First evidence of subclinical renal tubular injury during sickle-cell crisis

International audienceBACKGROUND: The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. METHODS: In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. RESULTS: During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. CONCLUSIONS: These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC

B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.

International audiencePrimary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. Rituximab, a B cell-depleting agent, has become the first-line treatment for ITP; however, patients with refractory disease usually require splenectomy. We identified antibody-secreting cells as the major splenic B cell population that is resistant to rituximab. The phenotype, antibody specificity, and gene expression profile of these cells were characterized and compared to those of antibody-secreting cells from untreated ITP spleens and from healthy tissues. Antiplatelet-specific plasma cells (PC) were detected in the spleens of patients with ITP up to 6 months after rituximab treatment, and the PC population displayed a long-lived program similar to the one of bone marrow PC, thus explaining for most of these patients the absence of response to rituximab and the response to splenectomy. When analyzed by multiplex PCR at the single-cell level, normal splenic PC showed a markedly different gene expression profile, with an intermediate signature, including genes characteristic of both long-lived PC and proliferating plasmablasts. Surprisingly, long-lived PC were not detected in untreated ITP spleens. These results suggest that the milieu generated by B cell depletion promotes the differentiation and settlement of long-lived PC in the spleen

PURPURA THROMBOPENIQUE IMMUNOLOGIQUE ET HELICOBACTER PYLORI

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Impact of Pregnancy On the Course of Immune Thrombocytopenic Purpura: An Observational Study On 44 Cases.

Abstract Abstract 1320 Poster Board I-342 Backgound Adult's immune thrombocytopenic purpura (ITP), now referred as immune thrombocytopenia, is an autoimmune disease affecting preferentially women of child-bearing age. The risk of relapse or worsening of the disease during pregnancy in women with a previous history of ITP or followed for a chronic ITP is not well known and the monitoring of such patients is therefore not consensual. In order to better asses the impact of pregnancy on ITP' course and natural history, a study was initiated at the national referral center for adult's immune cytopenias at Creteil, France. Patients and Methods This was an observational single center study. To be included into the study, all women had to fulfill the following inclusion criteria: 1) A previous history of definite ITP outside pregnancy with a platelet count &lt; 50×109/L at time of diagnosis and 2) Occurrence of at least one pregnancy within 10 years after ITP diagnosis. Patients diagnosed with secondary ITP (lupus-associated or other) or in whom ITP was diagnosed during a previous pregnancy could not be included. All available clinical and biological ITP-related data available before, during and after each pregnancy were extensively reviewed and analyzed. Results Data on 44 pregnancies in 33 women (mean age: 25 ± 7 years) were analyzed. The mean delay between ITP diagnosis and first pregnancy was 52 ± 19,8 months. At the beginning of pregnancy, ITP was considered “active” (i.e platelet count &lt;100×109/L) in 11/44 (25%) cases, with a platelet count below 50 ×109/L in 6 cases whereas ITP was in remission (platelet count &gt; 100 × 109/L) in 75% of the cases, either off therapy (82%) or on treatment (18% of the cases). In total, the platelet count remained stable during pregnancy In 25/44 of the cases (57%) without the need of any treatment except for one patient who received corticosteroids for an associated autoimmune hemolytic anemia diagnosed during pregnancy (Evans' syndrome). A slight decrease in the platelet count (between 50 and 100×109/L) was observed in 12 cases (27%), 6 of which occurred at the end of pregnancy. In nine of these cases, patients were given a short course of corticosteroids in preparation for delivery. Lastly, a decrease of the platelet count below 50×109/L was observed in only 7 of the 44 pregnancies (16%). In 6 of these 7 cases, patients were given corticosteroids, either alone (n=2) or in combination with intravenous immunoglobulin (n=4 cases); one patient was also given a platelet transfusion. No severe bleeding episode (mucosal bleeding or any hemorrhage) occurred in any of these cases prior to, during or after delivery. A miscarriage occurred in 6 of the 44 pregnancies (13.5%), a C-section was performed in 18% of the cases which is the usual average rate in France. In total, a treatment for ITP had been considered useful in 15 pregnancies (34%) mainly at the end of the third trimester. The mean platelet count at time of delivery was 107 ± 17 × 109/L, None of the patients had a relapse or a significant decrease of the platelet count within 6 months after delivery except for a one patient who presented with a severe (platelet count &lt; 20 × 109/L) and symptomatic (cutaneous and mucosal bleeding) thrombocytopenia on day 2 after delivery. Conclusion Based on these preliminary data, pregnancy does not seem to have a negative impact on the course of the disease in women with chronic non-refractory ITP nor to increase the risk of relapse in those with a previous history of ITP. A significant decrease of the platelet count may occur in about 15% of the cases, mainly during the third trimester. In women with a platelet count between 50 and 100 × 109/L at term, a short course of treatment could be indicated in preparation for delivery and especially if an epidural analgesia is planned. Disclosures No relevant conflicts of interest to declare. </jats:sec

Prevalence and Clinical Significance of Elevated Antiphospholipid Antibodies in Adults with Immune Thrombocytopenic Purpura.

