Correlation between prolonged bleeding time and depletion of platelet dense granule ADP in patients with myelodysplastic and myeloproliferative disorders.

Nine patients with myelodysplasia or myeloproliferative syndrome were studied with respect to platelet count and volume, 51Cr and 14C-serotonin platelet kinetics, bleeding time, and platelet dense and alpha-granule contents. Platelet counts ranged from 45,000 to 293,000 platelets/microliters. The bleeding time was significantly longer (greater than 4 minutes) than the predicted value in seven of nine patients. All patients had significant dense granule storage pool depletion (thrombin-releasable ADP was 0.59 +/- 0.30 vs. 2.41 +/- 0.20 mumol per 10(11) platelets in patients compared with normal volunteers; total platelet ADP was 0.97 +/- 0.29 vs. 2.72 +/- 0.15, and total platelet ATP/ADP was 4.77 +/- 1.89 vs. 1.65 +/- 0.11). The prolongation in bleeding time correlated inversely with thrombin-releasable ADP (r = -0.637, p less than 0.01) and with total ADP (r = -0.832, p less than 0.005), and directly with the ATP/ADP ratio (r = 0.781, p less than 0.005). When autologous platelets were doubly labeled with 14C-serotonin and 51Cr to test for loss of dense granule contents, marked preferential shortening of the 14C-serotonin platelet disappearance curve with relation to 51Cr platelet survival was observed in five of the six patients (six normal participants uniformly showed 14C-serotonin platelet disappearance patterns that were 15% to 20% longer than 51Cr platelet survivals). Reduction in alpha-granule contents was less striking and occurred less frequently than dense granule depletion (two of nine values were significantly reduced for platelet factor 4 content, whereas all patients had significantly reduced dense granule ADP levels). Mean plasma levels of both platelet factor 4 and beta-thromboglobulin were elevated in patients compared with normal participants (4.1 +/- 3.2 and 26.6 +/- 12.3 vs. 1.8 +/- 1.0 and 6.0 +/- 3.6 ng/ml; p less than 0.01 and p less than 0.01, respectively). Two patients had elevated urinary platelet factor 4. There was no correlation between platelet factor 4 content and thrombin-releasable platelet ADP levels (r = 0.167, p greater than 0.1). These patients had acquired storage pool deficiency of platelet dense granule ADP that correlated directly with platelet dysfunction, as measured by prolongation of bleeding time. The reduction in dense granule constituents appears to be the consequence of an ongoing loss of dense granule contents from circulating platelets.