ABSTRACT:Congenital thrombotic thrombocytopenic purpura (cTTP) is caused by a severe inherited ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) deficiency. Although acute episodes are life-threatening, long-term burden of ischemic complications, and effectiveness of prophylactic strategies remain underexplored. We conducted a 25-year national, multicenter study of 88 patients with cTTP enrolled in the French Thrombotic Microangiopathy registry. Patients were stratified by age and clinical context at disease onset: pediatric (n = 42), pregnancy (n = 33), and adult onset (n = 13). Clinical features, genotypes, treatment regimens, and long-term ischemic outcomes were analyzed. Pediatric patients exhibited early-onset disease (median age at diagnosis, 2 years [interquartile range, 0-13]) with recurrent episodes and a high burden of neurological complications. In patients with pregnancy-onset disease, no relapses were observed outside pregnancy. Adult-onset patients, typically diagnosed aged >50 years, showed prevalent cardiovascular disease, stroke, and kidney injury. Mental health disorders were common across all groups. Despite long-term plasma prophylaxis, organ dysfunction persisted, particularly in pediatric- and adult-onset groups. In pregnancy-onset cTTP, tailored midterm prophylaxis during pregnancy reduced maternal and fetal complications. Thirty-nine patients received recombinant human ADAMTS13 (rhADAMTS13) prophylaxis (median follow-up, 5 months [interquartile range, 6-17]). Prophylactic treatment significantly improved relapse-free survival, with a comparable outcome using intensive plasma-derived products and rhADAMTS13 in pediatric-onset cases, although adverse events were more prevalent using plasma therapy. Our findings highlight the clinical and genetic heterogeneity of cTTP and the burden of organ dysfunction. Intensive prophylaxis improves relapse-free survival. rhADAMTS13 represents a safe and promising first-line option that should help reduce long-term organ damage and improve quality of life.

Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e., > 30 days) due to persistent ADAMTS13 deficiency, raising cost and tolerance concerns. Therefore, we investigated whether anti-ADAMTS13 antibodies titer and their trajectory during the acute phase of the disease could predict ADAMTS13 improvement (i.e., activity ≥ 20% before day-30 post-TPE). From a cohort of 286 patients receiving the triplet regimen, we identified on diagnosis a cut-off value for anti-ADAMTS13 IgG antibodies of 90.5 U/mL, with a modest discriminating ability (AUC: 0.57) for predicting long-term response, precluding its use to guide therapeutic strategies. Nonetheless, the analysis of anti-ADAMTS13 IgG antibodies titer trajectory from diagnosis revealed that the proportion of iTTP patients with ADAMTS13 activity improvement was higher in patients who decreased (Dec+) their antibodies titer within the 7-14 days interval post-TPE compared to those without decrease (Dec-) (65% vs. 25% of cases, respectively, p < 0.001), a finding confirmed in a validation cohort (N = 51). These results highlight the possibility of intensifying immunosuppression in an early period post-TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti-ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B-cell depleting agents when appropriate.

Introduction: The diagnosis of thrombotic microangiopathy (TMA) relies on common biological parameters, the diagnostic value of which are unknown. Methods: The presence of common biological parameters was assessed in 967 patients with TMA from 2009 to 2023 (ClinicalTrials.gov: NCT05991245). Results: The median age was 49 (36–64) years and 53.2% were male. All TMA causes were represented (atypical hemolytic uremic syndrome [aHUS]: 41.6%, drugs: 24.9%, malignancy: 21.4%, autoimmune disease: 18.8%, infection: 7.6%, complement-mediated HUS: 6.8%, organ transplantation: 5.8%, pregnancy: 3.8%, bone marrow transplantation [BMT]: 2.9%, Shiga toxin Escherichia coli hemolytic uremic syndrome [STEC-HUS]: 0.6%, and thrombotic thrombocytopenic purpura [TTP]: 0.6%). The presence of TMA-related parameters concerned virtually all patients with TTP but varied widely for the other patients as follows: anemia: 81.7%, high lactate dehydrogenase (LDH) (75.4%), low haptoglobin (53.7%), and thrombocytopenia (40.3%). Their diagnostic performance was accurate only for TTP. Eleven distinct ways were used for schistocyte metrics and reporting. Relying on schistocyte presence as the single diagnostic criterion would lead to missed diagnosis in 23.8% (STEC-HUS) to 86.4% (BMT) of patients (for anemia: 8.2%–22.3%; thrombocytopenia: 31.8%–67.9%; high LDH: 10.0%–40.7%, low haptoglobin: 0%–70.4%, according to the causes of TMA). The overall risk of missed diagnosis using these parameters was ≥ 50% in all TMA, except in TTP. The best diagnostic performances were obtained when fibrinogen levels were < 5 g/l, creatinine ≥ 300 μmol/l, prothrombin time (PT) < 90%; and when TMA causes were TTP, STEC-HUS, infection, or complement-mediated HUS. Conclusion: Common biological parameters miss the diagnosis in more than 50% of TMA except when fibrinogen is < 5 g/l, creatinine ≥ 300 μmol/l, and PT < 90%. Schistocyte reporting is heterogenous, and its results are usually deceptive in TMA.

