Cancer-related thrombotic microangiopathy and disseminated intravascular coagulation in a patient with bone marrow carcinomatosis of unknown primary origin: A case report.

BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare type of Coombs-negative hemolytic anemia, which is caused by malignancy and has a poor prognosis. CASE: A 76-year-old female was referred to our hospital due to Coombs-negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet-ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR-TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site. CONCLUSION: Although CR-TMA is an extremely rare phenomenon, clinicians who suspect CR-TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.

Unveiling the Incidence and Graft Survival Rate in Kidney Transplant Recipients With De Novo Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis.

De novo thrombotic microangiopathy (TMA) is a rare and challenging condition in kidney transplant recipients, with limited research on its incidence and impact on graft survival. This study conducted a systematic review and meta-analysis of 28 cohorts/single-arm studies and 46 case series/reports from database inception to June 2022. In meta-analysis, among 14,410 kidney allograft recipients, de novo TMA occurred in 3.20% [95% confidence interval (CI): 1.93-4.77], with systemic and renal-limited TMA rates of 1.38% (95% CI: 06.5-2.39) and 2.80% (95% CI: 1.27-4.91), respectively. The overall graft loss rate of de novo TMA was 33.79% (95% CI: 26.14-41.88) in meta-analysis. This study provides valuable insights into the incidence and graft outcomes of de novo TMA in kidney transplant recipients.

Red blood cell-derived arginase release in hemolytic uremic syndrome.

BACKGROUND: Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from red blood cells. Increased arginase activity leads to reduced L-arginine, as it is converted to urea and L-ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. The objective of this study was to investigate arginase release in HUS patients and laboratory models and correlate arginase levels to hemolysis and kidney injury. METHODS: Two separate cohorts of patients (n = 47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n = 35) were investigated. Two mouse models were used, in which mice were either challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. An in vitro model of thrombotic microangiopathy was developed in which Shiga toxin 2- and E. coli O157 lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma were perfused over glomerular endothelial cells. Two group statistical comparisons were performed using the Mann-Whitney test, multiple groups were compared using the Kruskal-Wallis test followed by Dunn's procedure, the Wilcoxon signed rank test was used for paired data, or linear regression for continuous variables. RESULTS: HUS patients had excessively high plasma arginase 1 levels and activity (conversion of L-arginine to urea and L-ornithine) during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Both mouse models exhibited significantly elevated plasma arginase 1 levels and activity. Plasma arginase 1 levels correlated with lactate dehydrogenase activity, alpha-1-microglobulin and urea levels, the latter indicative of kidney dysfunction. In the in vitro model of thrombotic microangiopathy, bioactive arginase 1 was released and levels correlated to the degree of hemolysis. CONCLUSIONS: Elevated red blood cell-derived arginase was demonstrated in HUS patients and in relevant in vivo and in vitro models. The excessively high arginase levels correlated to the degree of hemolysis and kidney dysfunction. Thus, arginase inhibition should be investigated in HUS.

Adult-onset Still's disease with concurrent thrombotic microangiopathy: Observations from pooled analysis for an uncommon finding.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated. METHODS: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co-occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis. RESULTS: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p = .829. CONCLUSIONS: A majority of patients with AOSD-associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk-stratify high-risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD-associated TMA.

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with possible complication of thrombotic microangiopathy.

This case study illustrates a 63-year-old Japanese woman who presented with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis. She was administered a therapeutic regimen consisting of corticosteroids, tacrolimus, and cyclophosphamide. However, after a month of treatment, symptoms of confusion and depressive tendencies emerged, followed by the manifestation of hematuria, thrombocytopenia, and fragmented erythrocytes. A disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 activity was 45%. Thrombotic microangiopathy was contemplated, yet a definitive diagnosis remained elusive. She died 2 months after admission. Although the occurrence of thrombotic microangiopathy in patients with dermatomyositis is rare, the prognosis is poor, emphasizing the importance of prompt diagnosis and treatment.

Incidence and Role of Recipient-Specific Antibodies in Allogeneic Hematopoietic Cell Transplantation from Mismatched Related Donors.

