Masias, Camila

Background: Since publication of the American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia (ITP), new clinical trials have been completed and new treatments have become available. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are a focused update of the 2019 ASH ITP guidelines, centering on treatment of adults with primary ITP. Methods: ASH formed a multidisciplinary guideline panel including two patient representatives that was balanced to minimize potential bias from conflicts of interest. The University of Oklahoma supported the guideline development process, including updating or performing systematic evidence reviews (up to July 19, 2025). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and identification of areas with new data or where application of new methods would be of benefit. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks and the GRADE framework for multiple comparisons, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on recommendations in adults with primary ITP regarding initial therapy and second-line treatment in patients who failed first-line corticosteroids. The panel also issued good practice statements on thrombopoietic agent switching and splenectomy. Conclusions: Novel recommendations of these guidelines include: (1) initial therapy with a combination of rituximab plus corticosteroids or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation) and (2) a thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line corticosteroids.

Abstract Systems-based hematology (SBH) is an emerging discipline focused on optimizing care delivery for patients with hematologic disorders within complex health care systems. Despite its growing importance, the field lacks a formal definition, standardized curriculum, and clear career pathway, hindering widespread adoption and training of future SBH experts. We sought to define core principles, competencies, challenges, and future directions of SBH to identify foundational components for a potential educational curriculum. Semistructured interviews were conducted with 8 SBH experts. Expert participants were identified through their committee involvement with the American Society of Hematology. Five overarching themes emerged: (1) The accidental expert: SBH careers have developed organically and reactively in response to pressing institutional needs, not through formal training; (2) Defining the unseen: experts define the field pragmatically by its function and roles; (3) The SBH toolkit: success requires a hybrid skillset combining clinical hematology expertise with health systems science (HSS) principles; (4) The architect's dilemma: the field's growth is hindered by interdependent challenges of building a curriculum, awareness, and securing resources; and (5) Charting the future: the discipline is poised for growth, driven by increasing health care complexity and specialization. SBH represents the nexus of HSS principles and hematology care. Formalizing SBH requires a multipronged approach, including developing a standardized curriculum that equips learners with a hybrid skillset, creating clear value for health systems and patients, and fostering a community of practice through professional societies. These findings provide a foundational framework for developing educational resources and institutional support necessary to continue advancing SBH.

Abstract Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy due to a severely deficient ADAMTS13 activity caused by ADAMTS13 autoantibodies. Pregnancy is a recognized risk for precipitating acute episodes of iTTP. iTTP is immediately life-threatening to both mother and fetus. This scoping review explores the neonatal outcomes of pregnant mothers with iTTP. Methods: We performed a comprehensive literature search (1990 to 2023) in major scientific databases using the Ovid MEDLINE, Embase, EBM Reviews (Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), and Scopus to identify studies related to iTTP and pregnancy outcomes. Eligible studies included those published in English that reported women with a diagnosis of iTTP that later become pregnant, or women that were initially diagnosed with iTTP during pregnancy or postpartum. Cases were included if there was documentation of confirmed ADAMTS13 deficiency and ADAMTS13 inhibitor was positive or if the author indicated cases were acquired or iTTP. Results were displayed descriptively. Two authors reviewed titles and abstracts, and a third author resolved conflicts. Relevant studies were extracted and analyzed descriptively. Results: 125 publications underwent full review; 52 publications (38 manuscripts, 13 abstracts) consisting of case series (n=18) and case reports (n=33) were included in final analysis. 