Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study.

BACKGROUND: Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy. METHODS: We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. RESULTS: We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 109 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up. CONCLUSIONS: Our study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our study adds practical, real-world experience to the literature, but future research remains imperative.

Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: an analysis of the National Inpatient Sample Database.

Immune thrombocytopenia (ITP) is a known autoimmune complication of chronic lymphocytic leukemia (CLL). Currently, there is limited data regarding the risk CLL confers on hospitalization outcomes in patients admitted with ITP.The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases (ICD) codes to identify hospitalizations for ITP and then subclassified the data into hospitalizations with and without CLL. A multivariate logistic regression was designed to account for patient characteristics and comorbidities. The primary outcome was all-cause mortality. Secondary outcomes included major bleeding, gastrointestinal bleeding, intracranial bleeding, and the need for platelet transfusions, intravenous immunoglobulin, and splenectomy. Among 662,171 cases of ITP between 2005 and 2019, 15,672 had concurrent CLL. CLL patients were significantly older and had more comorbidities compared to patients without CLL. Multivariate analysis revealed CLL patients with ITP had a risk of all-cause mortality (odds ratio: 1.28, 95% CI: 1.19-1.37; p < 0.01). CLL patients also had a higher risk of complications, second-line ITP treatments, blood transfusions, and bleeding, with the exception of intracranial hemorrhage. Our study suggests CLL is an independent risk factor for increased morbidity and mortality among hospitalized patients with ITP. Prospective studies are needed to determine if refractoriness to conventional treatments for ITP can account these results.

Can we lower the platelet threshold of ≥ 50 × 109/L for performing a lumbar puncture safely in patients with hematological malignancies?

Lumbar punctures (LP) are routinely used to administer intrathecal chemotherapy for children and adults with hematologic malignancies. The current guidelines suggest a platelet threshold of ≥ 50 × 109/L prior to LP for intrathecal chemotherapy (ITC). This can be challenging in patients with hematological malignancies who are thrombocytopenic. We conducted a retrospective chart review of 900 LPs for ITC and compared adverse events in patients with a platelet count of ≥ 50 × 109/L and < 50 × 109/L. Cohort 1 included 682 LPs (75.8%) with a pre-procedure platelet count ≥ 50 × 109/L, and cohort 2 included 218 LPs (24.2%) with a pre-procedure platelet count < 50 × 109/L. Cohort 2 was further subdivided into pre-procedure platelet counts of 41 × 109/L-49 × 109/L (n = 43), 31 × 109/L-40 × 109/L (n = 77), 21 × 109/L-30 × 109/L (n = 84), and 11 × 109/L-20 × 109/L (n = 14). Among 900 LP procedures, a pre-procedure platelet count < 50 × 109/L did not demonstrate a higher rate of post-procedure adverse events (6.5% vs 6.8%, p = 0.8237). When cohort 2 was further stratified, the cohort with a pre-procedure platelet count of 21 × 109/L-30 × 109/L had the highest percentage of complications from LP (9.5%) and the highest rates of traumatic taps with observed LP RBC count > 200 (35.7%, p = 0.0015). The rate of red blood cells (RBC) in the CSF was significantly higher in the group with platelets < 50 × 109/L with observed LP RBC count ≥ 200 (31.2% vs 20.5%, p = 0.0016), ≥ 500 (27.1% vs 14.6%, p < 0.0001), and ≥ 1000 (23% vs 11.6%, p < 0.0001). No instances of epidural hematomas were seen. We found no significant difference in bleeding complications between patients undergoing LPs for ITC with a platelet count above or below 50 × 109/L.

Plasma of Acute Lymphoblastic Leukemia Patients React to the Culture of a Mycovirus Containing Aspergillus flavus.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus. This culture was subjected to electron microscopy, purification, and mass spectrometry. Using enzyme-linked immunosorbent assay technique, plasma of patients with ALL and long-term survivors of this disease were tested for antibodies, utilizing supernatant of the culture of this organism. The results were compared with 3 groups of controls, including healthy individuals, patients with sickle cell disease, and solid tumors. Using electron microscopy, the isolated A. flavus contained mycovirus particles. In chemical analysis, this organism did not produce any aflatoxin. Using an enzyme-linked immunosorbent assay technique, the supernatant of the culture of the mycovirus containing A. flavus could differentiate ALL patients from each group of controls (P<0.001). These studies provide a new technique for the detection of ALL and may add information for future research regarding leukemogenesis.