Background C3 nephritic factors, that is, autoantibodies that stabilize the C3 convertase of the alternative pathway are the most frequent acquired abnormality in C3 glomerulopathy and primary Ig-mediated membranoproliferative GN (Ig-MPGN). Methods Our study included 27 patients with C3 glomerulopathy (n=21) or Ig-MPGN (n=6), of whom 78% were children at disease onset. At the time of sampling, 13/19 patients (68%) with low C3 levels and 8/8 patients (100%) with normal C3 levels were positive for C3 nephritic factors by hemolytic assay. Using novel Luminex assays, we performed a screening for IgG that recognize and affect the formation and/or the stabilization of the alternative pathway C3 convertase (C3bBb). Results Using Luminex assays, an increase in C3bBb formation and/or stabilization was observed in the presence of IgG from 18/27 patients, including nine with a double-function, six only enhancing the C3bBb formation, and three that exclusively stabilized C3bBb. All patients presenting a formation and stabilization function had a low C3 level versus 55% without this double-function. The level of C3bBb formation correlated to the plasmatic C3 but not soluble C5b-9 levels. The stabilization of C3bBb did not correlate with C3 or soluble C5b-9 levels. At the last follow-up, 5/27 patients (19%) reached kidney failure after a median delay of 87 (52-119) months. The patients positive for double-function anti-C3bBb antibodies had a 5-year kidney survival of 70% compared with 100% in those negative (P = 0.02). Conclusions Our findings highlight the association of the dual function of C3bBb formation and stabilization with severe C3 consumption and poor kidney survival in C3 glomerulopathy and Ig-MPGN.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 μmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies, but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represent a very high proportion of patients with TMA and results from virtually all known causes of TMA, includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA, but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. Among 73 TMA cases (mean age 46.9 ± 16 years (range 21–87 years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP. At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions.

Background Cancer-associated thrombotic microangiopathy (TMA) is a rare disease, with a poor prognosis. The classical treatment is urgent chemotherapy. Few data are available on the efficacy of plasma exchange (PE) and eculizumab in these patients. Methods Cases of cancer-related TMA treated between January 2008 and December 2019 in 12 French treatment centres were retrospectively analysed, excluding cases associated with chemotherapy and stem cell transplantation. Patients were divided into four groups depending on the treatment received: none, PE therapy alone, chemotherapy, with or without PE therapy, or eculizumab, with or without chemotherapy and PE therapy. Results The data of 59 patients with cancer-associated TMA were analysed. Twenty of these cases were related to a cancer recurrence. The cancer was metastatic in 90% of cases (53/59). Bone marrow invasion was observed in 20/41 biopsies. Some laboratory results, including disseminated intravascular coagulation high ferritin and C-reactive protein, were suggestive of cancer. None of the 16 patients whose alternative complement pathway was assessed had abnormal levels of protein expression or activity. The median survival time was 27 days. Chemotherapy was significantly associated with improved survival, with a 30-day survival rate of 85% (17/20) among patients who received PE and chemotherapy, versus 20% (3/15) among patients who received PE alone. Patients treated with eculizumab in addition to chemotherapy and PE therapy did not have longer overall survival or higher haematological remission rates than those treated with chemotherapy and PE therapy alone. Renal remission rates were non-significantly higher, and times to remission non-significantly shorter, in the eculizumab group. Conclusions Nephrologists and oncologists should make themselves aware of cancer diagnoses in patients with TMA and bone marrow biopsies should be performed systematically in these cases. All 59 patients had poor survival outcomes, but patients treated with urgent initiation of chemotherapy survived significantly longer than those who were not.

