Erik Stoffersen

Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis

Unlike arachidonic acid (eicosatetraenoic acid, C20:4omega-6, A.A.), eicosapentaenoic acid (C20:5omega-3, E.P.A.) does not induce platelet aggregation in human platelet-rich plasma (P.R.P.), probably because of the formation of thromboxane A3 (T.X.A3) which does not have platelet aggregating properties. Moreover, E.P.A., like A.A., can be utilised by the vessel wall to make an anti-aggregating substance, probably a delta17-prostacyclin (P.G.I3). This finding suggests that, in vivo, high levels of E.P.A. and low levels of A.A. could lead to an antithrombotic state in which an active P.G.I3 and a non-active T.X.A3 are formed. Eskimos have high levels of E.P.A. and low levels of A.A. and they also have a low incidence of myocardial infarction and a tendency to bleed. It is possible that dietary enrichment with E.P.A. will protect against thrombosis.

On the inhibitory effect of albumin on platelet aggregation

Abstract Thrombin induced aggregation of washed aspirin and non-aspirin treated platelets was found to be inhibited by albumin, the inhibitory effect was most pronounced in non-aspirin treated platelets. The threshold concentration of ADP necessary to induce a secondary wave of platelet aggregation was found to be lower in 5 patients with a nephrotic syndrome than in 5 age and sex matched controls. When albumin was added to the blood samples, these threshold concentrations rose to above normal levels. It is suggested that hypoalbuminemia plays a role in the hypercoagulability seen in patients with a nephrotic syndrome and that these patients with severe hypoalbuminemia should be treated with vitamin K antagonists and anti-platelet aggregatory drugs.

Acetylsalicylic acid, bleeding time and age

Abstract Bleeding time was determined before (BTo) and after ingestion of 1 (BT1), 3.5 (BT3.5) and 25 (BT25) mg acetyl-salicylic acid (ASA)/kg in 50 men and 20 women of varying age. It was found that BT falls with age in men maybe due to a reduction in PGI2/TXA2 ratio. The changes in bleeding time could be abolished by ASA ingestion. The index Ia = (BT25-BTo)/BT25 increased with age in both men and women. While all age groups increased bleeding time upon administration of a small dose of aspirin only in the younger age groups did the bleeding time thereafter fall significantly, when the dose was increased to 25 mg/kg.

Hydrocortisone inhibits platelet prostaglandin and endothelial prostacyclin production

Summary Hydrocortisone (HC) at concentrations above 0.5 mg/ml inhibited both ADP and thrombin induced aggregation as well as malondialdehyde (MDA) formation induced by thrombin in normal platelets, while even higher concentrations only produced minimal inhibition of aggregation of platelets with blocked prostaglandin synthesis. The inhibition produced by HC in normal platelets could easily be overcome by addition of small amounts of arachidonic acid and HC did not inhibit arachidonic acid induced platelet MDA formation. HC at concentrations above 0.4 mg/ml almost completely inhibited spontaneous prostacyclin release from pieces of rat aortic tissue. This inhibition could easily be overcome by addition of exogenous arachidonic acid. These results indicate an inhibitory effect of HC on the phospholipase enzymes in both platelets and endothelial cells.

Prostacyclin (PGI2) and the effect of phosphodiesterase inhibitors on platelet aggregation

Summary It can be expected, that phosphodiesterase inhibitors potentiat and prolong the effect of prostacyclin (PGI 2 ) on platelet aggregation, since PGI 2 is believed to be a stimulator of adenylcyclase. The effect of PGI 2 on thrombin induced aggregation of washed, acetylated platelets was greatly prolonged by the phosphodiesterase inhibitors theophylline and dipyridamole. A potentiating effect was also demonstrated.

C3 polymorphism in Greenland Eskimos.

The C3 phenotypes were determined by high-voltage agarose gel electrophoresis in 125 Greenland Eskimos. The frequency of the C3F gene was significantly lower than in a control group

Platelet dysfunction in patients with vitamin B12 deficiency.

10 cases of pernicious anaemia are reported in which 6 had abnormal aggregation with epinephrine, 3 with fibrinogen, 2 with ADP, and 2 with ristocetin. 5 patients had thrombocytopenia and 3 of these had a prolongation of the bleeding time. These abnormalities were normalized after vitamin B12 treatment. After treatment, platelet size changed toward a smaller diameter, but platelet size, however, was not significantly different from the normal platelet size distribution.

Antithrombin III and dietary intake of polyunsaturated fatty acids

Immunoreactive antithrombin III and antithrombin III activity was found to be significantly higher in 81 Greenland Eskimos than in 50 Caucasian Danes. Sixteen Eskimos who had emigrated to Denmark had significantly lower immunoreactive antithrombin III levels than the Greenland Eskimos, though higher than the Danes. The immunoreactive antithrombin III increased significantly while the increase in antithrombin III activity was insignificant in 20 male Caucasian Danes upon 3 weeks supplementation of the diet with 10 ml daily of a cod liver oil concentrate. The high antithrombin III level in the Eskimos may at least partly be a consequence of a high dietary intake of polyunsaturated fatty acids. It may also play a role for the low incidence of thrombosis apparently found in Greenland Eskimos.

Antithrombin III in Uremia

Antithrombin III (AT-III) was measured immunologically in 20 uremic patients on maintenance hemodialysis and in 10 non-dialysed uremic patients. The dialysed patients had slightly elevated AT-III levels. The non-dialysed patients had significantly elevated AT-III levels. A negative correlation was found between AT-III and serum creatinine and between AT-III and serum albumin. AT-III did not correlate to the heparin amount required for hemodialysis. A negative correlation was found between the heparin requirement and serum albumin. It is suggested, that serum albumin might facilitate the action of AT-III and heparin. It is also suggested, that AT-III levels may be high in active renal disease, decreasing as uremia advances.

C3 Polymorphism in Patients with Chronic Uremia

The C3 polymorphism phenotypes were determined by high-voltage agarose gel electrophoresis in 83 patients with chronic uremia on maintenance hemodialysis. In 45 patients with chronic pyelonephritis, the frequency of C3F and C3FS was significantly lower than in 38 patients with chronic glomerulonephritis and in a large control group.