[Factor V-specific circulating anticoagulant and enteropathy. 2 cases]. / Anticoagulant circulant spécifique du facteur V et entéropathie. Deux observations.

Two patients with Factor V-specific circulating anticoagulant are presented: one had coeliac disease, the other Crohn's disease. In both patients the inhibitor appeared during flare-ups of the disease and disappeared during remission. This sequence was repeated after 1 year in one case, which seems to exclude a fortuitous association. No haemorrhage was observed. None of the usual aetiological circumstances was noted, which suggests that the condition was most probably auto-immune.

[Thrombocytopenia induced by heparin and cardiac surgery with extracorporeal circulation]. / Thrombopénie induite par l'héparine et chirurgie cardiaque sous circulation extracorporelle.

A case of mitral and aortic valvular replacement combined with double coronary artery bypass grafting is reported in a 64-year-old woman who presented with a history of heparin-induced thrombocytopenia. The use of a conventional dose of heparin did not induce the formation of a plasma platelet-aggregation factor. The necessity of postoperative anticoagulation was ensured by the prescription of antivitamin K, started on the morning of the operative day.

Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients--relationship with plasma insulin.

Type 2 diabetic patients are known to frequently have a high insulin level and were recently described as having high plasminogen activator inhibitor (PAI) activity, compared to normal controls. As we have shown in several clinical conditions (normal subjects, obese patients, angina pectoris patients) that plasma PAI activity was linked with plasma insulin, we have studied in 38 type 2 diabetic patients the relationship between PAI activity, insulin and other parameters. Patients showed higher level of PAI activity, as well as plasma glucose, insulin, triglyceride, cholesterol and Apolipoprotein B levels than normal controls; highest values were observed with diabetic patients also affected by coronary artery disease. A significant correlation was found between PAI activity and insulin (r = 0.60, p less than 0.001), body mass index (r = 0.32, p less than 0.05) and Apolipoprotein B (r = 0.33, p less than 0.05). The two latter correlations disappeared after adjustment for insulin. These results are in agreement with our previous report showing an in vitro effect of insulin on the synthesis of PAI by a hepatocellular cell line. Hyperinsulinemia presented by type 2 diabetic patients may increase the hepatic synthesis of PAI, inducing an hypofibrinolysis, which could play a role in the development of the vascular complications. Attempts to reduce hyperinsulinemia could have a favorable effect by lowering PAI activity.

[Circulating anticoagulants in immunodeficiency virus infection. Results of a prospective study of 157 seropositive patients]. / Les anticoagulants circulants au cours de l'infection par le virus de l'immunodéficience humaine. Résultats d'une étude prospective effectuée chez 157 patients séropositifs.

One hundred and fifty-seven HIV seropositive patients were included in a prospective study of coagulation parameters. Activated partial thromboplastin time, prothrombin time, thrombin time and specific factor assays of the intrinsic pathway were performed using standard techniques. The tissue thromboplastin inhibition test and antiphospholipid antibodies were used to establish the presence of circulating lupus anticoagulant. Among the 46 patients with a prolonged activated partial thromboplastin time, an anti-prothrombinase was present in 33. Of the 111 patients with a normal activated partial thromboplastin time, anti-prothrombinase was present in 51. Circulating lupus anticoagulant seems to be common in HIV seropositive patients, since it was found in 84 patients (53.5%). Our findings confirm that the presence of circulating anticoagulants is not particularly associated with opportunistic infections or the development of the disease. It is possible that these inhibitors could be mediated by anti-phospholipid antibodies. In HIV seropositive patients, defective T cell regulation of B cells leads to polyclonal hypergammaglobulinemia. These antibodies may be directed against endogenous or exogenous phospholipids.

[The effect of pentoxifylline and propentofylline on the membrane fluidity of red blood cells in uncontrolled insulin-dependent (type 1) diabetic patients]. / Etude de l'effet de la pentoxifylline et de la propentofylline sur la fluidité membranaire de globules rouges de sujets diabétiques insulino-dépendants (type 1) déséquilibrés.

Fluorescence polarization of red blood cell (RBC) membranes evaluated using DPH was measured in patients with uncontrolled insulin-dependent diabetes mellitus and in controls. The effect of in vitro addition of pentoxifylline and propentofylline (10(-5) and 10(-4) M) was studied. The fluorescence polarization parameter (P) was lower in the diabetic patients (p = 0.20 +/- 0.03, n = 8) as compared to the controls (p = 0.28 +/- 0.02), n = 8), reflecting an increase in probe mobility in the hydrophobic environment in the depth of the double lipid layer. In vitro addition of pentoxifylline had no effect on the fluorescence parameter of RBC membranes from controls, whereas both concentrations of pentoxifylline studied (p = 0.24 +/- 0.03) significantly increased the fluorescence parameter of RBC membranes from diabetics. Propentofylline had no effect. These findings suggest that the active site responsible for improved membrane fluidity of RBC from diabetics is located on the methyl radical present in the pentoxifylline molecule but not in the propentofylline molecule.

[The significance of the levels of D-dimer in thrombotic conditions]. / Intérêt du dosage des D-Dimères dans les états thrombotiques.

