PREVENTION OF THROMBOTIC COMPLICATIONS OF THE NEPHROTIC SYNDROME BY THE LOW-MOLECULAR-WEIGHT HEPARIN ENOXAPARIN

The nephrotic syndrome (NS) carries one of the highest risks of thromb otic complications. Consequently, over the last 15 years, some nephrol ogists have treated patients at risk (i.e. those with albuminemia <20 g/l and membranous nephropathy) with anticoagulants: either subcutaneo us heparin (Kakkar protocol) or antivitamin K. Low-molecular-weight he parin (LMWH) has a longer plasma half-life and better bioavailability than standard heparin and can thus be administered as a single daily i njection. LMWH also carries a lower risk of hemorrhage. We prospective ly studied the safety and efficacy of the LMWH Enoxaparin for preventi ve anticoagulation in NS. In a preliminary study, 10 adult nephrotic p atients with biological markers of thrombosis risk (severe hypoalbumin emia and/or anomalies of the fibrinolytic pathway and/or deficiency in coagulation inhibitors) were given 40 mg (4,000 U) of Enoxaparin dail y for at least 3 months; 3 patients were treated for 3 months, 1 for 6 months and 6 for 12 months. Patients were assessed for silent thrombo sis, using renal vein Doppler ultrasonography, lower leg vein Doppler ultrasonography and lung ventilation-perfusion scintigraphy, before en try to the trial and subsequently at 3-month intervals. As LWMH caused no obvious side effects and no thrombosis was observed during the pil ot study, we then placed 55 adult nephrotic patients free of thrombosi s on the same treatment. Patients were seen according to the usual cal endar required by their individual illnesses. At each examination, pat ients were assessed for clinical signs and symptoms of thrombosis and side effects; plasma D-dimer and urinary fibrin-fibrinogen degradation products were also measured at each visit. Twenty-five of the 55 pati ents (minimal-change disease, n=15; membranous nephropathy, n=2; syste mic lupus erythematosus, n=2; other forms of glomerulonephritis, n=6) received LMWH for less than 4 months. No side effects or thrombosis we re observed, with the exception of 1 patient who had local intolerance to Enoxaparin but not to Teldeparin. The other 30 patients (membranou s nephropathy, n=14; segmental glomerulosclerosis, n=13; other nephrop athies, n=3) received LMWH for at least 6 months (median, 13 months; r ange, 6-48 months). No side-effects or thrombosis were observed. Enoxa parin caused no changes in bone density in patients at risk of osteopo rosis, as determined by absorptiometry. The self-administered LMWH the rapy was well accepted by patients, most of whom found it straightforw ard and painless. The results of this prospective study suggest that t he LMWH Enoxaparin given at a dose appropriate for adult NS patients w ith a high thrombotic risk is safe, effective and easily self-administ ered. The incidence of bleeding was low. Our findings provide argument s for the adoption of LMWH as first-line preventive anticoagulation in NS.