Management of pediatric hemolytic uremic syndrome.

Classical clinical triad of hemolytic uremic syndrome (HUS) is microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury associated with endothelial cell injury. Several situations, including infections, medications, malignancies, and transplantation can trigger endothelial damage. On the HUS spectrum, atypical hemolytic uremic syndrome (aHUS) deserves special attention in pediatric patients, as it can cause endstage kidney disease and mortality. A dysfunction in the alternative complement pathway, either acquired or genetic, has been shown to be the main underlying cause. In the last decades, breathtaking advances have been made in understanding the pathophysiology of this rare disease, which has led to more efficient treatment. Recent studies have implicated genes in pathways beyond the alternative complement system, such as DGKE, TSEN2, and INF2 highlighting the importance of personalized management. Eculizumab has brought about dramatic improvements in the treatment of aHUS. Beyond eculizumab, there are many alternative therapeutics in the pipeline that target the complement system. Because of the rarity of aHUS, data from multiple patient registries are very important. The present report aimed to summarize the most important aspects of diagnosing and treating aHUS based on the Turkish national registry and the literature so as to improve clinical practice.

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.

Clinical Evaluation and Management of Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and organ injury that stems from endothelial damage and vascular occlusion. There are several disease states with distinct pathophysiological mechanisms that manifest as TMA. These conditions are associated with significant morbidity and mortality and require urgent recognition and treatment. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are traditionally considered to be primary forms of TMA, but TMA more commonly occurs in association with a coexisting condition such as infection, pregnancy, autoimmune disease, or malignant hypertension, among others. Determining the cause of TMA is a diagnostic challenge because of limited availability of disease-specific testing. However, identifying the underlying etiology is imperative as treatment strategies differ. Our understanding of the conditions that cause TMA is evolving. Recent advances have led to improved comprehension of the varying pathogenic mechanisms that drive TMA. Development of targeted therapeutics has resulted in significant improvements in patient outcomes. In this article, we review the pathogenesis and clinical features of the different TMA-causing conditions. We outline a practical approach to diagnosis and management and discuss empiric and disease-specific treatment strategies.

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.

Púrpura trombótica trombocitopénica en pediatría. Reporte de un caso / Thrombotic thrombocytopenic purpura in pediatrics. A case report

La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.

Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.

Ischemic cerebrovascular complications with initial presentation of genetic atypical hemolytic uremic syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease, with scarce reports of neurologic manifestations in the acute setting. Ischemic cortical infarcts concurrently with aHUS presentation have not been described in adult patients. CASE DESCRIPTION: A 46-year-old male presented with acutely declining mental status and progressive weakness, in the setting of longstanding hypertension and known type B aortic dissection. Urgent neuroimaging showed bilateral multifocal multiterritorial ischemic infarcts, concerning for an embolic source or hypercoagulable state. Systemic workup was notable for microangiopathic hemolytic anemia and acute kidney injury. Empiric plasmapheresis was initiated for presumed thrombotic thrombocytopenic purpura. Broad workup did not support such a diagnosis, and kidney biopsy showed findings compatible with aHUS. Additional blood testing showed increased complement pathway activity. Shiga toxin was negative, and overall clinical picture fit with aHUS as diagnosis. Treatment with complement inhibitor was started and patient gradually recovered. Genetic testing confirmed a pertinent pathogenic mutation, CFHR1 homozygous deletion. CONCLUSION: Acute multifocal multiterritorial ischemic infarcts and systemic thrombotic microangiopathy may be a manifestation of aHUS, and with associated genetic mutation, even in adult population.

A case report: Hemophagocytic lymphohistiocytosis and thrombotic thrombocytopenic purpura in an otherwise healthy woman.

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) with hemophagocytic lymphohistiocytosis (HLH) is very rare, and both of these rare blood diseases have high mortality. There have been few reports of 2 diseases being combined at the same time. We provide a rare case with a clear diagnosis, prolonging the patient's survival through aggressive treatment, providing clinicians with our experience in early diagnosis and early treatment of this disease. PATIENT CONCERNS: A 56-year-old woman presented with a 1-month history of fever. DIAGNOSES: She was diagnosed with HLH due to elevated levels of ferritin and lactase dehydrogenase, which were confirmed by the presence of hemophagocytosis in the bone marrow. TTP was diagnosed based on the presence of symptoms characteristic of TTP and significantly low levels of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). INTERVENTIONS: Systemic corticosteroids and plasma exchange using 2 L of virus-inactivated frozen plasma per day were initiated as specific treatment. OUTCOMES: The patient's consciousness improved posttreatment and platelets also increase gradually. In a follow-up after 1 month, the patient was generally well and without specific discomfort. LESSONS: HLH patients themselves can have a significant reduction in platelet, as with TTP, it is very easy to misdiagnose or delay the diagnosis. How to diagnose early, actively find the primary disease, and treat it is crucial to improve the prognosis of HLH.

