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Abnormal platelet response to thromboxane A2. 1981

K K Wu, and G C Le Breton, and H H Tai, and Y C Chen

To determine the pathogenetic mechanism of a hereditary primary platelet release disorder, arachidonic acid metabolism via the cyclooxygenase pathway was investigated. The propositus' platelets exhibited defective release reaction and second-wave aggregation when stimulated by sodium arachidonate or U46619, a thromboxane A2 (TXA2) agonist. The lack of platelet response to U46619 suggested that the defect was beyond the thromboxane synthetase level. Furthermore, thromboxane B2 (TXB2) formation in the propositus' platelets (558.52 ng/10(8) platelets) was within the normal range (574.29 +/- SD 27.39 ng/10(8) platelets) and TXA2 formation appeared to be adequate for aggregating normal platelets. The results were indicative of an abnormal platelet response to TXA2. Failure of the propositus' platelets to aggregate in response to TXA2 formed in normal platelet-rich plasma induced by arachidonate confirmed this notion. To gain further insight, platelet cyclic (c) AMP content was determined. Prostacyclin induced a significant elevation of the propositus' platelet cAMP level comparable to normal values. U46619 suppressed prostaglandin I2-induced cAMP elevation in normal subjects but had no such effect in the patient. We conclude that the primary release disorder observed in this kindred is due to an abnormal platelet respnse to TXA2 possibly because of TXA2/PGH2 receptor abnormalities.

UI MeSH Term Description Entries
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D011450 Prostaglandin Endoperoxides, Synthetic Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds. Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D001791 Blood Platelet Disorders Disorders caused by abnormalities in platelet count or function. Thrombocytopathy,Blood Platelet Disorder,Disorder, Blood Platelet,Disorders, Blood Platelet,Platelet Disorder, Blood,Platelet Disorders, Blood,Thrombocytopathies
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001095 Arachidonic Acids Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic

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