Myristoylation of proteins in platelets occurs predominantly through thioester linkages

L

Covalent modification of proteins by arachidonate and eicosapentaenoate in platelets

L

Factor XIII and inflammatory cells

Factor XIII is a coagulation factor with multiple plasmatic and cellular functions part of which is outside of the field of traditional hemostasis. The aim of the review is to provide a brief summary on the relationship between coagulation factor XIII (FXIII) and the cells of the immune system. In the first part the structure and biochemical functions of plasma and cellular FXIII are briefly summarized. Then, the interaction between leukocytes and factor XIII is discussed. This part includes the activation of FXIII by human neutrophil elastase, the down-regulation of activated FXIII (FXIIIa) by granulocyte proteases within the clot, and the effect of FXIIIa on leukocytes. In the following part data on the expression and subcellular distribution of FXIII in monocytes/macrophages are summarized. Another part of the review is devoted to changes of FXIII expression during monocyte differentiation and monocyte activation by the classical or the alternative pathway. In the final part reports on the possible functions of cellular FXIII in monocytes and macrophages are evaluated

Factor XIII: What does it look like?

L

Comparison of a New P2Y12 Receptor Specific Platelet Aggregation Test with Other Laboratory Methods in Stroke Patients on Clopidogrel Monotherapy

BACKGROUND: Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel. OBJECTIVES: To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy. PATIENTS/METHODS: Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute. RESULTS: The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3', 5'-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency. CONCLUSION: The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential