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Hemolytic Uremic Syndrome (hemolytic + uremic_syndrome)
Selected AbstractsBrief Communication: Successful Isolated Liver Transplantation in a Child with Atypical Hemolytic Uremic Syndrome and a Mutation in Complement Factor HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010W. Haller A male infant was diagnosed with atypical hemolytic uremic syndrome (aHUS) at the age of 5.5 months. Sequencing of the gene (CFH) encoding complement factor H revealed a heterozygous mutation (c.3644G>A, p.Arg1215Gln). Despite maintenance plasmapheresis he developed recurrent episodes of aHUS and vascular access complications while maintaining stable renal function. At the age of 5 years he received an isolated split liver graft following a previously established protocol using pretransplant plasma exchange (PE) and intratransplant plasma infusion. Graft function, renal function and disease remission are preserved 2 years after transplantation. Preemptive liver transplantation prior to the development of end stage renal disease is a valuable option in the management of aHUS associated with CFH mutations. [source] Favorable Long-Term Outcome after Liver-Kidney Transplant for Recurrent Hemolytic Uremic Syndrome Associated with a Factor H MutationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2006J. M. Saland A male child initially presented with atypical hemolytic uremic syndrome (HUS) at the age of 4 months and progressed within weeks to end stage renal disease (ESRD). At the age of 2 years he received a live-related kidney transplant from his mother, which, despite initial good function, was lost to recurrent disease after 2 weeks. Complement factor H analysis showed low serum levels and the presence of two mutations on different alleles (c.2918G > A, Cys973Tyr and c.3590T > C, Val1197Ala). His survival on dialysis was at risk because of access failure and recurrent bacteremic episodes. Therefore, at the age of 5 years he received a combined liver-kidney transplant with pre-operative plasma exchange. Initial function of both grafts was excellent and this has been maintained for over 2 years. This report suggests that despite setbacks in previous experience, combined liver-kidney transplantation offers the prospect of a favorable long-term outcome for patients with HUS associated with complement factor H mutations. [source] Epidemiological Approach to Identifying Genetic Predispositions for Atypical Hemolytic Uremic SyndromeANNALS OF HUMAN GENETICS, Issue 1 2010Maren Sullivan Summary Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility genes. A registry including analyses of susceptibility genes, familial occurrence and genotype-phenotype correlation should provide classification insights. Registry data of 187 unrelated index patients included age at onset, gender, family history, relapse of aHUS and potentially triggering conditions. Mutation analyses were performed in the genes CFH, CD46 and CFI and in the six potential susceptibility genes, FHR1 to FHR5 and C4BP. Germline mutations were identified in 17% of the index cases; 12% in CFH, 3% in CD46 and 2% in CFI. Twenty-nine patients had heterozygous mutations and one each had a homozygous and compound heterozygous mutation. Mutations were not found in the genes FHR1-5 and C4BP. In 40% of the patients with familial HUS a mutation was found. Penetrance by age 45 was 50% among carriers of any mutation including results of relatives of mutation-positive index cases. The only risk factor for a mutation was family history of HUS (p = 0.02). Penetrance of aHUS in carriers of mutations is not complete. Occurrence of homo- and heterozygous mutations in the same gene suggests that the number of necessary DNA variants remains unclear. Among clinical information only familial occurrence predicts a mutation. [source] Anti-Factor H Autoantibodies in a Fifth Renal Transplant Recipient with Atypical Hemolytic and Uremic SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. Le Quintrec Hemolytic uremic syndrome (HUS) associated with anti-Factor H (anti-FH) autoantibodies is a recently described pathophysiological entity. Monitoring of anti-FH IgG titer may be a sensitive marker of disease activity and guide treatment to eliminate circulating anti-FH antibodies. We report here a case of atypical HUS (aHUS) in which anti-FH autoantibodies were detected during the course of a fifth kidney transplant, 30 years after the first flare of aHUS. This exceptional case suggests that early, specific management based on immunosuppressive therapy and plasma exchanges monitored by anti-FH IgG titer may result in long-term graft survival. [source] A