Further Studies on the Effect of Dextran of Various Molecular Weight on the Coagulation Mechanism

Abstract

SummaryDextran fractions of different molecular weights were given to dogs in order to ascertain at which molecular weight dextran interferes with the coagulation factors.1. Infusions of dextran with an average molecular weight of 130,000 (Intradex®) and in doses of 1.5 g dextran per kg body weight induced a moderate coagulation defect. There was a slight prolongation of the bleeding time and a slight drop in platelet count. Values for AHF, factor V, prothrombin and factor VII, and fibrinogen declined by 10 to 40% of the original values.2. Infusions of dextran with an average molecular weight of 75,000 (Macrodex®) in doses of 1.5 g per kg body weight did not produce any significant changes in bleeding time and platelet count. The AHF level decreased by 40% and the levels of prothrombin and factor VII, factor V and fibrinogen by about 10% of the original values. In a dose of 2 g per kg body weight this fraction produced a significant coagulation defect with a fall of the various coagulation factors by about 40 to 50%.3. A dextran fraction with an average molecular weight of 60,000 in doses of 1.5 g per kg body weight did not prolong the bleeding time and caused only a very slight decrease in platelet count. There were no changes in the values for AHF, factor V, prothrombin and factor VII but a slight drop occurred in the fibrinogen levels.4. Dextran with an average molecualr weight of 40,000 (Rheomacrodex ® ) in doses of 1.5 g per kg body weight did not affect the bleeding time or the platelet count. Nor did any significant decline occur in the amounts of the other coagulation factors.No changes in the Duke or in the Ivy bleeding times were observed in human beings given Macrodex® and Rheomacrodex® in doses of 1 g per kg body weight.Intradex® and Macrodex® in doses of up to 1-1.5 g per kg bodyweight to persons with normal blood coagulation are considered not associated with any appreciable risk of haemorrhage, but they are contraindicated in patients with haemorrhagic diathesis. The experiments indicate that Rheomacrodex® in similar doses does not incur any risk of haemorrhage.

Blood Replacement

“…They measured the bleeding time as well as coagulation time, number of thrombocytes, prothrombin consumption, fibrinogen level, and factors V and VII. This study was extended and also confirmed in humans by NILSSON and EIKEN [1084] and by CRONBERG et al [316].…”

“…DEUTSCH [347] and FISCHER et al [445, 445 a] believe that dextran can activate the fibrinolytic system. This view is contrary to the results of NILSSON [1084] and CRONBERG [316]. O'NEILL [1104] has shown that increased fibrinolysis occurs in all patients on bypass; this fibrinolysis is increased by the presence of dextran 40, but his experiments were all made under hypothermia.…”

Treatment of Shock with Dextrans and Gelatins

“…As might be expected, thrombopénie patients or animals -subjected, for instance, to whole body irradiation -suffer hemostatic impairment following a dose of dextran which is without effect in the intact organism [1,2,4,116]. Generally speaking, the severity of hemostatic defects increases with the average molecular weight of the dextran administered [2,19,117,158], but a molecular weight (Mw) of 86,000 suffices to produce the maximum thrombocyte coating effect [166].…”

“…1.5 g/kg or 15 ml/kg of the commercial 10% solution affect the bleeding time to some degree [67] but do not yet suffice to alter the coagulation status [158], provided the hemostatic mechanisms are not strained by additional factors. As with clinical dextran, however, additive effects are to be anticipated.…”

Further Evaluation of the Effects of 7.5% NaCl/6% Dextran-70 (HSD) administration on Coagulation and Platelet Aggregation in Hemorrhaged and Euvolemic Swine

“…Of major concern are reports that dextrans can interfere with the blood clotting mechanism [9,10]. Although the incidence of clotting abnormalities are low considering the large number of doses of dextrans given over the past 50 years, clotting abnormalities have been most pronounced following infusion of large molecular weight (MW) dextrans (MW>130,000) or after the infusion of large doses (>1.5 g/kg body weight) of dextrans of average MW>60,000 [9,11,12]. In addition, recent studies have suggested that infusion of hypertonic saline (HS) alone can prolong clotting times and decrease platelet aggregation [13,14].…”