A Rare Intersection: Managing Thrombotic Thrombocytopenic Purpura in the Context of Dengue Fever.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening condition that can lead to severe morbidity and mortality if untreated. This case report discusses a 31-year-old male with dengue fever who developed TTP, resulting in fatality despite timely diagnosis and comprehensive treatment. The patient presented with worsening symptoms, including body aches, gastrointestinal bleeding, and neurological issues. Initial treatment focused on managing dengue hemorrhagic fever, but TTP was later suspected, leading to the cessation of platelet transfusions and initiation of plasma exchange, steroids, and rituximab. Despite these efforts, the patient's condition deteriorated. This case underscores the challenges in managing TTP, especially when triggered by infections like dengue. The use of the PLASMIC score can be highly effective in suspecting TTP in these patients, allowing for the initiation of early management. While standard treatments include plasma exchange and immunosuppressive therapy, emerging treatments such as caplacizumab and the potential use of splenectomy may offer hope for better outcomes in the future.

Anti-Inflammatory Cytokine Profiles in Thrombotic Thrombocytopenic Purpura-Differences Compared to COVID-19.

Thromboinflammation/immunothrombosis plays a role in several diseases including thrombotic thrombocytopenic purpura (TTP) and COVID-19. Unlike the extensive research that has been conducted on COVID-19 cytokine storms, the baseline and acute phase cytokine profiles of TTP are poorly characterized. Moreover, we compared the cytokine profiles of TTP and COVID-19 to identify the disease-specific/general characteristics of thromboinflammation/immunothrombosis. Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors, and growth factors) were measured by multiplex bead-based LEGENDplex™ immunoassay from 32 COVID-19 patients (32 non-vaccinated patients in three severity groups), 32 TTP patients (remission/acute phase pairs of 16 patients), and 15 control samples. Mainly, the levels of innate immunity-related SMs changed in both diseases. In TTP, ten SMs decreased in both remission and acute phases compared to the control, one decreased, and two increased only in the acute phase compared to remission, indicating mostly anti-inflammatory changes. In COVID-19, ten pro-inflammatory SMs increased, whereas one decreased with increasing severity compared to the control. In severe COVID-19, sixteen SMs exceeded acute TTP levels, with only one higher in TTP. PCA identified CXCL10, IL-1RA, and VEGF as the main discriminators among their cytokine profiles. The innate immune response is altered in both diseases. The cytokine profile of TTP suggests a distinct pathomechanism from COVID-19 and supports referring to TTP as thromboinflammatory rather than immunothrombotic, emphasizing thrombosis over inflammation as the driving force of the acute phase.

Autoantibodies to ADAMTS13 in human immunodeficiency virus-associated thrombotic thrombocytopenic purpura.

BACKGROUND AND OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal thrombotic microangiopathic disorder that can result from human immunodeficiency virus (HIV) infection. The pathogenesis involves a deficiency of the von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs member 13) and the presence of anti-ADAMTS13 autoantibodies. However, there is insufficient information regarding the epitope specificity and reactivity of these autoantibodies. This study aimed to perform epitope-mapping analysis to provide novel insights into the specific epitopes on ADAMTS13 domains affected by autoantibodies. MATERIALS AND METHODS: The study analysed 59 frozen citrate plasma samples from HIV-associated TTP patients in South Africa, measuring ADAMTS13 activity using Technozyme® ADAMTS13 activity test, total immunoglobulin (Ig) M and IgA antibodies levels using ELISA kit and purifying IgG antibodies using NAb™ Protein G spin columns. A synthetic ADAMTS13 peptide library was used for epitope mapping. RESULTS: Overall, 90% of samples showed anti-ADAMTS13 IgG autoantibodies, with 64% of these antibodies being inhibitory, as revealed by mixing studies. Samples with ADAMTS13 antigen levels below 5% showed high anti-ADAMTS13 IgG autoantibody titres (≥50 IU/mL), whereas those with 5%-10% levels had low autoantibody titres (<50 IU/mL).The metalloprotease, cysteine-rich and spacer domains were 100% involved in binding anti-ADAMTS13 IgG antibodies, with 58% of samples containing antibodies binding to the C-terminal part of the ADAMTS13 disintegrin-like domain, indicating different pathogenic mechanisms. CONCLUSION: The metalloprotease, cysteine-rich and spacer domains are the primary targets for anti-ADAMTS13 IgG autoantibodies in patients with HIV-associated TTP. These findings suggest potential effects on the proteolytic activity of ADAMTS13, highlighting the complex nature of the pathogenic mechanisms involved.

