RARE DISEASE
Thrombotic microangiopathy
Thrombotic microangiopathy
Thrombotic microangiopathy
Synonyms: TMA
Synonyms: TMA
Synonyms: TMA
Drug discovery
4
drugs
With orphan designations
Overview
Thrombotic microangiopathy (TMA) is a group of life-threatening disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis causing ischemic organ damage. Etiologies include primary conditions like thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS), as well as secondary causes (e.g., malignancies, infections, pregnancy). Diagnosis hinges on lab findings of schistocytes, elevated LDH, and organ dysfunction. Prompt plasma exchange and targeted therapies (e.g., complement inhibitors for aHUS) are critical to reduce mortality [1][6][12].
Population
Annual incidence of 3–4 cases/million for TTP and aHUS, with 94% of TMAs being secondary to triggers like sepsis, cancer, or autoimmune conditions [2][9][16]
Higher prevalence in women, Black individuals, and those with comorbidities (e.g., hypertension, malignancies) [9][14]
Pediatric cases linked to Shiga toxin-producing E. coli (STEC-HUS), while adults more frequently develop TTP or chemotherapy-associated TMA [12][13]
Burden
Mortality rates reach 23–40% in secondary TMA and 8–25% in primary TMA, with HSCT-associated TMA showing 40% 1-year mortality [4][7][9]
50–62% require ICU care; 20–30% develop renal failure requiring dialysis [2][7][13]
Long-term sequelae include chronic kidney disease (30%), thromboembolic events (30%), and relapse rates >30% in TTP [9][11][13]
Therapies
TTP: Plasma exchange (PEX), corticosteroids, rituximab, and caplacizumab (anti-vWF therapy) [8][17]
aHUS: Complement inhibitors (eculizumab/ravulizumab) and PEX [13][17]
Secondary TMA: Address underlying cause (e.g., discontinue nephrotoxic drugs, treat infections) ± supportive care (dialysis, transfusions) [3][6]
Categories: rare renal diseases
Research Papers
2,431 drug discovery papers about Thrombotic microangiopathy, with 6 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,431 drug discovery papers about Thrombotic microangiopathy, with 6 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Thrombotic Microangiopathy-Like Phenotype in Patients With Infection-Associated Disseminated Intravascular Coagulation Treated With Thrombomodulin Alfa.
Despite disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) sharing features of thrombocytopenia, organ dysfunction, and bleeding, the relationship between these two conditions remains unclear. We therefore conducted a post hoc analysis of post-marketing surveillance data from Japan to evaluate the clinical characteristics of 2362 patients with DIC (TMA-like phenotype DIC, n = 217; and non-TMA-like phenotype DIC, n = 2145) who received thrombomodulin alfa (TM-α). TMA-like phenotype DIC was defined as platelet count < 15 × 104/μL, hemoglobin < 10 g/dL and lactate dehydrogenase > 500 IU/L. Approximately 9% of the registered infection-associated cases of DIC were TMA-like phenotype DIC. Patients with TMA-like phenotype were younger and had more renal dysfunction and liver dysfunction than those with non-TMA-like phenotype. Regarding the hemostatic examinations, fibrin/fibrinogen degradation products, D-dimer, and thrombin-antithrombin complex levels were higher in patients with TMA-like phenotype than in those with non-TMA-like phenotype. Patients with TMA-like phenotype had worse resolution of DIC and 28-day survival rates than those with non-TMA-like phenotype; however, the coagulation and fibrinolysis parameters in both groups showed improvement after TM-α administration. These findings describe a clinically severe subgroup of infection-associated DIC and should be interpreted as exploratory given that confirmatory TMA testing was unavailable.
2026-08-13 | Sirolimus application in patients with autoimmune-associated kidney diseases based on mTORC1 activation: a preliminary exploration and future perspectives.
The mTORC1 pathway drives pathogenesis in autoimmune kidney diseases. We hypothesized that intrarenal mTORC1 activation could identify patients likely to benefit from sirolimus, irrespective of their specific diagnosis. In this prospective proof-of-concept series, we screened eight patients with active autoimmune kidney disease for mTORC1 activation by immunohistochemistry on renal biopsy. Five positive patients (staining intensity: + to +++) received sirolimus, presenting with lupus nephritis atypical hemolytic uremic syndrome (aHUS), thrombotic microangiopathy (TMA), or IgA nephropathy (IgAN) associated with lung cancer. Over a mean follow-up of 25 months, four patients exhibited improved or stable renal function. All responders demonstrated moderate-to-high (++ to +++) mTORC1 staining, whereas the single non-responder who progressed to end-stage renal disease had only weak (+) staining. Proteinuria declined to <1 g/day in most responders. Sirolimus was well-tolerated. In two patients with concurrent malignancy, sirolimus did not aggravate stable breast cancer but was discontinued due to lung adenocarcinoma progression. This study indicates that intrarenal mTORC1 activation levels may help identify patients more likely to respond to sirolimus across various autoimmune kidney diseases, warranting further investigation as a precision-medicine approach.
