Obstetric complications associated with the lupus anticoagulant.

We identified eight patients with the lupus anticoagulant (an autoantibody acquired by some patients with systemic lupus erythematosus), by observation of an increased activated partial thromboplastin time and abnormal results on a tissue thromboplastin-inhibition test. The patients had experienced a total of 30 spontaneous abortions and fetal deaths in 31 previous pregnancies (96.8 per cent).

Hereditary thrombosis in a Utah kindred is caused by a dysfunctional antithrombin III gene.

Maximum likelihood analysis of linkage between antithrombin III (ATIII) DNA polymorphisms and ATIII deficiency in a large Utah kindred suggests that thrombotic disease in this family is caused by a dysfunctional ATIII gene. ATIII-deficient family members were identified on the basis of: (1) reduced anticoagulant activity and (2) the presence of an electrophoretically abnormal inhibitor molecule in their plasmas. Affected individuals have two copies of the ATIII structural gene, and both alleles appear normal at the resolution of whole genome Southern blotting.

False assignment of familial antithrombin III deficiency with the von Kaulla assay.

As a serum assay, the von Kaulla assay for antithrombin III has been criticized on the grounds that consumption of antithrombin III during in vitro blood clotting may lead to falsely low assay values. Use of the assay to screen a Utah pedigree for familial antithrombin III deficiency lends support to this criticism. In all, the assay was performed on 150 persons.

The improving hematologic picture in long-term surviving calves with total artificial hearts.

A coagulopathy associated with severe hemolysis was a limiting factor in obtaining long-term survivors among calves with total artificial hearts in 1969. Conversion of design from sac-type hearts to flexible diaphragm hearts, and from Silastic Dacron-fibril intimas to smooth polyurethane intimas, resulted in an abatement of the coagulopathy. In the most recent series of animals studied at this laboratory, platelet counts are normal and platelet survivals are half of normal.

131I-labeled fibrinogen in the diagnosis of deep vein thrombosis of the lower extremities.

Autologous 131I-labeled fibrinogen was administered to 17 patients during 19 episodes of suspected lower extremity deep vein thrombosis in an attempt to assess its diagnostic accuracy. Serial rectilinear scanning and probe counting of the lower extremities and pelvis were performed and compared with ascending contrast venography. The sensitivities of imaging and counting were 67% and 47%, respectively, and both had a specificity of 95%.

Radioactive labeling of protein carboxyl groups on factor VIII: use of carbodiimides for nuclear medicine.

Carbodiimides have been used to study macromolecular structure and to produce immunologically active antigens. We have used this method to label a labile coagulation protein, factor VIII, with 14C-glycine-ethyl-ester. No discernible chemical change, loss of biologic function in vitro, or alteration of the plasma disappearance of factor VIII resulted.

Factor-VIII activity and antigen, platelet count and biochemical changes after adrenoceptor stimulation.

Adrenaline, isoprenaline and salbutamol were administered by intravenous infusion to human subjects. Isoprenaline was covered with practolol in an attempt to reduce the unpleasantness of the circulatory effects. Changes were recorded in pulse rate and blood pressure, and in blood levels of factors V, VIII, X, XI, and XII, platelet count, lactate, pyruvate, potassium and free fatty acids.

Noninvasive diagnosis of deep venous thrombosis.

Eighty-five patients suspected of having lower-extremity deep venous thrombosis (DVT) participated in a prospective study to test the diagnostic accuracy of four noninvasive techniques: Doppler ultrasonic flow study, electrical impedance plethysmography, the serial dilution protamine sulfate test, and an extensive physical examination. Ascending radiocontrast phlebography was the diagnostic standard of reference. We found that (1) when both Doppler and impedance examinations were positive, the diagnosis of DVT could be considered virtually certain; (2) impedance and Doppler examinations, when used in combination, were reliable screening tests capable of establishing or excluding the presence of thigh DVT; (3) physical examination and the serial dilution protamine sulfate test were unreliable screening techniques for DVT; (4) techniques other than the noninvasive methods investigated were needed to reliably detect or to exclude popliteal and call DVT.

A three-month survival of a calf with an artificial heart.

An artificial heart constructed from Biomer, a polyurethane, kept a calf alive for more than three months after its natural heart was removed. During this time all of the calf's vital organs apparently functioned well. We had been able to keep similar animals alive with Jarvik III hearts made from Silastic for one month.

Heparin metabolism and heparin-release lipase activity during long-term estrogen-progestin treatment.

Short-term oral contraceptive therapy has been reported to decrease postheparin lipolytic activity (PHLA). Resistance to heparin has been held responsible for this effect. To test several alternative explanations, we studied both PHLA and heparin concentrations in nine control women and nine women receiving long-term estrogen-progestin therapy after they were given heparin intravenously (10 units/kg).

Multiple myeloma, cryoglobulinemia and xanthomatosis. Distinct clinical and biochemical syndromes in two patients.

Studies were carried out in two patients with multiple myeloma (immunoglobulin G, [IgG], K light chain), cryoglobulinemia and xanthomatosis with clinical features and lipid transport abnormalities which were quite different. One patient had nodular xanthomatosis and lipemia with delayed triglyceride and apolipoprotein removal. In vivo heparin resistance was present and heparin-paraprotein interaction was shown in vitro.

One-stage assay of heparin.

A simple and rapid one-stage plasma heparin assay based on the heparin-dependent neutralization of activated factor X (Xa) is described. Factor Xa is prepared in a concentration adjusted to produce a clotting time of 18 to 20 seconds when heparin-free plasma is tested in the system. The assay incubation mixture contains "standard human plasma", the heparinized test plasma, cephalin, and factor Xa.

A rapid, quantitative determination of clottable fibrinogen unaffected by heparin.

A turbidimetric assay for clottable plasma fibrinogen which is not sensitive to heparin or Pyran inhibition is described. The basis of the assay is the substitution of Reptilase-R for the thrombin usually employed. The assay correlates very well with a thrombin turbidimetric method and also has other advantages, including better stability of the clotting enzyme and more rapid attainment of equilibrium.