Management Of Thrombotic Thrombocytopenic Purpura Research Articles

Overview of ADAMTS13 Protein in Diagnosis and Patient Management of TTP

The accurate diagnosis and effective management of Thrombotic Thrombocytopenic Purpura (TTP), a rare but life-threatening hematologic disorder, rely critically on the assessment of ADAMTS13 activity. ADAMTS13, a von Willebrand factor-cleaving protease, plays a pivotal role in the pathophysiology of TTP. This review synthesizes current understanding and recent advancements in the role of ADAMTS13 in the diagnosis and therapeutic monitoring of TTP, with a specific focus on the implementation of a fluorescence resonance energy transfer (FRET)-based assay for ADAMTS13 activity. Our retrospective analysis of 50 suspected TTP cases, including 19 confirmed diagnoses, revealed that the FRET-based assay significantly improved the sensitivity and specificity of TTP diagnosis compared to traditional qualitative methods. Furthermore, the FRET assay facilitated timely initiation of appropriate therapies and monitoring of disease activity, underscoring its utility in clinical practice. Our findings highlight the FRET-based ADAMTS13 activity assay's contribution to enhancing the diagnostic accuracy and management efficiency of TTP, suggesting its potential as a standard diagnostic tool in clinical settings. The review aims to provide a comprehensive overview for hematologists and laboratory medicine practitioners, encouraging the adoption of the FRET-based assay to improve patient outcomes in TTP management.

Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group.

Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.

Epidemiology, Clinical Presentation, and Treatment of Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura (TTP) is a critical medical condition characterized by thrombocytopenia, hemolytic anemia, and organ damage due to microvascular clotting. This review delves into TTP's epidemiology, clinical presentation, and treatment methods. Advances in understanding the disease's pathophysiology have allowed significant improvements in management strategies. The shift from traditional therapies like therapeutic plasma exchange and corticosteroids to innovative, targeted treatments such as rituximab and caplacizumab marks a significant positive effect. These novel therapies offer less invasive, patient-centric approaches, heralding a new era in TTP treatment. The review also highlights the future directions of TTP research and therapy, emphasizing the need for continued innovation and tailored care strategies. This evolution in TTP management underscores a move towards personalized medicine, focusing on improving outcomes and the quality of life for patients. The dynamic nature of TTP treatment is shifting towards more effective, patient-focused therapeutic options, reflecting the ongoing advancements in the field.

Does Caplacizumab for the management of thrombotic thrombocytopenic purpura increase the risk of relapse, exacerbation, and bleeding? An updated systematic review and meta-analysis based on revised criteria by the International Working Group for thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening condition marked by abnormal blood clotting and organ damage. Caplacizumab is a potential treatment for the TTP management. This systematic review and meta-analysis aimed to assess Caplacizumab's effectiveness and safety in the TTP management. A comprehensive database search identified nine studies, including randomized controlled trials and observational studies. Primary outcomes included TTP exacerbation, relapse, and major bleeding. Major bleeding risk was evaluated using updated definitions recommended by the International TTP Working Group in 2021. Revised criteria proposed by the IWG for TTP recurrence were employed for a comprehensive assessment of Caplacizumab's impact on relapse and exacerbation. Analysis revealed Caplacizumab significantly reduced all-cause mortality in TTP patients. Some studies raised concerns about bleeding risk, but overall, it did not significantly differ from standard treatment. Likewise, there was no significant difference in TTP relapse rates between Caplacizumab and standard care. This study supports Caplacizumab as a potential adjunct therapy for TTP. However, careful consideration of its advantages and risks is crucial in clinical practice. Further research is needed to address concerns related to adverse effects like bleeding risk and relapse rates associated with Caplacizumab in the TTP management. The findings emphasize the importance of weighing potential benefits and risks when considering Caplacizumab as an adjunct therapy for TTP.

Comparative Analysis of Hospital Outcomes for Thrombotic Thrombocytopenic Purpura between 2018 and 20120: A National Inpatient Sample Database Study