High titer of donor-specific antibodies (DSAs) increases the risk of graft rejection after mismatched related hematopoietic cell transplantation (HCT). There are no data regarding the incidence of anti-HLA recipient-specific antibodies (RSAs) and their role after transplantation. Here we aimed to identify the incidence of RSAs in a mismatched related hematopoietic cell donor population and their possible impact on immune-mediated complications, such as acute graft-versus-host disease (aGVHD), and complications resulting from endothelial injury, such as transplantation-associated thrombotic microangiopathy (TA-TMA) and veno-occlusive disease (VOD). We prospectively analyzed the incidence of anti-HLA antibodies in 28 mismatched related pairs of recipients and their donors who underwent HCT at our center between 2020 and 2022. In positive samples screened for anti-HLA class I and/or II antibodies, the specificity of the HLA antibodies was analyzed. All recipients had a hematologic malignancy and received a myeloablative conditioning regimen and immunosuppression consisting of post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Patients were tested for TA-TMA and aGVHD development during routine post-transplantation visits up to 100 days post-transplantation. We used modified Jodele criteria for TA-TMA diagnosis, and based aGVHD grading on the MAGIC criteria. VOD was assessed using the European Society for Blood and Marrow Transplantation. Anti-HLA antibodies were detected in 12 donors (43%) and in 9 recipients (32%). There were no significant differences between donors and recipients according to age (median, 42 years [range, 17 to 69 years] versus 39 years [range, 8 to 68 years]), sex, or pregnancy history. No transfusion history was noted in the donor group (P < .05). RSA antibodies were present more often than DSAs and were detected in 9 out of 12 (75%) anti-HLA-positive donors and in only 2 out of 9 (22%) recipients, respectively (P < .05). During the follow-up, 11 patients (39%) developed aGVHD, including grade I-II in 9 (32%) and grade III-IV in 2 (7%). Twelve patients (43%) met the criteria for TA-TMA, and only 1 patient (3.5%) was diagnosed with VOD by day 100 post-HCT. RSAs were detected significantly more often in the TA-TMA group; among 12 patients diagnosed with TA-TMA, 7 (58%) had RSAs (P < .05). We did not find a correlation between RSAs and aGVHD. The patient with VOD did not have an RSA-positive donor. There was no difference in membrane attack complex (MAC) concentration in the RSA-positive group on day 30 and day 60 post-HCT; however, there was a trend toward higher MAC concentration in the RSA-positive group on day 100 (median, 912 ng/mL [range, 788 to 1120 ng/mL] versus 616 ng/mL [range, 352 to 1244 ng/mL]; P = .055). Patients with RSA suffered more often from platelet and red blood cell decreases or transfusion refractoriness, and increased lactate dehydrogenase activity was observed in all RSA-positive cases. The donor immune status and the presence of RSA may be associated with higher rates of TA-TMA in mismatched HCT recipients. Antibody-mediated complement activation might be an additional factor influencing TA-TMA occurrence.

Spectrum of renal vascular lesions among patients with lupus nephritis: An experience from a tertiary care center.

Background: Lupus nephritis (LN) is the assemblage of glomerular, tubulointerstitial and vascular changes. Despite the fact that glomerular changes are overemphasized in pathological classification and scoring system, but the existence of vascular damage negatively impact the clinical course. Aims and Objective: This study was conducted to determine the clinicopathological spectrum of renal vascular lesions in lupus nephritis. Materials and Methods: Renal microvascular lesions in biopsy proven lupus nephritis were classified into 5 major categories-thrombotic microangiopathy, true vasculitis; lupus vasculopathy, uncomplicated vascular immune deposits, and arterial. Clinical details, laboratory parameters and histopathological variables were compared among all groups. Summary of chronic changes was also assessed. Results: Biopsies from 56 patients revealed thrombotic microangiopathy (2), lupus vasculopathy (3), uncomplicated vascular immune deposit (6), PAN type vasculitis (1) and arterial sclerosis (13). No renal vascular lesions were found in 35.18% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older Nephritis subtype. Activity indices were higher in lupus vasculopathy group whereas patients with arteriosclerosis showed highest chronicity index. Conclusions: Renal vascular lesions are common in systemic lupus erythematosus patients with nephritis and may be associated with aggressive clinical course.

[Clinical analysis of sirolimus as an alternative GVHD prophylaxis for patients with kidney injury undergoing allo-HSCT].

