Fluorecescence Intensity-. The blue peak corresponds to a healthy donor sample and the orange peak to a patient after 7 days in ECLS.
Figure 2
Graphs from T-TAS® System. Lines show the kinetics of the thrombi formation for the sample before -blue- and after adding purified VWF -Haemate-P- -red- from two different ECLS treated patients with bleeding complications. There was a significant decrease in the time to reach the maximal pressure after adding Haemate-P.
To cite this abstract in AMA style:
Moreno-Castaño A, Sandoval E, Pino M, Samanbar S, Bonastre L, Molina P, Fernández S, Ventosa H, Escolar G, Castro P, Diaz-Ricart M. Dysfunctional Hemostasis in Patients under Extracorporeal Life Support. A Rapid Diagnostic Approach with Therapeutical Guidance Intentions [abstract]. https://abstracts.isth.org/abstract/dysfunctional-hemostasis-in-patients-under-extracorporeal-life-support-a-rapid-diagnostic-approach-with-therapeutical-guidance-intentions/. Accessed September 29, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/dysfunctional-hemostasis-in-patients-under-extracorporeal-life-support-a-rapid-diagnostic-approach-with-therapeutical-guidance-intentions/