Thrombin Metz: characterization of the dysfunctional thrombin derived from a variant of human prothrombin.

Thrombin Metz and normal thrombin, resulting from activation of the respective prothrombins by factor Xa in the presence of calcium, phospholipid, and factor Va, were purified by chromatography on sulfopropyl Sephadex. By physicochemical criteria, thrombin Metz is identical to normal thrombin. Its functional properties were investigated in some reactions in which thrombin is classically involved.

Albumin, fibrinogen, prothrombin and antithrombin III variations in blood, urines and liver in rat nephrotic syndrome (Heymann nephritis).

Albumin, fibrinogen, prothrombin and antithrombin III (AT III) variations have been studied in blood, urines and liver during an experimental nephrotic syndrome in rats (Heymann nephritis). A quantitative morphometric study (light microscopy) has been performed in the liver using an immunocytochemical technique--(PAP) method--to evaluate the protein synthesis by the number of protein-containing hepatocytes. Some sections were also studied by electron microscopy.

Fibrinogen Bondy: a new case of dysfibrinogenemia. Isolation of the abnormal fibrinogen molecules.

In a 81 year old health woman, gross abnormalities of fibrin formation led to the discovery of an abnormal fibrinogen named fibrinogen Bondy. Clottability of purified fibrinogen Bondy was only 53% compared to 95-98% for normal fibrinogen. Functional studies revealed (i) delayed coagulation by thrombin and batroxobin (Reptilase), (ii) incomplete release of fibrino-peptides A and B, (iii) poor fibrin monomer aggregation, (iv) delayed fibrin proteolysis by plasmin.

A new variant of human prothrombin: prothrombin Metz, demonstration in a family showing double heterozygosity for congenital hypoprothrombinemia and dysprothrombinemia.

Investigation of a mild hemorrhagic tendency in a French family revealed the father to be heterozygous for hypoprothrombinemia while the mother was heterozygous for dysprothrombinemia. All possible genetic combinations could be demonstrated. Among the children the double heterozygosity encountered in 3 of them allowed us to discover an abnormal prothrombin, prothrombin Metz, which generates an abnormal thrombin less sensitive to inactivation by antithrombin III than normal thrombin.

Respective roles of antithrombin III and alpha 2 macroglobulin in thrombin inactivation.

In order to investigate the mechanism of thrombin inactivation in the presence of both antithrombin III (AT III) and alpha 2-macroglobulin (alpha 2 M), thrombin and the inhibitors have been purified from human material and thrombin inactivation studied using purified reagents either alone or added to defibrinated plasma. Comparison of clotting and amidolytic activities of residual thrombin allowed to measure the amount of thrombin bound to alpha 2 M. In a purified reagent system as well as in plasma, part of exogenous thrombin is bound to alpha 2 M.

Antithrombin III versus prothrombin in liver cirrhosis.

In patients with liver cirrhosis, a close relationship was observed between the respective levels of antithrombin III and prothrombin, both below 50% in 20 our 27 patients. The absence of any thrombotic complication, despite low plasma antithrombin III, suggests that the preserved balance between the inhibitor and the zymogens of the inhibited enzymes could have a protective effect against thrombotic tendency.

[Severe blood coagulation disorder as the first sign of a peritoneal hemangio-endothelioma: a new therapeutic approach (author's transl)].

The authors describe a 3 1/2 month old infant with hemangio-endothelioma and a severe blood coagulation disorder. The tumor was inoperable and the severe blood coagulation disorder posed considerable therapeutic problem. After treatment with massive amounts of blood clotting factors, an antifibrinolytic drug and radiotherapy, the child's condition improved.

[Familial thromboembolic disease associated with antithrombin III deficiency (author's transl)].

The authors report the observation of a new kindred with hereditary antithrombin III deficiency. In the last three generations, the family comprised 10 subjects, 7 of whom were affected: the grandmother had recurrent thrombophlebitis; her three sons died from pulmonary embolism at 22, 26 and 28 respectively and her daughter had repeated bouts of thrombophlebitis. In patients with hereditary antithrombin III deficiency, venous thrombosis occurs under similar conditions as, and is clinically similar to, thrombosis in patients without this defect.