Objective: To explore the feasibility of sirolimus as an alternative graft versus host disease (GVHD) prophylaxis in patients with kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective case series study. Medical records of 11 patients in Peking University People's Hospital from 1 August 2008 to 31 October 2022, who received sirolimus instead of cyclosporine to prevent GVHD, due to renal insufficiency after allo-HSCT, were analyzed retrospectively. Incidence of GVHD, infection, and transplant-associated thrombotic microangiopathy (TA-TMA), as well as renal function, were evaluated. Results: Among the 11 patients who received sirolimus, 6 were treated with haploidentical donor HSCT, and 5 were treated using matched sibling donor HSCT. The median (range) time of sirolimus administration was 30 (7-167) days after allo-HSCT, and the median (range) sirolimus course duration was 52 (9-120) days. During sirolimus treatment, 1 case did not undergo combined treatment with other prophylactic drugs, 3 cases received combined mycophenolate mofetil (MMF), and 1 case underwent combined CD25 monoclonal antibody treatment, while 6 cases had combined therapy with both MMF and CD25 monoclonal antibody. Of the 11 patients, 2 developed Grade Ⅲ acute GVHD, 1 developed severe pneumonia and died, and 1 developed TA-TMA, while nine patients had normal or improved renal function. Median (range) follow-up time was 130 (54-819) days. Non-relapse mortality was observed in 1 patient. Relapse mortality was also observed in 1 patient. Conclusion: Sirolimus-based alternative GVHD prophylaxis is a potentially viable option for patients undergoing allo-HSCT who cannot tolerate cyclosporine, but its efficacy and safety require further optimization and verification in prospective studies.

Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by a genetic dysregulation of the alternative complement pathway, characterized by thrombocytopenia, hemolytic anemia, and acute kidney injury, and included in the group of thrombotic microangiopathies. With the introduction of humanized monoclonal antibodies that inhibit C5 activation, the natural history of aHUS completely changed, with a better prognosis, a quick recovery of renal function, and a significant reduction of end-stage renal disease incidence. Nowadays, there is an increasing interest in the molecular and genetic bases of this severe disease. The aim of this narrative review is to provide readers with a practical guide about different possible involved genes, elucidating the specific role of each transcribed protein in the pathogenesis of aHUS. Moreover, we analyzed the main current evidence about the relationship among genetic mutations, outcomes, and the risk of recurrence of this manifold disease.

Clinical features of women with thrombotic microangiopathy in pregnancy: A case series from a single Japanese tertiary perinatal care center.

AIM: Although perinatal thrombotic microangiopathy has become increasingly understood, the racial characteristics of patients with this condition remain unclear. Herein, we report the characteristics of patients with perinatal thrombotic microangiopathy at a single institution in Japan. METHODS: We conducted a retrospective study over a 5-year period from January 1, 2017, to December 31, 2021, using the electronic medical records of pregnant women who delivered at the perinatal center of our hospital. We extracted the data of those who developed perinatal thrombotic microangiopathy and evaluated their characteristics at the time of disease onset, final diagnosis, and maternal and fetal outcomes. RESULTS: Of the 10 224 deliveries that occurred during the 5-year period, only seven patients (0.06%) had perinatal thrombotic microangiopathy. The median pre-pregnant body mass index was 18.65 kg/m2 (minimum 17.3 kg/m2 , maximum 20.7 kg/m2 ). More than half of the patients were conceived by in-vitro fertilization, and 42% these had twin deliveries. Four patients had a history of rheumatic disease. The other three patients without underlying diseases developed thrombotic microangiopathy with HELLP syndrome, and one patient transitioned to atypical hemolytic uremic syndrome. CONCLUSIONS: Based on low body mass index and in-vitro fertilization, which are characteristic of Japanese women, medical complications and twin pregnancies may be a risk for thrombotic microangiopathy. Additionally, depending on the cause of thrombotic microangiopathy, its timing and onset differed.

Increased Body Mass Index Augments Endothelial Injury and Clinical Outcomes after Hematopoietic Stem Cell Transplantation.

