[Disseminated intravascular coagulation induced by heparin. Treatment with a combination of low-molecular weight heparin and concentrated antithrombin III].
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Biomedical subjects
Publications and source records attributed to M Gouault-Heilmann.
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An attempt was made to prevent heparin inactivation during the time that lapses between blood collection and laboratory assay. The blood collection in a combination of citric acid, theophylline, adenosine, dipyridamole - C.T.A.D. mixture - was found to reduce greatly the heparin loss during blood centrifugation and storage whatever the temperature for these two steps (centrifugation at 4 degrees C, 12 degrees C or 25 degrees C; storage at 4 degrees C or 20-25 degrees C). With this mixture the influence of centrifugation temperature upon the heparin loss appeared negligible. The heparin loss during the initial 5 hours storage at 20 degrees-25 degrees C was found to be 4.4 +/- 4% for a heparin concentration of 0.45 +/- 0.05IU/ml. The combination of the platelet active drugs with citric acid in C.T.A.D. mixture did not interfere either with the amidolytic heparin assay (anti IIa) or clotting tests such as activated partial thromboplastin time and calcium thrombin time. Thus the C.T.A.D. mixture appears to be useful in routine use because it is effective, cheap, stable, does not interfere with the tests currently used for monitoring heparin therapy and thus helps overcome the main cause of error in heparin assays.
The occurrence of thromboembolism in nephrotic syndrome has been recently correlated with acquired antithrombin III (AT III) deficiency (and this raised the question of the prevention and treatment of thromboembolism with heparin). We studied AT III levels in plasma and urine in 39 adults with nephrotic syndrome. Three patients have had thromboembolic manifestations (before treatment with heparin). Their albuminemia was less than 18 g/l, their plasmatic AT III levels were normal and one had an elevated urine AT III level. Plasmatic AT III levels and albuminemia were positively correlated (r = 0.34; p less than 0.05) but AT III levels remained in the normal range being moderately diminished in only 3 patients never less than 70 p. 100. There was no correlation between plasmatic AT III level and proteinuria or urinary AT III levels. We conclude that the risk of thromboembolism in adults with nephrotic syndrome is not correlated with plasmatic AT III levels. This suggests that heparin therapy would be effective in preventing thromboembolism in this disorder. Indeed, no such episodes were seen in our patients under heparin.
250 consecutive cases of AML in adults were diagnosed over a 6 year period in the same institution. Pretreatment blood and bone marrow smears and also cytochemical markers were taken into account in the study. All cases were reviewed by three different observers and classified according to the FAB criteria. The final diagnosis resulted from agreement of at least two observers. Some discrepancies occurred in the classification and are discussed. The prognostic implication of AML subclassification was assessed as the percentage of complete remission in 100 cases.
Screening tests for circulating anticoagulant were performed systematically in fifteen patients with different stages of syphilis. The lupus-type anticoagulant, an inhibitor of the prothrombin activator complex, was demonstrated in one primary and three secondary stages, without any hemorrhagic complications. The possible relationship between the occurrence of this type of inhibitor and positive antilipoidal tests is discussed in reference to the well-known association of circulating anticoagulant and biologic false positive serologic tests for syphilis observed in patients with SLE.
This report describes a patient without evident underlying disease, in whom an acquired von Willebrand's syndrome was discovered before surgery. Coagulation abnormalities included a borderline bleeding time, a low retention of platelets on glass beads, decreased levels of factor VIII procoagulant activity (VIIIAHF), factor VIII-related antigen (VIIIAg), and ristocetin-induced agglutination cofactor (VIIIVWF). After cryoprecipitate infusion the patient did not have the expected rise and there was no secondary increment in VIIIAHF. The patient was treated with prednisone for three weeks without significant improvement in the laboratory findings. Spontaneous resolution was observed long after this therapy. The haemostatic abnormalities were attributable to the presence of an inhibitor directed against VIIIVWF. The inhibitor was found in the IgM fraction. Its autoimmune nature is probable although we failed to demonstrate any inhibitory effect of Fab obtained from the patient's purified IgM. Despite the lack of inhibitory effect against VIIIAHF and VIIIAg, the low levels of all three activities of the factor VIII complex could be explained by the short half-life of immune complexes between factor VIII and the inhibitor.