novel, promoter-based, target-specific assay identifies 2-deoxy- d -glucose as an inhibitor of globotriaosylceramide biosynthesisFEBS JOURNAL, Issue 18 2009Tetsuya Okuda Abnormal biosynthesis of globotriaosylceramide (Gb3) is known to be associated with Gb3-related diseases, such as Fabry disease. The Gb3 synthase gene (Gb3S) codes for ,1,4-galactosyltransferase, which is a key enzyme involved in Gb3 biosynthesis in vivo. Transcriptional repression of Gb3S is a way to control Gb3 biosynthesis and may be a suitable target for the treatment of Gb3-related diseases. To find a transcriptional inhibitor for Gb3S, we developed a convenient cell-based chemical screening assay system by constructing a fusion gene construct of the human Gb3S promoter and a secreted luciferase as reporter. Using this assay, we identified 2-deoxy- d -glucose as a potent inhibitor for the Gb3S promoter. In cultured cells, 2-deoxy- d -glucose markedly reduced endogenous Gb3S mRNA levels, resulting in a reduction in cellular Gb3 content and a corresponding accumulation of the precursor lactosylceramide. Moreover, cytokine-induced expression of Gb3 on the cell surface of endothelial cells, which is closely related to the onset of hemolytic uremic syndrome in O157-infected patients, was also suppressed by 2-deoxy- d -glucose treatment. These results indicate that 2-deoxy- d -glucose can control Gb3 biosynthesis through the inhibition of Gb3S transcription. Furthermore, we demonstrated the general utility of our novel screening assay for the identification of new inhibitors of glycosphingolipid biosynthesis. [source] Inducible stx2 phages are lysogenized in the enteroaggregative and other phenotypic Escherichia coli O86:HNM isolated from patientsFEMS MICROBIOLOGY LETTERS, Issue 1 2000Sunao Iyoda Abstract We characterized two Shiga toxin-producing Escherichia coli (STEC) O86:HNM isolates from a patient with hemolytic uremic syndrome (HUS) or bloody diarrhea. Both of them did not possess the eaeA gene. However, the isolate from a HUS patient carried genetic markers of enteroaggregative E. coli (EAEC) and showed aggregative adherence pattern to HEp-2 cells. The other isolate from bloody diarrhea, which was negative with EAEC markers, was diffusely adhered to HEp-2 cells. The stx2 gene in both E. coli O86:HNM strains was encoded in each infectious phage, which was partially homologous to that of strain EDL933, a STEC O157:H7. These results will help to explain the genotypic divergences of STEC. [source] Infection frequently triggers thrombotic microangiopathy in patients with preexisting risk factors: A single-institution experienceJOURNAL OF CLINICAL APHERESIS, Issue 2 2010Kenneth W. Douglas Abstract Thrombotic microangiopathies are rare conditions characterized by microangiopathic hemolytic anemia, microthrombi, and multiorgan insult. The disorders, which include hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, are often acute and life threatening. We report a retrospective analysis of 65 patients presenting to our institution from 1997 to 2008 with all forms of thrombotic microangiopathy. Therapeutic plasma exchange was a requirement for analysis and 65 patients were referred to our institution; 66% of patients were female and median age at presentation was 52 years. Bacterial infection was the most commonly identified etiologic factor and in the multivariate model was the only significant variable associated with survival outcome (odds ratio 5.1, 95% confidence interval, 1.2,21.7). As infection can be considered a common trigger event for thrombotic microangiopathy, patients with hepatobiliary sepsis may benefit from elective cholecystectomy. We conclude that bacterial infection frequently triggers TTP and other thrombotic microangiopathies in patients with preexisting risk factors and propose a model for the development of these syndromes. © J. Clin. Apheresis 2010. © 2010 Wiley-Liss, Inc. [source] Predictors of complications in therapeutic plasma exchangeJOURNAL OF CLINICAL APHERESIS, Issue 6 2009Carsten P. Bramlage Abstract Plasma exchange (PE) is used for blood purification to modulate proteins involved in pathological processes. As the number of patients receiving PE treatment and the heterogeneity of the underlying diseases is steadily increasing, we evaluated the most frequent complications and analyzed causes leading to adverse reactions. 