AN EXPERIMENTAL-MODEL FOR TESTING VON-WILLEBRAND-FACTOR FUNCTION - SUCCESSFUL SLA-MATCHED CROSSED BONE-MARROW TRANSPLANTATIONS BETWEEN NORMAL AND VON-WILLEBRAND PIGS

To assess the relative in vivo roles of von Willebrand factor (vWF) of different origins, we performed crossed bone marrow transplantations (BMTs) among normal pigs and pigs with the von Willebrand disease (vWD ). The two groups were fully compatible immunologically according to t yping by swine leukocyte antigen (SLA). After total-body irradiation ( 8-10 Gy), all pigs received 0.5x10(9) to 10(10)/kg mononuclear bone ma rrow cells without any immunosuppression. The nadir of aplasia occurre d between days 5 and 7 after irradiation (white blood cell [WBC] count 0.6x10(9)/L, platelet [Pit] count 76x10(9)/L). Three weeks after the graft, WBC and Pit counts had returned to normal levels. Animals were followed for at least 50 days, during which no bone marrow rejection o ccurred; no evidence of graft-vs.-host disease (GVHD) was observed. Ea ch BMT was confirmed by karyotype analysis. In the six homozygous pigs with vWD grafted with normal marrow, platelet vWF antigen (vWFAg) and platelet vWF activity rose from <3 to 450 U/dL with a normal multimer ic pattern; plasma vWF increased slightly. No correction of bleeding t ime was observed. In the five normal pigs grafted with bone marrow fro m pigs with vWD, platelet vWFAg and platelet vWF activity decreased fr om >100 U/dL to undetectable levels; bleeding time and plasma vWFAg re mained unchanged. A derivative of normal porcine plas ma, a concentrat e containing factor VIII and vWF, was infused into a homozygous vWD pi g before and after BMT from a normal pig. No correction of bleeding ti me was obtained, even though plasma and platelet vWFAg levels were nor mal. We conclude that crossed BMT among SLA-identical pigs is a feasib le model of studying the synthesis and the roles of vWF in hemostasis and thrombosis.