BACKGROUND:C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative GN (Ig-MPGN) are rare complement-mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described. METHODS:Three hundred ninety-eight patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102) from a national registry were screened for three complement genes: factor H ( CFH ), factor I ( CFI ), and C3 . Patients with rare variant (minor allele frequency <0.1%) were included. Epidemiologic, clinical, and immunologic data at diagnosis and kidney outcomes of patients were retrospectively collected. RESULTS:Fifty-three different rare variants, including 30 (57%), 13 (24%), and ten (19%) in CFH , CFI , and C3 variants, were identified in 66/398 (17%) patients. Thirty-eight (72%) variants were classified as pathogenic, including 20/30 (66%) and 11/13 (84%) variants in CFH and CFI , respectively, impairing synthesis of factor H or factor I regulators. Fifteen of 53 (27%) variants were of unknown significance. At diagnosis, 69% of patients were adult (median age of 31 years). With the exception of biologic stigma of thrombotic microangiopathy, which was more frequent in patients with CFI variants (5/14 [36%] versus 1/37 [3%] and 0% in the CFH group and C3 group, respectively, P < 0.001), the clinical and histologic features were similar among the three variants groups. The kidney outcome was poor regardless of the age at onset and treatment received. Sixty-five percent (43/66) of patients with rare variant reach kidney failure after a median delay of 41 (19-104) months, compared with 28% (55/195) after a median delay of 34 (12-143) months in the nonvariant group. Among 36 patients who received a kidney transplant, 2-year recurrence was frequent, occurring in 39% (12/31), without difference between variant groups, and led to graft failure in three cases. CONCLUSIONS:In our cohort, 17% of C3 glomerulopathy/Ig-MPGN cases were associated with rare variants in the CFH , CFI , or C3 genes. In most cases, a quantitative deficiency in factor H or factor I was identified. The presence of a rare variant was associated with poor kidney survival. PODCAST:This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000252.mp3.

Progress in short-term kidney graft survival has decreased since 2000 which suggests an unmet need for innovation regarding early kidney graft function optimization.1 Previous studies have revealed that optimal perioperative fluid therapy was associated with a lower incidence of delayed graft function after kidney transplantation.2–4 Contrary to earlier studies, large volume administration is no longer recommended, and an individualized approach is now encouraged to balance the graft perfusion and the possible complications of fluid overload.