883 PE procedures in 113 patients between the years 2000 to 2006 were retrospectively analyzed with respect to complications. Additionally, underlying diseases and settings of PE procedure were analyzed to identify high-risk patients and respective PE settings. A total of 226 adverse reactions were recorded (25.6% of all PE procedures). Most complications were mild (n = 121, 13.7%) or moderate (n = 98, 11.0%). In seven cases (n = 7, 0.7%), severe, life-threatening adverse events were induced by PE either due to severe allergic reactions (n = 4, 0.5%) or to sepsis (n = 3, 0.3%). Patients with neurologic diseases had a significantly higher risk to develop complications compared to those with internal diseases (P = 0.013). This was due to a higher rate of PE associated adverse events (in particular hypotension) and complications associated with vascular access. Among patients from internal medicine those with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) had the highest risk to develop complications. Patients with neurological diseases compared to those with medical conditions and patients with HUS/TTP compared to those with other diseases had a higher risk to develop complications. However, severe adverse events are rare. Thus, PE seems to be a safe and recommendable procedure. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Lessons learned from the Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome RegistryJOURNAL OF CLINICAL APHERESIS, Issue 4 2008James N. George Abstract The Oklahoma TTP-HUS Registry provides a complete community perspective of thrombotic thrombocytopenic purpura (TTP). This is possible because plasma exchange is the essential treatment for TTP and the Oklahoma Blood Institute provides all plasma exchange procedures for a region encompassing most of the State, including 58 of Oklahoma's 77 counties. The Registry is an inception cohort of consecutive patients for whom plasma exchange treatment was requested for a diagnosis of either TTP or hemolytic uremic syndrome (HUS). All 382 patients identified from January 1, 1989 to December 31, 2007 have consented to be enrolled. Complete follow-up is available for 380 of 382 patients. Patients are described both by clinical categories, related to their associated conditions and clinically apparent etiologies, and by the presence of severe ADAMTS13 deficiency. ADAMTS13 activity has been measured on 235 (93%) of 254 patients since 1995. Registry data have provided new perspectives on the definition and diagnoses of these syndromes as well as their outcomes. Long-term follow-up has documented that relapse is common among patients with ADAMTS13 deficiency but rarely occurs in patients without ADAMTS13 deficiency. Long-term follow-up has also documented persistent abnormalities of health-related quality-of-life and cognitive function. In addition to providing new perspectives on the natural history of these syndromes, The Oklahoma TTP-HUS Registry provides a support group for our patients, information about evaluation and management for community physicians, and a resource for research and educational programs. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source] Shiga toxin enhances functional tissue factor on human glomerular endothelial cells: implications for the pathophysiology of hemolytic uremic syndrome,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2005E. NESTORIDI Summary.,Background:,The pathogenesis of Shiga toxin (Stx)-mediated childhood hemolytic uremic syndrome (HUS) is not fully delineated, although current evidence implicates a prothrombotic state. We hypothesized that the tissue factor (TF) pathway plays a major role in the pathophysiology of HUS. Materials and methods:,We measured cell surface TF activity in response to tumor necrosis factor-, (TNF-,) (20 ng mL,1, 2,144 h), Stx-1 (10,11 mol L,1, 4,144 h), or their combination (TNF-, 22 h and Stx-1 for the last 0.5,4 h of TNF-, incubation) on human glomerular (microvascular) endothelial cells (HGECs) and human umbilical vein (macrovascular) endothelial cells (HUVECs). Results and conclusions:,We observed that while TNF-, caused an increase in cell surface TF activity on both cell types, the combination of TNF-, and Stx-1 differentially affected HGECs. On these cells, TF activity was increased further by 2.67 ± 0.38-fold (n = 38, P < 0.001), consistent with our parallel observation that Stx-1 binds to HGECs but not to HUVECs. Anti-TF antibody abolished functional TF while anti-tissue factor pathway inhibitor antibody enhanced TF activity. Stx-1 alone did not induce TF activity on either cell type. Measurement of TF antigen levels and quantitative real-time polymerase chain reaction demonstrated that exposure to TNF-, markedly increased TF protein and TF mRNA for HGECs, but the exposure to the combination of TNF-, and Stx-1 did not increase further the amount of either TF protein or TF mRNA. We conclude that cytokine-activated HGECs, but not HUVECs, undergo