Validation of the Khorana score in acute myeloid leukemia patients: a single-institution experience.

BACKGROUND: Although patients with acute myeloid leukemia (AML) were shown to have an increased risk of thrombosis, no thrombosis risk assessment scoring system has been developed for AML patients. The Khorana Risk Score (KRS), which has been widely used for thrombosis risk assessment in the clinical setting, was developed on the basis of solid tumor data and has not been validated among AML patients. This study aims to validate the use of the KRS as a thrombosis risk-scoring system among patients with AML. METHODS: Using data from H. Lee Moffitt Cancer Center and Research Institution's Total Cancer Care Research Study, we retrospectively identified patients who were histologically confirmed with AML from 2000 to 2018. Clinical and laboratory variables at the time of AML diagnosis were characterized and analyzed. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 867 AML patients were included in the analysis. The median age at AML diagnosis was 75 years (range, 51-96), and the majority were male (65%, n = 565). A total of 22% (n = 191), 51% (n = 445), 24% (n = 207), and 3% (n = 24) of patients had a KRS of 0, 1, 2, and 3, respectively. A total of 42 thrombotic events (3% [n = 6/191] with a KRS of 1; 5% [n = 23/445] with a KRS of 2; 6.3% [n = 13/207] with a KRS of 3) were observed, with a median follow-up of 3 months (range, 0.1-307). There was no statistical difference in the risk of thrombosis between these groups (P = .1949). CONCLUSIONS: Although there was an increased risk of thrombosis associated with a higher KRS among AML patients with a KRS of 1 to 3, the difference was not statistically significant. Furthermore, only a few patients were found to have a KRS > 3, and this was largely due to pancytopenia, which is commonly associated with AML. These results indicate the need for a better thrombotic risk-scoring system for AML patients.

C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional "hits" and outcomes with subsequent therapy.

BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS: This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS: The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in <4 months. CONCLUSIONS: Patients with MYC-positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC-negative counterparts, but their survival is dismal irrespective of additional "hits" and HCT, representing an unmet medical need. Cancer 2017;123:4411-8. © 2017 American Cancer Society.

Diffuse large B-cell lymphoma with primary treatment failure: Ultra-high risk features and benchmarking for experimental therapies.

The outcomes of patients with DLBCL and primary treatment failure (PTF) in the rituximab era are unclear. We analyzed 331 patients with PTF, defined as primary progression while on upfront chemoimmunotherapy (PP), residual disease at the end of upfront therapy (RD) or relapse < 6 months from end of therapy (early relapse; ER). Median age was 58 years and response to salvage was 41.7%. Two-year OS was 18.5% in PP, 30.6% in RD and 45.5% in ER. The presence of PP, intermediate-high/high NCCN-IPI at time of PTF or MYC translocation predicted 2-year OS of 13.6% constituting ultra-high risk (UHR) features. Among the 132 patients who underwent autologous hematopoietic cell transplantation, 2-year OS was 74.3%, 59.6% and 10.7% for patients with 0,1 and 2-3 UHR features respectively. Patients with PTF and UHR features should be prioritized for clinical trials with newer agents and innovative cellular therapy.

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Geographic and Racial Disparities in Chimeric Antigen Receptor-T Cells and Bispecific Antibodies Trials Access for Diffuse Large B-Cell Lymphoma.

