P-selectin - a novel protein in hemostasis

Originally, P-selectin played an important role in the vascular response to inflammation. In the first half of the nineties there were published papers demonstrated that P-selectin also played a significant role in blood coagulation and thrombosis. In these experiments anti-P-selectin antibodies blocked fibrin formation and suppressed the developing of thrombus. Shortly thereafter, P-selectin was shown to upregulate tissue factor (TF) generation on monocytes. The active role of P-selectin in hemostasis was supported also with our findings that overexpression of soluble P-selectin (sP-sel) can induce a procoagulant state in plasma/blood. I have focused in my postgraduate study on pathophysiology of sP-sel , its role in formation of microparicles (MPs) bearing TF. In the detail study of sP-sel we found, that procoagulant state in plasma is due to procoagulant MPs, part of them contained TF. We confirmed that recently characterized "blood-borne" TF could be induced by sP-sel. Moreover, because the production of microparticles was suppressed by inhibiting antibody against PSGL-1 (receptor of P-selectin on leukocytes), we proposed the origin of MPs from leukocytes. Recruitment of TF-bearing MPs from monocytes I demonstrated later with FACS screening of presence of specific CD-markers. I realized that..

A common origin of the 4143insA ADAMTS13 mutation

Severely deficient activity of the von Willebrand Factor (VWF) cleaving metalloprotease, ADAMTS13, is associated with thrombotic thrombocytopenic purpura (TTP). The mutation spectrum ofADAMTS13 is rather heterogeneous, and numerous mutations spread across the gene have been described in association with congenital TTP. The 4143insA mutation is unusual with respect to its geographic concentration. Following the initial report from Germany in which the 4143insA mutation was detected in four apparently unrelated families, we have now identified this mutation in a further eleven patients from Norway, Sweden, Poland, Germany, the Czech Republic and Australia. Confirmation that the Australian patient is of German ancestry, together with the Northern and Central European origin of most of the other patients, suggests that the 4143insA mutation has a common genetic background. We established ADAMTS13 haplotypes by analyzing 17 polymorphic intragenic markers. The haplotypes linked to 4143insA were identical in all informative families. Three novel candidate mutations, C347S, P671L and R1060W, as well as the known mutation R507Q, were also identified during the course of the study. We conclude that 4143insA has a common genetic background and is frequent among patients with hereditary ADAMTS13 deficiency in Northern and Central European countries