Biphasic Aggregation Responses to ADP and Epinephrine in Some Storage Pool Deficient Platelets: Relationship to the Role of Endogenous ADP in Platelet Aggregation and Secretion

Bruce Lages; Harvey J Weiss

doi:10.1055/s-0038-1650037

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1980; 43(02): 147-153
DOI: 10.1055/s-0038-1650037

Original Article

Schattauer GmbH Stuttgart

Biphasic Aggregation Responses to ADP and Epinephrine in Some Storage Pool Deficient Platelets: Relationship to the Role of Endogenous ADP in Platelet Aggregation and Secretion

Bruce Lages

Department of Medicine, Division of Hematology, St. Luke’s-Roosevelt Hospital Center, and College of Physicians and Surgeons, Columbia University, New York, U.S.A.

,

Harvey J Weiss

Department of Medicine, Division of Hematology, St. Luke’s-Roosevelt Hospital Center, and College of Physicians and Surgeons, Columbia University, New York, U.S.A.

› Author Affiliations

Abstract

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Summary

Biphasic aggregation responses to ADP and epinephrine have been consistently observed in platelets of two patients with storage pool deficiency (SPD) despite marked reductions in platelet ADP contents. The nature of these aggregation responses was examined in relation to the role of secreted ADP as a mediator of secondary aggregation. Platelets from these patients secreted greater quantities of ADP after stimulation by epinephrine than did SPD platelets with comparable ADP deficiencies and absent second-phase aggregation, and were more sensitive than both other SPD platelets and normal platelets to the aggregating effects of low concentrations of ADP. Epinephrine-induced secondary aggregation was also associated with measurable, though less than normal, MDA formation in these patients' platelets, whereas no MDA formation occurred in SPD platelets with impaired epinephrine responses. CP/CPK did not inhibit epinephrine-induced responses in the SPD patients showing biphasic aggregation, whereas these responses in normal platelets were inhibited only with higher levels of CP/CPK than those required for inhibition of the responses to exogenous ADP. These findings suggest that secondary aggregation responses may be mediated by both prostaglandin endoperoxide production and secreted ADP, and are consistent with the possibility that such mediation is primarily an intracellular process.

