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Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974., (© 2023 by The American Society of Hematology.)

Objective: To assess the effectiveness of corticosteroids on outcomes of patients with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen without mechanical ventilation., Methods: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18-80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting., Results: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio (wHR) 0.92, 95%CI 0.61-1.39) nor cumulative death rate (wHR 1.03, 95%CI 0.54-1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥3 L/min (wHR 0.50, 95%CI 0.30-0.85) or C-reactive protein level ≥100 mg/L (wHR 0.44, 95%CI 0.23-0.85). The number of hyperglycaemia events was higher for patients with corticosteroids than for those without, but the number of infections was similar., Conclusions: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18-80 years old, with COVID-19, hospitalized in settings non intensive care units. However, the treatment was associated with a reduced risk of intubation or death for patients with ≥3 L/min oxygen or C-reactive protein level ≥100 mg/L at baseline. Further research is needed to confirm the right timing for corticosteroids in patients with COVID-19 requiring oxygen only., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Rituximab has been used for immune thrombocytopenia (ITP) for almost 20 years and is now considered a valid off-label second-line treatment. About 60% to 70% of patients with ITP show initial response to rituximab, but in half of these patients, the disease will eventually relapse. Therefore, in 30% of patients with persistent or chronic ITP, one course of rituximab at 375 mg/m 2 /week for 4 weeks or 2 fixed 1000-mg rituximab infusions allows for a sustained response rate at 5 years. Unfortunately, to date, no robust predictor of long-term sustained response has been found to assist the physician in deciding to treat with rituximab on an individual basis, and the choice of rituximab or another second-line treatment must be individualized and shared with the patient. Retreatment with rituximab has been found efficient, with a similar or higher magnitude and duration of response in most patients. Rituximab is usually well tolerated, with mainly mild and easily manageable infusion-related adverse events. Severe infections are uncommon, including in the long-term, and occur in patients with at least another contributing factor in more than two thirds. Several issues remain to be resolved. Indeed, head-to-head comparisons with other and new treatments in ITP and robust predictors of long-term response are urgently needed to better determine the position of rituximab in the therapeutic armamentarium for adult ITP. Additionally, the place of combination therapies, maintenance therapy with rituximab and rituximab in newly-diagnosed ITP deserve additional studies., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Multirefractory immune thrombocytopenia (ITP) is defined by the absence of response to TPO receptor agonists, rituximab and splenectomy (or contraindicated or refused) and the need of treatment. The approach to multirefractory ITP must be systematic and firstly involves reconsidering the diagnosis. Inherited thrombocytopenia, lymphoid hemopathies and myelodysplastic syndrome are the main causes to be mentioned. Multirefractory ITP is often associated with secondary ITP with signs of clinical or biological autoimmunity, monoclonal gammopathy of undetermined significance and a poor response to corticosteroids. Therapeutic management is complex and is based on the combination of treatments. New treatments are being developed., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

B-cell depletion with anti-CD20 monoclonal antibodies is widely used for the treatment of autoimmune diseases. This review will discuss mechanisms contributing to success or failure of B-cell depletion therapy in antibody-mediated autoimmune diseases. It will also explain how key information about disease pathogeny can be provided by the different outcomes observed after B-cell depletion therapy. These findings provide the basis for future innovative therapeutic strategies aiming at an optimized B cell and/or plasma cell depletion to increase long-term disease remission., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome frequently secondary to infectious disease, especially in immuno-compromised patients. We report a HLH secondary to disseminated nocardiosis and Streptomyces spp pulmonary infection., Case Report: A 69-years-old women had recent subcutaneous nodules of the forearms and loins associated with peripheral neuropathy and pulmonary nodule of the right upper lobe. Cutaneous biopsy revealed granuloma. Cutaneous lesions worsened and the patient developed a HLH with probable cardiac and neurological involvement, associated with cutaneous granulomatosis and diffuse polyclonal lymphocyte proliferation. Nocardia PCR was positive in cutaneous biopsy. Pulmonary samples revealed Streptomyces in culture and Nocardia in PCR. The evolution under antibiotic treatment was favorable., Conclusion: Recent diagnosis of HLH without obvious etiology should lead to etiological investigation, including the search for infections with slow-growing bacteria such as Nocardia or Streptomyces spp., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Essentials Risk factors of bleeding in adult immune thrombocytopenia are not known. This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset. Platelet count thresholds associated with bleeding were < 20 × 10 9 L -1 and < 10 × 10 9 L -1 . Exposure to anticoagulants was a major risk factor of severe bleeding., Summary: Background The aim of this cross-sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds. Methods We selected all newly diagnosed ITP adults included in the Cytopénies Auto-immunes Registre Midi-PyrénéEN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models. Results Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 10 9 L -1 . In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 10 9 L -1 versus ≥ 20 × 10 9 L -1 , odds ratio [OR] 48.2, 95% confidence interval [CI] 20.0-116.3; between 10 × 10 9 L -1 and 19 × 10 9 L -1 versus ≥ 20 × 10 9 L -1 , OR 5.2, 95% CI 2.3-11.6), female sex (OR 2.6, 95% CI 1.3-5.0), and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1-20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3-14.1). Conclusions Platelet counts of < 20 × 10 9 L -1 and < 10 × 10 9 L -1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding., (© 2018 International Society on Thrombosis and Haemostasis.)

