Edward Genton

Platelet Function Studies in Coronary Artery Disease

Platelets have been implicated and abnormal platelet function proposed in the pathogenesis of coronary artery disease (CAD). This investigation examines platelet function in men with stable, arteriographically defined CAD and correlates results with lipid pattern, history of angina or myocardial infarction and smoking habits. Platelet survival (51Chromium method), adhesiveness, and aggregation were measured in 21 men with CAD. Twelve patients had Type IV hyperlipoproteinemia and nine patients had normal lipoprotein level. Eighteen had angina and 13 had had infarction.The average platelet survival for the total group was normal (6.8 ± 0.24 days, avg ± SEM), but survival was shortened in 11 and normal in ten. There was no significant difference between: (1) patients with hyperlipoproteinemia (6.8 ± 0.30 days) and those with normal lipoproteins (6.9 ± 0.41 days); (2) patients with angina (6.8 ± 0.28 days) and without (6.6 ± 0.26 days); (3) patients with infarction (6.8 ± 0.26 days); and without (6.8 ± 0.50 days); (4) patients with varying patterns of arteriographic involvement; and (5) with varying smoking histories. Adhesiveness was normal in all. Aggregation was normal in 14. Neither adhesiveness nor aggregation correlated with platelet survival or defined the subgroups of CAD. Results suggest an abnormal short platelet survival frequently occurs in patients with CAD, but there is no discernible difference in platelet survival among the various clinical subgroups of CAD.

History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease

The history and physical examination were assessed in 215 patients with acute pulmonary embolism uncomplicated by preexisting cardiac or pulmonary disease. The patients had been included in the Urokinase Pulmonary Embolism Trial or the Urokinase-Streptokinase Embolism Trial. Presenting syndromes were (1) circulatory collapse with shock (10 percent) or syncope (9 percent); (2) pulmonary infarction with hemoptysis (25 percent) or pleuritic pain and no hemoptysis (41 percent); (3) uncomplicated embolism characterized by dyspnea (12 percent) or nonpleuritic pain usually with tachypnea (3 percent) or deep venous thrombosis with tachypnea (0.5 percent). The most frequent symptoms were dyspnea (84 percent), pleuritic pain (74 percent), apprehension (63 percent) and cough (50 percent). Hemoptysis occurred in only 28 percent. Dyspnea, hemoptysis or pleuritic pain occurred separately or in combination in 94 percent. All three occurred in only 22 percent. The most frequent signs were tachypnea (respiration ate 20/min or more) (85 percent), tachycardia (heart rate 100 beats/min or more) (58 percent), accentuated pulmonary component of the second heart sound (57 percent) and rales (56 percent). Signs of deep venous thrombosis were present in only 41 percent and a pleural friction rub was present in only 18 percent. Either dyspnea or tachypnea occurred in 96 percent. Dyspnea, tachypnea or deep venous thrombosis occurred in 99 percent. As a group, the identified clinical manifestations, although nonspecific, are strongly suggestive of acute pulmonary embolism. Conversely, acute pulmonary embolism was rarely identified in the absence of dyspnea, tachypnea or deep venous thrombosis.

Altered Platelet Function in Patients with Prosthetic Mitral Valves Effects of Sulfinpyrazone Therapy

Platelet survival time and platelet adhesiveness and aggregation were examined in 16 patients with prosthetic mitral valves. Subsequently, nine patients were treated with sulfinpyrazone in doses of 400 mg and 800 mg/day, and the studies were repeated after a treatment period of 5 to 8 weeks. 51Chromium survival time was shortened in 15 of 16 patients, and the mean value for the entire group was 5.49 ± 0.23 days (normal, 6.73 ± 0.21 days; P < 0.001). Mean platelet adhesiveness in glass bead columns was 53 ± 5% (normal, 30 to 60%). Platelet aggregation (turbidometric technic of Born) was normal. Treatment with 400 mg of sulfinpyrazone daily reduced platelet adhesiveness to 40 ± 5% (P < 0.05), but effected no change in platelet survival time or platelet aggregation. Therapy with 800 mg of sulfinpyrazone daily corrected platelet survival time to normal, 6.68 ± 0.57 days (P < 0.01), but it produced no further decrease in adhesiveness and no change in aggregation. It is concluded that platelet abnormalities regularly occur in patients with prosthetic mitral valves and may contribute to thromboembolism in this group. Platelet survival time is a more sensitive measure of altered platelet kinetics than platelet adhesiveness or platelet aggregation. Therapy with 800 mg of sulfinpyrazone per day corrects demonstrated abnormalities and may be useful for prevention of thromboembolism in patients with prosthetic mitral valves.

The spectrum of Ebstein's anomaly☆

Abstract Seventeen cases of Ebsteins anomaly have been presented; the diagnosis was confirmed by autopsy in 6, and made on clinical grounds in the other 11. The series includes the youngest patient dying of the lesion, a stillborn infant, and the fifth oldest patient thus far reported (64 years). The features associated with this condition are presented as found in this series and compared with those observed by previous authors. It is emphasized that the history and physical and laboratory examinations are sufficiently characteristic to allow the diagnosis to be made with a high degree of accuracy in the majority of cases. As with any condition, the entity is represented by a spectrum in every regard; and as to the cases on either end of the spectrum, one must combine a high degree of suspicion with a knowledge of the spectrum, else the true diagnosis will only be made at the autopsy table or at the time of ill-advised operative procedures. Particular emphasis is given to the group of patients over 50 years of age who represent about 5 per cent of the patients with Ebsteins anomaly. They may be, and in fact generally are, unusual in all respects when compared to the “typical” case. Comments are made on the natural history of the young patient, and it is urged that extensive diagnostic or surgical procedures be delayed until signs of deterioration appear, since tolerance of such procedures may be poor. The etiology of the anomaly remains obscure, and a practical and satisfactory therapeutic approach remains for the future.

