Libman‐sacks endocarditis exclusively involving the tricuspid valve in a patient with systemic lupus erythematosus

Libman‐Sacks endocarditis, characterized by sterile verrucous vegetations, is a rare but typical cardiac manifestation of systemic lupus erythematosus. It primarily leads to lesions of the mitral and aortic valves, but isolated tricuspid valve involvement is exceptional. We report the case of a 40‐year‐old woman with large tricuspid valve vegetations, thickening, and regurgitation. Clinical findings and laboratory tests confirmed the diagnosis of systemic lupus erythematosus. The patient successfully recovered following tricuspid valve replacement. Echocardiography is the definitive imaging modality for assessing cardiac valvular involvement, choosing appropriate therapy, and evaluating the prognosis of Libman‐Sacks endocarditis in systemic lupus erythematosus. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43 :265–267, 2015     

SLE继发抗磷脂抗体综合征合并Libman-Sacks心内膜炎一例

临床部分SLE患者可继发抗磷脂抗体综合征（APS）,但同时合并非细菌性心内膜炎的患者则较为罕见。该文报道1例SLE继发APS合并Libman-Sacks心内膜炎患者的诊治过程。该患者入院前有发热、关节痛、咽痛和皮疹,入院后UCG示二尖瓣前叶赘生物形成,查狼疮抗体、抗磷脂抗体、狼疮样抗凝物试验阳性,经抗感染治疗后病情未缓解,后患者突发头晕、口周麻木、构音不清、吞咽困难,查头颅MRI见一新发的延髓梗死灶。结合患者临床表现、体征及辅助检查,诊断为APS,Libman-Sacks心内膜炎,延髓梗死,SLE。予免疫抑制、免疫调节、低分子肝素抗凝等治疗后患者病情好转出院。该例的诊治提示,在UCG发现赘生物时,不仅要考虑感染性心内膜炎,同时需要考虑SLE继发APS可能,尤其是对于既往无明确心瓣膜病病史的年轻女性,早期诊断APS合并Libman-Sacks心内膜炎,并给予个体化抗凝治疗,可取得良好疗效。     

An international multicentre‐laboratory evaluation of a new assay to detect specifically lupus anticoagulants dependent on the presence of anti‐beta2‐glycoprotein autoantibodies

Summary. Background: Antiphospholipid syndrome (APS) is diagnosed by the simultaneous presence of vascular thrombosis and/or pregnancy morbidity and detection of antiphospholipid antibodies in plasma. Objectives: We have shown that prolongation of clotting time by anti‐beta2‐glycoprotein I (beta2GPI) antibodies correlates better with thrombosis than a positive classic lupus anticoagulant (LAC) assay in a single center study. To confirm or falsify this finding we have conducted a multicenter study. Methods and results: In 325 LAC‐positive samples, we found that the beta2GPI‐dependent LAC correlated 2.0 times better with thrombosis than the classic LAC assay. Although significant, this was a minimal improvement compared with the ‘classic’ LAC. It was published that calcium influences the behavior of anti‐beta2GPI antibodies in coagulation assays. To investigate whether calcium plays a role in the present study, we divided the patient population into two groups: (i) blood was collected in 0.109 m sodium citrate and (ii) blood was drawn in 0.129 m sodium citrate as anticoagulant. We found that a positive result with the beta2GPI‐dependent LAC assay correlated better with thrombosis [odds ratio (OR): 3.3, 95% confidence interval (CI) 1.9–5.8] when 0.109 m sodium citrate was used compared with 0.129 m sodium citrate (OR: 0.4, 95% CI 0.1–1.1). Conclusion: We were able to confirm in an international multicenter study that a positive result in a beta2GPI‐dependent LAC assay correlates better with thrombosis than the classic LAC assay, but that the assay needs further study as it is sensitive to external factors such as the sodium citrate concentration used as anticoagulant in the test sample.     