Main features of ischemic stroke in patients with acute immune-mediated thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a microangiopathy often characterized by acute neurological involvement including ischemic stroke (IS). The characteristics of IS in iTTP remain largely unknown. AIMS: To evaluate the epidemiology, neuroimaging patterns and risk factors of IS in iTTP patients. METHODS: We performed a cross-sectional study of patients enrolled in the Milan TTP Registry presenting with neurological signs/symptoms and underwent neuroimaging evaluation during their first acute iTTP episode. RESULTS: Seventy-eight patients were enrolled, the majority of patients were female (72 %), with a median age of 46 years. Computed tomography (CT) was performed in all patients, and magnetic resonance (MRI) was performed in 38 % of patients. IS was confirmed in 18 out of 78 patients (23 %), most of whom (70 %) showed a non-lacunar pattern with multifocal involvement. In the subgroup of patients who had MRI (n = 30), IS was identified in 12 patients (40 %) and of them 6 (50 %) had a false negative result with CT scan. Patients with IS were slightly older than those without, whereas the prevalence of cardiovascular risk factors and iTTP-related parameters were comparable between the two groups. CONCLUSION: 23 % of patients presenting with neurological manifestations at their first acute TTP episode, showed brain IS. As expected, MRI showed higher sensitivity in detecting ischemic lesions underscoring its usefulness over CT in this setting. An unexpected prevalence of non-lacunar and multifocal stroke patterns warrants further investigation. Cardiovascular risk factors and iTTP-related clinical and laboratory parameters were similarly distributed in patients with and without IS.

Initial US tertiary health care system experience using caplacizumab in patients with immune thrombotic thrombocytopenic purpura.

Several international registries have reported on the efficacy of caplacizumab for the treatment of immune thrombotic thrombocytopenic purpura (iTTP). Similar real-world data from the United States (US) are limited. In this single center retrospective study, we sought to describe caplacizumab prescribing patterns and review clinical outcomes for US patients with iTTP. Subjects were eligible for inclusion if they were diagnosed with acute iTTP and received care at University of Pittsburgh Medical Center-affiliated hospitals from 2012 to 2022. Subjects were divided into an historical cohort who received standard of care therapy alone, and early and late administration cohorts (EA and LA) who received caplacizumab within and greater than 72 h of admission, respectively, plus standard of care. Clinical data were collected from the electronic record. Thirty-two subjects were included: 16 historical, 12 EA, and 4 LA subjects. Refractoriness occurred more frequently in the LA and historical cohorts as compared to the EA cohort (4 (100%) vs. 6 (38%) vs. 3 (25%), p = 0.02). The LA cohort also experienced longer lengths of hospital stay, required more TPE procedures, and were exposed to the greatest amount of donor plasma (p < 0.05 for all) as compared to the other cohorts. Time to platelet count normalization was longest in the LA cohort (p = 0.013). There were no significant between-group differences in bleeding events. Because we are unable to predict which patients will develop refractoriness, we recommend frontline administration of caplacizumab to all patients with iTTP.

Association of Sjögren's syndrome with immune-mediated thrombotic thrombocytopenic purpura and posterior reversible encephalopathy syndrome: A case report.

Background: A patient with Sjögren's syndrome (SS), immune-mediated thrombotic thrombocytopenic purpura (ITTP), and posterior reversible encephalopathy syndrome (PRES) was reported, and all published cases with thrombotic thrombocytopenic purpura (TTP), PRES, and SS were retrieved and analysed. The patient's clinical data and treatment procedure have been discussed. Case summary: A 45-year-old Chinese female was hospitalized with headache and low platelet count. She had previously presented to a local hospital with a 7-month history of epigastric discomfort and anorexia, and was diagnosed with SS and ITTP. Laboratory investigations after admission showed platelet (PLT) of 13*10^9/L, red blood cell (RBC) fragments of 6 %, ADAMTS13 Activity＜0.2 %, anti-ADAMTS13 IgG of 88.3U/mL. Brain magnetic resonance imaging (MRI) showed gyriform restricted diffusion along with increased T2-FLAIR signal in the left frontal cortex and bilateral parietal temporal cortex. She was diagnosed with SS, ITTP and PRES, and received the treatment of methylprednisolone, cyclosporine, plasma exchange, IVIG, and rituximab. This patient did not experience the recurrence during the 8-month follow-up period. Conclusion: ITTP and PRES are rare manifestations of SS. After a suspected or confirmed diagnosis of ITTP, plasma exchange and immunosuppressive therapy should be immediately administered. We suggest that rituximab could have additional therapeutic value for SS combined with ITTP and PRES.

