Graft-derived VWF drives platelet activation and thrombocytopenia during porcine liver xenotransplantation to brain-dead human recipients - PubMed
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- #xenotransplantation
- #VWF
- #thrombocytopenia
- Genetically engineered porcine livers are being developed as a bridge therapy for acute liver failure.
- Severe thrombocytopenia is a major limitation in porcine liver xenotransplantation.
- Platelet kinetics were studied in human decedents undergoing cross-circulation with transgenic porcine livers.
- Rapid platelet clearance (80%-90%) was observed, inconsistent with marrow suppression or hypersplenism.
- Antibody and complement inhibition did not improve thrombocytopenia.
- Porcine von Willebrand factor (pVWF) mediated platelet activation, similar to human Type IIb von Willebrand disease.
- Caplacizumab, an anti-VWF nanobody, blocked pVWF-mediated platelet activation ex vivo.
- In a fourth decedent, caplacizumab prevented aberrant platelet activation but full recovery was limited by pre-existing DIC.
- Thrombocytopenia in xenotransplantation is primarily driven by pVWF-mediated platelet activation, not immune or splenic mechanisms.
- Targeted VWF blockade with caplacizumab may improve the safety of porcine liver support in acute liver failure.