Jon Dale

Prevention of arterial thromboembolism with acetylsalicylic acid: A controlled clinical study in patients with aortic ball valves

Prevention of arterial thromboembolism with acetylsalicylic acid (ASA) was studied in 148 patients with single Starr-Edwards aortic ball-valve prostheses. These patients are suitable for such a study because they have a high incidence of arterial emboli derived mainly from thrombi formed on the valves. They were given either 1 Gm. of ASA daily or placebo in combination with anticoagulants, and were observed for 2 years. Only two emboli occurred in patients receiving ASA, none of them severe. In the placebo group 12 thromboembolic episodes were diagnosed in 10 patients, and three with cerebral emboli died; in one a subdural hematoma unrelated to the embolus was found. In addition, one fatal and the one nonfatal intracranial bleeding occurred in each group, whereas gastrointestinal complications were seen more frequently in patients taking ASA. It is concluded that ASA combined with anticoagulants offered a significantly better protection against arterial thromboembolism than did anticoagulant therapy alone.

The effects of nifedipine, a calcium antagonist, on platelet function

Platelet function was studied before and 1 hour after ingestion of 20 mg nifedipine, a new calcium antagonist, in 20 patients with coronary heart disease. Platelet counts remained unchanged. Platelet adhesiveness, measured as retention in glass bead columns with Hellems method for native blood, did not drop significantly eigher when 0.9 or 3.6 ml of blood was used. Platelet aggregation, which is dependent on extracellular calcium, was induced in citrated platelet-rich plasma. The mean maximal rate of primary aggregation, initiated with three different concentrations of adenosine diphosphate, was reduced by 20% to 26%. The rate of irreversible collagen-induced aggregation was on average 23% lower after nifedipine. The mean bleeding time was 36 seconds, or 12%, longer after ingestion of the drug. The moderate, but significant reduction of platelet aggregation and prolongation of the bleeding time by nifedipine may be mediated through inhibition of calcium transport across the platelet membrane.

Bleeding during acetylsalicylic acid and anticoagulant therapy in patients with reduced platelet reactivity after aortic valve replacement

Abstract Bleeding complications were evaluated in 148 patients with single Starr-Edwards aortic ball valve prostheses in a study designed to prevent arterial thromboembolism. They received either one gm. of ASA daily or placebo in combination with anticoagulants, and were observed for two years. Only two embolic episodes occurred in patients on combined therapy, as compared to 12 episodes in the placebo group. Fifteen bleeding complications developed in patients receiving ASA, seven during the first month. Two patients suffered intracranial hemorrhage and one died, the others recovered completely. Six episodes occurred in patients on anticoagulants alone; three intracranial complications caused two deaths. The higher incidence of bleeding induced by the combined therapy was entirely due to gastrointestinal hemorrhage, indicating that irritation of mucosa was important in addition to the ASA-induced inhibition of hemostasis. The intensity of anticoagulation correlated significantly with the occurrence of bleeding, and severe blood loss developed only after intensive therapy. This raises the question whether a slightly less intensive anticoagulation in combination with ASA will maintain a satisfactory antithrombotic effect at a lowered risk of bleeding. Platelet adhesiveness, which is partly responsible for primary hemostasis, was reduced in the ball valve patients, and more in those who bled than in the others. It is concluded that the higher incidence of gastrointestinal bleeding in patients who received ASA and anticoagulants than in those on anticoagulants alone was acceptable when compared to the antithrombotic effect achieved with the combined treatment.

Erythrocyte Destruction in Different Types of Starr-Edwards Aortic Ball Valves

Increased destruction of red blood cells follows the insertion of ball valves into the heart in most cases. Usually, hemolysis is slight, but in some patients uncompensated hemolytic anemia develops. To study the influence on hemolysis of the mechanical properties of the prostheses, the degree of erythrocyte destruction was evaluated in patients with Starr-Edwards aortic prostheses of different types and size.Fifty-six patients with Starr-Edwards aortic ball valves were examined; 13 had prostheses of the 1200 series with silastic rubber balls, and 43 had valves of the 2300 series with hollow Stellite (metallic) balls. Thirty-one patients had valves with an orifice area of 1.8 cm2 or less; the others had larger-sized valves.The degree of hemolysis was predicted from the serum lactic dehydrogenase activity, which has previously been shown to correlate well with the red blood cell survival. The half-life of 51Cr-labelled red cells was also determined in 16 cases.Hemolysis was significantly higher in patients with Stellite ball valves than in those with silastic rubber ball valves, and red blood cell destruction was more pronounced in patients with small prostheses than in patients with larger valves. Hemolysis was not higher in three patients with paravalvular leakage than in patients with competent prostheses. Valve type and size seem to be the most important factors in producing hemolysis.

Effects of a selective thromboxane synthetase inhibitor, dazoxiben, and of acetylsalicylic acid on myocardial ischemia in patients with coronary artery disease

Thromboxane A2 (TxA2) may aggravate myocardial ischemia by inducing vasoconstriction and platelet aggregation in small coronary vessels, whereas prostacyclin (PGI2) counteracts these effects. Acetylsalicylic acid (ASA) inhibits the formation of TxA2 as well as PGI2, whereas dazoxiben, a thromboxane synthetase inhibitor, reduces TxA2 formation selectively. In 25 patients with coronary artery disease, 2 identical atrial pacing stress tests were performed: before and after the administration of dazoxiben (200 mg) in 15 patients and before and after ASA (250 mg) in 10. The ischemic response, quantified by coronary sinus and aortic lactate levels and by ST depression, was significantly reduced after administration of dazoxiben (p less than 0.02) but not after ASA. Heart rate at rest, myocardial extraction of free fatty acids and the arteriovenous oxygen difference was unaffected by medication. Both drugs reduced TxB2 levels to the same extent, whereas collagen-induced aggregation was more reduced after ASA than after dazoxiben. The effect of dazoxiben on ischemia was probably a result of inhibited TxA2 and preserved PGI2 production, which increased blood flow to ischemic regions.