BACKGROUND: We investigate the geographical and racial disparities in accessing CAR-T and bispecific antibodies trials for DLBCL. MATERIALS AND METHODS: ClinicalTrials.gov was searched, and 75 trials with at least 1 open site in the US were included. 2020 US Census Bureau data was used to obtain data on race and ethnicity. SPSS version 26 was used for analysis. RESULTS: There were 62 CAR-T and 13 bispecific antibodies trials with 6221 enrolled or expected to enroll patients. Eighty-five percent of the clinical trials were only open in the US, and the majority 64% were pharmaceutical-funded. There were 126 unique study sites distributed over 31 states with 11 (0-51) mean number of trials per state and 4.5 (1-26) and 4.4 (1-24) mean number of CAR-T and bispecific antibodies trials per site, respectively. Southern states had the most number of trials 31%, followed by Midwestern 25%, Northeastern 24%, and Western 20%. The highest number of study locations were in California 13, New York 9, and Pennsylvania 9, while the highest number of open studies were in California 51, Texas 32, and New York 23. Twenty states had no open CAR-T or bispecific antibodies trials. Only 33% of African Americans (AA) lived in a county with a trial, and 7 out of 10 states with the highest proportion of AA residents (18.6%-41.4%) have no or less than 4 trial sites. Of the 62 counties analyzed, 92% were White predominant, while only 8% were AA predominant (P = .009). CONCLUSIONS: Strategies should be framed to address the observed disparities and to improve access.

Incidence of Thrombosis in COVID-19 Patients Compared to Non-COVID-19 Sepsis Patients in the Intensive Care Unit.

Background/Objectives: The hypercoagulable state associated with COVID-19 infection is associated with adverse outcomes and mortality. Studies have also demonstrated high rates of venous thromboembolism (VTE) events among patients with sepsis. We aimed to evaluate how the increase in thrombotic events in critically ill patients with COVID-19 infection compares to that of critically ill patients with non-COVID-19 sepsis. Methods: A chart review was performed of patients 18 years or older admitted to the intensive care unit (ICU) at Tampa General Hospital between 1 January 2020 and 31 December 2020 diagnosed with COVID-19 or sepsis secondary to other pathogens. Non-COVID-19 sepsis patients and COVID-19 patients were propensity-matched 3:1 on the Charlson Comorbidity Index. Multivariate analyses adjusting for confounding were conducted to report odds ratio (OR) and 95% confidence intervals (95% CIs) of predictors for thrombotic events and overall mortality. Results: After propensity score matching, 492 sepsis patients and 164 COVID-19 patients were included in the analysis. COVID-19 patients were significantly older (p = 0.021) and showed higher BMI (p < 0.001) than sepsis patients. COVID-19 patients did not show significantly higher odds of thrombosis after adjustment for confounders (OR 0.85, 95% CI 0.42-1.72), but had significantly lower odds of mortality than sepsis patients (OR 0.33, 95% CI 0.16-0.66). Conclusions: Our results suggest that further study is required to lower the rate of VTE in COVID-19 and non-COVID-19 sepsis patients admitted to the ICU; it is also reasonable to consider similar thromboembolism practices between these two patient groups.

First description of atrial fibrillation and congenital thrombotic thrombocytopenic purpura treated by left atrial appendage occlusion.

Given an increased risk of both thrombosis and bleeding, thrombotic thrombocytopenic purpura (TTP) presents a unique challenge when anticoagulation is required for comorbid disease, particularly in the setting of major bleeding events. We present for the first time a patient with TTP and atrial fibrillation, presenting with recurrent stroke, but unable to tolerate anticoagulation due to prior intra-cerebral hemorrhage. To address both issues concomitantly, we describe the successful application of a novel management approach to facilitate left atrial appendage occlusion, there by offering a non-pharmacologic means of stroke prevention without added bleeding risk.

Insights into the Impact of Hesitancy on Cancer Care and COVID-19.

World Health Organization findings indicate that the COVID-19 pandemic adversely affected cancer diagnosis and management. The COVID-19 pandemic disrupted the optimal management of outpatient appointments, scheduled treatments, and hospitalizations for cancer patients because of hesitancy among patients and health-care providers. Travel restrictions and other factors likely affected medical, surgical, and radiation treatments during the COVID-19 pandemic. Cancer patients were more likely to be affected by severe illness and complications if they contracted COVID-19. A compromised immune system and comorbidities in cancer patients may have contributed to this increased risk. Hesitancy or reluctance to receive appropriate therapy or vaccination advice might have played a major role for cancer patients, resulting in health-care deficits. The purpose of this review is to evaluate the impact of COVID-19 on screening, entry into clinical trials, and hesitancy among patients and health-care professionals, limiting adjuvant and metastatic cancer treatment.