Previous data have suggested that B-cell-depletion therapy may induce the settlement of autoreactive long-lived plasma cells (LLPCs) in the spleen of patients with autoimmune cytopenia. To investigate this process, we used the AID-CreERT2-EYFP mouse model to follow plasma cells (PCs) engaged in an immune response. Multiplex polymerase chain reaction at the single-cell level revealed that only a small fraction of splenic PCs had a long-lived signature, whereas PCs present after anti-CD20 antibody treatment appeared more mature, similar to bone marrow PCs. This observation suggested that, in addition to a process of selection, a maturation induced on B-cell depletion drove PCs toward a long-lived program. We showed that B-cell activating factor (BAFF) and CD4 + T cells play a major role in the PC survival niche, because combining anti-CD20 with anti-BAFF or anti-CD4 antibody greatly reduce the number of splenic PCs. Similar results were obtained in the lupus-prone NZB/W model. These different contributions of soluble and cellular components of the PC niche in the spleen demonstrate that the LLPC expression profile is not cell intrinsic but largely depends on signals provided by the splenic microenvironment, implying that interfering with these components at the time of B-cell depletion might improve the response rate in autoimmune cytopenia., (© 2018 by The American Society of Hematology.)

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8 + T cells also participate to thrombocytopenia by increasing platelet apoptosis. Besides this peripheral platelet destruction, inappropriate bone marrow production also exacerbates thrombocytopenia, due to an immune response against megakaryocytes. Moreover, the level of circulating thrombopoietin, the main growth factor of megakaryocytes, is low during ITP. In this review, the major mechanisms leading to thrombocytopenia, the role of the different immune cells and the different targets of treatments are described., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Autoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD., Method: Forty cases were recruited from 4 IBD centers and 2 AIC tertiary centers. Controls were recruited from the MICISTA registry., Results: From the MICISTA registry, incidences were estimated at 4.1/100,000 patient-years and 12.5/100,000 patient-years after IBD diagnosis for AIHA and ITP, respectively. All AIHA patients (n=14) had colonic involvement (13/14 with UC), whereas CD (52%) and UC (48%) diagnoses were evenly distributed among ITP patients. Compared to control IBD patients, cases were characterized by a higher frequency of extra-intestinal manifestations (37.5% vs 17%, p<0.001) and by the presence of IBD severity's hallmark. AIHA and IBD ran mainly in parallel, and 12 out of 14 AIHA were warm AIHA. In isolated cases, rituximab and infliximab were efficient to treat IBD and AIC, respectively. IBD surgery may induce AIC remission in some cases., Conclusion: Although low, incidence of AIC appears higher in IBD patients compared to the general population. The association seems to be mainly non-fortuitous, especially for colitis-associated AIHA., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP., Methods: We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed., Results: Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock)., Conclusions: The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease., (© 2016 by The American Society of Hematology.)

Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β2GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40-10.99]; it was 2.14, 95% CI [1.11-4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-β2GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies., (Copyright © 2015. Published by Elsevier B.V.)

Introduction: B-cell depletion with rituximab (RTX) is widely used to treat autoimmune diseases, especially as second-line therapy for immune thrombocytopenia (ITP). The incidence of RTX-induced hypogammaglobulinemia is unknown because of heterogeneous follow-up and confounding factors such as concomitant immunosuppressive treatments in most patients. We describe 3 cases and attempted to determine the incidence of RTX-induced hypogammaglobulinemia by a systematic review of the literature., Methods: We retrospectively analyzed 189 ITP patients receiving RTX in 3 referral centers in France and conducted a systematic review of 32 studies (results published 2001-2014) reporting the use of RTX for ITP, particularly searching for symptomatic secondary hypogammaglobulinemia. We also searched for case reports of hypogammaglobulinemia after RTX initiation for ITP., Results: Of the 189 patients, 3 showed symptomatic hypogammaglobulinemia more than 2years after RTX infusion (initial immunoglobulin level was normal). All 3 presented recurrent severe infections. In 2, the outcome suggested common variable immunodeficiency. In patient 3, the peripheral blood lacked CD19(+)CD20(+) B cells and the bone-marrow B-cell precursor level was impaired. Among 1245 ITP patients in the literature who received RTX for ITP, gammaglobulin level was monitored before and after RTX initiation for 351 (28%). For 192 (55%), dosages were available and we identified 21 patients with secondary hypogammaglobulinemia, usually not symptomatic, 14 of whom had received concomitant dexamethasone. Finally, we found 4 case reports of ITP and symptomatic hypogammaglobulinemia possibly related to RTX according to the authors., Conclusions: This large analysis led us to recommend monitoring serum immunoglobulin level before and repeatedly after RTX initiation for ITP. Physicians should be aware of hypogammaglobulinemia as a rare but severe complication of RTX., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Management of primary immune thrombocytopenia (ITP) has changed, and clinical practice broadens the use of thrombopoietin receptor agonists and anti-CD20 antibody as options for second-line therapy, as alternative to splenectomy. Splenectomy remains a successful, definitive curative treatment. The purpose of this review about the complications of the splenectomy, in the context of ITP, is to increase the awareness of clinicians towards the preventive measures, which are often not correctly applied., (Copyright © 2013. Published by Elsevier SAS.)

The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RTX- nonresponder patient group, the CD8(+) T-cell repertoire displays a restricted pattern. In the blood, the phenotype of CD8(+) T cells before and after RTX treatment is not modified in responders or nonresponders. Altogether, these results demonstrate for the first time an activation of splenic CD8(+) T cells in ITP patients who did not respond to RTX and suggest their involvement in platelet destruction in these patients.

Treatments for immune thrombocytopenic purpura (ITP) providing durable platelet responses without continued dosing are limited. Whereas complete responses (CRs) to B-cell depletion in ITP usually last for 1 year in adults, partial responses (PRs) are less durable. Comparable data do not exist for children and 5-year outcomes are unavailable. Patients with ITP treated with rituximab who achieved CRs and PRs (platelets > 150 × 10(9)/L or 50-150 × 10(9)/L, respectively) were selected to be assessed for duration of their response; 72 adults whose response lasted at least 1 year and 66 children with response of any duration were included. Patients had baseline platelet counts < 30 × 10(9)/L; 95% had ITP of > 6 months in duration. Adults and children each had initial overall response rates of 57% and similar 5-year estimates of persisting response (21% and 26%, respectively). Children did not relapse after 2 years from initial treatment whereas adults did. Initial CR and prolonged B-cell depletion predicted sustained responses whereas prior splenectomy, age, sex, and duration of ITP did not. No novel or substantial long-term clinical toxicity was observed. In summary, 21% to 26% of adults and children with chronic ITP treated with standard-dose rituximab maintained a treatment-free response for at least 5 years without major toxicity. These results can inform clinical decision-making.

Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 10(9)/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 10(9)/L (interquartile range, 75-167 × 10(9)/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 10(9)/L (interquartile range, 35-44 × 10(9)/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181.

Unlabelled: Serum ferritin levels may be increased in many conditions: renal diseases, liver diseases, human immunodeficiency virus infection. The purpose of this study was to assess the aetiological spectrum of high serum ferritin levels in a 1200-bed university hospital, to compare our results with the data already published and to assess a potential association between aetiology and ferritin levels., Patients and Methods: Patients with a serum ferritin level higher than 600 microg/l were retrospectively included between 15 November 2003 and 15 January 2004, and their medical records were reviewed., Results: Ninety-eight patients (38 women and 60 men; median age: 59,5 years [19-92]) were recruited in departments of hepatology and gastroenterology (22%), haematology (14%) and internal medicine (18%). Diagnosis performed were: non-HIV systemic infections (23,8%), haematological diseases (16,1%), alcoholism (11,2%) and malignancies (9,8%). Dialysed chronic renal failure, liver diseases, haemochromatosis and systemic inflammatory diseases counted for 4.2 to 5.2% of cases. Serum ferritin level lied between 600 and 1000 microg/l for 50 patients, between 1000 and 1500 microg/l for 24, and over 1500 microg/l for 24. There was no significant difference between the three groups as regards the etiological distribution., Discussion: In our study, chronic renal failure was not a major cause of high ferritin level: this is probably due to the current use of erythropoietin, which has decreased the use of blood transfusions. The two major aetiology of hyperferritinemia were non-HIV infections and malignancies.