Efficacy and safety of daratumumab in multiresistant immune-mediated thrombotic thrombocytopenic purpura.

The immunosuppressive treatment of immune-mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B-cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell-directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab. Nine episodes from seven patients were identified. Treatment was administered for A Disintegrin And Metalloproteinase with ThromboSpondin-1 motifs, 13th member (ADAMTS13) relapses while patients were otherwise in clinical response (N = 8), or during the acute phase of the disease following rituximab intolerance (N = 1). Patients have received a median of three previous therapeutic lines. ADAMTS13 activity improved in eight cases following daratumumab administration, including three cases where ADAMTS13 normalized. ADAMTS13 relapses occurred in three patients; in two cases, retreatment with daratumumab was successful. Median ADAMTS13 relapse-free survival was not reached; 12-month ADAMTS13 relapse-free survival was 56%. Daratumumab-related adverse events occurred in five cases and were non-severe infusion-related reactions in all cases. These results suggest that daratumumab may be an effective treatment option for iTTP patients with intolerance or refractoriness to rituximab.

Caplacizumab as an add-on therapy in a 7-year-old girl with exacerbated immune-mediated thrombotic thrombocytopenic purpura, a case report and literature review.

The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections.

Legionella Pneumophila Presenting as a Rare Cause of Acute Thrombocytopenia: A Case Report and Review of Literature.

Introduction: Legionella pneumophila can cause a wide spectrum of clinical manifestations, ranging from a mild flu-like illness to fulminant multi-organ involvement, characterised by severe pneumonia, diarrhoea, encephalopathy, shock, hepatic dysfunction and renal failure. Very rarely, it can be associated with haematologic conditions such as thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS) and immune thrombocytopenic purpura (ITP). We report a rare case of L. pneumophila causing ITP and review previously published cases of thrombocytopenia associated with Legionellosis in the literature. Case description: A 53-year-old male presented with fevers, chills, a productive cough and severe haemoptysis. Blood work was remarkable for leukocytosis, severe thrombocytopenia and hyponatraemia. Computed tomography (CT) imaging showed left lower lobe lung consolidation, and a peripheral blood smear showed giant platelets consistent with ITP. Legionella urine antigen testing returned positive. He was treated with intravenous immunoglobin, steroid taper and a ten-day course of azithromycin, which led to normalisation of his platelet count and resolution of the pneumonia. Discussion: L. pneumophila can lead to complement-mediated destruction of platelets resulting in ITP. Antibodies against L. pneumophila can also cross-react with the enzyme ADAMTS13, inhibiting its function and resulting in TTP and HUS. Additionally, L. pneumophila can infect vascular endothelial cells causing their death and stimulating release of von Willebrand factor (vWF) multimers into the bloodstream, promoting thrombosis and platelet consumption. Conclusion: It is important for internists to consider L. pneumophila in the differential for any patient presenting with pneumonia and severe thrombocytopenia. Earlier detection and intervention can lead to prevention of critical bleeding and better outcomes. LEARNING POINTS: Legionella pneumophila is rarely associated with different haematologic disorders resulting in severe bleeding diathesis as well as thrombosis.It is important for internists to consider Legionella pneumophila in the differential diagnosis for any patient presenting with pneumonia and severe thrombocytopenia.Earlier detection and intervention can lead to prevention of critical bleeding and better outcomes.

A comparative study of anti-ADAMTS-13 antibody dynamics in immune-mediated thrombotic thrombocytopenic purpura.

Background: Thrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management. Objectives: To compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti-ADAMTS-13 autoantibodies (AAbs) in patients with iTTP. Methods: This study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL). Results: For ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [-0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (P < .001, Cohen's g = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations. Conclusion: While CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%.