Primary immune thrombocytopenia: a 'diagnosis of exclusion'?

Current diagnosis of primary immune thrombocytopenia (ITP) is presumptive, centered on excluding other causes of thrombocytopenia. The diagnosis of ITP is challenging because of the wide range of potential inherited and acquired causes of thrombocytopenia. The treatment of ITP is empiric with steroids, high-dose immunoglobulin, immunosuppressants and thrombopoietin agonists with potential side effects. We searched Medline and Cochrane databases, reviewed the study data and analyzed the individual diagnostic tests for their evidence-based role in the diagnosis of ITP. We then analyzed the strength of the scientific evidence for each diagnostic test in the diagnosis of ITP and identified gaps in the diagnostic accuracy. The diagnostic challenges in ITP include: insufficient evidence for the individual test for diagnosis of ITP, no standardized protocol/guideline for diagnosis, hurdles in accessing the available resources and failure to correlate the clinical data while reviewing the blood smear. We did not identify a diagnostic test that clinicians can use to confirm the diagnosis of ITP. In the absence of a diagnostic test of proven value in ITP, the clinician is best served by a comprehensive history and physical examination, complete blood count and review of the peripheral blood smear in evaluating thrombocytopenia.

Assessment of Bleeding Risk in Hospitalized COVID-19 Patients: A Tertiary Hospital Experience during the Pandemic in a Predominant Minority Population-Bleeding Risk Factors in COVID-19 Patients.

Introduction: In the wake of the SARS-CoV-2 (COVID-19) pandemic, our world has faced multiple challenges. Infection with this virus has commonly been associated with thrombotic events. However, little is known about bleeding risk and anticoagulation therapy. This study aims to determine factors that are associated with increased risk of bleeding in COVID-19 patients. Methods: A retrospective cohort study was conducted using the records of COVID-19 patients admitted during the COVID-19 pandemic from March 2020 through May 2020. Using patient charts, investigators manually collected data regarding patient characteristics and bleeding. Patients were included in the analysis if they had a confirmed COVID-19 PCR test, were older than 18 years of age and were admitted to the hospital. Patients who were pregnant or had incomplete charts were excluded from the study. ANOVA and logistic regression were used to determine the statistical significance of the data using SPSS version 27. Results: A total of 651 patients were included in the analysis out of 685 patients located in the database of COVID-19 infected patients during that time frame. The general characteristics of the patients were as follows: 54.2% were males; females 45.8% ages ranged from 28 to 83 years old (median age = 66 years old). There were 31 patients (4.9%) who required more than 1 unit of packed red blood cell (PRBC). A total of 16 (2.85%) patients had a documented gastrointestinal bleed (GIB), of which 8 received a total of 29 units of PRBC transfusions. The HAS-BLED score (without alcohol/drug due to inadequate charting) is calculated for patients who had a documented GI bleed and who received more than one unit of PRBC. It was noted that the higher the HAS-BLED score the greater the likelihood of having a GI bleed (p < 0.001). The HAS-BLED score (not including alcohol/drug) was also predictive for patients who received more than one unit of PRBC during their hospital stay (p < 0.001). Discussion: Using the HAS-BLED score without alcohol/drugs, patients with COVID-19 can be stratified in regard to their risk of GI bleeding and their risk of transfusion while in the hospital. When administering anticoagulation therapy, cautious monitoring should be carried out. Decisions regarding anticoagulant therapy should be based on individual patient characteristics.

An evaluation of the content of hematology and medical oncology fellowship websites.