Thrombotic microangiopathy in patients with malignant hypertension.

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

Adolescent acquired thrombotic thrombocytopenic purpura: An analysis of the Pediatric Health Information System database.

The outcomes and characteristics of acquired thrombotic thrombocytopenic purpura (TTP) in adolescents is poorly understood due to an absence of studies focused on this population. To better understand the life-threatening disorder in this age, we performed an analysis of adolescent patients (ages 10-21) with TTP in the Pediatric Health Information Systems database from 2009 to 2020. The primary outcomes evaluated were in-hospital mortality and rate of TTP relapse. Secondary outcomes included rates of hemorrhagic and thrombotic complications during hospitalizations for TTP. Patients were included if they had a thrombotic microangiopathy diagnostic code, ADAMTS13 lab obtained, and received therapeutic plasmapheresis. Patients that received treatment for other non-TTP microangiopathies were excluded. A total of 99 patients with 123 hospitalizations for TTP treatment were identified. In-patient mortality occurred in 6 % (n = 6) and TTP relapse in 20 % (n = 20) of the cohort. Median time from initial admission to relapse was 33 days (IQR 15, 92). A hemorrhagic complication was identified in 29 % (n = 36) and thrombotic complication in 15 % (n = 19) of the cohort. The presence of underlying comorbidities was not associated with TTP relapse and only a diagnosis of cancer was associated with increased mortality. The rate of mortality and relapse in adolescent TTP is lower than that seen in adult registries. Long term prospective studies are needed to understand the long-term consequences of adolescent onset acquired TTP.

Hereditary thrombotic thrombocytopenic purpura (TTP) with co-occurring autosomal dominant polycystic kidney disease (ADPKD).

Hereditary thrombotic thrombocytopenic purpura (TTP) and autosomal dominant polycystic kidney disease (ADPKD) are two distinct genetic diseases that may affect the kidneys through different mechanisms. ADPKD is a common genetic disorder that leads to exponential formation and growth of cysts replacing all segments of nephrons. Hereditary TTP is a rare autosomal recessive disorder that leads to the disseminated formation of arteriolar platelet-rich thrombi, which produce manifestations of various organs dysfunction. We present a case of a pregnant female with hereditary TTP co-occurring with ADPKD. To our knowledge, this is the first case in the literature describing the co-occurrence of ADPKD and hereditary TTP. We aim to describe the clinical course including the renal and the pregnancy outcomes, describe the consanguinity and family history, and try to explain the potential effect of one disease on the clinical course of the other.

Thrombotic Thrombocytopenic Purpura Triggered by Acute Myeloid Leukemia: A Case Report.

BACKGROUND Acute myeloid leukemia (AML) is a myeloid progenitor malignancy characterized by clonal expansion of immature blasts. Complications of AML can result from disease-related or treatment-related complications and commonly include bleeding and disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome characterized by a mechanical hemolytic anemia and a consumptive thrombocytopenia resulting in end-organ damage from thrombotic occlusion of small vessels. CASE REPORT We describe a case of TTP at our institution that developed after diagnosis of AML, an exceedingly rare phenomenon with only one such documented case in the current literature. We were advised to see this patient after development of renal failure and encephalopathy. Suspicion for TTP was initially low, as our patient had a low pre-test probability of TTP by the PLASMIC score. Our patient was treated for disseminated intravascular coagulopathy, without response. Plasma exchange pheresis (PLEX) was eventually begun 3 days after presentation upon result of ADAMTS13 activity at 10%, with presence of inhibitor. ADAMTS13 activity levels were used to guide continuation of PLEX, given our patient's persistent pancytopenia. CONCLUSIONS Our case demonstrates the challenges of identifying and managing TTP in patients with concomitant hematologic malignancies. ADAMTS13 activity levels should be collected in patients presenting with evidence of hemolytic anemia, even if the pre-test probability of TTP is low.

Thrombotic Microangiopathy Syndromes-Common Ground and Distinct Frontiers.

Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic purpura results from von Willebrand factor multimerization, Shiga toxin-mediated hemolytic uremic syndrome causes toxin-induced endothelial dysfunction, while atypical hemolytic uremic syndrome results from complement system dysregulation. Drug-induced TMA, rheumatological disease-induced TMA, and renal-limited TMA exist in an intermediate space that represents secondary complement activation and may overlap with atypical hemolytic uremic syndrome clinically. The existence of TMA without microangiopathic hemolytic features, renal-limited TMA, represents an undiscovered syndrome that responds incompletely and inconsistently to complement blockade. Hematopoietic stem cell transplant-TMA represents another more resistant form of TMA with different therapeutic needs and clinical course. It has become apparent that TMA syndromes are an emerging field in nephrology, rheumatology, and hematology. Much work remains in genetics, molecular biology, and therapeutics to unravel the puzzle of the relationships and distinctions apparent between the different subclasses of TMA syndromes.

Thrombocytopenia: the good, the bad and the ugly.

New thrombocytopenia may be associated with a variety of conditions and diagnosis can be challenging. Presentation can vary from life-threatening bleeding or thrombosis to an incidental finding in an asymptomatic patient. New thrombocytopenia requires urgent investigation. Investigations are mainly guided by findings from the clinical history, physical examination, full blood count and blood film analysis. Aside from the actively bleeding patient, rare but life-threatening causes of thrombocytopenia must be identified early as they require urgent treatment. These include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, suspicion of new acute promyelocytic leukaemia, and vaccine-induced prothrombotic immune thrombocytopenia. Here, we discuss how to approach a patient with new thrombocytopenia, along with key differentials not to be missed.

Thrombotic thrombocytopenic purpura in HIV-infected patients: new twists on an old disease.

OBJECTIVE: Investigate the presence of inflammation, endothelial dysfunction and complement activation in patients with HIV-associated thrombotic thrombocytopenic purpura (HIV-TTP) to support the hypothesis that these processes probably contribute to the development of this thrombotic microangiopathy. DESIGN: A prospective, investigational cohort study of 35 consecutive patients diagnosed with HIV-associated TTP presenting to three academic, tertiary care hospitals in Johannesburg, South Africa over 2 years. METHODS: The patients with HIV-TTP received therapeutic plasma therapy and supportive treatment. Demographic data, the results of routine investigations and patient outcomes were recorded. Peripheral blood samples were collected prior to and on completion of plasma therapy and the following additional parameters were assessed at both time points: activity of the von Willebrand factor (VWF) cleaving protease, a-disintegrin-and-metalloproteinase-with-thrombospondin-motifs 13 (ADAMTS-13) and the presence of ADAMTS-13 autoantibodies, levels of pro-inflammatory cytokines, interleukin-6 and tumour necrosis factor-alpha, and two endothelial cell adhesion molecules. Complement activation was assessed by sequential measurement of C3 and C4 as well as levels of the complement inhibitor, factor H. RESULTS: The inflammatory and endothelial activation markers were significantly ( P  < 0.001) elevated in the cohort of patients prior to plasma therapy compared with levels on discharge. Complement was activated and normalized with therapy. The ADAMTS-13 levels were reduced with significant auto-antibodies to this protease at presentation. CONCLUSION: Inflammation in HIV mediates endothelial damage and complement activation. This study proposes that these processes are probably contributory to the development of HIV-TTP, which can therefore be characterized in part as a complementopathy, resembling TTP-like syndrome.

Complete recovery of deep venous thrombosis from Coombs (+) thrombotic thrombocytopenic purpura: case report.

BACKGROUND: Acute thrombotic thrombocytopenic purpura (TTP) is an aggressive thrombotic microangiopathy that if not treated, can have a 90% mortality rate. Timely, extensive plasma exchange (PEX) has been indicated to reduce the mortality rate to < 10%, but its side effects are not well-known. We present here a case of a patient presented with Comb (+) TTP and developed catheter-associated deep vein thrombosis (DVT). CASE PRESENTATION: A 27-year-young man presented with persistent thrombocytopenia and Coombs positive anemia was firstly diagnosed with Evans syndrome. However, he was refractory to a methylprednisolone pulse therapy with a combination of platelet transfusion and eventually developed microangiopathy of central nerve system. Several pathological manifestations of the disease were prevented by PEX. The immediate start of PEX (1500 mL/d) induced a complete remission of acquired TTP and disappearance of neurological signs and symptoms. However, external iliac and femoro-popliteal venous thrombosis was diagnosed subsequently, inferior vena cava filter (IVC) filter was immediately implanted accompanied with anticoagulation therapy. Meanwhile, PEX session was sustained as well as oral anticoagulant (rivaroxaban). 14 days later, the patient got full recovery. CONCLUSIONS: Catheter-related DVT under the setting of TTP should be cautious. It is necessary to start anticoagulation and antiplatelet therapy for thrombosis early, especially in such cases when PLT count > 50 × 109/L.