Arterial thromboembolic complications in patients with Björk-Shiley and Lillehei-Kaster aortic disc valve prostheses.

Arterial thromboembolic complications were studied in 196 patients who had either a single Björk-Shiley or Lillehei-Kaster aortic disc valve implanted. Eight patients suffered from such complications in the course of the first postoperative month and three of them died, two from myocardial infarction and one from cerebral embolism. Nineteen late thromboembolic complications developed in 18 of the 164 patients who survived the postoperative period, the incidence bein 5.9 episodes per 100 patients per year. The two valve types wer found to be equallly thrombogenic, and the rate was not lower than that in patients with Starr-Edwards aortic ball valves of series 2,300 previously studied. Particularly serious was valve malfunction caused by thrombi that limited the movement of the discs. Early recognition of this condition is essential, because the only effective therapy is removal of the thrombus. Three patients with a Björk-Shiley and one with a Lillehei-Kaster valve suffered this complecation and two died, while cerebral embolism caused a third late death. Two of the three patients who had not received anticoagulants developed thromboembolic complications, while most episodes occurred in spite of well-maintained anti-coagulant treatment. It is concluded that arterial thromboembolic complications remain a considerable problem also after aortic disc valve implantation, and that thrombotic valve malfunction is particularly serious and requires special attention.

Arterial thromboembolic complications in patients with Starr-Edwards aortic ball valve prostheses

Aterial thromboembolic complications were studied in 253 patients who had a single aortic Starr-Edwards ball valve implanted. During the first postoperative month, six patients died from myocardial infarction, one was reoperated because of leakage caused by thrombus on the valve, and five others suffered six thromboembolic episodes. Forty-six late thromboembolic complications occurred in 40 of the 216 patients who survived the postoperative period. Seven died, four from cerebral emboli and three from myocardial infarction. The late incidence was 7 episodes per 100 patients per year. Valves of series 1200 carried a significantly higher risk of arterial thromboembolism than did those of series 2300, and most episodes occurred in patients with cell controlled anticoagulant treatment. The incidence was not influenced by time since operation, continuous arrhythmia, concomitant mitral valve disease, heart size, or the degree of intravascular hemolysis. It is concluded that arterial thromboembolic complications represent a major threat to patients with aortic ball valves even several years after operation and in spite of intense anticoagulant therapy.

Effects of dipyridamole and acetylsalicylic acid on platelet functions in patients with aortic ball-valve prostheses

The effects of dipyridamole and ASA on platelet functions were studied in patients with aortic ball-valve prostheses. Before ingestion, platelet adhesiveness was markedly reduced and platelet survival time slightly, but insignificantly shortened. ASA prolonged the bleeding time, reduced collagen-induced platelet aggregation, and inhibited secondary aggregation initiated by adrenalin. Similar effects were obtained with 2 Gm. of ASA alone as with 1 Gm. daily in combination with 225 mg. of dipyridamole. Platelet adhesiveness remained low. Depyridamole alone, 375 mg. daily, did not influence any of these parameters. The mean platelet half-life was prolonged from 3.52 to 3.72 days by each drug and to 4 days by the combined treatment. None of the differences was, however, statistically significant. A clinical study with ASA has been started in a larger series of patients to evaluate the effect on arterial thromboembolism.

Platelet functions in patients with aortic ball valves

Platelet functions were studied in normal subjects and patients with single Staff-Edwards aortic ball valves of series 1200 and 2300. The most pronounced changes were found in platelet adhesiveness, measured with Hellems modified method. The mean percentage of adhesive platelets was reduced from 71.8 in normal subjects to 50.9 in patients with valve type 1200 and to 27.2 in those with type 2300. An inverse correlation was found between platelet adhesiveness and the degree of intravascular hemolysis, as reflected by serum LDH levels. The mean bleeding time was significantly prolonged in patients with valve 2300, and the individual values correlated inversely to the adhesiveness. The mean values of platelet counts, or irreversible aggregation induced by collagen or epinephrine, and of platelet survival were all moderately-but significantly-reduced as compared to normal. The most important mechanism behind the disturbed platelet reactivity is probably mechanical damage of the platelets by the valve, whereas refractoriness of platelets toward ADP liberated from red cells as well as consumption of adhesive platelets by thrombus formation is thought to have limited influence on platelet behavior. Platelet function was altered to the same extent in patients with a history of arterial thromboembolic complications as in those without. The disturbed platelet reactivity may predispose to bleeding, but may also offer some protection against arterial thromboembolism.

False suspicion of coronary heart disease: a 7 year follow-up study of 36 apparently healthy middle-aged men.

Latent coronary heart disease was suspected in 115 of 2014 apparently healthy middle-aged men after a baseline cardiovascular survey. One hundred five of these men underwent angiography and 36 were found to have normal coronary arteries (group 1). A 7 year follow-up survey revealed that: (1) three had died of sudden cardiac death, (2) four had received a diagnosis of cardiomyopathy, (3) one had developed aortic dilatation/aortic regurgitation since the baseline survey, (4) they all had a significantly more rapid decline in their physical performance and maximal heart rate levels from the time of the baseline survey to follow-up than did randomly selected normal controls (group 2), and (5) thallium study results were normal in both groups (27 and 26 patients), but technetium ventriculography revealed a subnormal increase in ejection fraction during exercise (less than 5% units) in 14 of 27 group 1 subjects and in 4 of 26 group 2 subjects. Thus, incipient heart disease may be present in subjects in whom coronary angiographic examination has removed a previous suspicion of coronary heart disease.