Factor‐VIII Activity and Antigen, Platelet Count and Biochemical Changes after Adrenoceptor Stimulation

Abstract

Adrenaline, isoprenaline and salbutamol were administered by intravenous infusion to human subjects. Isoprenaline was covered with practolol in an attempt to reduce the unpleasantness of the circulatory effects. Changes were recorded in pulse rate and blood pressure, and in blood levels of factors V, VIII, X, XI, and XII, platelet count, lactate, pyruvate, potassium and free fatty acids. Factor VIII was studied by clotting assays, by reactions with two rabbit antisera and two human antibodies, and by desulphated agarose chromatography. At the rate at which they were adiminstered, all three drugs increased the pulse rate by 20-40 beats/min. Factor VIII rose c. 2.5 X with adrenaline but only c. 1.5 X with isoprenaline and salbutamol; but other clotting factors did not alter. Chromatography provided no evidence of a change in the size of the molecule carrying factor-VIII clotting activity. The rate of clearance of the heightened plasma activity could not be shown to differ from that of "ordinary" factor VIII infused into haemophiliacs. The platelet count rose after adrenaline, fell after salbutamol and did not change significantly after isoprenaline. Among the biochemical responses, the only significant difference between the drugs was that lactate rose after adrenaline and salbutamol but did not change after isoprenaline. The rise in factor-VIII clotting activity after adrenaline is considered to represent a real increase in blood concentration, presumably by release of additional factor VIII from stores. The evidence suggests that this could be classified as a beta2 effect; and that the quantity which can be released is unrelated to the current plasma level. The rise in platelet count produced by adrenaline may be the resultant of an alpha-mediated rise due to contraction of the exchangeable splenic pool and a beta2-mediated fall, the alpha effect predominating.

Correlation between Changes Induced by Venous Occlusion on Factor VIII-von Willebrand Factor Components and Fibrinolytic Activity

“…A similar relationship has been reported in normal subjects in basal condi tions, at least between F VIII:C and F VIIIR:AG [1,3,7,11,18], while there are discordant reports for F VIIIR:RCof [1,5,21], The significant correlations between the F VIII-VWF components found in our cases after VO, notwithstanding their striking and heterogeneous rise, are in agreement with previous observations made using stimuli such as catecholamine administration [7,12] and physical exercise [2,7,17], A highly significant activation of fibrino lysis was recorded following VO, the results of ELT and DBCLT being strictly correlated. This finding supports the belief that the two methods basically measure the same phe nomenon, the release of plasminogen activa tor.…”

Blood Coagulation and Platelet Function following Maximal Exercise: Effects of Beta-Adrenoceptor Blockade

“…While long-term |3-blockade has no effect on VIII:C levels [9] the rise in VIII:C after exercise is thought to be due to |3-adrenergic stimulation [16] and can be blocked by prior intravenous administration of propranolol [32]. We have been unable to show that oral propranolol can block the rise in VIII:C with exercise, a finding also noted by KorsanBengtsen and Conradson [33], who adminis tered double the oral dose of propranolol to that used in our study.…”

“…Since the main haemodynamic bene fits of p-blockade occur with exercise and since platelet aggregation [10][11][12][13][14] and prosta cyclin [15] have been shown to increase fol lowing acute exercise we wished to see if pblockade could alter the platelet aggregation or prostaglandin response following strenu ous exercise. In addition, since exercise-in duced release of factor VIII is thought to be mediated by p2-adrenergic stimulation [16], modification of the factor VIII complex by P-blockade was also studied. The mechanism for exercise-induced fibrinolysis is probably not related to adrenergic stimulation [ 17] but the resting level of fibrinolytic activity may be altered by P-blockade [18][19][20] and so the fibrinolytic pathway was also examined.…”

Some Observations on the Release of Extrinsic and Intrinsic Plasminogen Activators during Exercise in Man

“…Venous occlusion and adrenaline infusion both produce a similar effect and it has been suggested that a good response to these challenges is desirable (Shaper et al, 1975). Factor VIII levels are also elevated by adrenaline infusion {Ingram et al, 1977) but there is no change in circulating fibrinogen level, nor is there any change in plasminogen turnover or production of fibrin(ogen) degradation products, both signs of systemic fibrinolysis (Colien and Verstraete, 1978). Our results suggest that the abrupt increase in plasma activator activity after exercise does not lead to a marked systemic fibrinolytic state; antiplasmin and plasmin ogen levels remained virtually constant but the generation of small amounts of fragment X indicates that some fibrinogenolysis was taking place.…”