1 review article with a case series was also included. Data regarding 206 pregnancies (antepartum iTTP: n=91, postpartum iTTP: n=24, and pregnancies in patients with a history (hx) of iTTP but no iTTP during current pregnancy: n=91) from 158 patients was included. Antepartum iTTP presented in the first, second and third trimesters in 21%, 38.7%, and 40 % respectively. When reported (n=67), plasma exchange (TPE) was used in 92.5% cases of iTTP. In 3 pregnancies, FFP was used instead of TPE, Rituximab was used in 19 (7 antepartum) and caplacizumab was used in 6 (2 antepartum) cases of ITTP. Of pregnancies with antepartum iTTP or with a hx of iTTP (n=182), fetal outcomes were available in 161 pregnancies. Of these, there were 46 fetal deaths (28.6%) and 31/46 (67.4%) occurred in those with antepartum iTTP. Fetal outcomes were available in 84/91 pregnancies with a hx of iTTP with no acute iTTP at current pregnancy and 82% (69/84) resulted in a live birth. ADAMTS13 activity was available in 58/91 pregnancies with a hx of iTTP with no acute iTTP and 88 % of these pregnancies had ADAMTS13> 20%. Of pregnancies with a hx of iTTP and available ADAMTS13, there were 7 fetal deaths; one was unrelated to iTTP. The remainder occurred in the first trimester (n=4) and second trimester (n=2); ADAMTS13 was < 20% in 3 patients, and > 20% in 3 patients. Of those with pregnancy losses with ADAMTS13> 20%, one patient had two other miscarriages (one before diagnosis of iTTP and one after diagnosis but no ADAMTS13 available). Another had a pregnancy with a live birth 2 years later (no ADAMTS13 available) and the third patient had ADAMTS13> 20% with a positive inhibitor. In pregnancies with both fetal outcomes and ADAMTS13 activity (n=53), live-births trended towards higher ADAMTS13 activities compared to fetal demise (p, 0.066). There were 5 maternal deaths associated with pregnancy (antepartum iTTP:4, postpartum iTTP: 1). Of those not receiving TPE (n=5), one pregnancy was associated with maternal and fetal death due to late iTTP recognition, one patient was lost to follow-up post-delivery to a live infant. The other three patients received FFP, and steroids; one of these patients suffered a fetal loss. Fetal outcomes were available in 5/7 pregnancies using antepartum rituximab and 4/5 were associated with fetal demise. In pregnancies using antepartum caplacizumab, there was one fetal death and one live birth. Conclusions: Pregnancy in patients with a diagnosis of iTTP carries significant associated morbidity and mortality. To our knowledge, this is the most comprehensive report on fetal mortality. With 28.6% of fetal demise, it is significantly higher than the fetal mortality in the general population (5.5 fetal deaths per 1000 live births). In the current cohort, 82% of pregnancies occurring in women with a hx of iTTP but without acute iTTP resulted in a live birth. This supports benefit of optimizing ADAMTS13 activity in women with a hx of iTTP interested in pregnancy.

Abstract Background Pregnancy is a known trigger for thrombotic thrombocytopenia purpura (TTP); however, there is limited data on the impact of a TTP diagnosis on pregnancy outcomes. Study design We used retrospective data from the National Inpatient Sample database to identify all hospital admissions of pregnant patients (≥18 years), with and without TTP from 2012 to 2021 using ICD‐9/10 codes. To describe the impact of TTP on maternal and fetal morbidity, we identified different morbidity indicators using standard CDC definitions. Results We identified 7,397,411 pregnancy hospitalizations with a mean age of 29 years. Of these, 233 had TTP , with 73 receiving therapeutic plasma exchange ( TPE ) during admission, which was treated as a surrogate for active TTP . Severe maternal morbidity rates were several‐fold higher in women with TTP (133 per 100 admissions; 95% CI 112–155) compared to those without TTP (6.75 per 100 admissions; 95% CI 6.74–6.79) ( p < 0.001). This included significantly higher rates of acute myocardial infarction, acute renal failure, acute respiratory distress syndrome ( ARDS ), disseminated intravascular coagulation ( DIC ), pulmonary edema/acute heart failure, puerperal cerebrovascular disorders, sepsis, shock, air/thrombotic embolism, blood transfusion, and mechanical ventilation. Amongst fetal outcomes, fetal growth restriction (6.9% vs. 2.3%) was more common in TTP , while there was no statistical difference between the two groups in rates of preterm delivery. In the multivariate analysis, Charlson comorbidity index ( CCI ) ≥ 1 and age ≥ 35 years were associated with higher likelihood of morbidity. Conclusion Pregnancy associated with TTP is associated with inferior maternal and fetal health outcomes.

