Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: Relationship with platelet count

We present a 4-year follow-up of a 42-year-old patient with primary thrombocythemia whose clinical course was complicated by two major mucocutaneous bleeding episodes. On both occasions an acquired functional von Willebrand factor deficiency was demonstrated. In contrast to what is reported in the literature, an inverse relationship between platelet number and plasma high-molecular-weight multimers of von Willebrand factor was established

Fibrinolysis during liver transplantation is enhanced by using solvent/detergent virus-inactivated plasma (ESDEP)

After the introduction of solvent/detergent-treated plasma (ESDEP) in our hospital, an increased incidence of hyperfibrinolysis was observed (75% vs 29%; P = 0.005) compared with the use of fresh frozen plasma for liver transplantation. To clarify this increased incidence, intraoperative plasma samples of patients treated with fresh frozen plasma or ESDEP were analyzed in a retrospective observational study. During the anhepatic phase, plasma levels of D-dimer (6.58 vs 1.53 microg/mL; P = 0.02) and fibrinogen degradation products (60 vs 23 mg/L; P = 0.018) were significantly higher in patients treated with ESDEP. After reperfusion, differences increased to 23.5 vs 4.7 microg/mL (D-dimer, P = 0.002) and 161 vs 57 mg/L (fibrinogen degradation products, P = 0.001). The amount of plasma received per packed red blood cell concentrate, clotting tests, and levels of individual clotting factors did not show significant differences between the groups. alpha(2)-Antiplasmin levels, however, were significantly lower in patients receiving ESDEP during the anhepatic phase (0.37 vs 0.65 IU/mL; P < 0.001) and after reperfusion (0.27 vs 0.58 IU/mL; P = 0.001). Analysis of alpha(2)-antiplasmin levels in ESDEP alone showed a reduction to 0.28 IU/mL (normal >0.95 IU/mL) because of the solvent/detergent process. Therapeutic consequences for the use of ESDEP in orthotopic liver transplantation are discussed in view of an increased incidence of hyperfibrinolysis caused by reduced levels of alpha(2)-antiplasmin in the solvent/detergent-treated plasma. IMPLICATIONS: The use of solvent/detergent virus-inactivated plasma is of increasing importance in the prevention of human immunodeficiency virus and hepatitis C virus transmission. Since the use of this plasma during orthotopic liver transplantation has increased, the incidence of hyperfibrinolysis was observed. Clotting analysis of the patients revealed small alpha(2)-antiplasmin concentrations because of the solvent/detergent process

Acute effect of cigarette smoking on cardiac prostaglandin synthesis and platelet behavior in patients with coronary heart disease

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The in vitro effect of the new antithrombotic drug candidate ALX-0081 on blood samples of patients undergoing percutaneous coronary intervention

Compound ALX-0081 is a bivalent humanised Nanobody® that binds the A1-domain of von Willebrand factor (VWF) with high affinity. Consequently, it can block the interaction between VWF and its platelet-receptor- glycoprotein Ib, which leads inevitably to formation of arterial thrombi. It was the objective of this study to assess the in vitro effects of ALX-0081 on platelet adhesion and aggregation in coronary artery disease (CAD) patients to determine the optimal concentration of ALX-0081 and the effect of co-medication. We included nine CAD patients, who were scheduled for elective percutaneous coronary intervention (PCI), and 11 healthy volunteers. At admission all patients received aspirin, clopidogrel and heparin. Blood was drawn 24 hours (h) before and 1 h after start of the PCI procedure and was subsequently spiked with different concentrations of ALX-0081 or buffer. The efficacy of ALX-0081 was assessed by in vitro experiments: flow chamber ex- periments, ristocetin-induced platelet aggregation (RIPA), and the platelet function analyser (PFA-100TM). VWF levels in CAD patients were significantly higher than in healthy controls. During PCI VWF levels did not rise. In all in vitro experiments, ALX-0081 led to complete inhibition of platelet adhesion and aggregation. However, the required effective concentration was higher in patients than in controls and was related to plasma VWF levels. In conclusion, ALX-0081 is able to completely inhibit in vitro platelet adhesion and aggregation in CAD patients scheduled for elective PCI. The efficacy of ALX-0081 is not influenced by PCI or co-medication. However, due to higher VWF levels in CAD patients a higher effective concentration of ALX-0081 was required than in healthy individuals