Platelet function in bleeding disorders

Abstract

The first bleeding diathesis we studied was hemophilia A. Since FVIII activity level does not always correlate with the bleeding tendency in individual patients, bleeding tendency must also be influenced by other factors. Earlier studies excluded the remaining clotting factors and FVIII genotype as determinants of bleeding phenotype in hemophilia A. To look into the role of platelets, we set up four studies. In Chapter 2, we studied differences in platelet reactivity between patients with mild, moderate and severe hemophilia A and healthy individuals. In Chapter 3, the influence of FVIII concentrate infusion, on primary hemostasis was studied. In Chapter 4, we investigated if differences in platelet reactivity could explain differences observed in bleeding phenotype of severe hemophilia A patients. To better understand the relationship between factor VIII and platelets, we investigated the capability of platelets to take up FVIII in Chapter 5. The next patient group drawing our attention is patients with chronic kidney disease. In this patient category, both an increased bleeding tendency and a increased thrombotic tendency is observed. In Chapter 6, we investigated platelet reactivity in patients with chronic kidney disease, to determine if platelets contribute to either the bleeding or the thrombotic tendency in these patients. The last patient group we investigated here were children with chronic ITP. In chronic ITP, patient platelet count does not always correlate to the bleeding tendency in individual patients. To investigate a possible role of platelet function in this, we adapted the platelet reactivity assay for measurement in samples with very low platelet counts. In Chapter 7, we investigate platelet function in patients with chronic ITP related to bleeding phenotype of these patients. The platelet reactivity assay, which was used in above studies to determine platelet functionality, is a test which requires only a very small amount of whole blood. Since only 250 microliters of blood is sufficient to test platelet reactivity to five (ant-)agonists, capillary sampling could be used to collect this small amount. In Chapter 8 we investigate if capillary sampled blood can be used for functional platelet testing via the platelet reactivity assay. First this chapter focuses on the differences introduced by capillary sampling compared to venous sampling on platelet function. Second we focus on minor modifications to the capillary sampling, with which platelet reactivity testing becomes possible in capillary sampled blood.