Introduction: Systems-based hematology (SBH) is an emerging field focused on improving hematology care delivery through quality improvement (QI) and health systems science (HSS). However, a universal definition and standardized training curriculum are lacking. This study aimed to explore experts' perspectives on defining SBH, identify core knowledge and skills, and discuss challenges and opportunities in developing a curriculum. Methods: Semi-structured interviews were conducted with eight hematologists who have expertise in SBH through practical experience, scientific publications, and serve on related committees for the American Society of Hematology. These interviews were automatically transcribed through Microsoft Teams. Thematic analysis, using both inductive and deductive coding, was employed to identify themes and subthemes from the verbatim interview transcripts. This was accomplished with a large language model (LLM; Google Gemini Advanced, June 2024). Results: In combination, these semi-structured interviews lasted approximately 400 minutes and generated 231 pages of transcript text with 63117 words for analysis. Five main themes and associated subthemes were identified. (1) Defining SBH: experts highlighted the lack of a universal definition for SBH, emphasizing the reason it is often defined by its functions, such as improving healthcare delivery, ensuring appropriate use of resources, and addressing disparities in care. They often compared SBH to other fields like antimicrobial stewardship or implementation science to illustrate its expansive role and scope. (2) The Role and Scope of SBH: experts described SBH as encompassing a broad range of activities, including improving healthcare delivery, implementing QI initiatives, conducting pragmatic research, and advocating for policy changes at various levels. They emphasized the importance of data-driven approaches and collaboration with other healthcare professionals. (3) Training and Education in SBH: the lack of formal training programs and curricula for SBH was a recurring theme. Experts suggested that a comprehensive curriculum should include QI methodologies, implementation science, clinical informatics, health economics, leadership skills, and hematology-specific examples and case studies. They proposed various delivery methods, including asynchronous online modules, virtual workshops, and in-person sessions, targeting hematology fellows, junior faculty, and other healthcare professionals involved in hematology care. They unanimously agreed that a SBH curriculum could borrow heavily from an established HSS curriculum but should incorporate hematology-specific examples. (4) Challenges and Barriers to Implementing SBH: experts identified several challenges, including the lack of awareness and recognition of SBH among healthcare professionals and administrators, resource constraints, and the need for institutional buy-in. They also highlighted the technical difficulty of measuring and demonstrating the value of SBH interventions, particularly in terms of cost savings and improved patient outcomes. (5) The Future of SBH: despite the challenges, experts expressed optimism about the future of SBH, predicting its growing importance and expanding scope, including malignant hematology, community practice, and pediatrics. They envisioned SBH playing a crucial role in addressing rising healthcare costs, quality concerns, and disparities in care. They also anticipated the integration of new technologies like artificial intelligence, “virtual” care delivery, and molecular genetics into SBH practice. Conclusions: This study provides valuable insights into the current state of SBH and the need for a standardized curriculum. The findings can inform the development of educational resources and training programs to equip future practitioners with the necessary knowledge and skills to effectively practice SBH and improve hematology care delivery. This study also sheds light on the utility of qualitative research within SBH and the emerging analytical tools that will require further exploration and standardization (e.g., LLM prompt engineering).

