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.