Introduction: The growing demand for Hematology and Oncology services has greatly piqued the interest of potential residents towards this specialty. Since the programs' official websites are now becoming the primary source of information that potential residents turn to, we aimed to analyze program websites' content and availability across parameters that have been used by evaluators of websites. Methods: & Materials: A list of 181 fellowship programs were identified using The Fellowship and Residency Electronic and Interactive Database (FRIEDA). 160/181 were accessed via a hyperlink or Google search. Content of these websites was evaluated on a 40-point criteria system in 10 distinct domains. Websites without accessible links were excluded from the search. Results: The 160 programs were divided based on the region with the North-East having the most programs (32.5%) and the West having the least programs (12.4%). Exactly 3/4th of the websites had been updated with the latest available information. "Program overview" (89%) was the most common domain present on the websites while "Alumni" was the least common, present on only (25%) of the websites. Conclusion: When compared with previous similar research, there have been a few significant improvements across the programs' websites, however many still lack important information regarding certain domains. The content and availability of the program's website can encourage or deter an applicant, in their decision to apply to the program, hence making it necessary for programs to augment their websites.

Outcomes using direct-acting antiviral hepatitis-C treatment in older versus younger Veterans.

BACKGROUND: Historically, older adults have been excluded from trials evaluating hepatitis C virus (HCV) treatment, in part, due to the adverse effects associated with previous regimens. Veterans are at high risk of HCV infection. Ledipasvir/sofosbuvir (LED/SOF) is a once daily antiviral regimen with demonstrated efficacy and tolerability among the younger population. We examined the tolerability and effectiveness of LED/SOF in Veterans age ≥65 years versus those <65 years who were treated at the Atlanta VA Health Care System (AVAHCS). METHODS: Using the VA Clinical Case Registry, all persons who filled a LED/SOF prescription at the AVAHCS from January 1, 2015, through March 31, 2016, were identified. The electronic medical records were reviewed to identify basic demographic information: comorbidities; polypharmacy; and outcomes. Sustained virologic response (SVR) was defined as an undetectable HCV RNA, at least 12 weeks after completing treatment. Descriptive statistics were employed using SAS v9.2. RESULTS: We identified 345 Veterans who filled LED/SOF during the study period; 94 were excluded due to exposure to ribavirin and IFN containing regimens; 97 (38.6%) were ≥65 years. Veterans were predominantly black (57%) and male (97%). Cancer was more prevalent among older Veterans (p = 0.047) as was polypharmacy (p = 0.001). Treatment completion rates between older and younger Veterans were not significantly different (99 vs. 95%, respectively; p = 0.16), but significantly more older Veterans achieved SVR (98 vs. 91%; p = 0.03). CONCLUSIONS: LED/SOF was a well-tolerated and effective regimen in an older Veteran population despite their multiple comorbidities and polypharmacy presence.

Post Approval Experience with Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura at a Single Institution.

Caplacizumab prevents platelet adhesion and has been approved for acquired thrombotic thrombocytopenic purpura (aTTP). This study was retrospective, including all patients diagnosed with aTTP and treated with caplacizumab since commercial availability in 2019 until 28 February 2021 at a single academic hospital with no exclusion criteria. Results used definitions for outcomes in aTTP from the International Working Group Consensus. Ten patients with aTTP received caplacizumab. The median age was 52 years. Six (60%) patients had refractory aTTP while 4 (40%) had newly diagnosed aTTP. The median laboratory values prior to therapy demonstrated: platelet count (PC) 29/uL, LDH 518 U/L (182-1850), ADAMTS13 activity 3% and ADAMTS13 inhibitor 1.4 BU. Everyone received glucocorticoids, rituximab, therapeutic plasma exchange (TPE) and caplacizumab. The median number of TPE was 12 days. Caplacizumab was started at a median of 5 days after the first TPE and the median treatment duration was 31 days. Normalization of PC, LDH and ADAMTS13 activity in days were 5, 3.5, and 32.5, respectively. Six (60%) patients achieved complete response, 3 (30%) had refractory disease and 1 (10%) had relapsed aTTP. No subject suffered abnormal bleeding, or thrombotic event. There were no deaths. Caplacizumab with TPE, glucocorticoids and rituximab was a safe and effective therapy for aTTP.