[Activated protein C resistance and factor V Leiden: clinical interest]. / Résistance à la protéine C activée et facteur V Leiden : intérêt clinique.

Activated protein C resistance (APCR) is a coagulation abnormality often linked to FV Leiden mutation, a single nucleotide G1691A substitution resulting in arginine 506→glutamine missense factor V mutation. FV Leiden has a frequency of 20 to 30% in groups of patients with venous thrombosis while it is of 4 to 10% in normal subjects. FV Leiden is considered as a weak risk factor of thrombosis except in homozygote. FV Leiden is implicated in deep venous thrombosis occurrence. Duration of oral anticoagulant treatment is six months in patients developing a first venous thrombosis except in patients with combined defects or a clinical context suggesting a high risk of severe relapse. Detection of APCR by coagulation methods is often used in first intention with a high specificity if plasmas tested are diluted in factor V deficient plasma. Genotyping study is essential to establish the heterozygote or homozygote statute and certain teams perform it directly. Nevertheless, APCR not related to FV Leiden could be an independent thrombosis risk factor. APCR and FV Leiden are included in laboratory investigations of thrombophilic markers in patients less than 50 years with venous thrombosis. In arterial thrombosis, FV Leiden implication is weak or absent. FV Leiden increases the risk of thrombosis in other situations as in patients with cancer. An association with recurrent miscarriages and other vasculoplacental complications is also reported in many studies but the data concerning the efficacy of antithrombotic treatment to prevent recurrence are currently insufficient.

[Resistance to curative treatment by unfractionned heparin]. / Les résistances aux traitements curatifs par l'héparine non fractionnée.

Unfractionated heparin has been used as antithrombotic therapy for many years. Its main effect is attributed to the activation of antithrombin (AT), the heparin/AT complex inactivating both factor IIa (thrombin) and factor Xa. Resistance to unfractionated heparin with clinical or biological expression is uncommon. The occurrence of venous or arterial thrombosis or the extension of thrombosis in a patient receiving unfractionated heparin, should always raise suspicion of either AT deficiency or type 2 heparin-induced thrombocytopenia (HIT type 2). HIT type 2 is not a true heparin resistance but an immune complication that requires heparin discontinuation and the use of alternative anticoagulants. Biological heparin resistance is suspected in the presence of a normal or not prolonged activated partial thromboplastin time despite the administration of increasing dose of heparin. Measurement of anti-Xa activity is useful to adjust heparin treatment. Isolated biological heparin resistance is encountered in several physiological and pathological situations including inflammatory and infectious disorders, pregnancy and thrombocytosis. It also occurs in acquired antithrombin deficiency of nephrotic syndrome, l-asparaginase treatment or cardiopulmonary bypass. Biological heparin resistance is relatively common, but clinically significant resistance to heparin is rare and should always raise suspicion of either AT deficiency or type 2 heparin-induced thrombocytopenia.

[Association of tow thrombotic risk factors: factor V Leiden and hyperhomocysteinemia. A case report]. / Association de deux facteurs de risque thrombotique: facteur V Leiden et hyperhomocystéinémie. A propos d'un cas.

The identification of constitutional and/or acquired risk factor is of major importance in the treatment of thromboembolic disease in young people; it contributes to evaluate the risk of recurrence and to define the period of oral prophylactic anticoagulant treatment. Several congenital or acquired abnormalities of haemostasis are actually defined. In this paper, we report the case of a 34-year-old man who developed a deep venous thrombosis, five months before the diagnosis of megaloblastic anemia, probably due to pernicious anemia. The thrombosis was partially explained by the acquired hyperhomocysteinemia induced by vitamin B12 deficiency. Moreover, activated protein C resistance due to factor V Leiden, was revealed in our patient. This latter improved under anticoagulant treatment combined with vitamin B12. Combination in one individual, of different risk factors predisposing to inherited and/or acquired thrombophilia, results in increased risk for thrombo-embolic disease, suggesting synergic interaction between these factors.

Detection of serum hemolysins in autoimmune hemolytic anemia.

BACKGROUND: Some patients with autoimmune hemolytic anemia (AIHA) have in their sera autohemolysins able to hemolyze RBCs in vitro by activation of complement. We describe three autohemolysins in patients with AIHA and we study clinical correlations. STUDY DESIGN AND METHODS: Thirty-two patients with AIHA were explored by immuno-hematological investigations (DAT, elution and serum testing). RESULTS: Three autohemolysins were detected in three patients. All of these autoantibodies were likely IgM and reacted in vitro only with enzyme-treated RBCs. Two warm autohemolysins were detected in patients with warm-type AIHA. The first one was active at neutral pH with low title. The second, having a wide thermal amplitude reacting at 22 degrees C and a title of 16, was acid. The hemolysin detected in patient 3 with cold hemagglutinin disease, was active at 4 and 22 degrees C, at acid pH. The thermal optimum was 4 degrees C and the title 64. It was also detected at 37 degrees C with the same title, but only at neutral pH. CONCLUSION: Although these autohemolysins were incomplete, hemolyzing in vitro only enzyme-treated RBCs, they were associated for the three patients with severe hemolysis.