Caplacizumab improves clinical outcomes and is well tolerated across clinically relevant subgroups of patients with immune-mediated thrombotic thrombocytopenic purpura.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) may lead to microvascular thrombosis and mortality, despite patients receiving appropriate standard of care treatment (immunosuppressive therapy and therapeutic plasma exchange). Caplacizumab directly inhibits von Willebrand factor-platelet interaction and consequently prevents microthrombi formation. Objectives: This study aimed to determine the efficacy and safety of caplacizumab in diverse, clinically relevant patient subgroups. Methods: In this post hoc analysis of phase 3 HERCULES study (NCT02553317), patients were categorized by clinically relevant subgroups (prior iTTP history, iTTP severity at presentation, and initial immunosuppression regimen). Results: In patients with previous acute iTTP episodes, less severe disease at presentation, or those who received a corticosteroid-only initial immunosuppression regimen, time to platelet count response was shorter with caplacizumab vs placebo. Across all subgroups, fewer patients experienced a composite outcome of iTTP-related death, exacerbation, or major thromboembolic event on caplacizumab vs placebo. Placebo-treated patients remained at risk of exacerbations and refractoriness on either initial immunosuppression regimen (ie, corticosteroids only or corticosteroids plus rituximab). In the corticosteroids plus rituximab group, no exacerbations were reported in caplacizumab-treated patients, but 8 of the 16 (50%) patients experienced exacerbations in the placebo group. Safety outcomes were consistent with the findings of the main HERCULES study. Conclusion: Caplacizumab treatment of acute iTTP, in combination with therapeutic plasma exchange and immunosuppression, was safe and effective regardless of prior iTTP history, severity, or initial immunosuppression regimen and improved patient outcomes across clinically diverse subgroups. These findings emphasize the need for treatments with rapid onset of action that can reduce mortality and iTTP-related complications.

Thrombotic Thrombocytopenia Purpura (TTP) following emergent aortic valve replacement after a complicated TAVR procedure: a case report and review of the literature.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disorder. The occurrence of TTP subsequent to an emergent aortic valve replacement after a TAVR procedure is exceedingly uncommon with only a few reported cases worldwide. CASE PRESENTATION: We report the case of a 70-year-old female patient diagnosed with aortic insufficiency. Following a transcatheter aortic valve replacement, she underwent emergency aortic valve replacement under cardiopulmonary bypass on the subsequent day due to heart valve displacement. The postoperative diagnosis revealed TTP and symptomatic treatment involving plasma exchange was administered. After demonstrating steady improvement, the patient was eventually discharged. CONCLUSION: Aortic valve replacement after TAVR is a high-risk procedure and increases susceptibility for developing secondary TTP. The diagnosis and treatment of secondary TPP is considerably challenging, and early diagnosis with symptomatic treatment including plasma exchange can increase patient survival.

Small Bowel Ischemia and Ischemic Colitis Secondary to Thrombotic Thrombocytopenic Purpura in a Patient With Systemic Lupus Erythematous: A Rare Clinical Entity.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening hematologic disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction. This report highlights a rare case of small bowel ischemia and ischemic colitis caused by TTP in a 35-year-old woman with systemic lupus erythematosus (SLE), hypertension, and end-stage renal disease on hemodialysis. She presented with severe abdominal pain, diarrhea, vomiting, and bloody bowel movements. Diagnosed through CT, EGD, and colonoscopy and confirmed by ADAMTS13 levels, she was treated with plasma exchange, steroids, and rituximab. After standard therapies failed, resection anastomosis surgery led to clinical improvement. This case underscores the importance of early recognition and treatment of TTP in SLE patients to improve prognosis and reduce morbidity and mortality.

Refractory Thrombotic Thrombocytopenic Purpura in a Patient With Triple X Syndrome.

Clinical manifestations of triple X syndrome (karyotype 47, XXX) can include autoimmune diseases. We describe the occurrence of acquired thrombotic thrombocytopenic purpura (TTP), an autoimmune condition, refractory to plasmapheresis and rituximab in a patient with triple X syndrome who required vincristine administration for disease remission. To our knowledge, this rare coexistence is the first of its kind reported in Brazil.

Atypical Presentation of Thrombotic Thrombocytopenic Purpura (TTP) as an Initial Manifestation of Systemic Lupus Erythematosus (SLE) in a Young Male.