2026-08-12 | Cytomegalovirus viremia associated with systemic thrombotic microangiopathy after kidney transplantation: a case report.
Post-transplant thrombotic microangiopathy (PT-TMA) is an uncommon but severe complication of kidney transplantation associated with graft dysfunction and poor outcomes. Although infections have been recognized as potential triggers, systemic thrombotic microangiopathy associated with cytomegalovirus (CMV) infection remains rarely reported. Experimental and clinical evidence suggests that CMV may promote endothelial injury and complement activation, mechanisms that could contribute to the development of microangiopathic processes in transplant recipients. We report the case of a 78-year-old kidney transplant recipient who developed de novo systemic thrombotic microangiopathy associated with CMV infection. The patient presented with thrombocytopenia, microangiopathic hemolytic anemia, and progressive graft dysfunction. Drug-induced TMA related to recent tacrolimus initiation was initially suspected; however, hematologic abnormalities persisted despite calcineurin inhibitor withdrawal. Further evaluation revealed significant CMV viremia (54,000 copies/mL), while additional viral, gastrointestinal infectious, and autoimmune evaluations did not identify a more likely alternative explanation. Intravenous ganciclovir therapy was initiated and later transitioned to oral valganciclovir. Following comprehensive management, including withdrawal of tacrolimus and targeted antiviral therapy, hemolysis resolved, platelet counts normalized, CMV viral load progressively declined until clearance, and renal graft function improved. Immunosuppression was subsequently reintroduced using a calcineurin inhibitor-free regimen with belatacept. CMV infection should be considered a plausible trigger of de novo post-transplant thrombotic microangiopathy, particularly in patients with persistent disease despite withdrawal of calcineurin inhibitors. Although post-transplant TMA is frequently multifactorial, early recognition of CMV viremia and timely comprehensive management addressing all contributing factors may be associated with favorable hematologic recovery and improvement of graft function.
2026-08-10 | Analysis of causes and outcomes of principal secondary thrombotic microangiopathy: a 9-year cohort study from a tertiary pediatric center in China.
Few large-scale cohort studies have reviewed consecutive cases of thrombotic microangiopathy (TMA), especially in children. The aim of our study was to evaluate causes and outcomes of TMA at a tertiary pediatric center in China over a 9-year period. We retrospectively analyzed consecutive pediatric TMA patients admitted to Beijing Children's Hospital from December 2015 to January 2025. The primary endpoint was death or progression to kidney failure. Multivariable Cox regression identified independent predictors of this composite endpoint. We retrospectively analyzed 303 consecutive pediatric patients with a first episode of TMA. Secondary TMA was the most common type (n = 172; 57%), followed by atypical hemolytic uremic syndrome (n = 93; 31%), thrombotic thrombocytopenic purpura (n = 24; 8%), and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (n = 14; 5%). Among the 172 cases of secondary TMA, the most common causes were hematopoietic stem cell transplantation (n = 95; 55%) and systemic diseases (n = 40; 23%). After a median follow-up of 35 months, death or kidney failure occurred in 53 (31%), 7 (8%), 1 (4%), and 0 patients with secondary TMA, atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome, respectively. Multivariate Cox regression showed that secondary TMA (hazard ratio [HR], 3.57; 95% CI, 1.53-8.30; P < .01), the presence of heart failure and/or shock at onset (HR, 2.21; 95% CI, 1.24-3.93; P = .01), and the need for mechanical ventilation support due to respiratory failure (HR, 3.88; 95% CI, 2.19-6.88; P < .001) were independent risk factors for death or kidney failure. This study shows that secondary TMA is the predominant form of pediatric TMA. Secondary TMA, heart failure/shock, and the requirement for mechanical ventilation were identified as independent risk factors for death or kidney failure in children.
2026-08-07 | Delayed Recognition of Thrombotic Thrombocytopenic Purpura Following Platelet Transfusion: A Clinical Pitfall.