A D Dimer ELISA test (Asserachrom D Di Stago) was used to quantify the modification of plasmatic D Dimer levels in two kinds of thrombotic diseases: DIC and deep venous thrombosis. Very high values were obtained in these two situations (m +/- sd): DIC (n = 22): 15.2 +/- 18.5 micrograms/ml. (Normal values were defined in 20 healthy subjects: 0.15 +/- 0.04 micrograms/ml). In DIC highest values were a bad prognosis, they were found in patients who died during the ten days following the diagnosis. In deep venous thrombosis the increase was not related to the size of the clot but to the endogenous fibrinolysis. An elevated concentration of D Dimer was often related to a good phlebographic evolution. During heparin therapy with standard heparin or low molecular weight heparin (LMWH) a greater decrease of D Dimer level was observed in patients with a good phlebographic evolution. Results expressed in percentage of decrease were (successful group against the failure group): J3/J10: 46.4 +/- 29.2 p. cent/13.4 +/- 11.0 p. cent (p less than 0.05); J7/J10: 52.3 +/- 31.5 p. cent/24.2 +/- 26.3 p. cent (p less than 0.05). The intensity of the decrease may have an indicative value for in vivo thrombolysis. This could be explained by a smaller clot mass to be lysed in successful group. During streptokinase treatment the D Dimer levels were very high (greater than 50 micrograms/ml). A problem of specificity could be evoked in presence of a massive quantity of fibrinogen degradation products levels.

Correction by pentoxifylline of the abnormal fluorescence polarization of erythrocyte membranes from diabetic patients.

Erythrocytes from diabetic patients show abnormal rheology. Pentoxifylline, a methylxanthine, improves the abnormal deformability of diabetic erythrocytes, but its mechanism of action remains unclear. We have studied the effect of pentoxifylline on the lipid order of erythrocyte membranes from controls and patients with Type I diabetes. We studied the structural organization of membrane lipids in individual erythrocyte ghosts by fluorescence polarization using a cell sorter. Fluorescence polarization values (P) for 17 controls (P = 0.244) and 20 diabetic patients (P = 0.215) were significantly different. Pentoxifylline added in vitro had no effect on normal membranes, but significantly increased at 10(-5) mol X l-1 (P = 0.233), and normalized at 10(-4) mol X l-1 (P = 0.243), the P value of membrane ghosts from diabetics.

Rapid modifications of biophysical and biochemical parameters of red blood cell membrane from insulin dependent diabetics after insulin administration.

We have previously shown that red blood cell (RBC) filtrability in uncontrolled insulin dependent diabetics is abnormal compared to healthy subjects, but is corrected by insulin added in vivo or in vitro. We have now found biophysical abnormalities of the RBC membrane in such patients: Fluorescence polarization value (p) evaluated using DPH as probe is significantly lower in patients; insulin added in vitro increases and normalises the p value of diabetic RBC membrane, and has no effect on normal RBC membrane. As there is a relationship between the lipid bilayer and membrane cytoskeleton proteins, this abnormality of RBC membrane fluidity, correctable by insulin, may be an important determinant of the rheological behaviour of the RBC. In parallel, biochemical abnormalities of the RBC membrane are shown in the same patients: Higher cholesterol/phospholipid ratio, lower content in unsaturated fatty acids and higher content in saturated fatty acids. Decreased activity of ouabaine sensitive Na+K+ ATPase and increased activity of Mg++ ATPase. All of these RBC biochemical abnormalities are corrected after 24 h of normoglycaemia obtained by insulin treatment given in vivo with a biostator. Our results show the importance to check the degree of control of glycaemia when studying rheological parameters in diabetes mellitus.

Correction by insulin added in vitro of abnormal membrane fluidity of the erythrocytes from type 1 (insulin-dependent) diabetic patients.

Filtrability of erythrocytes obtained from uncontrolled Type 1 (insulin-dependent) diabetic patients is abnormal, but is corrected by insulin added in vivo or in vitro. As erythrocyte filtrability depends on several determinants, we chose to study a membrane property of erythrocytes from diabetic subjects. Membrane fluidity was studied by fluorescence polarization using a lipophilic probe, the diphenyl-hexatriene and the Coulter Epics V together with a laser Spectra-physics 2000. Fluorescence polarization values obtained for 31 normal subjects (0.253 +/- 0.043 SD) and 31 uncontrolled Type 1 diabetic patients (0.231 +/- 0.043 SD) were significantly different (p less than 0.01). Insulin (2.5.10(-9) mol/l) added in vitro increased the fluorescence polarization values of red cell membranes from diabetic patients (without insulin, fluorescence polarization values = 0.210 +/- 0.032 SD; with insulin, fluorescence polarization values = 0.253 +/- 0.024 SD, p less than 0.001, n = 15), but had no effect on normal membranes (without insulin fluorescence polarization values = 0.255 +/- 0.037 SD, with insulin, fluorescence polarization values = 0.251 +/- 0.026 SD; n = 12). Given a relationship between the lipid bilayer and membrane cytoskeleton proteins, this insulin-correctable abnormality of erythrocyte membrane fluidity may be an important determinant of the rheological behaviour of erythrocytes from diabetic patients.

Possible participation of adenosine 5'-diphosphate, arachidonic acid and paf-acether in the platelet pro-aggregating effect of uncontrolled insulin-dependent diabetic erythrocytes in vitro.

The red blood cells (RBC) from uncontrolled insulin-dependent diabetics (U.IDD) induce aggregation of platelets from control subjects. This effect was not observed when using platelets made unsensitive to adenosine 5'-diphosphate (ADP), arachidonic acid (AA) or paf-acether. Since RBC from U.IDD are less deformable than those from control subjects, we treated normal RBC in vitro with glutaraldehyde. These rigid RBC were used to study aggregation of normal platelets and of those unsensitive to ADP, AA or paf-acether. Results obtained with glutaraldehyde-treated RBC were comparable to those obtained with RBC from U.IDD, i.e. aggregation was obtained with untreated platelets but not with platelets unsensitive to ADP, AA or paf-acether. It is hypothesized that aggregation of control platelets induced by RBC from U.IDD is purely mechanical at its origin but is ultimately mediated by ADP, AA or paf-acether.