a significant augmentation of cell surface TF activity following exposure to Stx, suggesting an important role for TF in the coagulopathy observed in HUS. [source] Toxic epidermal necrolysis and hemolytic uremic syndrome after allogeneic stem-cell transplantationPEDIATRIC TRANSPLANTATION, Issue 6 2007Johan Arvidson Abstract:, TEN and HUS are challenging complications with excessive mortality after HSCT. We report the development of these two conditions in combination in a nine-yr-old boy after HSCT from an unrelated donor. TEN with skin detachment of more than 90% of body surface area developed after initial treatment for GvHD. Within a few days of admission to the burns unit, the patient developed severe hemolysis, hypertension, thrombocytopenia, and acute renal failure consistent with HUS, apparently caused by CSA. The management included intensive care in a burns unit, accelerated drug removal using plasmapheresis, and a dedicated multi-disciplinary team approach to balance immunosuppression and infections management in a situation with extensive skin detachment. The patient survived and recovered renal function but requires continued treatment for severe GvHD. Suspecting and identifying causative drugs together with meticulous supportive care in the burns unit is essential in the management of these patients and long-term survival is possible. [source] Anemia in children after transplantation: etiology and the effect of immunosuppressive therapy on erythropoiesisPEDIATRIC TRANSPLANTATION, Issue 4 2003Amira Al-Uzri Abstract: Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein,Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient. [source] Prognosis and pathological characteristics of five children with non-Shiga toxin-mediated hemolytic uremic syndromePEDIATRICS INTERNATIONAL, Issue 2 2007ICHIRO KAMIOKA Abstract Background: The three major signs of hemolytic uremic syndrome (HUS) are hemolytic anemia, thrombopenia and acute renal failure. HUS is classified into Shiga toxin-mediated HUS (Stx-HUS) and non-Shiga toxin-mediated HUS (nStx-HUS). The prognosis of nStx-HUS is reported to be less favorable than that of Stx-HUS. Although the association between the prognosis and pathological characteristics of HUS have been reported such that the prognosis was considered to be poor for thrombotic microangiopathy (TMA) with predominant arterial involvement (arterial TMA), good for TMA with predominant glomerular involvement (glomerular TMA) and dependent on the extent of necrosis in cases of renal cortical necrosis, it is not yet clear whether pathological findings are also related to the renal prognosis of nStx-HUS cases. Therefore the purpose of the present paper was to analyze renal biopsy findings and prognosis for five children with nStx-HUS. Methods: Clinical records of five cases of nStx-HUS among 74 cases of diagnosed HUS were reviewed, and information and data were summarized. Results: Histological examination of the kidney led to the diagnosis of arterial TMA in three cases, and glomerular TMA and severe renal cortical necrosis in one case each. Analysis of the relationship between renal histological findings and the prognosis found that three patients with arterial TMA and one patient with severe renal cortical necrosis later developed end-stage renal failure while one patient with glomerular TMA has continued to show normal renal function. Conclusions: These findings indicate that pathological findings are closely related to the prognosis in cases of nStx-HUS. [source] Brief Communication: Successful Isolated Liver Transplantation in a Child with Atypical Hemolytic Uremic Syndrome and a Mutation in Complement Factor HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010W. Haller A male infant was diagnosed with atypical hemolytic uremic syndrome (aHUS) at the age of 5.5 months. Sequencing of the gene (CFH) encoding complement factor H revealed a heterozygous mutation (c.3644G>A, p.Arg1215Gln). Despite maintenance plasmapheresis he developed recurrent episodes of aHUS and vascular access complications while maintaining stable renal function. At the age of 5 years he received an isolated split liver graft following a previously established protocol using pretransplant plasma exchange (PE) and intratransplant plasma infusion. Graft function, renal function and disease remission are preserved 2 years after transplantation. Preemptive liver transplantation prior to the development of end stage renal disease is a valuable option in the management of aHUS associated with CFH mutations. [source] Thrombotic Microangiopathy After Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010M. Noris Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation that often causes graft failure. TMA may occur de novo, often triggered by immunosuppressive drugs and acute antibody-mediated rejection, or recur in patients with previous history of hemolytic uremic syndrome (HUS). Recurrent TMA is very rare in patients who had developed end-stage renal failure following HUS caused by Shiga-toxin producing E. scherichia coli, whereas disease recurrence is common in patients with atypical HUS (aHUS). The underlying genetic defect greatly impacts the risk of posttransplant recurrence in aHUS. Indeed recurrence is almost the rule in patients with mutations in genes encoding factor H or factor I, whereas patients with a mutation in membrane-cofactor-protein gene have a good transplant outcome. Prophylactic and therapeutic options for posttransplant TMA, including plasma therapy, combined kidney and liver transplantation and targeted complement inhibitors are discussed in this review. [source] Successful Renal Transplantation in Factor H Autoantibody Associated HUS with CFHR1 and 3 Deficiency and CFH Variant G2850TAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010A. M. Waters Factor H (CFH) autoantibodies are associated with atypical hemolytic uremic syndrome (aHUS). Peritransplantation plasma exchange therapy and intensification of immunosuppression, with adjuvant use of anti-CD20 monoclonal antibodies has recently been advocated for cases of CFH-autoantibody associated aHUS. In this report, we describe successful deceased donor renal transplantation in a case of CFH-autoantibody associated aHUS with combined CFHR1 and 3 deficiency in addition to the CFH sequence variant, (cG2850T, pGln950His). CFH-autoantibodies were detected 2 weeks prior to transplantation. Disease recurrence was not observed using basiliximab, an IL2-receptor antagonist and high-dose corticosteroids with mycophenolate mofetil. Adjuvant therapies such as Rituximab nor intensification of plasma therapy were employed. Consequently, careful consideration needs to be given to the use of additional immunosuppression in certain cases of CFH-autoantibody associated aHUS. Serial measurement of CFH-autoantibodies is required in the immediate pre- and posttransplantation period to further clarify their role as a factor in the recurrence of aHUS posttransplantation. Furthermore, delineation of the functional significance of CFH-autoantibodies is warranted in individual cases. [source] Successful Renal Transplantation in a Patient with Atypical Hemolytic Uremic Syndrome Carrying Mutations in Both Factor I and MCPAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009J. M. Cruzado Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) carrying mutations in the soluble complement regulators factor H (CFH) or factor I (CFI) is associated with elevated risk of disease recurrence and almost certain graft loss. In contrast, recurrence is unusual in patients with mutations in the membrane-associated complement regulator membrane cofactor protein (MCP) (CD46). Therefore, a panel of experts recently recommended the combined liver,kidney transplantation to minimize aHUS recurrence in patients with mutations in CFH or CFI. There was, however, very limited information regarding transplantation in patients carrying mutations in both soluble and membrane-associated complement regulators to support a recommendation. Here, we report the case of an aHUS patient with a heterozygous mutation in both CFI and MCP who received an isolated kidney transplant expressing normal MCP levels. Critically, the patient suffered from a severe antibody-mediated rejection that was successfully treated with plasmapheresis and IvIgG. Most important, despite the complement activation in the allograft, there was no evidence of thrombotic microangiopathy, suggesting that the normal MCP levels in the grafted kidney were sufficient to prevent the aHUS recurrence. Our results suggest that isolated kidney transplantation may be a good first option for care in aHUS patients carrying CFI/MCP combined heterozygous mutations. [source] Favorable Long-Term Outcome after Liver-Kidney Transplant for Recurrent Hemolytic Uremic Syndrome Associated with a Factor H MutationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2006J. M. Saland A male child initially presented with atypical hemolytic uremic syndrome (HUS) at the age of 4 months and progressed within weeks to end stage renal disease (ESRD). At the age of 2 years he received a live-related kidney transplant from his mother, which, despite initial good function, was lost to recurrent disease after 2 weeks. Complement factor H analysis showed low serum levels and the