Higher body mass index (BMI) is characterized as a chronic inflammatory state with endothelial dysfunction. Endothelial injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT) puts patients at risk for such complications as transplantation-associated thrombotic microangiopathy (TA-TMA) and acute graft-versus-host-disease (aGVHD). To evaluate the impact of increased BMI on endothelial injury after allo-HSCT in pediatric and young adult patients, we conducted a retrospective cohort study evaluating 476 consecutive allo-HSCT children and young adult recipients age 0 to 20 years. Our analysis was subdivided based on distinct age categories (<2 years and 2 to 20 years). BMI was considered as a variable but was also expressed in standard deviations from the mean adjusted for age and sex (z-score), based on established criteria from the World Health Organization (age <2 years) and the Centers for Disease Control and Prevention (age 2 to 20 years) to account for differences associated with age. Primary endpoints included the incidences of TA-TMA and aGVHD. Increased BMI z-score was associated with TA-TMA after allo-HSCT in patients age <2 years (median, 18.1; IQR, 17 to 20; P = .006) and in patients age 2 to 20 years (median, 18.7; IQR, 16 to 21.9; P = .02). Higher BMI z-score correlated with TA-TMA risk in both age groups, with a BMI z-score of .9 in the younger cohort and .7 (IQR, -.4 to 1.6; P = .04) in the older cohort. Increased BMI z-score was associated with an increased risk of TA-TMA in a multivariate analysis of the entire cohort (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.05 to 1.37; P = .008). Multivariate analysis also demonstrated that patients with BMI in the 85th percentile or greater had an increased risk of developing TA-TMA compared to those with a lower BMI percentile (OR, 2.66; 95% CI, 1.62 to 4.32; P < .001). Baseline and day +7 ST2 levels were elevated in subjects with TA-TMA compared to those without TA-TMA in both age groups. Baseline sC5b-9 concentration was not correlated with BMI z-score, but sC5b-9 concentration was increased markedly by 7 days post-allo-HSCT in patients age <2 years who later developed TA-TMA compared to those who never developed TA-TMA (P = .001). The median BMI z-score was higher for patients with aGVHD compared to patients without aGVHD (.7 [range, -3.9 to 3.9] versus .2 [range, -7.8 to 5.4]; P = .03). We show that high BMI is associated with augmented risk of endothelial injury after HSCT, specifically TA-TMA. These data identify a high-risk population likely to benefit from early interventions to prevent endothelial injury and prompt treatment of established endothelial injury.

Complement Factor I Gene Variant in an Atypical Hemolytic Uremic Syndrome Triggered by Hypereosinophilia Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a condition characterized by acute kidney injury (AKI), thrombocytopenia, and microangiopathic hemolytic anemia secondary to complement pathway dysregulation. Several triggers have been identified as causing aHUS in genetically susceptible patients; however, hypereosinophilia syndrome (HES)-triggered aHUS has not been reported. In this article, we present a case of aHUS presented with generalized urticarial rashes and angioedema. The initial investigations revealed hypereosinophilia (maximal absolute eosinophil count of 6,840 cells/µL) with normal bone-marrow analyses; hence, idiopathic HES was diagnosed. During hospitalization, the patient developed convulsion, stuporous, and full-blown thrombotic microangiopathy (TMA), with AKI requiring temporary hemodialysis. A kidney biopsy confirmed the existence of renal TMA. Next-generation sequencing of the coding regions of aHUS-related genes was performed, revealing an underlying complement factor I (CFI) deficiency, a heterozygous variant p.P64L of CFI gene. The patient was successfully treated with high-dose steroids and extended duration of plasmapheresis.

Clinicopathological Characteristics and Impacts on Clinical Outcomes of Thrombotic Microangiopathy Lesions in Patients with Immunoglobulin A Nephropathy in Thailand.

INTRODUCTION: More reports of thrombotic microangiopathy (TMA) in immunoglobulin A (IgA) nephropathy suggest its association with poor clinical outcomes. However, the prevalence and clinical significance of TMA in IgA nephropathy have not been widely studied in different populations. METHODS: Kidney biopsies of all patients with primary IgA nephropathy from 1995 to 2015 at the King Chulalongkorn Memorial Hospital, Thailand, were retrospectively reviewed and reclassified by two pathologists following the Oxford MEST-C classification. TMA lesions were detected based solely on light microscopic findings. Associations between the presence of TMA and clinical data, other pathologic findings, and clinical outcomes were studied. RESULTS: Among 267 patients with primary IgA nephropathy, 166 had adequate clinical data and kidney tissues for the analysis. TMA was observed in 21 patients (13%) and was associated with higher mean arterial pressure (MAP), history of malignant hypertension, higher proteinuria, and lower estimated glomerular filtration rate (eGFR) at diagnosis compared to those without TMA. According to the Oxford MEST-C classification, TMA showed a significant association with severe tubular atrophy/interstitial fibrosis (T2) but not with mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), or crescents (C1-2). After a median follow-up of 50 months, patients with TMA had a significantly higher risk of progression to end-stage kidney disease (ESKD) (hazard ratio [HR] 5.8, 95% confidence interval [CI]: 3.1-10.9) and all-cause mortality (HR 3.4, 95% CI: 1.3-8.8). After adjusting for baseline eGFR, MAP, proteinuria, and other pathological lesions, TMA remained an independent predictor of ESKD (adjusted HR 2.4, 95% CI: 1.1-5.4). CONCLUSIONS: Kidney TMA in IgA nephropathy is associated with advanced disease stages, carries a poor prognosis, and thus should be considered in the pathological classification of IgA nephropathy.

Thrombotic microangiopathy and disseminated intravascular coagulation in a patient with carcinomatosis of the bone marrow due to gastric adenocarcinoma: Case report.