We read with great interest the article by Dupont et al.1Dupont V. Bonnet-Lebrun A.S. Boileve A. et al.A pilot study on the association between early fluid status indicators after kidney transplantation and graft function recovery.Kidney Int Rep. 2022; 7: 1416-1419Abstract Full Text Full Text PDF Scopus (2) Google Scholar who reported an association between elevated intra-abdominal pressure (IAP) and day 30 glomerular filtration rate. The authors concluded that the formers are clinically “relevant fluid status indicators” after kidney transplant. Although we congratulate the authors on these novel and important findings, we like to highlight several points. First, the notion that IAP is a surrogate of volume status is unsupported by the literature or authors’ own findings.1Dupont V. Bonnet-Lebrun A.S. Boileve A. et al.A pilot study on the association between early fluid status indicators after kidney transplantation and graft function recovery.Kidney Int Rep. 2022; 7: 1416-1419Abstract Full Text Full Text PDF Scopus (2) Google Scholar,2Dupont V. Debrumetz A. Leguillou A. et al.Intra-abdominal hypertension in early post-kidney transplantation period is associated with impaired graft function.Nephrol Dial Transplant. 2020; 35: 1619-1628https://doi.org/10.1093/ndt/gfaa104Crossref PubMed Scopus (5) Google Scholar More frequent etiologies for elevated IAP in the early postoperative period than volume overload include the following: ileus, obesity, and sliding down in bed from elevated head of bed position.3Hermans M.H. Call E. Failure to reposition after sliding down in bed increases pressure at the sacrum and heels.Wounds. 2015; 27: 191-198PubMed Google Scholar,4Holte K. Kehlet H. Postoperative ileus: a preventable event.Br J Surg. 2002; 87: 1480-1493https://doi.org/10.1046/j.1365-2168.2000.01595.xCrossref Scopus (479) Google Scholar In addition, volume overload severe enough to cause intra-abdominal hydrostatic edema will usually have other signs of generalized edema. Second, as depicted in Figure 1 of Dupont et al.,1Dupont V. Bonnet-Lebrun A.S. Boileve A. et al.A pilot study on the association between early fluid status indicators after kidney transplantation and graft function recovery.Kidney Int Rep. 2022; 7: 1416-1419Abstract Full Text Full Text PDF Scopus (2) Google Scholar IAP further increased between 36 hours and 48 hours, despite a decrease in weight gain and central venous pressure.1Dupont V. Bonnet-Lebrun A.S. Boileve A. et al.A pilot study on the association between early fluid status indicators after kidney transplantation and graft function recovery.Kidney Int Rep. 2022; 7: 1416-1419Abstract Full Text Full Text PDF Scopus (2) Google Scholar This additional elevation in IAP cannot be ascribed to an increased fluid status. Third, we wholeheartedly agree with the authors’ statement elsewhere5Dupont V. Debrumetz A. Wynckel A. Rieu P. [How to explain glomerular filtration rate decrease in intra-abdominal hypertension?]. Comment expliquer la baisse du débit de filtration glomérulaire en cas d’hypertension intra-abdominale?.Nephrol Ther. 2018; 14: 24-28https://doi.org/10.1016/j.nephro.2017.04.005Crossref PubMed Scopus (3) Google Scholar that IAH-induced decrease in glomerular filtration rate is multifactorial and insufficiently understood, with renal venous congestion playing an important, putative, pathophysiological role. In fact, the elevated IAP-mediated compression of the vena cava triggers pooling and increased pressure in upstream venous beds, with a simultaneous underfilling of the heart and ensuing multitude of compensatory mechanism that culminate in renal injury.S1 As a result, renal venous congestion may occur in both extraperitoneally and intraperitoneally grafted kidneys. Last, an additional plausible mechanism for IAP-mediated kidney injury is that elevated IAP subsequently increases intravesical and ureteral pressures and diminishes urinary flow, with resultant kidney injury. The differential diagnosis of elevated IAP is critical. Erroneously attributing elevated IAP to excess fluid may lead to fluid restriction, decreased preload, and exacerbation of acute kidney injury by prerenal azotemia.S1 Volume status is better estimated by CVP, pulmonary artery occlusive pressure, or noninvasively with B-type natriuretic peptide, chest X-ray, or bedside echocardiography. Intraoperatively and in patients on mechanical ventilation, stroke volume and pulse pressure variation (e.g., FloTrac) may be used to guide fluid therapy. Download .pdf (.01 MB) Help with pdf files Supplementary File (PDF) Supplementary Reference. In Reply to “Abdominal Pressure and Fluid Status After Kidney Transplantation”Kidney International ReportsVol. 7Issue 7PreviewWe thank Yehuda and Nicolau-Raducu1 for their commentary on our recent publication.2 They first question the use of intra-abdominal pressure (IAP) as a surrogate of hydration status. We previously established a positive correlation between IAP and both central venous pressure and weight gain in our cohort.3 We also reported that severe intra-abdominal hypertension was associated with higher fluid balance.3 Others have previously revealed a correlation between IAP and other fluid status indicators, such as extravascular lung water index. Full-Text PDF Open AccessA Pilot Study on the Association Between Early Fluid Status Indicators After Kidney Transplantation and Graft Function RecoveryKidney International ReportsVol. 7Issue 6PreviewProgress in short-term kidney graft survival has decreased since 2000 which suggests an unmet need for innovation regarding early kidney graft function optimization.1 Previous studies have revealed that optimal perioperative fluid therapy was associated with a lower incidence of delayed graft function after kidney transplantation.2–4 Contrary to earlier studies, large volume administration is no longer recommended, and an individualized approach is now encouraged to balance the graft perfusion and the possible complications of fluid overload. Full-Text PDF Open Access

Background:Amoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI.Methods:This multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292.Findings:Of the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003).Interpretation:AC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI.Funding:None.

