Shepard Shapiro

Prothrombin Estimation A Procedure and Clinical Interpretations.

Summary The difference between prothrombin times of whole and diluted plasma is a more reliable guide to prothrombin activity of the blood than is the prothrombin time of either alone. The difference has been found to be fairly constant in normal individuals. When prolonged, it indicates hypoprothrombinemia. When reduced, it may signify hyperprothrombinemia or an excess of anticoagulants in the blood. The procedure recommended is well suited for following the therapeutic effects of agents which influence the prothrombin level (or activity) such as dicumarol or vitamin K.

Studies on Prothrombin: IV. The Prothrombinopenic Effect of Salicylate in Man

Summary and Conclusions In man as in the rat, salicylate in adequate dosage induces prothrombinopenia which can be prevented by vitamin K compounds, if liver function is adequate. The effect on the prothrombin level (or activity) is detected most readily by the use of 12.5% plasma. The dietary intake particularly of vitamin K appears to play a significant role in determining the extent and duration of the prothrombinopenia. Cirrhosis of the liver and pre-existing prothrombinopenia augment the effect of salicylate. Acetyl salicylic acid appears to be a more potent agent than sodium salicylate. The action of salicylate is apparently identical with that of the anticoagulant dicumarol, but less effective. The two drugs can complement each other. This may be useful in the clinical application of dicumarol and should be realized to avoid excess prothrombinopenia.

Warfarin sodium derivative: (coumadin sodium); an intravenous hypoprothrombinemia-inducing agent.

Bishydroxycoumarin (dicumaroll~1) has prevented or favorably influenced thrombosis and embolism in many thousands of cases since its introduction into medicine about a dozen years ago. In a number of patients, the therapy has been inadequate particularly in urgent situations where need for smoother, sustained anticoagulant effect is required. Uncertainty of absorption of the hypoprothrombinemia-inducing agent from the intestine is an important factor which contributes to this. This is especially true in severely sick patients in whom nausea, vomiting or diarrhea is common or the need for deep sedation is required. There is great need for a clotting inhibitor with more prompt action and prolonged activity which will obviate the difficulties of absorption from the digestive tract. This paper reports clinical experiences with an intravenously administered 4-hydroxycoumarin drug which induces therapeutic hypoprothrombinemia of several days duration following a single dose. After bishydroxycoumarin (dicumarol@) was isolated and synthesized, Professor Karl Paul Link and his co-workers prepared and screened many analogs. One of these hypoprothrombinemia-inducing agents, warfarin [3(a-acetonyl benzyl)-4-hydroxy coumarin] was selected for rodent control .t The characteristics of the preparation, described below, led Professor Link to discuss with the writer the possible usefulness of the compound as a hypoprothrombinemiainducing agent in man and suggested the desirability of clinical trials. A fortuitous incident at this time yielded essential data which lent support to study of the drug on humans. Lieutenant Roy W. Holmes (M.C.) U.S.N. and Captain Julian Love, (M.C.) U.S.N. reported a detailed account of a suicide attempt with warfarin made by

Passage of a hollow needle into the venous blood stream to the heart, through the cardiac wall, and into the thorax

Abstract 1. 1. A case is reported in which a hollow needle entered the venous blood stream, was carried to the heart, penetrated its wall, and came eventually to lie in the prepericardial fat between the heart and the diaphragm, without producing any untoward symptoms. 2. 2. The pathways by which foreign bodies may enter the heart are described. 3. 3. The hazard described in this paper, although a rare one, warrants the recommendation that the flexibility and sturdiness of needles be carefully tested before they are put to intravenous use.

Prothrombin Studies: III. Effect of Vitamin K upon Hypoprothrombinemia Induced by Dicumarol in Man.

Conclusion In man, as has been demonstrated in animals, synthetic vitamin K administered in relatively large amounts has been found to counteract or neutralize the hypoprothrombinemia induced by a smallest single effectual dose of Dicumarol.

Treatment With Isosorbide Dinitrate

* Isordfl@ supplied by the Ives-Cameron Company, New York City 16, New York. The problem of angina pectoris is the problem of coronary disease. Seizures of angina pectoris may be signposts on the road to coronary occlusion or they may first appear after the myocardium has been infarcted. Regardless of the chronologic stage of coronary arteriosclerosis in which angina pectoris becomes evident, its pathogenesis is always the same: The attacks occur when the oxygen supply to the myocardium falls below the physiologic requirement of the moment. When this relative anoxia is transitory and reversible the pain subsides as the oxygen supply becomes adequate. When, on the other hand, this reversal fails to take place, the stage is set for ischemic necrosis.

Familial Regional Enteritis

Summary Six cases of regional enteritis in two family groups, father and son and brother, father and daughter and sister, are reported. In one family the son got his symptoms about the same time as his uncle, but about 12 years before his father. In the other family, daughter and father began to have symptoms about the same time.

PULMONARY EMBOLISM: ITS INCIDENCE AT NECROPSY IN RELATION TO PERIPHERAL THROMBOSIS

Excerpt The most dangerous complication of venous thrombosis is pulmonary embolism, with its mortality of about 20 per cent.1Such embolism has been reported by Barnes3to be responsible for 34,000 d...

An evaluation of methods of dicumarol administration

Abstract The physiological disposition of Dicumarol by the body is reviewed and its relationship to methods of Dicumarol dosage is discussed. An illustrative case in which Dicumarol was given by both the continuous (daily) and the intermittent dosage methods is presented. The case illustrates: (1) the relationship of prothrombin response to plasma Dicumarol concentration; (2) the difficulty of recognizing promptly when a given daily dose of Dicumarol is inadequate; (3) the danger of undetected accumulation of daily doses to excessively high plasma Dicumarol concentrations; (4) the importance of knowing not only what the prothrombin time is at the moment, but also the direction in which it is changing; and (5) the better control of prothrombin response afforded by the intermittent dosage method.

A simply prepared, standardized, and relatively stable thromboplastin extract for estimation of prothrombin time

Abstract A standardized preparation of thromboplastin which becomes ready for use after the addition of only distilled water and which is reliable and of optimum sensitivity is described. It is believed that this should add considerably to the safety of Dicumarol therapy, so that the goal of adequate therapeutic effect with minimum danger of hemorrhage can be achieved.