Mary Jane Patch

Defibrination after brain-tissue destruction: A serious complication of head injury

Abstract A prospective study was conducted to evaluate defibrination after acute head trauma. Defibrination was not observed in 13 patients In whom trauma apparently did not destroy brain tissue. In contrast, evidence of defibrination — hypofibrinogenemia, elevated levels of serum fibrinogen-related or fibrin-related antigen and low levels of factors V, VIII or platelets — was found in nine of 13 patients in whom brain-tissue destruction was established by direct inspection. All nine patients had a strongly positive protamine test, suggesting that intravascular coagulation had occurred. Since test results returned toward normal within hours, the active phase of defibrination apparently was brief. Nevertheless, hemostatic abnormalities were severe enough to have affected the neurologic consequences of intracranial bleeding. Clinical findings attributable to fibrin in the microcirculation (e.g., microangiopathic hemolytic anemia or renal failure) were not encountered. The potentially salvageable patient wit...

A functional assay for protein C in human plasma

We describe a functional assay for protein C in human plasma samples based on the ability of activated protein C to prolong the kaolin-cephalin activated partial thromboplastin time of normal plasma. Protein C is separated from its inhibitor by elution of a barium citrate precipitate, and activated by incubation with human alpha-thrombin for one hour. Thrombin is then inhibited by antithrombin III and heparin, heparin neutralized by protamine sulfate, and protein C activity measured in the partial thromboplastin time. 24 normal subjects had a mean protein C level of 94 +/- 12% (SD) of the activity in pooled normal plasma. Seven patients with severe liver disease had a mean protein C of 28%. Eleven patients with disseminated intravascular coagulation had a mean protein C of 29%. Eight patients receiving warfarin therapy had a mean protein C of 17%. The assay is relatively simple and should be suitable for general laboratory use.

Factor V anticoagulants: clinical, biochemical, and immunological observations

A patient who had received multiple transfusions for complications of acute hemorrhagic pancreatitis developed a potent factor V anticoagulant with bleeding due to defective hemostasis. Despite its potency, the anticoagulant disappeared within 15 days of its first manifestation. A second patient with adenocarcinoma of the colon developed an anticoagulant to factor V postoperatively after a single blood transfusion. The anticoagulants appeared to react stoichiometrically with factor V in normal plasma in vitro. They had the physicochemical properties of immunoglobulins, and their activity was neutralized by antihuman immunoglobulin antiserum. One anticoagulant appeared to be slightly more active against homologous than against autologous factor V, but it also inhibited heterologous factor V. Both anticoagulants progressively inactivated intrinsic prothrombin activator formed from normal reagents in the incubation mixture of the thromboplastin generation test, thus confirming that factor V is required for the effective action of the intrinsic prothrombin activator. Since the anticoagulants were immunoglobulins whose activity was consumed in their reaction with factor V, consumption of anticoagulant activity was used to detect factor V antigenic material in test materials. Human serum without factor V clotting activity was found to consume anticoagulant activity, i.e., to contain inactive factor V antigenic material. Plasma from two patients with hereditary factor V deficiency (parahemophilia) failed to consume significant anticoagulant activity. Thus, the lack of factor V activity in these patients represents a deficiency of factor V molecules rather than the synthesis of a defective molecule with impaired clotting activity.

Depression of functional and antigenic plasma antithrombin III (AT-III) due to therapy with L-asparaginase.

Eleven patients with leukemia and lymphoma were treated with 14 courses of E. coli L‐asparaginase. Abnormalities of the coagulation screening tests and decreased fibrinogen levels were observed in all patients during treatment. Significant depressions of functional (mean 32%) and antigenic (mean 48%) antithrombin III were observed by day 14 of therapy. There was no laboratory evidence of intravascular coagulation during 11/14 courses of L‐asparaginase. Crossed immunoelectrophoresis of plasma obtained at the antithrombin nadir did not demonstrate an abnormal pattern which can be associated with an abnormal antithrombin III or an increase in antithrombin III‐coagulation factor complexes. The major underlying mechanism of this depression is believed to be decreased hepatic synthesis, and the low levels of antithrombin III may be associated with an increased risk of thrombosis.

Severe Depression of Antithrombin III Associated with Disseminated Intravascular Coagulation in Women with Fatty Liver of Pregnancy

Serial coagulation studies were done in four women with acute fatty liver of pregnancy. All had coagulopathy, laboratory evidence of diffuse intravascular coagulation, and marked depletion of plasma antithrombin III. Two of these women had persistent intravascular coagulation for 4 days after delivery. The others had prompt control of intravascular coagulation coincident with elevation of the antithrombin III concentration by plasma transfusion. Severe antithrombin III depression may be a major cause of the persistent intravascular clotting and can be corrected by plasma transfusion.

Antithrombin III and anti‐activated factor X activity in patients with acute promyelocytic leukemia and disseminated intravascular coagulation treated with heparin

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed from the day of admission until completion of the first course of chemotherapy with serial coagulation studies including plasma levels of functional antithrombin III activity (AT III) by fluorometric analysis and antiactivate Factor X activity (anti‐Xa) by coagulation assay. Both patients were treated with intravenous heparin and the presence of heparin in plasma was followed by the thrombin time. Consistently normal levels of AT III (>80%) were found despite evidence of intravascular coagulation. However, plasma levels of anti‐Xa were often low (<70%) and increased only in the presence of heparin. The significance of these results in relationship to heparin therapy for disseminated intravascular coagulation of APL is discussed.