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Electra 600 D has been used in our laboratory for 3 years. The Quick's prothrombine time is the only test routinely performed with satisfactory results. The measure of activated partial thromboplastin time, the assays of factor II, factor V and complex VII + X are unsatisfactory, probably because of the type of the reagents which are used.
The authors describe in this paper the considerations which led to the installation of a computer in an hematology laboratory. The different functions of the system are analyzed. Reception and identification of samples, codes for patients and analysis, print out of working lists, print out of results and monitoring of archives. A new system for differential counts is also described. Advantages of the system are discussed.
Thrombo-embolic accidents are extremely common during nephrotic syndrome (8 p. 100). They share the garvity of thrombo-embolic accidents occurring under other circumstances (20 p. 100 mortality). They are accompanied by numerous disturbances in clotting factors the mechanisms of which are discussed. Nevertheless the study of these disturbances does not make it possible to predict the onset of a thrombo-embolic problem. By contrast, the degree of hypoalbuminaemia is significantly correlated with the thrombotic risk (p. 0.001) and serves as an indication for the necessity of preventive heparin therapy, in the form of calcium heparinate. In this way the authors have been successful in eliminating the thrombo-embolic risk in association with nephrotic syndrome.
During experimental Masugi nephritis in the rabbit, were demonstrated various disturbances in hemostasis: a) during the initial stage: immediate, severe and transient fall in the platelet count without any change in Factor V;b)during the secondary stage, from the 7th to the 8th day onwards, increase in platelets and fibrinogen, in relation with the intensity of the nephrotic syndrome; c) in parallel, appearance of urinary fibrinogen split products in relation to the intensity of the glomerular lesions, evidence for the presence of intraglomerular fibrin. These facts confirm the role played by platelets in coagulation phenomena secondary to the immune reaction. They indicate, furthermore, the existence of hemostasis disorders during the nephrotic syndrome.
Intravascular coagulation localized in glomeruli is of pathologic importance in human and experimental GN. The measure of fibrinogen related antigen (FRA) in serum and urine after concentration (Merskey's technique) was used to detect and estimate this phenomenon. In Rabbit Masugi GN, FRA were detected in urine 5 to 20 mg/24 h, in close correlation with the amount of proteinuria, the intesity of histological changes and the presence of fibrin deposits in glomeruli. In human GN, urine FRA were detected in many cases (0,5-10 mg/24 h) in correlation with the histological type of lesions (FRA + in primary or secondary proliferative GN) and with the evolutivity of disease (FRA + in cases with rapidly progressive kidney function deficiency). Urine FRA are also in correlation with intraglomerular fibrin deposits : this suggests that urine FRA originate from lysis of fibrin deposited within glomeruli. So urine FRA appears to be an indicator of type and severity of GN and probably of therapeutic measures, indicating anticoagulant and/or antithrombic therapy : the variations of urine FRA during treatment is of value to assess the effects of these drugs and to establish the prognosis of the disease.
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This open, randomised multicenter trial compares the efficacy and safety of Fragmin administered subcutaneously twice daily with standard heparin administered by continuous infusion in the treatment of deep vein thrombosis (DVT). The initial dose of Fragmin is 100 U anti-Xa/kg/12 h and the further doses are adjusted according to the anti-Xa activity between 0.5 and 0.8 U/ml, 3 hours after the morning injection. The initial dose of standard heparin is 240 UI/kg/12 h. The dose adjustments are based on the daily results of APTT (1.5 - 3 times the control). Treatments efficacy are appreciated when comparing the venography performed before and after 10 days of treatment. The safety is evaluated on clinical parameters and iterative biological tests. Sixty-six patients have been included in this study. Efficacy of the two treatments is equivalent with a phlebographic improvement in respectively 79.3 p. 100 (Heparin Group) and 71.0 p. 100 (Fragmin Group) of the cases and an aggravation in 3.4 p. 100 and 6.4 p. 100 (NS) respectively. The frequency of dosage adjustments is lower and the stability of biological tests is better in the Fragmin group. In conclusion, the administration of Fragmin twice daily by subcutaneous route seems to be equivalent at least to standard heparin continuous infusion in the treatment of recent DVT. The better convenience and safety of Fragmin have to be verified on a larger panel of patients.