PLASMA SUBSTITUTES 



73 



bleeding times in varying degrees witliout consistency 

 as to duration or onset of the hemostatic defect. The 

 data suggest that macromolecules, per se, are not the 

 basic factor invohed. Seegers and associates (92) show 

 that dextran in \ivo, in concentrations hkely to be 

 produced by infusion, interfered with the conversion 

 of prothrombin to a derivative by inhibition of 

 thrconc. They showed significant inhibition at con- 

 centrations of 1.68 mg of dextran ml. Inhibition was 

 pronounced at 5 mg ml and maximum at 10 mg/ml. 

 In the study made by these authors small molecular 

 weight dextran, 91,700, inhibited thrombin produc- 

 tion more than equal concentrations of a large fraction 

 average molecular weight, 1 94,900. Thrombin re- 

 verses the dextran inhibition of threone. 



Weil & Webster (iii) found that dextran of un- 

 stated type produced fibrinogen precipitation in 

 fresh plasma when the dextran to plasma ratio was 

 2 : 1 or more. Platelets were also decreased in blood 

 when the ratio of dextran to blood was 2 : i or more. 

 The clotting time was prolonged when the dextran 

 to blood ratio was 2 : i or more. In their study of pa- 

 tients receiving 500 to 1000 ml of dextran for operat- 

 ing room blood loss, none were found to have pro- 

 longed ijleeding time. They concluded that dextran 

 was safe if the volume infused was limited to 1000 ml. 



Jacobaeus (59) made an extensive study and review 

 of the effects of dextran on hemostasis. He used 

 Swedish Macrodex for his own studies. Decreases in 

 prothrombin, proaccelerin, and procon\ertin were 

 proportional to hemodilution. No decrease in platelets 

 was found at 24 and 96 hoiu's after infusions of 500 to 

 2000 ml of dextran. Prothrombin consumption was 

 reduced and delayed. There was a tendency to de- 

 layed clot retraction. Dextran had no influence on the 

 activation of procon\ertin or the interaction between 

 proconvertin and thromboplastin. Dextran inhibited 

 platelet activity, possibly due to an inactivation of 

 platelet factor 3. The authors thought the delay and 

 reduction of prothrombin consumption with dextran 

 was an important factor in the bleeding tendency. 

 They suggested that a molecular weight of dextran 

 between 60,000 to 80,000 might be least likelv to 

 cause trouble. The prothrombin consumption was 

 actually increased in the presence of low molecular 

 weight dextran (27,000). With 41,000 molecular 

 weight dextran the prothrombin consumption was the 

 same as with a saline diluent. With 83,000 molecular 

 weight dextran, prothrombin consumption was re- 

 duced. Langdell and associates (66) studied the effects 

 of dextran infusions upon the bleeding time in 22 

 women and 235 men. The dextrans used were 6% 



solutions; some were of British and some were of 

 American manufacture. In 42 '^c of the subjects the 

 infusion of i liter of 6 % dextran measurably prolonged 

 the bleeding time. In 8Tc of the subjects, the bleeding 

 time after infusion exceeded 30 min. The effect was 

 maximum at 3 to 9 hours after the infusion. It was 

 not accounted for by any demonstrable dilution or 

 reduction of fiisrinogen or thrombocytes. Comparison 

 of the de.xtran preparations showed that those with 

 the highest molecular weight had the most marked 

 effects in prolonging the bleeding time. Of 38 subjects 

 receiving dextran in the molecular weight range of 

 around 50,000 only 13'^'c had bleeding times greater 

 than 15 min. Of 52 subjects receiving dextran of 

 molecular weight greater than 100,000, 22T0 had 

 bleeding times greater than 15 min. Albumin solution 

 was infused into 40 subjects. Of these, one had a 

 bleeding time of 1 1 min. All others had a bleeding 

 time of less than 10 min. The albumin used was 1000 

 ml of 5% solution in sodium chloride. One liter of 

 3.5 '^'(' PVP was infused into 51 subjects. Of these, 7 de- 

 veloped a bleeding time of greater than 10 min and 2 

 a bleeding time greater than 15 min. The authors 

 attempted to correlate the bleeding prolongation with 

 the plasma volume expansion using chromium-51 

 tagged red cells. The initial increase in blood volume 

 was approximately looo ml after dextran. By 9 hours 

 the blood \olume had returned to about the control 

 level. There seemed to be no correlation between the 

 prolongation of the bleeding time and the increase of 

 blood \olume. Forty per cent of the bleeding times 

 greater than 10 min occurred at 3, 6, or 9 hours when 

 the blood \olume was increased by only 500 ml or less. 

 Two dogs bled 350 ml and immediately infused with 

 equal \olume of dextran solution showed a prolonga- 

 tion of bleeding time froin an original of i min to g 

 min after dextran. Reinfusion of the dog's own blood 

 into him several clays later did not produce any change 

 in bleeding time although the animal was temporarily 

 hypervolemic. The authors concluded that moderate 

 hypervolemia, per sc, does not alter the bleeding time. 

 Platelet counts were done simultaneously with 

 bleeding time determinations in 12 subjects who re- 

 ceived 1000 ml of dextran. Platelet counts done prior 

 to the infusion were in the range of 160,000 to 

 280,000 mm'. In all subjects the platelet count was 

 decreased after the infusion, but the decline was pre- 

 dictable on the basis of dilution by the amount of 

 fluid given. There was no direct correlation between 

 bleeding time and platelet counts. The mechanism of 

 the dextran inhibition of hemostasis was not clear, 

 but was believed to be due to an inhibition of 



