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Detection of functional differences between different platelet membrane glycoprotein Ibα variable number tandem repeat and Kozak genotypes as shown by the PFA-100 system
  1. H Douglas1,
  2. G J Davies1,
  3. K Michaelides2,
  4. D A Gorog1,
  5. H Timlin1,
  6. N Ahmed1,
  7. E G D Tuddenham2
  1. 1National Heart and Lung Institute, Hammersmith Hospital NHS Trust, London, UK
  2. 2Haemostasis Research Group, MRC Clinical Sciences Centre, The Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK
  1. Correspondence to:
    Professor Edward G D Tuddenham
    Haemostasis, MRC building, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK; Edward.Tuddenham{at}csc.mrc.ac.uk

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The interaction between the platelet membrane glycoprotein Ib/IX/V and von Willebrand factor (VWF) is the primary event in the formation of an occlusive thrombus under conditions of high shear stress.1 Several polymorphisms of glycoprotein Ibα (the functional binding site for surface bound VWF) have been reported.2 The relation of variable number tandem repeat (VNTR) and Kozak sequence polymorphisms with arterial thrombosis and coronary artery disease remains controversial. In our recent study we proposed that the glycoprotein Ibα genotypes CC of the VNTR and Kozak −5TT increased the risk of platelet plug formation under the condition of high shear stress generated by stenosed vessels and thus caused the increased risk of myocardial infarction (MI), which we observed in a group of patients with known coronary artery disease status who had those genotypes. We also observed the potential protective effect of the glycoprotein Ibα Kozak −5TC genotype.3 The objective of this study was to evaluate the effect of these polymorphisms on platelet function of the same group of patients by using the platelet function analyser system PFA-100 (Dade Behring), which mimics physiological conditions in vivo involving platelet binding to VWF and platelet adhesion/aggregation in response to collagen under conditions of high shear after activation by adrenaline (epinephrine) or ADP.

METHODS

From 256 patients who had previously been genotyped for the VNTR and Kozak sequence polymorphisms, 84 white men were consecutively selected (mean age 62.07 years). All the patients were taking aspirin 75 mg as their only antiplatelet medication. Patients who had an MI within the previous six months and those with bleeding diathesis, abnormal platelet counts, or abnormal haemoglobin were excluded from the study. A fasting venous blood sample was obtained between 8 am and 10 am with a 21 gauge butterfly cannula without a …

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