Carcinomatosis of the bone marrow is a rare clinical condition characterized by diffuse tumor infiltration of the bone marrow accompanied by hematological abnormalities, including thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). In patients with gastric carcinoma, this association is infrequent. Below we present a case of a 19-year-old female patient with no known pathological history who presented with upper digestive tract bleeding. Upon examination, anemia and thrombocytopenia were documented, with schistocytes in the peripheral blood smear and prolonged coagulation times. Endoscopic studies indicated a lesion in the Borrmann IV gastric body, and the bone marrow biopsy showed the presence of signet ring cells. Because there was no possibility of systemic therapy, the patient died during hospitalization. This case contributes to the medical literature by describing an unusual presentation of a very frequent pathology.

Long-term survival and renal outcomes of thrombotic microangiopathy in pregnancy: A retrospective cohort study.

OBJECTIVE: Thrombotic microangiopathy (TMA) in pregnancy can rapidly progress, leading to severe morbidities. This study aimed to compare baseline demographics and clinical outcomes between pregnant women with and without TMA. METHODS: Using the National Health Insurance Research Database, 207 patients with pregnancy-related TMA from January 1, 2006 to December 31, 2015 were enrolled. Their data were compared with a 1:4 propensity score-matched cohort of 828 pregnant women without TMA to evaluate mortality and end-stage renal disease (ESRD) risks. Cox proportional hazards models were used to estimate the adjusted hazard ratio and 95% confidence intervals. RESULTS: A total of 1035 participants were included. The risks of mortality and ESRD were 4.46 and 5.97 times higher for the TMA cohort, respectively. Subgroup analysis revealed higher mortality and ESRD risks in patients with TMA aged >40 years with a history of hypertension, stroke, cancer, concomitant stroke, malignant hypertension, or gastroenterocolitis than in the matched cohort. CONCLUSION: Pregnant patients with TMA, especially those older and with comorbidities and organ involvement, faced increased mortality and ESRD risks. Physicians should collaborate with obstetricians throughout the prenatal and postpartum periods for these patients.

Better late than never: Diagnosis of recurrent atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) comprising microangiopathic hemolytic anemia, consumptive thrombocytopenia, and end-organ damage. Risk of end-stage renal disease is increased as HUS usually manifests in native and transplanted kidneys. In transplants, while de novo disease can be seen, recurrent disease is more common. The etiology is variable, being either primary or secondary. aHUS often constitutes a diagnostic and therapeutic challenge, which may lead to a considerable delay in the diagnosis and treatment. During the last decades, great progress has been made in understanding the mechanisms and therapeutic options of this devastating condition. We present a case of a 50-year-old female who received her first kidney transplant from her mother at the age of 9 years. She experienced recurrent losses of transplants, and only after the loss of her fourth transplant did the diagnosis of aHUS become evident.

Catastrophic antiphospholipid syndrome accompanied by complement regulatory gene mutation.

BACKGROUND: Antiphospholipid syndrome (APS), particularly the catastrophic antiphospholipid syndrome (CAPS), is one of the rare causes of thrombotic microangiopathy (TMA). CAPS is the most severe form of APS, especially when accompanied by complement dysregulation, causes progressive microvascular thrombosis and failure in multiple organs. In this report, a case of CAPS with TMA accompanied by a genetic defect in the complement system is presented. CASE: A 13-year-old girl was admitted to the hospital with oliguric acute kidney injury, nephrotic range proteinuria, Coombs positive hemolysis, refractory thrombocytopenia, a low serum complement C3 level and anti-nuclear antibody (ANA) positivity. The kidney biopsy was consistent with TMA. She was first diagnosed with primary APS with clinical and pathological findings and double antibody positivity. As initial treatments, plasmapheresis (PE) was performed and eculizumab was also administered following pulsesteroid and intravenous immunoglobulin treatments. Her renal functions recovered and she was followed up with mycophenolate mofetil, hydroxychloroquine, low dose prednisolone and low molecular weight heparin treatments. The patient presented with severe chest pain, vomiting and acute deterioration of renal functions a few months after the diagnosis of TMA. A CAPS attack was considered due to radiological findings consistent with multiple organ thrombosis and intravenous cyclophosphamide (CYC) was given subsequent to PE. After pulse CYC and PE treatments, her renal functions recovered, she is still being followed for stage-3 chronic kidney disease. Complement factor H-related protein I gene deletion was detected in the genetic study. CONCLUSIONS: The clinical course of complement mediated CAPS tends to be worse. Complement system dysregulation should be investigated in all CAPS patients, and eculizumab treatment should be kept in mind if detected.