Introduction: Thrombotic thrombocytopenic purpura (TTP) has been previously described in pregnancy, however there is limited data available on the impact of TTP in this subset of patients. In this analysis, we evaluate the maternal and fetal morbidity outcomes of TTP in hospitalized pregnant patients. Methods: We used retrospective data from the National Inpatient Sample (NIS) to identify all hospital admissions of pregnant patients with and without TTP from 2012 to 2021 using ICD-9/10 codes. To describe the impact of TTP on maternal and fetal morbidity, we identified different morbidity indicators using standard Centers for Disease Control and Prevention (CDC) definitions with a particular focus on preeclampsia/eclampsia, thromboembolic events (venous and arterial), other organ failure, maternal morbidity and fetal outcomes including intrauterine growth restriction (IUGR) and fetal loss. To account for the effects of acute TTP during pregnancy versus a history of TTP, we separately analyzed hospitalizations that included plasma therapeutic plasma exchange (TPE). Predictors of maternal/fetal morbidities in pregnant TTP patients were determined using multivariable logistic regression analysis. Results: We identified 7,514,304 pregnancy hospitalizations with a mean age of 29 years. Of these, 234 women had a diagnosis of TTP, with 74 receiving TPE during admission (acute TTP during pregnancy). Compared to pregnancy-related hospitalizations in women without TTP, those with TTP were more likely to be African American, admitted to urban teaching hospitals, have lower income, and have a higher Charlson Comorbidity Index (CCI). Most maternal morbidity outcomes were significantly higher in hospitalizations with TTP as compared to those without TTP including increased eclampsia (2.1% vs 0.08%), acute myocardial infarction (1.7% vs 0.01%, p&lt;0.001), puerperal cerebrovascular disorders (8.1% vs 0.7%, p&lt;0.001), cardiac arrest (0.9% vs 0.01%), acute renal failure (35% vs 0.2%, p&lt;0.001), adult respiratory distress syndrome (ARDS) (6.4% vs 0.06%, p&lt;0.001), disseminated intravascular coagulation (DIC) (18% vs 0.2%, p&lt;0.001), pulmonary edema/acute heart failure (5.1% vs 0.1%, p&lt;0.001), sepsis (9% vs 0.22%, p&lt;0.001), shock (6.4% vs 0.1%, p&lt;0.001), air/thrombotic embolism (3.0% vs 0.05%, p&lt;0.001), blood transfusion requirement (25.6 vs 1.28%, p&lt;0.001), and ventilation requirement (6.4% vs 0.06%, p&lt;0.001). There was also a higher need for cesarean sections in TTP hospitalizations compared to non-TTP (57.1% vs 36.9%). For fetal morbidity outcomes, intrauterine growth restriction (IUGR) was more common in TTP hospitalizations (6.8% vs 2.4%, p&lt;0.001), while there was no statistical difference between the two groups in the rates of preterm delivery (3.9% vs 3.3%, p=0.651). In-hospital mortality (1.7% vs 0.02%, p&lt;0.001), and length of stay (11 vs 3 days, p&lt;0.001) were also significantly higher in hospitalizations with TTP. Patients with TTP who received TPE during the hospital stay had worse maternal morbidity outcomes than those who did not, likely reflecting the active nature of the disease in this cohort. In the multivariate analysis, CCI ≥ 1 (OR 3.52, 95% CI, 1.64-7.54) and receipt of TPE (OR 2.99, 95% CI, 1.52-5.86) were associated with higher likelihood of maternal/fetal morbidity in TTP hospitalizations. Conclusion: In conclusion, TTP has a significant impact on hospitalized pregnant patients, both on maternal and fetal outcomes. Further studies are needed to assess risk factors associated with TTP in pregnancy and ideal treatment regimens for these patients.

Abstract Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing disorder caused by autoantibody-mediated deficiency of ADAMTS13. Rituximab is frequently administered to prevent relapses, but whether the durability of rituximab effect is maintained with subsequent treatment courses has not been studied. Using the United States Thrombotic Microangiopathy Consortium (USTMA) retrospective iTTP registry, we evaluated clinical relapse-free survival (RFS) with subsequent courses of rituximab treatment in multiply relapsing patients. Separately, we evaluated overall RFS (composite of time to clinical relapse, ADAMTS13 relapse, or preemptive rituximab) in a prospective iTTP cohort from the Johns Hopkins University and the University of Minnesota. In the USTMA registry, median clinical RFS was shorter after the second or subsequent rituximab-treated episode than the first (2.1 vs 6.0 years; P = .04). White patients’ clinical relapse risk after the second and subsequent rituximab courses was not significantly different compared with the first (hazard ratio [HR], 1.86; 95% confidence interval [CI], 0.22-15.80; P = .57), whereas for Black patients, clinical relapse risk was significantly higher after the second or subsequent courses (HR, 2.82; 95% CI, 1.52-5.24; P = .001). In the prospective cohort, overall RFS progressively shortened after each episode of rituximab treatment with the first episode having the longest RFS (2.8 years; interquartile range, 2.0-6.0) and this loss of response durability was most pronounced in Black patients. The durability of rituximab’s effect declines with subsequent treatments, which is more pronounced in Black patients, who may benefit from closer monitoring and alternative immunomodulatory approaches such as maintenance rituximab and consideration of other agents.