Impairment of Phosphatidylinositol Metabolism in a Patient with a Bleeding Disorder Associated with Defects of Initial Platelet Responses

Bruce Lages; Harvey J Weiss

doi:10.1055/s-0038-1642749

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1988; 59(02): 175-179
DOI: 10.1055/s-0038-1642749

Original Articles

Schattauer GmbH Stuttgart

Impairment of Phosphatidylinositol Metabolism in a Patient with a Bleeding Disorder Associated with Defects of Initial Platelet Responses

Bruce Lages

The Department of Medicine, Division of Hematology and Oncology, St. Luke's-Roosevelt Hospital Center, and Columbia University College of Physicians and Surgeons, New York, N.Y., USA

,

Harvey J Weiss

The Department of Medicine, Division of Hematology and Oncology, St. Luke's-Roosevelt Hospital Center, and Columbia University College of Physicians and Surgeons, New York, N.Y., USA

› Author Affiliations

Abstract

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Summary

Phosphoinositide/polyphosphoinositide (PI/PPI) metabolism, measured by the increase of ³H-phosphatidic acid (PA) and the decrease of 3H-phosphatidylinositol (PI) in ³H-arachidonate- labeled platelet suspensions, was assessed in five patients whose platelet functional defects included impaired initial rates of ADP, epinephrine and U44069 aggregation in platelet-rich plasma (PRP). In one patient, ³H-PA formation induced by collagen and thrombin was reduced or absent on two of three occasions, and the decrease in 3H-PI was reduced on one of these two occasions in response to collagen and A23187, and on all 3 occasions in response to thrombin. The variations in the formation of ³H-PA in this patient on different occasions broadly paralleled the variations in the initial rates of ADP and U44069 aggregation and in epinephrine aggregation seen in PRP. No such abnormalities of PI metabolism were found in four other patients with similar, but not identical, functional defects. These results suggest an impairment affecting metabolism of PI/PPI via the PI/PPI cycle in this patient's platelets. The association of abnormalities of PI metabolism with defects of initial platelet responses provides further support for a physiological role of phosphoinositide metabolism in the early activation mechanisms of platelets.

Keywords

Platelets - Phosphoinositides - Phosphatidic acid - Blood platelet disorders

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References

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