Preservation of antithrombin III activity in stored whole blood.

Antithrombin III (AT-III) is the major inhibitor of thrombin, Factor Xa, and other coagulation enzymes. Congenital and acquired deficiencies of AT-III are thought to contribute to thrombosis and disseminated intravascular coagulation. Because a recent report suggested reduced AT III in stored blood, we evaluated blood bank storage effects. Serial samples were taken from 6 units of whole blood drawn into citrate-phosphate-dextrose-adenine over 42 days, and assays for AT-III functional activity were performed on the same day. The values (mean +/- SD) were as follows: day 0,91.8 +/- 10.7 percent; day 2, 101.9 +/- 10.7 percent; day 8, 107.3 +/- 7.4 percent; day 15, 118.9 +/- 11.1 percent; day 22, 105.4 +/- 9.8 percent; day 35, 93.4 +/- 8.8 percent; and day 42, 97.4 +/- 7.5 percent. The rise from day 0 to day 15 was significant but presumably secondary to interassay variation because analysis of frozen aliquots showed no significant change when all samples from each unit were assayed in one batch. Immunoassay of AT-III also showed no change with storage. The results indicate AT-III retains functional activity in whole blood stored at 2 to 6 degrees C for 42 days, and AT-III replacement does not require fresh blood or fresh-frozen plasma. Low values may reflect individual donor differences or dilution of plasma by anticoagulant.

Endotoxic shock in the primate: effects of aspirin and dipyridamole administration.

A primate model was utilized to study the cardiovascular and coagulation effects of endotoxic shock. The therapeutic effectiveness of drugs such as aspirin and dipyridamole, which diminish platelet aggregation and adherence, were evaluated. From the data, it appears that the kidney is a target organ in endotoxic shock, at least when a bolus injection of endotoxin is administered. The precipitate falls in the renal artery flow (p less than 0.01) and platelet count (p less than 0.01), which occur 3 minutes after the intravenous injection of endotoxin, can be prevented in part by pretreatment with aspirin (40 mg/kg of body weight). The changes in the coagulation profile were of less magnitude, and the fibrin degradation products appeared late in the group pretreated with aspirin as compared to the other groups. The combination of dipyridamole and aspirin was not as effective as aspirin alone in achieving the apparently protective effect. The study suggests that the administration of aspirin to patients with gram-negative infections may be beneficial.

Norlestrin-induced pseudopregnancy in the baboon. Effects on blood coagulation and endocrine glands during attempted production of Sheehan's syndrome.

Production of Sheehan's syndrome was attempted. As it was not possible to obtain pregnant baboons initially, pseudopregnancy was induced with norlestrin, 2.k mg., for 3 and 4 months, respectively. Sheehan's syndrome was not produced with massive hypovolemic shock but failure to obtain true pregnancy has given serendipitous information on the long-term action of norlestrin on the pituitary and its target organs. Unusual abundance of prolactin acidophils and decrease of growth hormone acidophils was found. Further studies will be necessary to show the possible significance of these findings. As fibrin degradation products did not appear in the serum, we can make no inference about the necessity of intravascular coagulation for the production of Sheehan's phenomenon. Finally one animal became pregnant. Sheehan's phenomenon was not produced in her despite induction of intrapartum hypovolemic shock. Histologic findings in her pituitary resemble those of the pseudopregnant animals.

Fibrinogen St. Louis: a new inherited fibrinogen variant, coincidentally associated with hemophilia A.

A patient with classical hemophilia (factor VIII deficiency) was found to have a new abnormal fibrinogen (fibrinogen St. Louis). Other family members exhibited either defect alone. Fibrinogen St. Louis was inherited as an autosomal dominant and was not associated with clinical bleeding. When compared with normal fibrinogen, fibrinogen St. Louis was found to have defective fibrin polymerization and possibly a slower release of fibrinopeptides. The prolonged thrombin times were partially corrected by calcium chloride and protamine sulfate. Ultracentrifugal sedimentation, electrophoretic mobility, DEAE chromatographic pattern, carbohydrate content, N-terminal amino acids, immunodiffusion, and immunoelectrophoretic patterns and electrophoresis of reduced and alkylated fragments were all normal. In contrast to fibrinogen St. Louis, the most similar other fibrinogen variant (fibrinogen Zurich) was found to be heterogeneous by several criteria and to have reduced hexose content.