The bleeding diathesis and abnormalities of platelet aggregation in the Fawn-Hooded (FH) rat, as in human patients with storage pool disease, have been attributed to decreased amounts of adenine nucleotides that are ordinarily stored with serotonin in the platelet dense granules. This study was undertaken in order to establish whether the platelet defect of the FH rat was present in young platelets, newly emerged from the bone marrow, or whether the platelets acquired this abnormality (possibly by a premature release reaction) during their circulation in the blood. FH and Wistar rats were made thrombocytopenic with one injection of anti-platelet serum (APS) and platelets were harvested during the recovery phase. The ATP content of “young” FH platelets harvested two days after injection of APS, was higher than that of platelets obtained from untreated FH rats, but was still only 50% of that found in “young” Wistar platelets. In addition, the adenine nucleotide content of FH platelets did not change during treatment with aspirin. “Young” FH platelets were also deficient in serotonin and, unlike Wistar platelets, their serotonin content did not increase appreciably with the increasing platelet age. The results of the study strongly suggest that the defect in FH platelets is present in platelets newly emerged from the bone marrow and is not due to premature release of the “storage” contents during their circulation in the blood.
* Present Address: Th. B. Tschopp, Department of Experimental Medicine, c/o F. Hoffmann-La Roche & Co., Ltd., CH-4002 Basel, Switzerland.
References
1
Brecher G,
Cronkite E. P,
Schneidermann M.
1953; The reproducibility and constancy of the platelet count. Journal of Clinical Pathology 23: 15.
3
Detwiler T. C,
Odell T. T,
McDonald T. P.
1962; Platelet size, ATP content, and clot retraction in relation to platelet age. American Journal of Physiology 203: 107.
4
Ebbe S,
Stohlman Jr F,
Donovan J,
Howard D.
1966; Platelet survival in the rat as measured with tritium-labelled diisopropylfluorophosphate. Journal of Laboratory and Clinical Medicine 68: 233.
6
Holmsen H,
Rozenberg M. C.
1968; Adenine nucleotide metabolism of blood platelets. 1. Adenosine kinase and nucleotide formation from endogenous adenosine and AMP. Biochimica Biophysica Acta 155: 326.
8
Holmsen H,
Day H. J.
1972; Further evidence for a deficient storage pool of adenine nucleotides in platelets from some patients with thrombocytopathia - “storage pool disease.”. Blood 39: 197.
9
Holmsen H,
Storm E,
Day H. J.
1972; Determination of ATP and ADP in blood platelets. A modification of the firefly luciferase assay for plasma. Analytical Biochemistry 46: 489.
11
Atkin SKarp.
1969; Heterogeneity of human platelets. II. Functional evidence suggestive of young and old platelets. Journal of Clinical Investigation 48: 1083.
12
Karpatkin S,
Charmatz A.
1969; Heterogeneity of human platelets. I. Metabolic and kinetic evidence suggestive of young and old platelets. Journal of Clinical Investigation 48: 1073.
19
Weiss H. J,
Aledort L. M,
Kochwa S.
1968; The effect of salicylates on the hemostatic properties of platelets in man. Journal of Clinical Investigation 47: 2169.
20
Weiss H. J,
Chervenick P. A,
Zalusky R,
Factor A.
1969; A familial defect in platelet function associated with impaired release of adenosine diphosphate. New England Journal of Medicine 281: 1264.
21
Weiss H. J,
Rogers J.
1972; Thrombocytopathia due to abnormalities in the platelet release reaction — Studies on six unrelated patients. Blood 39: 187.
22
Weiss H. J,
Ames R. P.
1973; Ultrastructural findings in storage pool disease and aspirin-like defects of platelets. American Journal of Pathology 71: 447.
23
Weiss H. J,
Tschopp T. B,
Rogers J,
Brand H.
1974; Studies of platelet 5-hydroxytryptamine (serotonin) in storage pool disease and albinism. Journal of Clinical Investigation 54: 421.
25
Zahavi J,
Marder V. J.
1974; Acquired “storage pool disease” of platelets associated with circulating anti-platelet antibodies. American Journal of Medicine 56: 883.