Skin necrosis due to fluindione treatment: a rare but serious complication.

In the setting of protein C deficiency, skin necrosis, which occurs most often at the initial phase of oral anticoagulants therapy, is a rare side effect. Six cases have previously been reported in the literature. In this case report, we present a protein C deficient 42-year-old woman who was being treated for venous thrombosis. Five days after the initiation of oral anticoagulant treatment, she developed extensive skin necrosis on her left calf, followed by a painful leg ulcer. The pathogenesis underlying skin necrosis caused by anticoagulation therapy is still not clear. Despite only a few cases being reported in the literature, it is important to recognise this complication since adequate therapeutic approaches leading to a stable anticoagulation state may prevent it.

[Review: delta-storage pool disease]. / Mise au point : la maladie du pool vide plaquettaire.

Platelet storage pool disease is a qualitative platelet disorder associated with variable degrees of reduction in the numbers and contents of dense granules (delta-granules). Electron microscopy is the major tool for biological diagnosis. Patients presenting with this platelet disorder generally show a mild bleeding syndrome.

Agreement between factor XIII activity and antigen assays in measurement of factor XIII: A French multicenter study of 147 human plasma samples.

INTRODUCTION: Factor XIII (FXIII) deficiency is a rare hemorrhagic disorder whose early diagnosis is crucial for appropriate treatment and prophylactic supplementation in cases of severe deficiency. International guidelines recommend a quantitative FXIII activity assay as first-line screening test. FXIII antigen measurement may be performed to establish the subtype of FXIII deficiency (FXIIID) when activity is decreased. METHODS: The aim of this multicenter study was to evaluate the analytical and diagnostic levels of performance of a new latex immunoassay, K-Assay® FXIII reagent from Stago, for first-line measurement of FXIII antigen. Results were compared to those obtained with the Berichrom® FXIII chromogenic assay for measurement of FXIII activity. Of the 147 patient plasma samples, 138 were selected for analysis. RESULTS: The accuracy was very good, with intercenter reproducibility close to 7%. Five groups were defined on FXIII activity level (<5% (n = 5), 5%-30% (n = 23), 30%-60% (n = 17), 60%-120% (n = 69), above 120% (n = 24)), without statistical differences between activity and antigen levels (P value >0.05). Correlation of the K-Assay® with the Berichrom® FXIII activity results was excellent (r = 0.919). Good agreement was established by the Bland and Altman method, with a bias of +9.4% on all samples, and of -1.4% for FXIII levels lower than 30%. One patient with afibrinogenemia showed low levels of Berichrom® FXIII activity but normal antigen level and clot solubility as expected. CONCLUSIONS: The measurement of FXIII antigen using the K-Assay® is a reliable first-line tool for detection of FXIII deficiency when an activity assay is not available.

[Anticoagulant clinics are they effective in France? Performance evaluation of six anticoagulant clinics concerning the management of vitamin K antagonists]. / Les cliniques d'anticoagulants sont-elles efficaces en France ? Évaluation des performances de six cliniques dans la gestion des traitements par antivitamines K.

PURPOSE: Recent data show that the quality of anticoagulation evaluated in patients receiving vitamin K antagonists (VKA) is not optimal in France. The aim of this retrospective study was to estimate the performances of six French anticoagulant clinics that manage VKA treatments over a 3-year period, from 2009 to 2011. METHODS: All clinics used the same rule based software. We determined the time spent in the therapeutic range (TTR), a surrogate end-point of quality of treatment with VKA. RESULTS: The overall duration of follow-up was 2755 patient-years concerning 2385 patients. The time spent in the therapeutic range 2 to 3 assigned for 89% of the patients, was 73%. On the other hand the time spent in the therapeutic range for the other two INR ranges (2.5-3.5 and 3-4.5) concerning 11% of patients with prosthetic heart valve was lower (63.7% and 68.8% respectively) with an imbalance in favour of the time below the range. In this study, warfarin (Coumadine(®)) and fluindione (Previscan(®)) allowed an equivalent quality of anticoagulation. The 1728 patients of age ranged from 60 to 100 years spent more time in TTR than the 651 younger patients. The percentage of time spent with an INR greater than 5 was extremely reduced which is a guarantee of safety. CONCLUSION: These results prove that anticoagulant clinics in France have the same good performances as their counterparts abroad. It can be assumed that a high TTR contributes to a low incidence of both bleedings and thrombosis.

[Pharmacologic heterogeneity of new anticoagulants]. / Hétérogénéité pharmacologique des nouveaux anticoagulants.

Amongst numerous promising anticoagulant molecules, rivaroxaban (Xarelto(®)), dabigatran (Pradaxa(®)) and apixaban (Eliquis(®)) have been registered outside the USA in the prevention of thromboembolic events in patients undergoing total hip or knee prosthetic replacement. Rivaroxaban however has been granted authorisation by the FDA for the thromboprophylaxis after surgery for total hip or knee surgery. Dabigatran has been granted authorisation by the FDA in non-valvular atrial fibrillation (RE-LY trial) while rivaroxaban is expecting approval in this same indication (ROCKET trial). Phase III results in the treatment and in the secondary prevention of established venous thrombosis and pulmonary embolism are encouraging. These small molecules are obtained by chemical synthesis, their molecular weight is lower than 500 daltons. Many coagulation tests may be affected by these molecules. Those modifications should be known in order to avoid misinterpretation of the tests but could also be used to measure plasma concentrations of these products. The choice of a non specific global and readily available test has been documented (Quick time for rivaroxaban and aPTT for dabigatran). Anti-Xa (for rivaroxaban) and anti-IIa (for dabigatran) activities should however be preferred, expressed in ng/ml with calibrated plasmas (containing predetermined concentration of the tested drug). The half-life is around 8 to 12 hours, with a peak activity 2 to 4 hours after ingestion. Dabigatran is mainly eliminated via the kidney, hence requiring dose-adjustment in case of moderate renal insufficiency, and contra-indicated in case of severe renal insufficiency. Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. No data are available in pregnancy or pediatrics, clinical trials are ongoing. There are few interactions with concomitant drugs, which should not be ignored. The short half-life of these new agents compensates for the lack of any specific antidote in many instances. Their oral administration, without the need for dose adjustment, and without requirement for a laboratory monitoring will increase their use in a large number of patients, in those indications for which an approval has been granted by health authorities.

Rituximab alone or in association with corticosteroids in the treatment of acquired factor VIII inhibitors: report of two cases.

Acquired haemophilia is a factor VIII (FVIII) deficiency due to autoantibodies directed against FVIII that can be responsible for severe haemorrhage. The therapeutic approach, in addition to the treatment of bleeding episodes with clotting factor infusion, relies on corticosteroids (CS), cyclophosphamide (CYC), and/or high-dose intravenous immunoglobulins (IVIg). However, the efficacy of IVIg is limited, and CS and CYC may cause a number of adverse effects. Recently, rituximab has been proposed, alone or in combination with CS and immunosuppressants in a small number of patients with acquired anti-FVIII antibodies with a good efficacy. We report here on two patients, aged 74 and 81, respectively, who developed acquired haemophilia, with high titre FVIII inhibitors and severe haemorrhage, in the absence of a detectable cause. Both of them received rituximab as a first line therapy with a marked and prolonged efficacy.