Theodore H. Spaet

Vascular Lesions: Possible Pathogenetic Basis of the Generalized Shwartzman Reaction

Evidence of vascular injury was found in rabbits after a single small dose of endotoxin from Escherichia coli. Eighty percent of the treated animals developed circulating endothelial cells, leukopenia, and thrombocytopenia, and 50 percent had aortic endothelial lesions as determined by electron microscopy. Prior anticoagulation with heparin did not prevent this response. No control animals showed these abnormalities.

Properties of Bovine Anti-Hemophilic Factor

Summary The anti-hemophilic factor (AHF) of human plasma is unstable to storage, and shows great loss with attempts at fractionation. Bovine AHF is stable to storage, and protein fractions can be obtained which show a good yield of AHF. Beef “AHF fraction” was prepared as an almost pure β2 globulin, and had about 70 times the AHF activity of fresh human plasma per mg of protein.

Ethionine-induced depression of plasma antihemophilic globulin in the rat.

Summary and Conclusions Parenteral administration of ethionine markedly depressed the AHF content of the blood in rats. This effect probably represents interference with synthesis of the protein rather than increased destruction. Although other coagulation factors were affected, the ethionine action did not involve all serum proteins, as shown by paper electrophoresis. Extensive tissue damage in ethionine-treated animals was confined to the pancreas, liver and bone marrow. Neither total pancreatectomy in dogs, nor carbon tetrachloride-induced liver damage in rats had any effect on plasma AHF levels. Studies are in progress to determine a possible role of the reticulo-endothelial system.

Some Properties of the Platelet-Connective Tissue Mixed Agglutination Reaction

Summary Platelets were agglutinated by a suspension of connective tissue fragments or by 6,000 MW Polybrene. In each case agglutination was inhibited by 2,800 MW Polybrene. The agglutination reaction with connective tissue was also inhibited by hypertonic electrolyte solutions, pH extremes, and trypsinization of the platelets. Incubation of trypsinized platelets with plasma failed to restore their ability to agglutinate with connective tissue. It is suggested that platelet-connective tissue mixed agglutination is an electrostatic charge reaction.

Clearance of blood coagulation product I in rabbits.

Summary Removal of blood coagulation product I was studied in rabbits. Intravenous injection of this reagent markedly shortened plastic tube clotting time, but restoration to normal occurred in a few minutes. There was no evidence of defibrination. Mixed with plasma in vitro, product I was inactivated slowly. It is suggested that product I is removed from the circulation as blood passes through various organs.

HYPERCOAGULABILITY AND THROMBOSIS: EFFECT OF INJECTED THROMBOKINASE AND ADENOSINE DIPHOSPHATE ON ESTABLISHED MICROTHROMBI IN RABBITS.

Summary Thrombi were produced in rabbit mesenteric veins by dry ice trauma. Intravenous infusion of thrombokinase to produce hyper coagulability or ADP to increase platelet agglutinability failed to augment thrombus growth. Regional per fusion of ADP caused dramatic increase in the size of thrombi, but the effects were transient and persisted only during the period of infusion. It is concluded that structured thrombi are primarily vascular in origin.

Blood Thromboplastin Its Preparation and Properties

Summary A reagent with activity resembling that of blood thromboplastin was sedimented on crude cephalin. Activity was lost if washing of sediment was undertaken in absence of calcium ion. The thromboplastic reagent normally clotted plasmas deficient in Stuart factor or factor V; activity was irreversibly destroyed following incubation with serum. Certain properties similar to those of tissue thromboplastin are indicated.

Effect of Intravenous Soy Bean Phosphatides on Blood Coagulation in Rabbits.

Summary Emulsions of soy bean phosphatides with platelet-like coagulant activity were given intravenously to rabbits. Small doses were followed by little change in blood coagulation, but larger doses produced depression of prothrombin, Ac globulin, and AHF. Fibrinogen and the “serum factors” were unaffected. The observed changes resulted from direct anticoagulant activity, and probably also from partial conversion of prothrombin.

The effects of phenazinemethosulfate and methylene blue on human platelet phospholipid synthesis.

Summary 1. In the present study phenazinemethosulfate (PMS) and methylene blue (MB) were shown to induce a pattern of glycerol incorporation into platelet phospholipids which resembles the pattern that Lewis and Majerus (1) observed when platelets were incubated with thrombin. 2. MB induced the release of platelet serotonin, but PMS did not cause the release of this amine. 3. The thrombin and MB-enhanced synthesis of platelet phosphatidylserine (PS) and associated release of platelet serotonin may be interrelated.

In vitro Inactivation of Rabbit Blood Thromboplastin by Macrophages.

Summary Under appropriate conditions rabbit peritoneal macrophages inactivated blood thromboplastin in vitro. In a similar system pulmonary macrophages were inert. The peritoneal macrophages appeared to remove radioactive thromboplastin from the medium, but the data were not as clear-cut. It was not possible to demonstrate increased oxygen uptake by peritoneal macrophages following exposure to thromboplastin since these cells appeared to have maximal oxygen consumption prior to mixing with the clotting reagent. It is concluded that reticuloendothelial cells treat laboratory blood thromboplastin as a foreign body.