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematologic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal impairment, and fever. The etiology of TTP often involves a severe deficiency in ADAMTS13 activity, resulting in the accumulation of ultra-large von Willebrand factor multimers and subsequent microvascular thrombosis. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, and although the initial presentation of SLE with TTP is rare, it necessitates a comprehensive diagnostic and therapeutic approach. We present a case of a 27-year-old male with no significant past medical history who developed altered mental status, headache, and right-sided numbness, leading to the diagnosis of TTP and subsequent detection of SLE.

The Phenomenon of Thrombotic Microangiopathy in Cancer Patients.

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.

A Systematic Review of the Epidemiology and Disease Burden of Congenital and Immune-Mediated Thrombotic Thrombocytopenic Purpura.

Congenital (cTTP) and immune-mediated (iTTP) thrombotic thrombocytopenic purpura are serious and rare clotting disorders resulting from a deficiency in the ADAMTS13 enzyme. A systematic review was conducted using the Ovid® MEDLINE & Embase databases to synthesize the epidemiology and burden of cTTP and iTTP worldwide (from January 1, 2010, to February 6, 2020, with an update that covered the period January 1, 2020-February 11, 2022). Outcomes of interest were incidence and prevalence of TTP, incidence of acute episodes, mortality, burden of illness (eg complications, healthcare utilization, patient-reported outcomes) and disease management. A total of 221 eligible observational studies were included. The incidence rate of acute episodes ranged from 0.19-0.35 person-years in adult patients with cTTP, and 1.81-3.93 per million persons per year for iTTP in the general population. Triggers of acute episodes were similar for cTTP and iTTP, with pregnancy and infection the most commonly observed. Exacerbation in patients with iTTP varied widely, ranging from 2.4-63.1%. All-cause mortality was observed in 0-13.4% of patients with cTTP, across studies and follow-up periods, and in 1.1% (median follow-up: 0.4 years) to 18.8% (1 year) of patients with iTTP during acute episodes. Cardiovascular, renal, and neurological disease were common complications. TTP also led to work disturbances, feelings of anxiety and depression, and general activity impairment. TTP treatment regimens used were generally reflective of current treatment guidelines. The evidence identified describes a high patient burden, highlighting the need for effective treatment regimens leading to improvements in outcomes. Considerable evidence gaps exist, particularly for disease epidemiology, patient-reported outcomes, costs of disease management, and associated healthcare resource utilization. This review may help increase disease awareness and highlights the need for additional real-world studies, particularly in geographical regions outside the United States and Western Europe.

ADAMTS13 in the New Era of TTP.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, often immune-mediated disease that affects 2-13 persons per million per year. Hemolytic anemia, thrombocytopenia, and end-organ damage due to the formation of microthrombi are characteristic of TTP. ADAMTS13 is a disintegrin, metalloproteinase, cleaving protein of von Willebrand factor (VWF) that processes the VWF multimers to prevent them from interacting with platelets and, in turn, to microvascular thrombosis. Prompt diagnosis of TTP is critical yet challenging. Thrombotic microangiopathies have similar clinical presentation. Measurement of ADAMTS13 activity helps in the differential diagnosis. Less than 10% ADAMTS13 activity is indicative of TTP. Laboratory ADAMTS13 activity assays include incubating the test plasma with the substrate (full-length VWM multimers) and detection with direct or indirect measurement of the cleavage product. The purpose of this study is to examine the diagnostic potential, advantages, and weaknesses of the ADAMTS13 potency in TTP.

Managing surgical relapse risk in acquired thrombotic thrombocytopenic purpura: a systematic review.

•Thrombotic thrombocytopenic purpura (TTP) may relapse after surgery.•In a systematic review, we assessed preoperative TTP prophylaxis.•Pre-emptive ADAMTS-13 activity measurement prior to surgery may improve relapse risk.•Preoperative TTP prophylaxis may lower surgical relapse risk.

Vitamin B12 deficiency misdiagnosed as TTP: What can we learn from it?

The case report by Dwyre et al. shows that vitamin B12 deficiency may be misdiagnosed as acute thrombotic thrombocytopenic purpura. Together with similar observations, this underlines that acquired vitamin B12 deficiency-besides the inherited disorder of intracellular cobalamin metabolism, cbl C disease-should be listed as a separate entity of the thrombotic microangiopathies. Commentary on: Dwyre et al. Microangiopathic thrombocytopenia caused by vitamin B12 deficiency responding to plasma exchange. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19625.