Urokinase therapy in pulmonary thromboembolism

Abstract Thirteen patients with angiographically confirmed pulmonary thromboembolism received thrombolytic therapy with urokinase for 8 to 12 hours. Cardiac catheterization lung scan and angiograms prior to and within 6 to 18 hours after completion of therapy were used to assess results. Five patients with acute symptoms had marked improvement in clinical and laboratory parameters. Of 4 patients with sub-acute symptoms, all had clinical improvement but objective studies were less changed than in the acute group. Three chronic patients were treated and failed to demonstrate significant change in any parameter. One patient with acute symptoms died and was found to have only old organized, adherent emboli, pointing out the difficulty in predicting the characteristics of emboli by presently available methods. The lytic state was tolerated well by even severely ill patients and bleeding into soft tissue represented the only recognized complication. Further controlled observations of this form of therapy are considered justified in patients with acute massive pulmonary embolism.

Platelet survival time following aortic valve replacement.

Thromboembolism continues to complicate the course of patients following aortic valve replacement. In patients with prosthetic and homograft mitral valves, platelet survival time has been shown to correlate with occurrence of thromboembolism. This study extends these observations to patients with aortic valve disease. Platelet survival time was measured (by the chromium-51 method) in 73 patients with aortic valve disease. Eighteen patients were studied preoperatively and had platelet survival times of 3.4 ± 0.14 days (mean ± standard error of the mean), almost the same as normal (3.7 ± 0.4 days). Platelet survival time was shortened (P < 0.001) following aortic valve replacement with Starr-Edwards prostheses — Model 1000: 2.5 ± 13 days (N = 6); Model 1200-1260: 3.0 ± 0.10 (N = 14); Model 2300-2320: 3.0 ± 0.15 days (N = 9) — and with stented aortic homografts: 3.0 ± 0.10 days (N = 16). Platelet survival time was normal following aortic valve replacement in patients with directly sewn aortic homografts 3.7 days ± 0.24 days (N = 10). Eleven patients with Starr-Edwards prostheses had a history of thromboembolism and all also showed shortened platelet survival time (2.7 ± 0.12 days, P < 0.001), a measurement which was significantly different (P < 0.01) from the 18 patients with Starr-Edwards prostheses and no thromboembolism (3.0 ± 0.09 days). Platelet suppressant therapy prolonged platelet survival in eight patients with Starr-Edwards devices, thromboembolism, and shortened platelet survival time. These results suggest that insertion of Starr-Edwards valves and stented aortic homografts alter platelet survival time but that direct homografts do not. A correlation between occurrence of thromboembolism after aortic valve replacement and shortened platelet survival time has been shown.

Platelet survival time in patients with hypoxemia and pulmonary hypertension.

Platelet survival time (autologous labeling with 85chromium) was measured in 63 patients in order to evaluate the role of platelets in the thromboembolic complications of patients with hypoxemia and pulmonary hypertension. Thirty-eight of these patients had chronic obstructive airways disease; 13, primary pulmonary hypertension; seven, recurrent pulmonary embolism; four, the Eisenmenger syndrome; and one, multiple pulmonary arteriovenous fistula. Forty-three patients were hypoxemic and 41 (95%) had shortened platelet survival. Platelet survival was weakly associated with arterial oxygen tension (r = 0.50), but not with the arterial carbon dioxide tension or the level of pulmonary artery pressure. Sulfinpyrazone lengthened platelet survival in 12 of 24 (50%) treated patients but this drug did not alter either arterial oxygen tension, arterial carbon dioxide tension, or pulmonary artery pressure. Our results suggest that hypoxemia is associated with shortened platelet survival time and that platelets may, therefore, be involved in the thromboembolic complications that develop in patients with hypoxemia.

Platelet survival in patients with a Beall valve. Relation to low incidence of thromboembolism.

Recent investigations demonstrating short platelet survival time in patients with prosthetic heart valves have suggested that platelets contribute to thromboembolism in this group. New prostheses have proved less thrombogenic than those previously employed, but platelet survival studies in patients with these valves are lacking. In this study, the Beall mitral prosthesis, known to be infrequently associated with thromboembolism, was used as a model, and platelet survival time and its relation to hemolysis, thrombosis and the surface area of the disc were determined in 9 patients. Platelet survival time was normal in 6 of 9 patients, and mean survival time (6.5 ± 0.29 days) did not differ significantly from normal (6.73 ± 0.21 days; P > 0.50). Platelet survival time was inversely related to increasing disc surface area but did not correlate with the presence or degree of hemolysis. The fact that platelet abnormalities were not demonstrable in patients with Beall valves may explain the low incidence of thromboembolism in this group. Platelet survival studies may be useful for determining the thrombogenic potential of valvular prostheses and for evaluating newer prosthetic materials and designs.

Procainamide-induced pericardial effusion

Abstract A case of hemodynamically significant pericardial effusion due to a procainamide-induced SLE-like syndrome is reported. This case emphasizes that the acute pleuropericardial syndrome seen after procainamide therapy is potentially dangerous. Close follow-up of patients taking procainamide is warranted.

Thrombolytic Agents: A Perspective

Excerpt The feasibility of dissolving intravascular fibrin deposits by enzymatic means (thrombolysis) appears established, and the prospect of clinical use of this method has stimulated efforts to ...