A prospective study of antibodies to β2-glycoprotein I and prothrombin, and risk of thrombosis

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.     

Clinical and laboratory characteristics of severe and non‐severe patients with COVID‐19: A retrospective cohort study in China

BackgroundPatients diagnosed with the novel coronavirus disease (COVID‐19) who develop severe symptoms need to be determined in advance so that appropriate treatment strategies are in place.MethodsTo determine the clinic features of patients diagnosed definitely with COVID‐19 and evaluate risk factors for severe outcome, the medical records of hospitalized patients were reviewed retrospectively by us and data were compiled. Laboratory data from 90 cases were analyzed, and COVID‐19 patients were classified into two groups (severe and non‐severe) based on the severity.ResultsSevere COVID‐19 cases on admission had higher leukocyte and neutrophil counts, neutrophil‐to‐lymphocyte ratio (NLR), D‐dimer, fibrinogen, C‐reactive protein levels, and lower lymphocyte counts compared with those of non‐severe cases (p < 0.05). The area under the curve (AUC) for leukocyte counts, neutrophil counts, and levels of C‐reactive protein was 0.778, 0.831, and 0.800, respectively. The thresholds were 7.70 × 10⁹/L for leukocyte counts, 5.93 × 10⁹/L for neutrophil counts, and 75.07 mg/L for C‐reactive protein, respectively. Logistic regression analyses indicated that higher white blood cell (WBC) counts (OR, 1.34; 95% CI, 1.05–1.71), neutrophil counts (OR, 1.35; 95% CI, 1.06–1.73), and C‐reactive protein levels (OR, 1.02; 95% CI, 1.0–1.04) were several predictive factors for severe outcome. Severe COVID‐19 patients had a reduction in WBC counts, D‐dimer, C‐reactive protein, and fibrinogen upon discharge from hospital, while lymphocyte counts increased (p < 0.05).ConclusionCounts of WBC, neutrophil, and lymphocyte, NLR, and levels of C‐reactive protein, D‐dimer, and fibrinogen are helpful for prediction of the deterioration trend in patients diagnosed with COVID‐19.     

Analytical and clinical performance of a new,automated assay panel for the diagnosis of antiphospholipid syndrome

Summary. Background: Anticardiolipin (aCL) and anti‐β₂glycoprotein I (aβ₂GPI) antibodies are part of the criteria for antiphospholipid syndrome (APS). Therefore they are widely measured and about 30 commercial kits are available. Objectives: To investigate the analytical and clinical performances of four fully automated, chemiluminescent assays: HemosIL AcuStar aCL IgG, HemosIL AcuStar aCL IgM, HemosIL AcuStar aβ₂GPI IgG, and HemosIL AcuStar aβ₂GPI IgM. Methods: Cut‐off values were assessed by testing 250 blood donors. Total coefficients of variation (CV) were determined with six plasma pools and two controls ranging from 4.3 to 2694 U mL^?1 depending on the assay. Samples from 218 well‐characterized patients and 103 controls were measured in three laboratories to determine inter‐laboratory variation. The results of the 321 samples were compared with three commercial assays (REAADS, INOVA and VARELISA). Results: Cut‐off values were assigned to 20 arbitrary units for all the tests. Total CV ranged from 4.3 to 11.2%. No interference of hemoglobin, bilirubin, triglycerides, heparins and rheumatoid factor was observed. Inter‐laboratory variability was low and no sample changed status. Overall status agreement between HemosIL assays and the comparator kits ranged from 82 to 96%. Sensitivity, specificity, agreement when predicting APS and the odds ratios when predicting a thrombotic or obstetric event gave comparable results between HemosIL AcuStar and the three other assays. Conclusions: Our study demonstrates that the fully automated HemosIL AcuStar aPL assay panel showed similar performances to the three commercial ELISAs commonly used by various laboratories to detect antiphospholipid antibodies.     