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency, usually due to autoantibody-mediated inhibition. Its presentation is heterogeneous and often lacks the classic pentad, leading to diagnostic delays. Neurological symptoms may predominate, masking the underlying hematologic emergency. In our case, a 37-year-old previously healthy woman presented with acute headache, speech disturbance, and altered mental status. Despite normal neuroimaging, laboratory tests revealed severe thrombocytopenia and normocytic anemia. Lack of response to erythrocyte and platelet transfusions prompted further evaluation, revealing microangiopathic hemolytic anemia with elevated lactate dehydrogenase, undetectable haptoglobin, indirect hyperbilirubinemia, reticulocytosis, and normal coagulation parameters. A PLASMIC score of 6/7 indicated a high probability of severe ADAMTS13 deficiency. Treatment with high-dose corticosteroids was initiated immediately, followed by plasma exchange and rituximab. ADAMTS13 activity confirmed severe deficiency at 0.3%, supporting the diagnosis of acquired TTP in the clinical context. The patient achieved rapid remission and complete neurological recovery. This case highlights the importance of early recognition of microangiopathic hemolysis and prompt treatment without waiting for confirmatory ADAMTS13 results to reduce morbidity and mortality.
2026-08-14 | Thrombotic Microangiopathy-Like Phenotype in Patients With Infection-Associated Disseminated Intravascular Coagulation Treated With Thrombomodulin Alfa.
Despite disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) sharing features of thrombocytopenia, organ dysfunction, and bleeding, the relationship between these two conditions remains unclear. We therefore conducted a post hoc analysis of post-marketing surveillance data from Japan to evaluate the clinical characteristics of 2362 patients with DIC (TMA-like phenotype DIC, n = 217; and non-TMA-like phenotype DIC, n = 2145) who received thrombomodulin alfa (TM-α). TMA-like phenotype DIC was defined as platelet count < 15 × 104/μL, hemoglobin < 10 g/dL and lactate dehydrogenase > 500 IU/L. Approximately 9% of the registered infection-associated cases of DIC were TMA-like phenotype DIC. Patients with TMA-like phenotype were younger and had more renal dysfunction and liver dysfunction than those with non-TMA-like phenotype. Regarding the hemostatic examinations, fibrin/fibrinogen degradation products, D-dimer, and thrombin-antithrombin complex levels were higher in patients with TMA-like phenotype than in those with non-TMA-like phenotype. Patients with TMA-like phenotype had worse resolution of DIC and 28-day survival rates than those with non-TMA-like phenotype; however, the coagulation and fibrinolysis parameters in both groups showed improvement after TM-α administration. These findings describe a clinically severe subgroup of infection-associated DIC and should be interpreted as exploratory given that confirmatory TMA testing was unavailable.
2026-08-13 | Sirolimus application in patients with autoimmune-associated kidney diseases based on mTORC1 activation: a preliminary exploration and future perspectives.
The mTORC1 pathway drives pathogenesis in autoimmune kidney diseases. We hypothesized that intrarenal mTORC1 activation could identify patients likely to benefit from sirolimus, irrespective of their specific diagnosis. In this prospective proof-of-concept series, we screened eight patients with active autoimmune kidney disease for mTORC1 activation by immunohistochemistry on renal biopsy. Five positive patients (staining intensity: + to +++) received sirolimus, presenting with lupus nephritis atypical hemolytic uremic syndrome (aHUS), thrombotic microangiopathy (TMA), or IgA nephropathy (IgAN) associated with lung cancer. Over a mean follow-up of 25 months, four patients exhibited improved or stable renal function. All responders demonstrated moderate-to-high (++ to +++) mTORC1 staining, whereas the single non-responder who progressed to end-stage renal disease had only weak (+) staining. Proteinuria declined to <1 g/day in most responders. Sirolimus was well-tolerated. In two patients with concurrent malignancy, sirolimus did not aggravate stable breast cancer but was discontinued due to lung adenocarcinoma progression. This study indicates that intrarenal mTORC1 activation levels may help identify patients more likely to respond to sirolimus across various autoimmune kidney diseases, warranting further investigation as a precision-medicine approach.
2026-08-12 | Cytomegalovirus viremia associated with systemic thrombotic microangiopathy after kidney transplantation: a case report.
Post-transplant thrombotic microangiopathy (PT-TMA) is an uncommon but severe complication of kidney transplantation associated with graft dysfunction and poor outcomes. Although infections have been recognized as potential triggers, systemic thrombotic microangiopathy associated with cytomegalovirus (CMV) infection remains rarely reported. Experimental and clinical evidence suggests that CMV may promote endothelial injury and complement activation, mechanisms that could contribute to the development of microangiopathic processes in transplant recipients. We report the case of a 78-year-old kidney transplant recipient who developed de novo systemic thrombotic microangiopathy associated with CMV infection. The patient presented with thrombocytopenia, microangiopathic hemolytic anemia, and progressive graft dysfunction. Drug-induced TMA related to recent tacrolimus initiation was initially suspected; however, hematologic abnormalities persisted despite calcineurin inhibitor withdrawal. Further evaluation revealed significant CMV viremia (54,000 copies/mL), while additional viral, gastrointestinal infectious, and autoimmune evaluations did not identify a more likely alternative explanation. Intravenous ganciclovir therapy was initiated and later transitioned to oral valganciclovir. Following comprehensive management, including withdrawal of tacrolimus and targeted antiviral therapy, hemolysis resolved, platelet counts normalized, CMV viral load progressively declined until clearance, and renal graft function improved. Immunosuppression was subsequently reintroduced using a calcineurin inhibitor-free regimen with belatacept. CMV infection should be considered a plausible trigger of de novo post-transplant thrombotic microangiopathy, particularly in patients with persistent disease despite withdrawal of calcineurin inhibitors. Although post-transplant TMA is frequently multifactorial, early recognition of CMV viremia and timely comprehensive management addressing all contributing factors may be associated with favorable hematologic recovery and improvement of graft function.