Background:The prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear.Methods:Using a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort's blood pressure profile to assess its impact on prognosis and diagnostic performances.Results:Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p < 0.001). The best threshold for iTTP diagnosis corresponded to a systolic blood pressure <150 mmHg. iTTP patients presenting with hypertension had a significantly poorer survival (hazard ratio 1.80, 95% confidence interval 1.07-3.04), and this effect remained significant after multivariable adjustment (hazard ratio = 1.14, 95% confidence interval 1.00-1.30). Addition of a blood pressure criterion modestly improved the French clinical score to predict a severe A disintegrin and metalloprotease with thrombospondin type 1 deficiency in patients with an intermediate score (i.e., either platelet count <30 × 109/L or serum creatinine <200 µM).Conclusions:Elevated blood pressure at admission affects the prognosis of iTTP patients and may help discriminate them from other TMA patients. Particular attention should be paid to blood pressure and its management in these patients.

C3 glomerulopathy (C3G) is a rare complement-mediated disease. Specific treatments are not yet available and factors predictive of kidney survival such as age, kidney function and proteinuria are not specific to C3G. The prognostic value of biomarkers of complement activation, which are pathognomonic of the diseases, remains unknown. In a large cohort of 165 patients from the French National registry, we retrospectively assess the prognostic value of C3, soluble C5b-9 (sC5b-9), C3 nephritic factor, and rare disease-predicting variants in complement genes in predicting clinical outcome of patients. By multivariate analysis age (adult onset), reduced kidney function (defined by estimated glomerular filtration rate under 60ml/min) and presence of rare disease-predicting variants in complement genes predicted risk of progression to kidney failure. Moreover, by multivariate analysis, normal C3/high sC5b-9 levels or low C3/normal sC5b-9 levels remained independently associated with a worse kidney prognosis, with the relative risk 3.7- and 8-times higher, respectively. Subgroup analysis indicated that the complement biomarker profiles independently correlated to kidney prognosis in patients with adult but not pediatric onset. In this subgroup, we showed that profiles of biomarkers C3 and/or sC5b-9 correlated with intra glomerular inflammation and may explain kidney outcomes. In children, only the presence of rare disease-predicting variants correlated with kidney survival. Thus, in an adult population, we propose a three-point C3G prognostic score based on biomarker profiles at risk, estimated glomerular filtration rate at presentation and genetic findings, which may help stratify adult patients into subgroups that require close monitoring and more aggressive therapy.

