Spontaneous Platelet Aggregation In A Hereditary ‘giant’ Platelet Syndrome (MPS)

Abstract

Spontaneous platelet aggregation (SA), induced by stirring citrated platelet-rich plasma (PRP), has been observed in a large number of patients with arterial insufficiency and shown to be mediated by plasma and/or platelet-released factors. Here we examine the characterisitcs of SA in a hereditary giant platelet syndrome, the Montreal Platelet Syndrome (MPS), and demonstrate a distinction from that observed for patients with arterial insufficiency. SA was quantitated by microscopy from the decrease in single platelet concentration in PRP. In contrast to normal PRP, a significant proportion (20-50%) of platelets in MPS-PRP occurred in micro-aggregates typically containing 2-6 discshaped platelets. Stirring MPS-PRP at 1000 rpm for 10 minutes further increased the fraction of platelets in aggregates by 10-170%: the % increase not being correlated to the donor's platelet count (5,000 - 220,000 μl-1). Normal platelets re-suspended in MPS platelet-free plasma (PFP) did not undergo SA, whereas MPS platelets re-suspended into normal PFP or calcium-poor Tyrode's continued to show SA. The increase in SA upon stirring was only partially inhibited by 1 μM PGEl (69-85% inhibition), 1 μM C1-adenosine (26-43%) and 0.3 mg/ml apyrase (18-25%), i.e. at concentrations equal to or greater than that necessary to completely inhibit SA in PRP from donors with arterial insufficiency. SA in ACD-PRP was much less than in PRP (e.g. 6% versus 30%); however, SA re-occurred on returning the pH to 7.4. SA was observed for 5/5 MPS donors, but only 1/3 of these donors had platelets with both reduced/altered glycoprotein I and reduced sialic acid while the other 2 siblings' platelets showed no such abnormalities. This indicates that neither of these entities are directly related to the etiology of SA in MPS. The above observations distinguish SA in MPS from that reported for arterial insufficiency and point to the existence of an as yet undetermined anomaly of the plasma membrane as the basis of the etiology of spontaneous aggregation in MPS.