2026-08-10 | Analysis of causes and outcomes of principal secondary thrombotic microangiopathy: a 9-year cohort study from a tertiary pediatric center in China.
Few large-scale cohort studies have reviewed consecutive cases of thrombotic microangiopathy (TMA), especially in children. The aim of our study was to evaluate causes and outcomes of TMA at a tertiary pediatric center in China over a 9-year period. We retrospectively analyzed consecutive pediatric TMA patients admitted to Beijing Children's Hospital from December 2015 to January 2025. The primary endpoint was death or progression to kidney failure. Multivariable Cox regression identified independent predictors of this composite endpoint. We retrospectively analyzed 303 consecutive pediatric patients with a first episode of TMA. Secondary TMA was the most common type (n = 172; 57%), followed by atypical hemolytic uremic syndrome (n = 93; 31%), thrombotic thrombocytopenic purpura (n = 24; 8%), and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (n = 14; 5%). Among the 172 cases of secondary TMA, the most common causes were hematopoietic stem cell transplantation (n = 95; 55%) and systemic diseases (n = 40; 23%). After a median follow-up of 35 months, death or kidney failure occurred in 53 (31%), 7 (8%), 1 (4%), and 0 patients with secondary TMA, atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome, respectively. Multivariate Cox regression showed that secondary TMA (hazard ratio [HR], 3.57; 95% CI, 1.53-8.30; P < .01), the presence of heart failure and/or shock at onset (HR, 2.21; 95% CI, 1.24-3.93; P = .01), and the need for mechanical ventilation support due to respiratory failure (HR, 3.88; 95% CI, 2.19-6.88; P < .001) were independent risk factors for death or kidney failure. This study shows that secondary TMA is the predominant form of pediatric TMA. Secondary TMA, heart failure/shock, and the requirement for mechanical ventilation were identified as independent risk factors for death or kidney failure in children.
2026-08-07 | Delayed Recognition of Thrombotic Thrombocytopenic Purpura Following Platelet Transfusion: A Clinical Pitfall.
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency, usually due to autoantibody-mediated inhibition. Its presentation is heterogeneous and often lacks the classic pentad, leading to diagnostic delays. Neurological symptoms may predominate, masking the underlying hematologic emergency. In our case, a 37-year-old previously healthy woman presented with acute headache, speech disturbance, and altered mental status. Despite normal neuroimaging, laboratory tests revealed severe thrombocytopenia and normocytic anemia. Lack of response to erythrocyte and platelet transfusions prompted further evaluation, revealing microangiopathic hemolytic anemia with elevated lactate dehydrogenase, undetectable haptoglobin, indirect hyperbilirubinemia, reticulocytosis, and normal coagulation parameters. A PLASMIC score of 6/7 indicated a high probability of severe ADAMTS13 deficiency. Treatment with high-dose corticosteroids was initiated immediately, followed by plasma exchange and rituximab. ADAMTS13 activity confirmed severe deficiency at 0.3%, supporting the diagnosis of acquired TTP in the clinical context. The patient achieved rapid remission and complete neurological recovery. This case highlights the importance of early recognition of microangiopathic hemolysis and prompt treatment without waiting for confirmatory ADAMTS13 results to reduce morbidity and mortality.
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Drug Discovery Landscape
4 orphan drug designations for Thrombotic microangiopathy, including 1 approved therapy.
4 orphan drug designations for Thrombotic microangiopathy, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ravulizumab | antibodies | FDA | 2020-11-25 | — | Alexion Pharmaceuticals, Inc. |
nomacopan | proteins | FDA | 2019-08-28 | — | Akari Therapeutics Plc |
narsoplimab-wuug [Yartemlea] | antibodies | FDA | 2018-10-22 | 2025-12-23 | Omeros Corporation |
Human monoclonal antibody inhibitor of mannan binding lectin-associated serine protease-2 (MASP-2) | antibodies | FDA | 2013-12-16 | — | Omeros Corporation |
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