Letter to Blood| April 21, 2022 Immune-mediated thrombotic thrombocytopenic purpura following COVID-19 vaccination Clinical Trials & Observations Adrien Picod, Adrien Picod 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;2Service de réanimation médico-chirurgicale, Hôpital Avicenne Assistance Publique–Hôpitaux de Paris (AP-HP), Bobigny, France; https://orcid.org/0000-0002-0639-5598 Search for other works by this author on: This Site PubMed Google Scholar Jean-Michel Rebibou, Jean-Michel Rebibou 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;3Service de Néphrologie, Centre Hospitalier Universitaire (CHU) Dijon Bourgogne, Dijon, France; Search for other works by this author on: This Site PubMed Google Scholar Antoine Dossier, Antoine Dossier 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;4Service de médecine interne, Hôpital Bichat-Claude Bernard, Assistance Publique–Hôpitaux de Paris, France; https://orcid.org/0000-0002-2008-2942 Search for other works by this author on: This Site PubMed Google Scholar Bérengère Cador, Bérengère Cador 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;5Service de médecine interne et immunologie clinique, CHU de Rennes, Rennes, France; Search for other works by this author on: This Site PubMed Google Scholar David Ribes, David Ribes 6Département de néphrologie et transplantation d’organes, centre de référence des maladies rénales rares, centre hospitalier Universitaire de Toulouse, Toulouse, France; Search for other works by this author on: This Site PubMed Google Scholar Claire Vasco-Moynet, Claire Vasco-Moynet 7Service de médecine interne, centre hospitalier de Libourne, Libourne, France; Search for other works by this author on: This Site PubMed Google Scholar Caroline Stephan, Caroline Stephan 8Département de médecine, unité de médecine transfusionnelle et d’immunohématologie, hôpitaux universitaires de Genève, Suisse; Search for other works by this author on: This Site PubMed Google Scholar Mathieu Bellal, Mathieu Bellal 9Service de médecine intensive et réanimation, CHU de Caen, Caen, France; Search for other works by this author on: This Site PubMed Google Scholar Alain Wynckel, Alain Wynckel 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;10Service de néphrologie, CHU de Reims, Reim, France; Search for other works by this author on: This Site PubMed Google Scholar Pascale Poullin, Pascale Poullin 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;11Service d’hémaphérèse autotransfusion, centre de compétences pour les microangiopathies thrombotiques, hôpital la conception, Marseille, France; Search for other works by this author on: This Site PubMed Google Scholar Edwige Péju, Edwige Péju 12Service de médecine intensive et réanimation, hôpital Cochin, Assistance Publique–Hôpitaux de Paris, France; https://orcid.org/0000-0001-7356-7858 Search for other works by this author on: This Site PubMed Google Scholar Laure Ricard, Laure Ricard 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;13Service d’hématologie, Hôpital Saint-Antoine, Assistance Publique–Hôpitaux de Paris, Sorbonne-Université (AP-HP.6), Paris, France; https://orcid.org/0000-0003-4416-3285 Search for other works by this author on: This Site PubMed Google Scholar Jean-Emmanuel Kahn, Jean-Emmanuel Kahn 14Service de médecine interne, Hôpital Ambroise Paré, Assistance Publique–Hôpitaux de Paris, Université Versailles-Saint Quentin-en-Yvelines, Boulogne-Billancourt, France; Search for other works by this author on: This Site PubMed Google Scholar Raïda Bouzid, Raïda Bouzid 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France; https://orcid.org/0000-0003-1419-3758 Search for other works by this author on: This Site PubMed Google Scholar Ygal Benhamou, Ygal Benhamou 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;15Département de médecine interne, Hôpital universitaire de Rouen, Université de Normandie, Rouen, France; Search for other works by this author on: This Site PubMed Google Scholar Bérangère Joly, Bérangère Joly 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;16Service d’hématologie biologique, laboratoire ADAMTS13, Hôpital Lariboisière, AP-HP.Nord, Université de Paris, Paris, France;17EA3518, Institut de recherche Saint Louis, Université de Paris, Paris, France; and Search for other works by this author on: This Site PubMed Google Scholar Agnès Veyradier, Agnès Veyradier 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;16Service d’hématologie biologique, laboratoire ADAMTS13, Hôpital Lariboisière, AP-HP.Nord, Université de Paris, Paris, France;17EA3518, Institut de recherche Saint Louis, Université de Paris, Paris, France; and Search for other works by this author on: This Site PubMed Google Scholar Paul Coppo Paul Coppo 1Centre National de Référence des MicroAngiopathies Thrombotiques, Paris, France;13Service d’hématologie, Hôpital Saint-Antoine, Assistance Publique–Hôpitaux de Paris, Sorbonne-Université (AP-HP.6), Paris, France;18INSERM UMRS 1138, Centre de Recherche des Cordeliers, Paris, France Search for other works by this author on: This Site PubMed Google Scholar Blood (2022) 139 (16): 2565–2569. https://doi.org/10.1182/blood.2021015149 Article history Submitted: December 13, 2021 Accepted: February 8, 2022 First Edition: March 10, 2022 Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Adrien Picod, Jean-Michel Rebibou, Antoine Dossier, Bérengère Cador, David Ribes, Claire Vasco-Moynet, Caroline Stephan, Mathieu Bellal, Alain Wynckel, Pascale Poullin, Edwige Péju, Laure Ricard, Jean-Emmanuel Kahn, Raïda Bouzid, Ygal Benhamou, Bérangère Joly, Agnès Veyradier, Paul