Samuel I. Rapaport

Coexistent hypercoagulability and acute hypofibrinogenemia in a patient with prostatic carcinoma

Abstract Acute hypofibrinogenemia, associated first with bleeding and then with hypercoagulability, developed in a patient with metastatic prostatic carcinoma. The hypercoagulability strongly suggests that intravascular clotting, rather than fibrinolysis, caused his acute hypofibrinogenemia. This case is thought to link the rare syndrome of acute hypofibrinogenemia with the common observation of venous thrombosis in malignancy.

Hemophilia A: Polymorphism Detectable by a Factor VIII Antibody

Plasma from 54 patients with hemophilia A was tested for neutralizing activity with a human antibody to factor VIII. The plasma from 52 patients had no demonstrable neutralizing activity. Two plasma samples had neutralizing activity equivalent to that of normal plasma despite the lack of factor VIII clotting activity. Apparently, most patients with hemophilia A do not synthesize factor VIII, whereas a few synthesize an inactive molecule with a presumed genetic structural mutation of the active site but with antigenic determinants in common with normal factor VIII. Thus, hemophilia A is a disease caused by more than a single genetic mechanism.

Formation of Intrinsic Factor-X-Activator Activity, with Special Reference to the Role of Thrombin

Summary When thrombin‐activated purified human factor VIII (factor VIIIt), purified human factor IXa, lipid and calcium were combined, a very rapid reaction occurred involving the lipid and at least one of the plasma clotting factors. No other interaction between the components of intrinsic factor‐X activator could be demonstrated. Full activity developed so rapidly as to suggest an instantaneous reaction. In contrast, when native factor VIII was used instead of factor VIIIt, insignificant factor‐X activator was found over 15 min. Further experiments with hirudin confirmed that a preliminary activation of factor VIII is an absolute requirement for the development of human intrinsic factor‐X activator activity. Both thrombin and trypsin effectively activated factor VIII, which suggests that activation results from proteolysis. Factor IXa, factor XIa, factor Xa, collagen, connective tissue, platelet fractions, plasmin and Reptilase ‘R’could not activate factor VIII within a physiologically significant time interval.

Tissue Clearance as a Measure of Nutritive Blood Flow and the Effect of Lumbar Sympathetic Block upon Such Measures in Calf Muscle

This paper reports the effect of procedures known to alter local blood flow upon the rate of removal of locally injected Na24 and I131. An evaluation of this clearance method as a measure of nutritive blood flow is made. A second purpose is to report the lack of effect upon clearance from calf muscle of lumbar sympathetic block, and to discuss its therapeutic implications.

Platelets and initiation of intrinsic clotting.

Summary. Comparison of activities in platelet rich and platelet poor plasmas from normal donors and patients deficient in either factor VIII, IX, XI or XII indicates that platelets contain activities which can partially substitute for plasma factors XI and XII. The factor‐XI‐like activity is expressed in a one‐stage activated partial thromboplastin assay and in an intact prothrombin consumption system. The factor‐XII‐like activity is scarcely detectable in a one‐stage assay but markedly enhances the defective prothrombin consumption of factor XII deficient plasma. Intact prothrombin consumption tests with platelet poor plasmas fortified with cephalin show that in the presence of high concentrations of platelet factor 3 activity only trace contact activation is required to promote good prothrombin consumption. The platelet, by supplying both platelet factor 3 and activities bypassing plasma contact activation factors XI and XII, may provide an important route for activating intrinsic clotting.

Separation of plasma thromboplastin antecedent (PTA) and Hageman factor (HF) from human plasma.

Summary 1) Hageman factor and plasma thromboplastin antecedent have been separated from human plasma and each other by ion exchange chromatography. 2) The defect in “exhausted plasma” is not corrected by purified PTA, purified HF, or a combination of the two.

The Effect of Smoking upon Blood Flow in the Sympathectomized Limb

The effect of smoking upon the blood flow of a sympathectomized limb was examined in 19 patients. Sympathectomy was found to abolish the peripheral vasoconstriction produced by smoking. The constriction, therefore, is mediated by sympathetic vasomotor fibers and not by humoral agents such as adrenaline or posterior pituitary hormone. There is no difference in the response of patients sympathectomized for thromboangiitis obliterans, arteriosclerosis or severe vasospasm. The relation between the vasoconstrictor effect of smoking and the action of tobacco in thromboangiitis obliterans is discussed.

Plasma thromboplastin antecedent levels in patients receiving coumarin anticoagulants and in patients with Laennec's cirrhosis.

Summary 1. Plasma thromboplastin antecedent (PTA) levels are normal in patients receiving Dicumarol, Coumadin, or phenylindanedione. 2. PTA levels are depressed in patients with Laennecs cirrhosis. Degree of depression parallels prothrombin time value.

Failure of fibrinogen degradation products to increase plasma fibrinogen in rabbits.

Summary Infusion of large quantities of early or late fibrinogen degradation products into rabbits failed to increase plasma fibrinogen levels or the incorporation of 75SeM into newly synthesized fibrinogen. Thus, no evidence could be obtained for a key role of fibrinogen degradation products in mediating the increased fibrinogen synthesis associated with pathologic states in this species.

Increased Fibrinogen Consumption Following Endotoxin Injection in Cortisone-Treated Rabbits

Summary Rabbits prepared with prior injections of cortisone were given a single intravenous dose of E. coli endotoxin, Boivin type, at 100 μg/kg. The cortisone treatment potentiated intravascular clotting in these rabbits. Thus, excess disappearance of plasma 125I-fibrinogen radioactivity was demonstrated after endotoxin in each of 12 rabbits treated with 4 daily intramuscular injections of 25 mg of cortisone acetate, whereas only 1 of 13 saline-treated control rabbits showed similar changes. Consumption of plasma fibrinogen in the 6 hr after endotoxin was calculated from plasma fibrinogen levels and plasma fibrinogen radioactivity. Mean values were as follows: cortisone group, 79.4 mg% or 33.9 mg/kg; control group, 37.4 mg% or 13.2 mg/kg. The GSR was found in 3 cortisone-treated rabbits but in no control rabbit. Enhancement of endotoxin-induced clotting represents one important mechanism whereby cortisone could prepare rabbits for the GSR. The authors thank Miss Mary Jane Patch for preparation of the figures.