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is defined by thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation, confirmed by severely deficient ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) to &lt;10%. It is caused by autoantibodies against the ADAMTS13 protease. Pregnancy can precipitate iTTP, but the diagnosis and treatment are challenging, since it is often difficult to differentiate from other TMAs associated with pregnancy The aim of this study was to describe the clinical presentation, treatment, and outcomes of pregnancy related iTTP. Methods: Data was obtained from the USTMA retrospective database, including 15 large USTMA referral centers. Patients were identified based on the diagnosis of iTTP provoked by pregnancy between 9/6/1990 and 6/18/2018. The study cohort included participants with a clinical diagnosis of iTTP, confirmed by ADAMTS13 activity &lt;10% who had a pregnancy or recent delivery within 30 days of presenting with iTTP. For participants diagnosed before the ADAMTS13 assay was developed (2006), the iTTP diagnosis was based on the clinical course and absence of alternative causes. iTTP exacerbation was defined as clinical disease recurrence within 30 days of PLEX (plasma exchange) discontinuation, and clinical relapse was defined as disease recurrence after 30 days of last PLEX. Maternal and fetal outcomes were additionally collected from 7/15 sites. Results: 42 patients had 55 iTTP episodes provoked by pregnancy. Median age for patients was 29. Sixteen (38.1%) were white, 20 (47.6%) were black. The most common presenting symptoms were headache and fatigue in 11/55 (20%) episodes. Thirty nine (70.9%) episodes had a platelet count &lt;30 x10 9/L, and 46 (83.6%) had laboratory findings concerning for hemolysis as evidenced by elevated lactate dehydrogenase (LDH) and/or schistocytes present on peripheral smear. Only 5 (9%) episodes presented with a creatinine &gt;2 mg/dL. ADAMTS13 activity was documented in 33 (60%) episodes and was &lt;10% in 30 (90.9%) (Table 1). Treatment with PLEX was described in 30 (54.5%) episodes with a median duration of 6 days (2-26 days). Further immunosuppression included prednisone in 38 (69.1%) episodes and rituximab in 11 (20%), of which 7 (63.6%) had no future exacerbations or relapses during the study period.Seventeen (40.5%) patients had a prior diagnosis of iTTP. There were 10 exacerbations in 8 patients (19%), and 34 relapses in 13 (30%) patients after the 55-pregnancy provoked iTTP episodes. Five of those relapses were triggered again by pregnancy. Pregnancy related outcomes were obtained in 16 patients. Twenty five percent (4/16) of patients had a prior history of iTTP; median time of last iTTP to current presentation was 34 months (10-108). Of 16 patients, iTTP occurred with first pregnancy in 8 patients. Of the remaining eight patients, iTTP occurred in the eleventh (n=1), ninth (n=1), sixth (n=1), fifth (n=1), fourth (n=2), and unknown (n=2) pregnancy. Only 13 of 16 patients had further pregnancy specific outcomes available (Table 2). Preeclampsia was noted in 3 patients. Seven and 1 patients, presented with iTTP within 30 days postpartum or after miscarriage, respectively. The remaining patients (n=5) developed iTTP during the antepartum period. Of these, 2 pregnancies were terminated due to iTTP (second trimester and third trimester). One of the three remaining pregnancies resulted in fetal demise at 24 weeks. The latter two patients delivered healthy infants. There were no maternal deaths in our cohort. Conclusions: This is first multicenter descriptive analysis of pregnancy related iTTP from the USTMA registry. The clinical presentation of this cohort is consistent with iTTP triggered by other causes, and the low rate of acute kidney injury is helpful in identifying iTTP from other TMAs in pregnancy. We observed that pregnancy is a risk not only for acute episodes of iTTP in first pregnancy, but also in subsequent pregnancies and in the relapse setting of those with previous diagnosis of iTTP. While there was a 20% and 30% exacerbation and relapse rate respectively, maternal mortality was not observed. Rituximab did not affect maternal mortality. Fetal mortality was affected by iTTP in the antepartum period. These findings will serve as bases of prospective USTMA study for standardize management of this population.

Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.