Göran Göransson

Impairment of Primary Hemostasis and Platelet Function after Alcohol Ingestion in Man

The effect of alcohol ingestion on primary hemostasis was investigated in fasting healthy humans. Primary hemostasis was measured with the template bleeding time and platelet aggregation assayed with the turbidometric method. Blood was collected to study coagulation and fibrinolysis. 1 h after ingestion of 2 ml/kg body weight of 40% alcohol the plasma alcohol concentration was 19.3 +/- 1.6 mmol/l. At this time there was a significant prolongation of the bleeding time accompanied by an impairment of platelet responsiveness to both collagen and ADP. A prolongation of the bleeding time and impairment of platelet function was also found 2 h after alcohol ingestion. Ingestion of this amount of alcohol did not affect parameters of coagulation or fibrinolysis. The data indicate that primary hemostasis is impaired in man after ingestion of moderate amounts of alcohol. This may explain the favorable effect of moderate alcohol consumption on ischemic heart disease but indicates an increased risk for patients with bleeding.

COMPARATIVE-EVALUATION OF LOCAL HEMOSTATIC AGENTS IN EXPERIMENTAL LIVER TRAUMA - A STUDY IN THE RAT

The efficacy of gelatin foam, oxidized regenerated cellulose, collagen fleece, and microcrystalline collagen as hemostatic agents was tested after standardized liver trauma in the rat. Experiments were divided into two series. In the first series all the above local hemostatic agents were tested on normal animals. Animals in which surgical gauze was applied to the traumatized surface served as controls. Nontreated animals bled profusely. Microcrystalline collagen and collagen fleece were more effective than gauze. In the second series collagen preparations were tested on animals with hemostatic disorders caused by administration of acetylsalicylic acid, ethanol intoxication, or infusion of bensylpenicillin. Collagen preparations were as effective as gauze in diminishing bleeding time and blood loss after liver trauma.

Effect of Acute Ethanol Intoxication on Primary Haemostasis, Coagulation Factors and Fibrinolytic Activity

The effect of ethanol intoxication on haemostasis was studied by transection of mesenteric microvessels and liver resection in the rat. Plasma concentrations of alcohol were within the range of those found in ethanol intoxication in man. Bleeding time and blood loss were increased 1 h after ethanol administration, regardless of the utilized technique. A significant positive correlation existed between bleeding time following liver resection and bleeding time after simultaneous transection of a mesenteric arteriole and venule. Coagulation mechanisms, assayed by whole blood clotting time, APT time, one-stage prothrombin time, recalcification time, thrombin time, Owrens P & P test and determination of plasma factor V and fibrinogen levels, were not significantly changed in ethanol-intoxicated animals. Administration of alcohol did not affect fibrinolytic activity, while it inhibited significantly ADP and collagen-induced platelet aggregation in the rat.

Acute portal hypertension after gastric administration of ethanol in the pig.

A single gastric administration of 15 ml/kg of 40% ethanol to anesthetized pigs resulted in an increased portal venous blood pressure which increased with increasing blood alcohol levels. For the first 2 h there was no significant alteration in liver blood flow, but 3 h after the administration of ethanol, when portal blood pressure reached its highest values, liver blood flow had decreased. This was probably caused by increased hepatic vascular resistance as shown in electron thin-section phase-contrast microscopy which at this time showed marked hepatocyte swelling, narrowing of the sinusoids and platelet aggregates in small portal branches.

Colloid-induced changes in bleeding following liver resection in the rat

SummaryThe effect of preoperative infusion of Ringers solution, Ringers acetate solution, dextran 70, dextran 40, degraded gelatin and hydroxyethyl starch on haemostasis after standardized liver resection was studied in the rat. Ringers and Ringers acetate solutions did not affect haemostasis more than expected from haemodilution. Dextrans, degraded gelatin and hydroxyethyl starch caused a significant increase in bleeding time and blood loss. APT time was significantly increased after infusion of hydroxyethyl starch. Dextran and hydroxyethyl starch impaired ADP- and collagen-induced aggregation. Platelet aggregation was not affected by the infusion of Ringers solution or Ringers acetate solution as compared to non-treated controls.

Defects in Hemostasis Produced by Antibiotics

The effect of preoperative infusion of benzylpenicillin, carbenicillin, ampicillin, chloramphenicol and doxycycline on hemostasis after standardized liver resection was studied in the rat. Plasma levels of each antibiotic were within the range of those found after administration of therapeutic doses in man. Bleeding time was prolonged and blood loss was increased in all cases of antibiotic administration compared with controls. APT time after liver resection was prolonged in the carbenicillin- and chloramphenicol-treated groups. Platelet function, assayed by ADP- and collagen-induced platelet aggregation was impaired in benzylpenicillin-, carbenicillin- and chloramphenicol-treated animals.

Effects of ethanol on platelet aggregation: an in vitro study

SummaryAlcohol ingestion results in the formation of circulating microaggregates in the pig. To investigate the underlying mechanism, the effects of alcohol on platelet aggregation using a Born-aggregometer, was investigated. After incubating unstirred platelet rich plasma (PRP) with moderate concentrations of alcohol (175 mmol/l) the aggregation induced by collagen was reduced. This was probably due to platelet refractoriness caused by platelet ADP release. We could also demonstrate that high concentrations of alcohol (630 mmol/l) caused platelet release in stirred PRP. Release of ADP from red cells, after incubating unstirred whole blood with low concentrations of alcohol (17 mmol/l), was the probable explanation to the observed platelet refractoriness to ADP and collagen. Alcohol causing release of ADP from red cells is likely the cause of platelet aggregation in circulating blood and is probably the mechanism in formation of circulating platelet aggregates after alcohol ingestion.

Acute Alcohol Intoxication and Traumatic Shock

The reaction to a standardized soft tissue trauma was investigated in pigs pre-treated with gastric administration of saline or 40% ethanol. Circulating microaggregates in vena cava, vena portae and a

Circulating Microaggregates after Gastric Administration of Ethanol in the Pig

Earlier in vitro experiments have shown microaggregate formation in pig and rabbit blood after addition of ethanol. In this study ethanol was given to pigs resulting in ethanol concentrations of 30-40 mmol/l 2-4 h after administration. As would be expected ethanol concentration was higher in the portal vein than in the hepatic vein, caval vein or aorta. Microaggregates in circulating blood were measured with screen filtration pressure (SFP). SFP rose to more than double the initial value in ethanol-intoxicated pigs whereas it remained unchanged in controls. The ethanol-intoxicated pigs developed hemoconcentration and metabolic acidosis. Our results indicate that microaggregates probably made up of aggregated platelets are formed in pig blood during acute ethanol intoxication.

Influence of Physiological Saline, Dextran 70, Hydroxyethyl Starch, Degraded Gelatin, and Fat Emulsion Solutions on Screen Filtration Pressure

The effect of 0.9% NaCl solution, dextran 70, hydroxyethyl starch, degraded gelatin and fat emulsion on Hb, Hct, platelet count and screen filtration pressure has been studied in the rabbit. Dextran 70, hydroxyethyl starch and degraded gelatin caused hemodilution and decreased platelet count. Screen filtration pressure increased after infusion of degraded gelatin and tended to decrease after dextran 70 and hydroxyethyl starch. 0.9% NaCl and fat emulsion caused less pronounced changes. Intraportal infusion of 7 ml/kg body weight of the same solutions gave results which at present are difficult to interpret.