Keywords

Biphasic aggregation - Storage pool deficiency - Platelet ADP

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References

References
1 Mustard JF, Packham MA. Factors influencing platelet function: adhesion, release, and aggregation. Pharmacol Rev 1970; 22: 97-187
2 Holmsen H. Biochemistry of the platelet release reaction. Ciba Foundation Symposia 1975; 35 (new series) 175-205
3 Weiss HJ. Platelet physiology and abnormalities of platelet function. N Eng J Med 1975; 293: 531-541 and 580-588
4 Kaplan KL, Broekman MJ, Chernoff A, Lesznik GR, Drillings M. Platelet α-granule proteins: studies on release and subcellular localization. Blood 1979; 53: 604-618
5 Mustard JF, Perry DW, Kinlough-Rathbone RL, Packham MA. Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol 1975; 228: 1757-1765
6 Holmsen H, Salganicoff L, Fukami M. Platelet behavior and biochemistry. in Haemostasis: Biochemistry, Physiology and Pathology;. Ogsten D and BennettB. John Wiley and Sons, N Y: 1977. p. 239-319
7 Hasiam RJ. Role of adenosine diphosphate in the aggregation of human blood platelets by thrombin and by fatty acids. Nature 1964; 202: 765-768
8 Charo IF, Feinman RD, Detwiler TC. Interrelations of platelet aggregation and secretion. J Clin Invest 1977; 60: 866-873
9 Ardlie NG, Han P. Enzymatic basis for platelet aggregation and release: the significance of the "platelet atmosphere" and the relationship between platelet function and blood coagulation. Brit J Haematol 1974; 26: 331-356
10 Huzoor Akbar, Ardlie NG. Further evidence for the role of thrombin in the platelet release reaction caused by various agents, and the nature of biphasic platelet aggregation. Brit J Haematol 1978; 38: 381-390
11 MacFarlane DE, Walsh PN, Mills DC B, Holmsen H, Day HJ. The role of thrombin in ADP-induced platelet aggregation and release: a critical evaluation. Brit J Haematol 1975; 30: 457-463
12 Kaplan KL, Nossel HL, Drillings M, Lesznik G. Radioimmunoassay of platelet factor 4 and ß-thromboglobulin: development and application to studies of platelet release in relation to fibrinopeptide A generation. Brit J Haematol 1978; 39: 129-146
13 Marcus AJ. The role of lipids in platelet function: with particular reference to the arachidonic acid pathway. J Lipid Res 1978; 19: 793-826
14 Gerrard JM, Townsend D, Stoddard S, Witkop CJ, White JG. The influence of prostaglandin G₂ on platelet ultrastructure and platelet secretion. Am J Pathol 1977; 86: 99-116
15 Charo IF, Feinman RD, Detwiler TC, Smith JB, Ingerman CM, Silver MJ. Prostaglandin endoperoxides and thromboxane A₂ can induce platelet aggregation in the absence of secretion. Nature 1977; 269: 66-69
16 Claesson H, Malmsten C. On the interrelationship of prostaglandin endoperoxide G₂ and cyclic nucleotides in platelet function. Eur J Biochem 1977; 76: 277-284
17 Weiss HJ, Rogers J. Thrombocytopathia due to abnormalities in platelet release reaction-studies on six unrelated patients. Blood 1972; 39: 187-196
18 Holmsen H, Storm E, Day HJ. Determination of ATP and ADP in blood platelets: a modification of the firefly-luciferase assay for plasma. Anal Biochem 1972; 46: 489-501
19 MacFarlane DE, Gardner S, Lipson C, Mills DC B. Malondialdehyde production by platelets during secondary aggregation. Thromb and Haemost 1977; 38: 1002-1009
20 Lages B, Scrutton MC, Holmsen H. Secretion by gel-filtered human platelets; response of platelet Ca, Mg and K to secretory agents. J Lab Clin Med 1977; 90: 873-882
21 Weiss HJ, Witte LD, Kaplan KL, Lages BA, Chernoff A, Nossel HL, Goodman DeWS, Baumgartner HR. Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in α-granules, platelet factor 4, ß-thromboglobulin, and platelet-derived growth factor. Blood 1979; 54: 1296-1319
22 Lages B, Scrutton MC, Holmsen H, Day HJ, Weiss HJ. Metal ion contents of gel-filtered platelets from patients with storage pool disease. Blood 1975; 46: 119-130
23 Holmsen H, Setkowsky CA, Lages B, Day HJ, Weiss HJ, Scrutton MC. Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease. Blood 1975; 46: 131-142
24 French PC, Holmsen H, Stormorken H. Adenine nucleotide metabolism of blood platelets VII. ATPase: subcellular localization and behavior during the thrombin-platelet interaction. Biochem Biophys Acta 1970; 206: 438-448
25 Minkes MS, Joist JH, Needleman P. Arachidonic acid-induced platelet aggregation independent of ADP-release in a patient with a bleeding disorder due to platelet storage pool disease. Thromb Res 1979; 15: 169-179
26 Ingerman CM, Smith JB, Shapiro SS, Sedar A, Silver MJ. Hereditary abnormality of platelet aggregation attributable to nucleotide storage pool deficiency. Blood 1978; 52: 332-344
27 Kinlough-Rathbone RL, Reimers H-J, Mustard JF, Packham MA. Sodium arachidonate can induce platelet shape change and aggregation which are independent of the release reaction. Science 1976; 192: 1011-1012
28 Packham MA, Kinlough-Rathbone RL, Reimers H-J, Scott S, Mustard JF. Mechanisms of platelet aggregation independent of adenosine diphosphate. in Silver MJ, Smith JB, Loesis JJ. Prostaglandins in Hematology, New York, Spectrum: 1977. pp. 247-276
29 Kinlough-Rathbone RL, Packham MA, Mustard JF. Synergism between platelet aggregating agents: the role of prostaglandin endoperoxides and thromboxane A₂ . Circulation 1976; 54 [Suppl. 2] 146
30 Broekman MJ, Handin RI, Cohen P. Distribution of fibrinogen and platelet factor 4 and XIII in subcellular fractions of human platelets. Brit J Haematol 1975; 31: 51-55