Abnormalities of Epinephrine-Induced Platelet Aggregation and Adenine Nucleotides in Myeloproliferative Disorders

Summary

Platelet aggregation was studied in 18 patients with myeloproliferative disorders, including 14 patients with chronic myelogenous leukemia, 2 with polycythemia vera, 1 with myelofibrosis and 1 with thrombocythemia. Fourteen patients (78%) were abnormal in epinephrine-induced platelet aggregation, while 3 (17%) and 4 (22%) cases showed impaired ADP or collagen induced platelet aggregation, respectively. A significant decrease of total ADP content in resting unstimulated platelets and of the amount released to the medium after aggregation was found in all six patients who were evaluated. ATP and AMP in resting platelets tended to be slightly higher in patients compared with the control group. Released ATP was also significantly less, and the percentage release of ADP and ATP was significantly decreased in patients. A storage pool deficiency of adenine nucleotides was considered to be responsible for abnormal platelet function in patients with myeloproliferative disorders.

Key words

Myeloproliferative disorders - Platelet aggregation - Adenine nucleotides - Storage pool deficiency

• References

• 1 Neemeh JA, Bowie EJ W, Thompson JH, Didisheim P, Owen CA. Quantitation of platelet aggregation in myeloproliferative disorders. Am J Clin Pathol 1972; 57: 336-347
• 2 Cardamone JM, Edson JR, McArthur JR, Jacob HS. Abnormalities of platelet function in the myeloproliferative disorders. JAMA 1972; 221: 270-273
• 3 Adams T, Schutz L, Goldberg L. Platelet function abnormalities in the myeloproliferative disorders. Scand J Haematol 1974; 13: 215-224
• 4 Mason JE, Devita VT, Canellos GP. Thrombocytosis in chronic granulocytic leukemia: incidence and clinical significance. Blood 1974; 44: 483-487
• 5 Tangün Y. Platelet aggregation and platelet factor 3 activity in myeloproliferative disorders. Thromb Haemostas 1971; 25: 241-251
• 6 Boneu B, Nouvel C, Sié P, Caranobe C, Combes D, Laurent G, Pris J, Biermé R. Platelets in myeloproliferative disorders I. A comparative evaluation with certain platelet function tests. Scand J Haematol 1980; 25: 214-220
• 7 Ginsburg AD. Platelet function in patients with high platelet counts. Ann Inter Med 1975; 82: 506-511
• 8 Gerrard JM, Stoddard SF, Shapiro RS, Coccia PF, Ramsay NK C, Nesbit ME, Rao GH R, Krivit W, White JG. Platelet storage pool deficiency and prostaglandin synthesis in chronic granulocytic leukaemia. Br J Haematol 1978; 40: 597-607
• 9 Macmillan DC. Secondary clumping effect in human citrated platelet-rich plasma produced by adenosine diphosphate and adrenaline. Nature 1966; 211: 140-144
• 10 Nishimura J, Okamoto S, Ibayashi H. Abnormalities of platelet adenine nucleotides in patients with myeloproliferative disorders. Thromb Haemostas 1979; 41: 787-795
• 11 Pareti FI, Gugliotta L, Mannucci L, Guarini A, Mannucci PM. Biochemical and metabolic aspects of platelet dysfunction in chronic myeloproliferative disorders. Thromb Haemostas 1982; 47: 84-89
• 12 Bom GV R, Cross MJ. The aggregation of blood platelets. J Physiol (Lond) 1963; 168: 178-195
• 13 Inceman S, Tangün Y. Platelet defect in the myeloproliferative disorders. Ann NY Acad Sei 1972; 201: 251-261
• 14 Weiss HJ, Chervenic PA, Zalusky R, Factor A. A familial defect in platelet function associated with impaired release of adenosine diphosphate. N Eng J Med 1969; 281: 1264-1270
• 15 Holmsen H, Weiss HJ. Hereditary defect in the platelet release reaction caused by a deficiency in a storage pool of platelet adenine nucleotides. Br J Haematol 1970; 19: 643-649
• 16 Holmsen H, Day HJ, Storm E. Adenine nucleotide metabolism of blood platelets VI. Subcellular localization of nucleotide pools with different functions in the platelet release reaction. Biochim Biophys Acta 1969; 186: 254-266
• 17 Wintrobe MM. Platelets and Megakaryocytes. In: Clinical Hematology, 8th edition. Wintrobe MM. (Ed) Lea & Febiger; Philadelphia: 1981. pp 356-357
• 18 Maldonado JE, Pintado T, Pierre RV. Dysplastic platelets and circulating megakaryocytes in chronic myeloproliferative diseases. I. The platelets: ultrastructure and peroxidase reaction. Blood 1974; 43: 797-809
• 19 Caranobe C, Sié P, Nouvel C, Laurent G, Pris J, Boneu B. Platelets in myeloproliferative disorders. 2. Serotonine uptake and storage: correlation with mepacrine labelled dense bodies and with platelet density. Scand J Haematol 1980; 25: 289-295
• 20 Boneu B, Sié P, Eche N, Caranobe C, Hugo B, Nouvel C. Platelet density analysis: a tool for the detection of acquired storage pool disease in man. Br J Haematol 1983; 55: 523-532
• 21 Viero P, Cortelazzo S, Bassan R, Barbui T. Effect of aspirin on platelet 5-hydroxytryptamine and beta-thromboglobulin plasma levels in patients with myeloproliferative diseases. Thromb Haemostas 1982; 48: 125-126
• 22 Okamoto S, Nishimura J, Motomura S, Ibayashi H. Reduced amounts of platelet 5-hydroxytryptamine in myeloproliferative disorders. Acta Haematol Jpn 1982; 45: 142-145
• 23 Cronberg S, Nilsson IM, Gydell K. Haemorrhagic thrombocythemia due to defect platelet adhesiveness. Scand J Haematol 1965; 2: 208-219
• 24 Boughton BJ, Corbett WE N, Ginsburg AD. Myeloproliferative disorders: a paradox of in-vivo and in-vitro platelet function. J Clin Pathol 1977; 30: 228-234