72 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



A single injection of 0.35 g/kg was given. Two 

 molecular sizes were used; 35,000 to 40,000 and about 

 150,000. Twelve to 19 g of the small size PVP gave 

 slight prolongation of bleeding time in only one of four 

 rabbits. Eight to 10.5 g of the large size P\'P pro- 

 duced prolonged bleeding time in each of four rabbits. 

 Some animals showed thrombocytopenia with poor 

 clot retraction which was not prevented by splenec- 

 tomy. These authors proposed four factors in the 

 hemostatic disturbance: /) damage to the endothelial 

 lining of the blood vessels; 2) degeneration of marrow 

 megakaryocytes which was demonstrated in the 

 autopsied rabbits; j) hypersensitivity; 4) platelet 

 agglutination. 



The authors caution that results similar to this are 

 not reported in man after PVP. Also they indicated 

 that the effects may be less drastic in oligemic animals. 

 Behrmann & Hartman (9) injected dogs daily with 

 20 ml/kg body weight of PVP, dextran, or methyl 

 cellulose. These animals showed a decline in 

 fibrinogen to one-half or less of the initial level, but 

 not after gelatin. After PVP, dextran, or methyl 

 cellulose there was initial fall in platelets. If the reticu- 

 loendothelial system was blocked by India ink, then 

 platelet recovery occurred in splenectomized dogs. 

 After PV'P, dextran, and methyl cellulose there was 

 swelling, granulation, and absence of platelet forma- 

 tion by megakaryocytes. These changes were not seen 

 after gelatin. Thrower & Campbell (104) gave to 

 four patients 500 to 1500 ml of 3.5% PVP. The 

 clotting and bleeding times of these patients were un- 

 affected. 



Adelson and associates ( i ) studied the bleeding 

 time after dextran in dogs before and after irradiation. 

 After irradiation, the tendency to increased bleeding 

 time was increased. This was not always correlated 

 with X-ray induced decrease of platelet count. The 

 prolonged bleeding time after dextran was thought 

 to be due to an effect upon the platelets, but not due 

 to simple dilution. Two dogs receiving intravenous 

 gelatin had platelet counts of 140,000 and 110,000 

 after radiation and 82,000 and 48,000 after intra- 

 venous gelatin; yet, no hemostatic defect developed. 

 Howard and associates (52) studied the effect of 

 various molecular weight fractions of dextran upon 

 bleeding time in human .subjects. They infused 1000 

 ml of dextran in saline intravenously in a i-hour 

 period. With fractions of 34,000 molecular weight 

 there was no bleeding time prolongation beyond the 

 normal 3 to 4 min. With the 51,000 molecular weight 

 fractions the bleeding time was 7 min, i hour after in- 

 fusion in one of three subjects. Witii infusion of the 



90,000 molecular weight fraction, the bleeding time 

 was 18 min after 12 hours in one of three subjects. 

 With infusion of a dextran average molecular weight 

 fraction of 135,900, the bleeding time was 8.5 min 

 in one of three subjects. With infusion of a molec- 

 ular weight fraction of 194,900, the bleeding time 

 was prolonged for 48 hours in all three subjects, two of 

 whom bled seriously. With Commercial Cutter dex- 

 tran the bleeding time was not prolonged in any 

 of five subjects. The average molecular weight of this 

 dextran was 80,000. Bleeding time prolongation was 

 not associated with thrombocytopenia. It would ap- 

 pear from these studies that bleeding time prolon- 

 gation is much more likely to occur with large mo- 

 lecular weight fractions of dextran. 



Carbone and associates (20) gave 1000 to 1500 ml 

 of dextran daily intravenously to each of i 1 patients 

 until their bleeding times exceeded i i min. The 

 amount required was from 1500 to 6500 ml. The 

 bleeding time exceeded 30 min in 7 subjects. The 

 bleeding time was maximal 9 to 1 2 hours after in- 

 fusion and returned to normal in 24 hours with one 

 exception. The prothrombin activity declined to 50 

 to 75 % of normal. The clotting times were not ab- 

 normal. The platelet counts were not below 150,000 

 per mm^, the normal being 200,000 to 300,000 per 

 mm'. Prothrombin consumption was normal and no 

 antitiirombin was demonstrated. Clot retraction was 

 normal. The plasma fibrinogen decreased from 400 

 to 500 mg/ioo ml to 200 to 300 mg/ioo ml and re- 

 turned to normal in 24 hours. Plasma fibrinogen was 

 not significantly depressed when the bleeding time 

 was maximal. Fifteen subjects received 500 ml of 

 dextran and showed an increase of bleeding time in 

 two from the normal of 3 to 4 min to 8 and 9 min. 

 Fifty subjects received a single infusion of 1000 ml of 

 dextran. Fourteen of the 50 developed a bleeding 

 time greater than 10 min within 9 hours. This study- 

 suggested that the prolongation was not due to lower- 

 ing of prothrombin which should be below 10% in 

 order to affect the bleeding time. The changes were 

 thought to be unrelated to increase of blood volume 

 since the changes were minimal when the blood vol- 

 ume was maximal. The authors comment that hemo- 

 static problems were not reported in 2000 battle 

 casualties receiving 4000 units of dextran. Hor\ath 

 and associates (51) gave to rabbits and dogs 40 ml kg 

 body weight of Plavolex (6 % dextran) or Expandex 

 (6% dextran) or 6% gelatin or 2.5% gelatin, or ^% 

 human serum albumin. The bleeding time was not 

 prolonged with human all^umin or modified fluid 

 gelatin (Knox). The other substances prolonged 