presence of two mutations on different alleles (c.2918G > A, Cys973Tyr and c.3590T > C, Val1197Ala). His survival on dialysis was at risk because of access failure and recurrent bacteremic episodes. Therefore, at the age of 5 years he received a combined liver-kidney transplant with pre-operative plasma exchange. Initial function of both grafts was excellent and this has been maintained for over 2 years. This report suggests that despite setbacks in previous experience, combined liver-kidney transplantation offers the prospect of a favorable long-term outcome for patients with HUS associated with complement factor H mutations. [source] Calcineurin Inhibitor-Free Immunosuppression in Renal Allograft Recipients with Thrombotic Microangiopathy/Hemolytic Uremic SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2006O. Øyen Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent serious threats to kidney allograft recipients. During a 4-year period, among 850 kidney transplantations, seven recipients with primary HUS and seven recipients (eight transplants) with previous or de novo TMA/HUS were identified and given calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL), mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were successful in the long term; resulting in a mean creatinine of 101 ,mol/L (16.4 months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS recurrences were observed. A high rate of acute rejections (53%) may indicate insufficient immunosuppressive power and/or a causative relationship between TMA/HUS and rejection. Wound-related complications were abundant (60%), and call for surgical/immunosuppressive countermeasures. Our experience supports the idea that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of TMA/HUS should be carefully explored in recurrent 'high responders'. [source] Epidemiological Approach to Identifying Genetic Predispositions for Atypical Hemolytic Uremic SyndromeANNALS OF HUMAN GENETICS, Issue 1 2010Maren Sullivan Summary Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility genes. A registry including analyses of susceptibility genes, familial occurrence and genotype-phenotype correlation should provide classification insights. Registry data of 187 unrelated index patients included age at onset, gender, family history, relapse of aHUS and potentially triggering conditions. Mutation analyses were performed in the genes CFH, CD46 and CFI and in the six potential susceptibility genes, FHR1 to FHR5 and C4BP. Germline mutations were identified in 17% of the index cases; 12% in CFH, 3% in CD46 and 2% in CFI. Twenty-nine patients had heterozygous mutations and one each had a homozygous and compound heterozygous mutation. Mutations were not found in the genes FHR1-5 and C4BP. In 40% of the patients with familial HUS a mutation was found. Penetrance by age 45 was 50% among carriers of any mutation including results of relatives of mutation-positive index cases. The only risk factor for a mutation was family history of HUS (p = 0.02). Penetrance of aHUS in carriers of mutations is not complete. Occurrence of homo- and heterozygous mutations in the same gene suggests that the number of necessary DNA variants remains unclear. Among clinical information only familial occurrence predicts a mutation. [source] Association of Helicobacter pylori with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantationCLINICAL TRANSPLANTATION, Issue 5 2004Hiroyuki Takatsuka Abstract:, Thrombotic microangiopathy (TMA) has attracted attention as a complication of bone marrow transplantation (BMT). The association of Helicobacter pylori (H. pylori) with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS) after BMT was studied. Among 74 consecutive patients undergoing transplantation, six developed TTP/HUS (the TTP/HUS group) and 68 did not (controls). These six patients were compared with the other 68 patients to investigate differences of the IL-12 and 8 levels, H. pylori and various clinical characteristics. The patients who developed TTP/HUS seemed not apparently different from those who did not in background characteristics, except that they had a significantly higher H. pylori -positive rate (p < 0.05). In the TTP/HUS group, however, the levels of interleukin-12 and interleukin-8 increased significantly during the leukocyte recovery after BMT and at the onset of TTP/HUS, respectively, to 45.8 ± 57.6 pg/mL and 274.8 ± 65.9 pg/mL (p < 0.05 for both), when compared with their levels of 5.0 pg/mL in the control group. Thus, H. pylori may play a role in the pathogenesis of TTP/HUS after BMT, with cytokines (interleukin-8 and interleukin-12) also being involved. [source] | |||||||||||||