Abstract Background: The clinical and pathogenic significances of the presence of antiphospholipid antibodies (APA) [anticardiolipin antibodies (aCL) and lupus-like anticoagulant (LA)] in patients with immune thrombocytopenic purpura (ITP) remain controversial. Objective: To determine the prevalence and clinical significance of positive APA in a large monocentric cohort of adults with newly diagnosed ITP. Methods: aCL (IgG and IgM) and LA were searched at time of diagnosis in 260 adults with ITP and a platelet count &lt; 50×109/L over a 15 years period. Thirty-five patients with definite systemic lupus, 5 with primary antiphospholipid syndrome and 4 with HIV infection were excluded and the analysis was performed on 216 patients. Results: APA (aCL and LA) were detected at ITP diagnosis in 55 patients (25%) including: IgG-aCL in 43 patients (20%) with a level between 15-39 UI/L in 31 and ≥40UI/l in 12; IgM-aCL in 11 patients (5%); and LA in 16 patients (7%). LA was associated with IgG-aCL in 14 patients, IgM-aCL in 1 patient, and was isolated in 1 patient. Positive test for LA was correlated with the presence of highly positive IgG-aCL (≥40UI/L) (p=0.001). Age, gender, initial platelet count, acute or chronic outcome of ITP were not associated with the presence of APA (aCL and LA), aCL and LA status except for age which was lower in LA positive group (mean age 22 years vs 42 years in LA negative group, p=0.002). After a median follow-up of 31 months (range: 1 to 185 months), 15/216 (7%) patients experienced a thrombosis (arterial = 3, deep venous thrombosis and/or pulmonary embolism = 12); 5 of whom (33%) had positive aCL (with a level ≥ 40 UI/L in 4). In 4 of these 5 patients, aCL were associated with positive LA. In multivariate analysis, thrombosis events were associated with age [Hazard ratio = 1.5 (IC95% : 1.1–2.0], presence of LA [Hazard ratio = 6.5 (IC95% : 1.7–25.5] or presence of IgG-aCL at high level (≥40UI/L) [Hazard ratio = 6.1 (IC95% : 1.6–23.7]. In contrast, there was no association of thrombosis events with sex, platelet count at diagnosis, acute or chronic evolution (≥ 6 months), antinuclear antibodies or treatments used. Conclusions: Prevalence of APA (25%) in adults with newly diagnosed ITP is lower in our cohort than previously observed in other studies. Though the incidence of thrombosis is significantly increased in patients with LA and/or highly positive aCL, this risk seems too low to recommend a systematic testing in patients with ITP and no previous history of thrombosis.</jats:p

Clinical spectrum of ischaemic arterial diseases associated with COVID-19: a series of four illustrative cases

Abstract Background Severe coronavirus-induced disease 2019 (COVID-19) leads to acute respiratory distress syndrome with an increased risk of venous thrombo-embolic events. To a much lesser extent, arterial thrombo-embolic events have also been reported in this setting. Case summary Here, we describe four different cases of COVID-19 infection with ischaemic arterial events, such as a myocardial infarction with high thrombus load, ischaemic stroke on spontaneous thrombosis of the aortic valve, floating thrombus with mesenteric, splenic and renal infarction, and acute limb ischaemia. Discussion Cardiovascular risk factors such as hypertension, obesity, and diabetes are comorbidities most frequently found in patients with a severe COVID-19 infection and are associated with a higher death rate. Our goal is to provide an overview of the clinical spectrum of ischaemic arterial events that may either reveal or complicate COVID-19. Several suspected pathophysiological mechanisms could explain the association between cardiovascular events and COVID-19 (role of systemic inflammatory response syndrome, endothelial dysfunction, activation of coagulation cascade leading to a hypercoagulability state, virus-induced secondary antiphospholipid syndrome). We need additional studies of larger size, to estimate the incidence of these arterial events and to assess the efficacy of anticoagulation therapy. </jats:sec