Unusual Presentation of Thrombotic Thrombocytopenic Purpura in a Newly Diagnosed Pediatric Patient With Systemic Lupus Erythematosus in the Setting of MIS-C.

The understanding of coronavirus disease 2019 (COVID-19) immune dysregulation is evolving. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with alternations in both innate and adaptive immunity, probably caused by a complex interplay of genetics and environmental exposure with various triggers. A rare hematological complication of SLE as well as recently reported in an adult with COVID-19 is thrombotic thrombocytopenic purpura. We report a pediatric case with features suggestive of the multisystem inflammatory syndrome in children with coronary artery ectasia, thrombotic thrombocytopenic purpura, and new-onset SLE.

A novel missense mutation in complement factor I predisposes patients to atypical hemolytic uremic syndrome: a case report.

BACKGROUND: Atypical hemolytic uremic syndrome, also called the nondiarrheal form of hemolytic uremic syndrome, is a rare disease characterized by the triad of thrombocytopenia, Coomb's test-negative microangiopathic hemolytic anemia, and acute renal failure. Approximately 60% of cases of atypical hemolytic uremic syndrome are associated with deficiencies of the complement regulatory protein, including mutations in complement factor H, complement factor I, or the membrane co-factor protein. CASE PRESENTATION: We report the case of a 26-year-old Asian man who presented with pulmonary infection, elevated blood pressure, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal biopsy revealed diffuse capillary fibrin deposition, endothelial swelling, and arteriole narrowing like "onion skinning" consistent with thrombotic microangiopathy. Bidirectional sequencing of CFH, CFHR5, CFHR1, CFI, DGKE, CFB, and MCP confirmed that the patient was heterozygous for a novel missense mutation, p.Cys67Phe, in CFI. This patient had rapid evolution to end-stage renal disease and needed renal replacement therapy. Plasma exchange seemed inefficacious in this patient. CONCLUSIONS: This report confirms the importance of screening patients with atypical hemolytic uremic syndrome for mutations in genes involved in complement system to clarify the diagnosis and demonstrates the challenges in the management of these patients.

Thrombotic thrombocytopenic purpura following administration of the Moderna booster vaccine.

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy that is characterized by microangiopathic haemolytic anaemia, consumption thrombocytopenia and organ injury. It is caused by a severe deficiency of ADAMTS13, which can be either congenital or acquired. There is a plethora of things that can cause the acquired form, including medications and infections. Vaccines have also been shown to cause TTP. In the midst of the COVID-19 pandemic, with multiple new vaccines being developed and distributed to the masses, the medical community needs to be aware of adverse events associated with these new vaccines. We present a case of TTP following administration of the Moderna booster vaccine.

Hematology Emergencies in Critically Ill Adults: Benign Hematology.

Hematologic conditions (malignant or benign) may progress to acute critical illness requiring prompt recognition and intensive management. This review outlines diagnostic considerations and approaches to management for intensivists of common benign hematologic emergencies, including the following: thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, disseminated intravascular coagulopathy, catastrophic antiphospholipid antibody syndrome, hemophagocytic lymphohistiocytosis, acute chest syndrome associated with sickle cell disease, and hyperhemolysis syndrome.

Cardiovascular disease is a leading cause of mortality among TTP survivors in clinical remission.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors experience high rates of adverse health sequelae and increased mortality over long-term follow-up. We conducted this multicenter cohort study to evaluate long-term mortality and causes of death in iTTP survivors. Between 2003 and 2020, 222 patients were enrolled in the Ohio State University and Johns Hopkins TTP registries and followed for a median of 4.5 (interquartile range [IQR], 75 0.4-11.5) years. Nine patients died during their first iTTP episode, and 29 patients died during follow-up. Mortality rate was 1.8 times higher than expected from an age-, sex-, and race-adjusted reference population. Cardiovascular disease was a leading primary cause of death (27.6%) tied with relapsed iTTP (27.6%), followed by malignancy (20.7%), infection (13.8%), and other causes (10.3%). Male sex (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.65-8.48), increasing age (HR, 1.04; 95% CI, 1.01-1.07), and number of iTTP episodes (HR, 1.10; 95% CI, 1.01-1.20) were associated with mortality in a model adjusted for African American race (HR, 0.70; 95% CI, 0.30-1.65), hypertension (HR, 0.47; 95% CI, 0.20-1.08), chronic kidney disease (HR 1.46; 95% CI, 0.65-3.30), and site (HR, 1.46; 95% CI, 0.64-3.30). There was a trend toward shorter survival in patients with lower ADAMTS13 activity during remission (P = .078). Our study highlights the need for survivorship care and investigation focused on cardiovascular disease and early mortality in TTP survivors.