Increase in antihaemophilic globulin activity following infusion of adrenaline

Abstract

Christie, Graham-Stewart & Ingram (1960) described an abdomino-perineal excision of the rectum in a haemophilic of moderate severity who received animal antihaemophilic globulin (AHG) to cover the operation and post-operative period. Responses to this material were measured by assaying the AHG activity in the patient's plasma before and after each dose; and on two occasions the responses were strikingly high. These peaks corresponded to episodes of acute haemorrhage requiring immediate blood transfusion; and there was also an intermediate peak coinciding with a lesser haemorrhage insufficient to necessitate transfusion. It was not clear whether the high responses correlated with the severity of the bleeding or with blood transfusion; but in another haemophilic an unexpectedly high AHG level was associated with haematemesis while the patient was under observation only. It seemed therefore that haemorrhage was the correlated factor; and in considering a possible mechanism, the extensive previous work on the acceleration of blood coagulation after the administration of adrenaline was recalled: this was reviewed by Forwell (1955), and the problem was reexamined by Forwell & Ingram (1957), who thought at that time that the effect depended on an increase in the activity of Factor V. A possible explanation of the observations in the haemophilics was that haemorrhage had led to a release of adrenaline (Greever & Watts, 1959), and that this had in turn brought about an increase in the activity of AHG in the patients' plasmas. Forwell & Ingram (1957) had not examined AHG in their experimental subjects who had received adrenaline; it therefore seemed of interest to extend the earlier work to include AHG. The results of these experiments are now presented. METHODS The healthy experimental volunteers taking part in the present investigation were senior male medical students. The haemophilic subjects were adult patients, also of course, males, and in good health apart from their haemophilia. Neither they nor the healthy subjects were fasted before testing.

Platelet activation and secretion associated with emotional stress.

“…Thrombin is another potential agonist that could trigger platelet secretion during emotional stress, since catecholamine infusions are associated with accelerated blood coagulation and increased plasma activities of factors V and VIII.38 39 We measured the plasma concentration of FPA as an indirect assay of thrombin activity and found no change during the period of stress when platelet secretion occurred. However, our earlier studies have demonstrated that platelet secretion of PF4 is stimulated by concentrations of thrombin lower than those required for fibrin formation.40 Therefore, the absence of an increased FPA concentration does not rule out thrombin as a mediator of this effect on platelets.…”

Activation of human endothelial cells from specific vascular beds induces the release of a FVIII storage pool

“…Given that the average FVIII level in plasma is 1 U/mL and that the half-life of FVIII is 12 hours, the steady state rate of FVIII production can be estimated at 0.042 U/mL plasma/h. By comparison, FVIII plasma levels increase by 1 to 3 U/mL within 30 minutes after epinephrine administration, 28 which is at least 40 times higher than the steady state rate of FVIII production. The rapid secretion of FVIII after epinephrine administration indicates that FVIII is For personal use only.…”

“…15,27,28 Interestingly, ␤2-receptor blockade also lowers sustained elevated FVIII:C in patients with deep vein thrombosis. 29 The amounts of FVIII released during acute physical stress are important by comparison to the steady state production of FVIII.…”

Platelet aggregation and strenuous exercise

“…The increased platelet aggregation, accelerated clotting and raised levels of fibrinolysis after exercise are probably a stress reaction. Increased fibrinolysis (Truelove, 1951) and a rise in factor VIII levels (Ingram, 1961) result from adrenaline injection. Adrenaline also causes platelet aggregation in plateletrich plasma (Clayton & Cross, 1963).…”