Coppo; Immune-mediated thrombotic thrombocytopenic purpura following COVID-19 vaccination. Blood 2022; 139 (16): 2565–2569. doi: https://doi.org/10.1182/blood.2021015149 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Clinical Trials and Observations, Free Research Articles, Thrombosis and Hemostasis TO THE EDITOR: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening form of thrombotic microangiopathy, which manifests by hemolytic anemia, consumptive thrombocytopenia, and diffuse microthrombi formation with organ damage resulting from a severe immune-mediated ADAMTS13 deficiency (activity below 10%).1 Recently, several cases of iTTP have been described after coronavirus disease 2019 (COVID-19) vaccination.2,3 These temporally associated events raise concerns about a potential causal link between vaccination and the development of the disease. Consequently, uncertainties persist regarding the best way to manage these cases as well as the approach to adopt in patients with known iTTP regarding vaccination. Finally, certain similarities with vaccine-induced thrombotic thrombocytopenia (VITT), a well-established complication of adenoviral vector–based vaccination,4 raise the question of the differential diagnosis between these 2 entities. The French Reference Center for Thrombotic Microangiopathies is a national network of French and... REFERENCES 1.Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846.Google ScholarCrossrefSearch ADS PubMed 2.Maayan H, Kirgner I, Gutwein O, et al. Acquired thrombotic thrombocytopenic purpura: a rare disease associated with BNT162b2 vaccine. J Thromb Haemost. 2021;19(9):2314-2317.Google ScholarCrossrefSearch ADS PubMed 3.Giuffrida G, Condorelli A, Di Giorgio MA, et al. Immune-mediated thrombotic thrombocytopenic purpura following Pfizer-BioNTech COVID-19 vaccine. Haematologica. 2021.Google Scholar 4.Greinacher A, Selleng K, Palankar R, et al. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood. 2021;138(22):2256-2268.Google ScholarCrossrefSearch ADS PubMed 5.Mariotte E, Azoulay E, Galicier L, et al; French Reference Center for Thrombotic Microangiopathies. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. Lancet Haematol. 2016;3(5):e237-e245.Google ScholarCrossrefSearch ADS PubMed 6.Coppo P, Schwarzinger M, Buffet M, et al; French Reference Center for Thrombotic Microangiopathies. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One. 2010;5(4):e10208.Google ScholarCrossrefSearch ADS PubMed 7.Scully M, Singh D, Lown R, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(23):2202-2211.Google ScholarCrossrefSearch ADS PubMed 8.Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496-2502.Google ScholarCrossrefSearch ADS PubMed 9.Données relatives aux personnes vaccinées contre la Covid-19. https://www.data.gouv.fr/fr/datasets/donnees-relatives-aux-personnes-vaccinees-contre-la-covid-19-1/. Accessed 15 March 2022. 10.Dykes KC, Kessler CM. First report of COVID-19 vaccine induced flare of compensated congenital thrombotic thrombocytopenic purpura. Blood Coagul Fibrinolysis. 2022;33(1):71-73.Google ScholarCrossrefSearch ADS PubMed 11.Pavord S, Scully M, Hunt BJ, et al. Clinical features of vaccine-induced immune thrombocytopenia and thrombosis. N Engl J Med. 2021;385 (18):1680-1689.Google ScholarCrossrefSearch ADS PubMed 12.Greinacher A, Langer F, Makris M, et al. Vaccine-induced immune thrombotic thrombocytopenia (VITT): Update on diagnosis and management considering different resources. J Thromb Haemost. 2022;20(1):149-156.Google ScholarCrossrefSearch ADS PubMed 13.Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021;137(14):1855-1861.Google ScholarCrossrefSearch ADS PubMed 14.COVID-19 and thrombotic thrombocytopenic purpura. https://www.hematology.org/covid-19/covid-19-and-ttp. Accessed 15 March 2022.15.Moor MB, Suter-Riniker F, Horn MP, et al. Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study. Lancet Rheumatol. 2021;3(11):e789-e797.Google ScholarCrossrefSearch ADS PubMed © 2022 by The American Society of Hematology2022 You do not currently have access to this content. Sign in via your Institution

Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined. In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being. In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32 years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = − 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS. This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.

Contrast medium administration is classically considered to cause or worsen kidney failure, but recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. Kidney injury does not constitute a contra-indication to the administration of iodinated contrast medium, as long as the benefit-risk ratio justifies it. Intravenous hydration with 0.9% NaCl or 1.4% sodium bicarbonate is the only validated measure for the prevention of post-iodine contrast nephropathy. This is necessary for intravenous or intra-arterial administration of iodinated contrast agent without first renal pass when the glomerular filtration rate is less than 30 mL/min/1.73 m(2), for intra-arterial administration of iodinated contrast agent with first renal passage when the glomerular filtration rate is less than 45 mL/min/1.73 m(2), or in patients with acute renal failure. The use of iodinated contrast medium should allow the carrying out of relevant examinations based on an analysis of the benefit-risk ratio and the implementation of measures to prevent toxicity when necessary. (C) 2021 Societe francaise de radiologie. Published by Elsevier Masson SAS. All rights reserved.