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Platelet biology: collagen activation mechanisms and their relevance to transfusion medicine

Platelets are the second most important cellular product issued by the National Blood Service of England. Per annum ∼ 220 000 adult units are prescribed with ∼ 50% for the prophylactic treatment to reduce the risk of bleeding in haemato-oncology and the other half for the treatment of bleeding in patients with a wide range of conditions. The trigger for prophylactic platelet transfusion is 10 × 10 9 /l. A further lowering of the trigger to 5 × 10 9 /l has been considered but there are concerns about a possible increase in the risk of severe bleeding. It would be attractive to use differential transfusion triggers informed by the patients’ estimated risk for bleeding at a low platelet count. Patients who are predetermined to ‘easy bleeding’ could be transfused at a higher trigger than patients who have a more robust haemostasis. We postulate that an individual’s bleeding tendency at a low platelet count is to a large extent genetically determined. Although studies on the heritability of ‘global haemostasis’ are lacking, there is evidence from the Framingham study that the response of platelets to activation by agonist is in part genetically controlled. With the completion of the sequencing of the human genome it becomes feasible to answer the question to which extent the risk of bleeding on the one hand and the risk of atherothrombosis on the other is genetically determined. The capacity to sequence large numbers of genes to define common sequence variation together with the availability of new genotyping platforms to interrogate DNA samples for thousands of single nucleotide polymorphisms (SNPs) in a single test provides unique opportunities for exciting clinical studies on the relation between sequence variation and haemostasis. Here we review the way we are conducting such studies using the interaction of platelets and collagen as a model.