Acquired Platelet Storage Pool Disease In Chronic Autoimmune Thrombocytopenia (ITP) And Marrow Dyspoiesis

Abstract

The mechanism underlying platelet dysfunction in patients with chronic ITP or marrow dyspoiesis has been characterized with respect to template bleeding times, platelet nucleotides and a granule contents. Ten patients with modest thrombocytopenia (93,000 plat/ul ± 53,000) due to chronic ITP (4), “preleukemia” (4), primary myelofibrosis (I), and polycythemia vera (I) were selected for study on the basis of discrepantly prolonged bleeding times in excess of that predicted by the platelet count, i.e. BT = 30.5 -platelet count/3850. Using high pressure liquid chromotography, adenosine diphosphate (ADP) and adenosine triphosphate (ATP) were measured in both whole platelet extracts and the supernatant of thrombin stimulated platelets. From these measurements it was possible to determine the relative distribution of ATP and ADP in the cytoplasmic and dense granule compartments. The α granule protein, platelet factor four (PF4), was determined by RIA.Whereas dense granule ADP was markedly reduced (mean 0.92 ± 0.58 u moles/1011 platelets compared with 2.41 ± 0.20 in 20 normal subjects; p < 0.01), platelet cytoplasmic ATP and ADP were not decreased 3.49 ± 0.45 and 0.40 ± 0.27 u moles/1011 platelets compared with 2.73 ± 0.27 and 0.3l ± 0.15 in normals respectively). The severity of the platelet dysfunction (difference in the observed bleeding times from predicted) varied directly with the decrease in dense granule ADP (R2 = 0.88). Only three patients (all with dyspoiesis) also demonstrated an associated α gronule abnormality as shown by partial depletion of the platelet content of PF4. Platelet survival studies done simultaneously with 51Cr and 14C-serotonin showed discrepantly shortened 14C-serotonin disappearance in 3 patients (I ITP, 2 dyspoiesis) suggesting preferential dense granule losses from circulating platelets. Possible mechanisms of platelet dense granule ADP depletion may include activation and release or leak of dense granule contents or defective platelet development in the marrow. We conclude that platelet dysfunction may occur in some patients with chronic ITP and hematodyspoiesis due to acquired dense granule storage pool disease.