[Anticoagulants with antithrombinase activity in systemic lupus erythematosus (author's transl)].

An anticoagulant with antithrombinase activity was looked for in 49 patients with systemic lupus erythematosus and found to be present in 14 of them. The latter were suffering from severe and progressive lupus, specially with arterial involvement. The presence of an isolated antithrombinase does not contraindicate a renal biopsy provided the platelet count and other coagulation factors are normal.

[Nephrotic syndrome, antithrombin III deficiency and recurrent thrombosis. The value of vitamin K antagonists].

In a 7 year-old girl presenting with nephrotic syndrome and repeated episodes of thrombosis, a decrease in antithrombin III and in vitro inactivity of heparin were observed. Treatment by vitamin K antagonists prevented further thromboembolic episodes.

[Initiation in vivo of blood coagulation. The role of white blood cells and tissue factor (author's transl)].

Tissue factor is an ubiquitous phospholipid-protein complex, which triggers blood coagulation through the so-called extrinsic pathway. Reactions initiated by tissue factor bypass many of the early stages of coagulation (contact phase) and involve factors VII, X, V, II and fibrinogen but also factor IX (and VIII) as it was recently demonstrated. So, it appears that tissue factor has a key-role in the haemostasic process as it has been suggested by the mildness or the absence of haemorrhagic syndrome in contact factors deficiencies.

[Heparin inhibition of the antithrombin activity of alpha-2-macroglobulin].

The interaction between thrombin and alpha-2-macroglobulin was studied on human purified materials, either in the presence or in the absence of heparin, by kinetic analysis of thrombin inhibition and polyacrylamide gel electrophoresis. In the absence of heparin, binding of thrombin to alpha-2-macroglobulin, shown by electrophoresis, leads to the loss of the coagulant property of the enzyme. In the presence of heparin the rate of inhibition of thrombin clotting activity by alpha-2-macroglobulin is strongly decreased.

[The system Hemalog D in paediatrics (author's transl)].

The Hemalog D was studied at the Childrens' Hospital to examine its performance in paediatrics. All the subjects studied were children with non-hematologic diseases; both venous and capillary blood samples were taken. The differential was performed in parallel by the Hemalog D and the technicians of the Hematology Laboratory.

[Influence of the hematocrit on the formation of Heinz bodies within the red cells (author's transl)].

The increased in vitro formation of Heinz bodies in erythrocytes exposed to oxidant agents (acetylphenylhydrazine) is an excellent screening test for the diagnosis of various congenital abnormalities of red blood cells (G-6-PD deficiency, unstable haemoglobins). This phenomenon is strongly dependent of the PCV of the test blood. Anemia by itself (hematocrit less than 30 p.

Tissue factor activity of rabbit peritoneal macrophages: influence of immune stimulation.

Rabbit peritoneal macrophages exhibit a potent tissue factor activity able to trigger the extrinsic pathway of blood coagulation. This activity is elicited by the inflammatory reaction. Local injection of antigen in immunized animals leads to a lowering of the macrophage procoagulant activity.

Factor V and VIII activation "in vivo" during bleeding. Evidence of thrombin formation at the early stage of hemostasis.

Factor V and VIII activity was measured by a one-stage assay on capillary blood issuing from a skin cut. This activity increases during bleeding. The phenomenon is suppressed by a previous injection of a low dose of heparin.

[Severe epistaxis in hemorrhagic syndromes (excepting Rendu-Osler disease)].

The existence of a general abnormality in haemostasis causes more copious and protracted haemorrhage but does not, in theory, cause epistaxis. Abnormalities in primary haemostasis are at the root of these serious haemorrhages (thrombocytopenia and Willebrand's disease). Haemophilia is more rarely the trigger for intractable epistaxis.