Evidence for heterogeneity of the obstetric antiphospholipid syndrome: thrombosis can be critical for antiphospholipid‐induced pregnancy loss

Summary. Background: Antiphospholipid antibodies are associated with thrombosis and repeated pregnancy losses during the antiphospholipid syndrome. Several experimental findings indicate that purified antiphospholipid antibodies are directly responsible for inflammation‐induced pregnancy losses, or for disruption of the annexin A5 shield at the trophoblastic interface. We previously showed that passive transfer of CIC15, a monoclonal antiphospholipid antibody binding to cardiolipin and annexin A5 that was isolated from a patient with primary antiphospholipid syndrome, induces fetal resorption in pregnant mice. Objectives: To investigate the mechanisms of CIC15‐induced pregnancy loss. Methods/results: We show that CIC15 induces fetal loss through a new mechanism that is probably related to procoagulant activity. The time course is different from those of previously described models, and histologic analysis shows that the placentas are devoid of any sign of inflammation but display some signs of thrombotic events. Despite these differences, the CIC15 and ‘inflammatory’ models share some similarities: lack of FcγRI/III dependency, and the efficacy of heparin in preventing fetal losses. However, this latter observation is here mostly attributable to anticoagulation rather than complement inhibition, because fondaparinux sodium and hirudin show similar efficiency. In vitro, CIC15 enhances cardiolipin‐induced thrombin generation. Finally, using a combination of surface‐sensitive methods, we show that, although it binds complexes of cardiolipin–annexin A5, CIC15 is not able to disrupt the two‐dimensional ordered arrays of annexin A5. Conclusions: This human monoclonal antibody is responsible for pregnancy loss through a new mechanism involving thrombosis. This mechanism adds to the heterogeneity of the obstetric antiphospholipid syndrome.     

Predictors of the post‐thrombotic syndrome with non‐invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis

Summary. Background: Post‐thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors are known. Objectives: To assess the incidence and potential predictors of PTS. Methods: We prospectively followed 111 consecutive patients for 2 years after a first episode of objectively documented DVT of the leg. With non‐invasive venous examinations, residual thrombosis, valvular reflux, calf muscle pump function and venous outflow resistance were assessed at 6 weeks, 3 months, 6 months, 1 year, and 2 years. The Clinical, Etiologic, Anatomic, and Pathophysiologi classification was used to record the occurrence and severity of PTS. Regression analysis with area under the receiver operating characteristic (ROC) curve was performed to identify potential predictors. Results: The cumulative incidence of PTS was 46% after 3 months, and the incidence and severity did not increase further. Men appeared to be at increased risk as compared with women (risk ratio [RR] 1.4, 95% confidence interval [CI] 0.9–2.2), as were patients over 50 years as compared with younger patients (RR 1.4%, 95% CI 0.9–2.1). Patients with thrombosis localized in the proximal veins at diagnosis had an increased risk of PTS as compared with patients with distal thrombosis (RR 2.3%, 95% CI 1.0–5.6). PTS developed in 32 of 52 patients (62%) with residual thrombosis in the proximal veins 6 weeks after diagnosis, as compared with 17 of 45 patients (38%) without residual proximal thrombosis, leading to a 1.6‐fold increased risk (95% CI 1.0–2.5). The presence of valvular reflux in the superficial veins was also a predictor at 6 weeks, with a 1.6‐fold increased risk as compared with patients without superficial reflux (95% CI 1.1–2.3). A multivariate analysis of these predictors yielded an area under the ROC curve of 0.72 (95% CI 0.62–0.82). Conclusions: PTS develops in half of all patients within 3 months, with no further increase being seen up to 2 years of follow‐up. Male sex, age over 50 years, proximal localization of the thrombus at entry, residual proximal thrombosis and superficial valvular reflux at 6 weeks seem to be the most important predictors of PTS in patients with a first episode of DVT. Duplex scanning 6 weeks after diagnosis appears to be clinically useful for the identification of patients at risk of PTS.