T. Lecompte

Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus—A meta-analysis

Objective: To describe the relative risk for venous thrombosis (VT) associated with antiphos pholipid antibodies (aPL) in systemic lupus erythematosus (SLE). Design: Systematic review and meta-analysis of 26 articles that examined the association between aPL and VT in SLE. Setting: Mostly secondary and tertiary referral centres. Patients: 2249 patients with SLE, 1120 tested for LA (lupus anticoagulant) and 1563 tested for aCL (anticardiolipin antibodies). Main outcome measures: A summary of study characteristics and a critical appraisal of study quality were done. Two statistical combinations of 18 primary studies that examined the association of VT and LA and of 14 studies that examined the association of VT and aCL were performed to estimate the risk for VT associated with aPL. Results: The odds ratios of the risk of VT related to the LA summarized from 18 studies were 5.61 [95% CI; 3.80-8.27] overall, 6.32 [CI; 3.71-10.78] for deep venous thrombosis and pulmonary embolism, 11.6 [3.65--36.91] for recurrent venous thrombosis after the first event. The odds ratios of the risk of VT related to aCL summarized from 14 studies were 2.17 [95% CI; 1.51-3.11] overall, 2.50 [CI; 1.51-4.14] for deep venous thrombosis and pulmonary embolism, 3.91 [1.14- 13.38] for recurrent venous thrombosis after the first event. Conclusions: Patients with SLE and LA are at approximately six times greater risk for VT than patients without LA, whereas patients with SLE and aCL are approximately two times greater risk for VT than patients without aCL. We have identified important methodologic limitations and differences in study characteristics. Other risk factors for VT have not been thoroughly evaluated in these studies. Further studies are needed that provide an accurate estimate of the absolute risk for aPL related VT.

Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis

Patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL) are at a greater risk for venous thromboembolism (VTE) than SLE patients without these antibodies. For patients without SLE there is a controversy about the risk associated with these antibodies and about their prognostic significance. We reviewed the degree of evidence and describe the odds ratio for VTE associated with aPL, namely the lupus anticoagulant (LA) and anticardiolipin antibodies (aCL), in patients without SLE. The study was a meta-analysis of seven observational studies of risk for antiphospholipid associated venous thromboembolism (VTE), excluding SLE patients. The strategies to identify published research included a computerized literature search and the review of citations in primarily relevant articles for the period 1983 to 1997. A summary of study characteristics and a critical appraisal of study quality were done. Summary odds ratios were obtained conducted using a random and a fixed effects-model. The overall odds ratio for aCL associated VTE obtained by fixed-effects model was 1.56 (95% CI, 1.10—2.24) and 1.64 (95% CI, 0.93—2.89) by random-effects model. The heterogeneity of these results appeared to be due in part to the detection limit of the aCL assay: the odds ratio was 3.21 (95% CI, 1.11—9.28) with both models when high titres only were considered. The overall odds ratio for LA associated VTE was 11.1 (95% CI, 3.81—32.3). In conclusion meta-analysis of the risk for antiphospholipid associated thrombosis demonstrated a higher risk in patients with the LA than in other patients. This risk was also higher than in patients with aCL even when high titres only were considered.

Monovalent binding of autoantibodies to beta2-glycoprotein I, detected using surface plasmon resonance at low antigen density.

The precise mechanism of interaction between autoantibodies and β2‐glycoprotein I (β2GPI) and the experimental conditions to be used for their detection are still under debate. Until now, these interactions have been studied under static conditions. We have investigated the interactions of purified IgG from 25 lupus anticoagulant‐positive patients with immobilized β2GPI under flow conditions by real‐time analysis based on surface plasmon resonance technology. Sensor chips were coated with purified human β2GPI coupled to dextran via amino groups at low densities (1·4, 1·8 or 2·4u2003ng β2GPI/mm2). Four patients IgG displayed efficient binding and had the highest so‐called antiphospholipid IgG levels by enzyme‐linked immunosorbent assay (ELISA) and the highest absorbance values in an anti‐ β2GPI ELISA at a β2GPI density reported to be around 12u2003ng/mm2. Binding of antibodies to the β2GPI sensor chips proved to be dependent upon the IgG concentration and β2GPI density and was inhibited by a rabbit antibody against β2GPI. Similar association and dissociation profiles were observed for the four efficient binders. The fast rate of dissociation limited the binding of autoantibodies to β2GPI and was highly suggestive of a monovalent association, confirmed by binding of Fab fragments under similar experimental conditions. In conclusion, monovalent binding of low‐affinity antibodies to β2GPI immobilized at a density as low as 1·8u2003ng/mm2 could be detected using surface plasmon resonance.

