Marion Dugdale

Platelet abnormalities in ischemic heart disease.

Forty-seven patients with well documented ischemic heart disease were studied with tests designed to detect “hypercoagulability”: platelet count, platelet aggregation response to dilutions of adenosine diphosphate (ADP) and collagen, determination of fibrinolytic activity and thromboelastography. No abnormalities were found in the thromboelastograms, fibrinolytic activity, platelet count or response of platelets to ADP. Most patients demonstrated abnormal platelet reactivity to collagen soon after myocardial infarction. Five patients (but none of the normal subjects or patients with nonischemic heart disease) had a persistent marked abnormality, with platelet hyperresponsiveness to collagen still present 10 to 16 months after infarction. These five patients differed from others with myocardial infarction by being younger, having a paucity of the recognized risk factors and having either normal coronary arteriograms or single obstructive arterial lesions. Each had significantly decreased 51 chromium platelet survival time many months after infarction, during an asymptomatic period. One of eight patients with chest pain of the anginal type and normal coronary arteriograms showed similar platelet hyperaggregability. We suggest that some patients with ischemic heart disease, perhaps as many as 10 percent, have chronic abnormal platelet function, best detected by the platelet aggregation response to dilutions of collagen and by platelet survival studies. This may be a primary abnormality in patients with ischemic heart disease whose arteriograms show no advanced coronary atherosclerotic obstructive lesions.

Hormonal contraception and thromboembolic disease: Effects of the oral contraceptives on hemostatic mechanisms: A review of the literature☆

Abstract Clinical and epidemiological data indicate that the oral contraceptives are thrombogenic. The important papers concerning the effects of oral contraceptives on hemostatic mechanisms were reviewed. This report summarizes the effects of oral contraceptives on: (1) platelet number and function; (2) tests of coagulation; (3) tests of specific clotting factors; and (4) tests of fibrinolysis and compares them with the findings in pregnancy, and in individuals taking estrogens or progestogens alone. Oral contraceptives, or estrogens alone, lead to an increase in platelet adhesiveness and aggregability. The oral contraceptives also enhance coagulability but induce little change in the fibrinolytic system. Progestogens alone enhance fibrinolysis without altering platelet function or coagulation. Pregnancy enhances coagulation and depresses fibrinolysis. It increases platelet reactivity but to a less extent than does the use of the hormonal contraceptives. Tentatively we conclude that the thrombogenic potential of the oral contraceptives appears to reside in the estrogenic components and may be due to their effect on platelet function rather than their effect on coagulation. Addition of this effect to the hormonally-induced vascular lesions and stasis may encourage thrombus formation. Further study of the effect of these hormones as it pertains to intravascular clotting is needed.

Cerebrovascular Diseases Associated with the Use of Oral Contraceptives: A Review of the English-Language Literature

This review summarizes clinical reports pathologic reports epidemiologic studies and mortality trends of cerebrovascular disease in oral contraceptive users in an attempt to determine possible associations and to discover biologic mechanisms of this disease. Clinical reports of cerebrovascular disease in otherwise healthy young women are increasing. Most of these reports show an elevated proportion of oral contraceptive use among cases. These young women resemble those in studies of cerebrovascular disease patients who were taking the pill in often aving a history of vascular headaches no atherogenic lesions but lesions usually confined to intracranial arteries. About one fourth of these women had vertebrobasilar artery distribution stroke. Sparse pathologic data suggest multiple fibrinoid degeneration and hemorrhagic infarction in small arteries prior to thrombosis of a major cerebral artery. Mortality statistics for this disease (ICD 332 334) are not increasing but this may reflect a decrease in cerebrovascular deaths related to pregnancy which masks an increase in death among pill users. Several case-controlled retrospective studies estimate about a 6-fold increase in relative risk of cerebral thrombosis for pill users.

Relationships between the chemical constitution of carbamoylpiperidines and related compounds, and their inhibition of ADP-induced human blood platelet aggregation

Abstract The effect of a series of carbamoylpiperidines and related compounds on ADP-induced human blood platelet aggregation was studied. The systematic and gradual changes in the chemical structure of these synthetic entities disclosed highly significant relationships between molecular constitution, physicochemical properties and biodynamic effects, and yielded data suggesting -for the first time- platelet membrane inhibitory target sites spaced at 8 A. Inhibitory potencies culminated with a compound active at 5 μM concentrations; the latter and a number of other derivatives were much more effective than aspirin.

Effects of ethanol and of other factors on ADP-induced aggregation of human blood platelets in vitro

Abstract In studying the inhibition of ADP-induced human platelet aggregation, it became necessary to ascertain exacting conditions for interpreting biodynamic responses generated by even minor alterations in molecular constitution. The influence of ethanol was evaluated along with the effect of post-venipuncture and incubation time. The experimental conditions were studied in the absence as well as in the presence of platelet-aggregationinhibitor aspirin.

Hemorrhagic studies with severe hemodilution in profound hypothermia and cardiac arrest

DURING THE EARLY 1960% profound hypothermia with cardiac arrest gained popularity in neurosurgery as an adjunct to the surgical treatment of intracranial aneurysms. The surgeon had the advantage of a wide operative exposure in a bloodless operative field. The techniques, physiology, and metabolic changes of profound hypothermia were described by several authorities [ 1, 3, 5, 7, 8, 11-141. During the late 1960’s, aneurysm surgery became more refined and these improvements along with the technical, metabolic and hemorrhagic problems encountered with profound hypothermia and cardiac arrest led to the general disuse of this procedure in neurosurgery. Our interests in profound hypothermia with cardiac arrest as an adjunct to the surgical treatment of certain intracranial vascular lesions has continued, and we agree wit’h Sundt and coworkers who recently stated “. . . there are aneurysms presently considered inoperable that might be approached utilizing profound hypothermia . . . [and] . . . it is suggested that the approach, virtually abandoned a