Thrombose veineuse rénale néonatale et double hétérozygotie pour le facteur V Leiden et la prothrombine

Resume Nous rapportons une observation de thrombose veineuse renale chez un nouveau-ne porteur dˈune double mutation a lˈetat heterozygote pour le facteurxa0Vxa0Leiden et pour la prothrombine. Observation.xa0– xa0Un nouveau-ne a terme etait traite par thrombolytiques et heparine a quatre jours de vie pour une thrombose de la veine renale avec extension a la veine cave et un hematome surrenalien. Apres quatrexa0jours de traitement anticoagulant et thrombolytique, la thrombose a disparu. Lˈevolution etait marquee par une atrophie renale. Le bilan de coagulation mettait en evidence la presence chez lˈenfant de deuxxa0mutations a lˈetat heterozygote, lˈune pour le facteurxa0Vxa0Leiden (FV–506xa0Q) et lˈautre pour la prothrombine (IIG20210A), transmises chacune par lˈun des parents. Conclusion. – Toute thrombose neonatale impose une etude de lˈhemostase, a la recherche de facteurs biologiques predisposant a la thrombose et exposant le patient a un risque de recidive. La thrombolyse semble efficace pour le traitement des thromboses veineuses. La prevention de la recidive thrombotique par un traitement anticoagulant prolonge reste debattue.

Definition and significance of high positivity aCL ELISA

We conducted a prospective study of anticardiolipin antibody (aCL) testing, performed in our university hospital. Among 6321 consecutive patients tested for both IgG and IgM aCL, 91 patients with medium or high positivity (>99th percentile) had a subsequent confirmatory test. Among them, 53 had a persistent positivity at 12 weeks. In this real world setting, patients with transient positivity had lower values than patients with persistent positivity.

Acanthocytes et hypocholestérolémie

We report on a child presenting with Andersons disease. Acanthocytes (spur cells) were observed on the blood smear, in accordance to the diagnosis. The defect in lipid metabolism lead to changes in erythrocytes membrane composition. We insist on morphological differences between acanthocytes and echinocytes (both are deformed erythrocytes), regarding separate clinical diagnosis.

Cas cliniqueAnticoagulation péri-opératoire par danaparoïde (Orgaran®) chez un patient ayant un syndrome de Budd-Chiari et une thrombopénie induite par l’héparinePeri-operative anticoagulation with danaparoid for a patient with Budd-Chiari syndrome and heparin-induced thrombocytopenia

We report a case of Budd-Chiari syndrome revealing a polycythemia vera and complicated by heparin-induced thrombocytopenia. A surgical porto-caval shunt was inserted with danaparoid as anticoagulant during the peri-operative period. The doses of danaparoid were as follows: a continous intravenous infusion of 200 U/h with a target between 0.5 et 0.8 U/ml antifactor Xa activity during the preoperative period, followed by 100 U/h with a target of 0.3 U/ml during the peroperative period; an increase in doses of danaparoid to 150 and 200 U/h with a target above 0.5 U/ml was used during the postoperative period. This case report is a rare situation of hypercoagulable state, in a surgical context, treated with danaparoid.

Anticoagulation péri-opératoire par danaparoïde (Orgaran®) chez un patient ayant un syndrome de Budd-Chiari et une thrombopénie induite par l'héparine

We report a case of Budd-Chiari syndrome revealing a polycythemia vera and complicated by heparin-induced thrombocytopenia. A surgical porto-caval shunt was inserted with danaparoid as anticoagulant during the peri-operative period. The doses of danaparoid were as follows: a continous intravenous infusion of 200 U/h with a target between 0.5 et 0.8 U/ml antifactor Xa activity during the preoperative period, followed by 100 U/h with a target of 0.3 U/ml during the peroperative period; an increase in doses of danaparoid to 150 and 200 U/h with a target above 0.5 U/ml was used during the postoperative period. This case report is a rare situation of hypercoagulable state, in a surgical context, treated with danaparoid.

Effets indésirables des traitements anticoagulants en dehors des hémorragies

Resume Les traitements anticoagulants (heparines et antagonistes de la vitamine K) sont largement prescrits. Il est important de connaitre leurs effets indesirables, certains pouvant compliquer serieusement la prise en charge du patient. Il sagit, en premier lieu, des thrombopenies induites par une heparine ; de nouveaux produits ont ete commercialises recemment et peuvent etre proposes comme traitement anticoagulant de remplacement (danaparoide, hirudine recombinante). Parmi dautres effets indesirables nous avons surtout envisage les manifestations cutanees et les priapismes. Les reactions indesirables doivent etre declarees a la pharmacovigilance, ce qui est un moyen daugmenter la base de donnees.

Comparative assessment of phospholipid-binding antibodies indicates limited overlapping.

The implication of autoantibodies with anticoagulant and/or so‐called antiphospholipid activities, under clinical circumstances with vascular obliteration, has led to the development of various types of tests allowing their detection. The most used tests involve investigation of the presence of an anticoagulant effect and of anticardiolipin IgG. It has also been proposed that the reactivity of patient samples toward other phospholipids or proteins be tested, but it remains difficult to appreciate which tests are redundant or complementary. Here we investigated whether the dissociation or association of anticoagulant and anticardiolipin correlated with specific ELISA reactivity to five other phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylcholine, and phosphatidylethanolamine. The study was performed with 70 samples, evenly partitioned as positive for either anticardiolipin antibodies or anticoagulant effect, or both. Our data clearly confirm that cardiolipin reactivity is an individual entity, likely to be complementary to other assays. Neither anticardiolipin nor anticoagulant levels correlated with assays investigating antibody levels toward the five other phospholipids, although higher mean levels were noted when both lupus anticoagulant and anticardiolipin antibodies are present. Individual patterns were evidenced in all groups. These data support the interest of current and further studies exploring the clinical relevance of individual reactivities to phospholipids.