Background: Thrombotic Thrombocytopenic Purpura (TTP) is a rare, life-threatening hematological emergency with a mortality rate of up to 20%. While plasma exchange and immunosuppression have long been the “pillars” of therapy, since 2019, a novel targeted therapy, caplacizumab, has become available. This study aims to analyze hospital outcomes before and after 2019 to assess the potential impact of this therapeutic advancement. Methods: A retrospective analysis of the United States (US) National Inpatient Sample (NIS) database was conducted using International Classification of Diseases (ICD-10) codes to identify TTP patients in 2018 and 2020. The data were analyzed using STATA version MP14.2. Fischer's exact test, student's t-test, and multivariate regression analysis were used to compare proportions and continuous variables and calculate the adjusted odds ratio. The database, however, did not consistently specify which patients received specific therapeutics like rituximab and caplacizumab and which patients did not. Results: The study included 1120 TTP hospitalization in 2018 and 975 in 2020. The majority of patients were African Americans (52.1% in 2018, 46.4% in 2020) and females (67.9% in 2018, 68.7% in 2020); 1.6% had COVID-19 infection in 2020, with a mean Charlson comorbidity Index (CCI) of 1.28 in 2018 vs. 1.34 in 2020. The multivariate analysis after controlling age, sex, CCI, and primary payer, revealed no significant change in the rates of stroke (AOR: 0.94, 95% CI: 0.64-1.40, P = 0.77), myocardial infarction (AOR: 1.01, 95% CI: 0.70-1.46, P = 0.95), acute kidney injury (AOR: 0.91, 95% CI: 0.72-1.14, P = 0.398), acute bleeding (AOR: 0.74, 95% CI: 0.51-1.09, P = 0.13), packed red blood cell transfusion (AOR: 0.95, 95% CI: 0.74-1.23, P = 0.71), and platelet transfusion (AOR: 1.20, 95% CI: 0.88-1.62, P = 0.25) in 2020 compared to 2018. Additionally, there were no significant changes in the mortality rate (AOR: 0.83, 95% CI: 0.52-1.33, P = 0.43) and mean length of hospital stay (12 vs. 11 days) in 2020. However, a significant increase in mean hospital cost ($189,749.9 vs. $267,835 US dollars, P<0.001), adjusted for inflation, was observed in 2020. A subgroup analysis was conducted for 50 patients who received caplacizumab in 2020, revealing higher average hospital costs ($465,665 vs. $241,665) and an increased rate of intracranial bleeding (10% vs. 1.6%) compared to patients whose caplacizumab usage was unknown. Mortality was observed in none of the known caplacizumab-treated samples, while 6.5% mortality was recorded among those without known caplacizumab use. Conclusion: Compared to 2018, 2020 hospitalizations had a substantial increase in costs without a significant change in patient outcomes. This probability is related to the COVID-19 pandemic and the advent of caplacizumab use in the US. We were unable to sort out the impact of other costly therapeutics like rituximab. However, it would be given less frequently. Further study is needed to explore this indirect inference from the NIS database analysis and the attendant cost-benefit implications in the management of TTP and its impact on patient outcomes.

Low ADAMTS13 Activity in Patients with Liver Disease- Thrombotic Thrombocytopenic Purpura or Not?

Introduction: Patients with liver injury have hemostatic defects including reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Severe deficiency of ADAMTS13 (ADMS13) activity (< 10%) is pathognomonic for thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy (TMA). Differentiating TTP from severe liver injury is complex for multiple reasons including 1) low baseline ADMS13 2) concomitant coagulopathies complicating differentiation from disseminated intravascular coagulation (DIC) 3) ADMS13 activity (ADMS13:AC) assay interference (hyperbilirubinemia (>30mg/dL) can cause artifactual reduction of ADMS13:AC). Here we sought to characterize the clinical presentation, management, and outcomes of patients with liver injury presenting with thrombocytopenia (TCP), microangiopathic hemolytic anemia (MAHA) and low ADMS13:AC at our institution. Methods: In this retrospective study, after IRB approval, electronic medical records (EMR) of institutional patients who had ADMS13:AC and inhibitor profile performed in our special coagulation laboratory between 2018 and July 17, 2023, were reviewed. Eligible patients had ADMS13:AC ≤20% were ≥ 18 years and had evidence of liver injury at time of ADMS13. Liver injury was defined as ALT or AST elevations greater than two times the upper level of normal within one month prior to ADMS13:AC testing, history of end stage liver disease or cirrhosis, or liver transplant with evidence of graft dysfunction. Details regarding clinical presentation, management and outcomes were extracted from the EMR. PLASMIC and ISTH DIC scores were retrospectively calculated. Results: 70 patients had at least one ADMS13:AC < 20% during the study period. 28/70 patients met liver injury inclusion criteria and 20/28 had TCP and MAHA. Of those 20 patients, median age at initial ADMS13:AC was 56.5 years (29-85). Most patients (n=14) had ADMS13:AC of 10-20%. ADMS13:AC was < 5% and 5-10% in 3 patients each. Eleven patients had a positive inhibitor with a median Bethesda titer of 1.85 BU (0.5-3.9). Etiology of liver included: ischemic hepatopathy (n=8), liver graft failure (n=4), liver metastasis (n=3), cirrhosis (n=2), alcoholic hepatitis (n=1), unknown (n=2). Median hemoglobin and platelet (plt) count at time of ADMS13 was 7 g/dL (6.4-13.2) and 30 x10 9/L (3-98), respectively. 7/20 patients had a PLASMIC score of ≥5; PLASMIC score was ≥5, in 2/6 patients with ADMS13:AC <10%. 16/18 patients had an ISTH DIC score ≥5. 18/20 patients had a creatinine > 2 mg/dL or were receiving renal replacement therapy the time of ADMS13: AC. 7/20 patients had total or direct bilirubin of >30mg/dL. Eight/20 patients were treated with plasma exchange (PEX) for a median duration of 7 days (2-13). 66.7% of pts with ADMS13:AC <10% received PEX. Glucocorticoids and Rituximab were used with the intent to treat TTP in 7 and 3 patients, respectively. Caplacizumab was used in 2 patients. 3/8 (37.5%) patients receiving PEX demonstrated normalization of MAHA. One of these patients demonstrated improvement but not normalization of plts (Table 1B, case 5). All patients had recurrence of hematologic abnormalities after PEX was stopped. One patient was treated with plasma infusion with stabilization in plt count. There were 13 and 15 deaths within 1 and 6 months of first ADMTS13:AC, respectively. One death was potentially attributable to management of TTP (Table 1B, case 1). There was no difference in time to death or mortality with the use of PEX. Repeat ADMS13:AC remote from PEX, TCP and MAHA was available for 1/5 surviving patients. This patient (Table1, case 2) had normalization of ADMS:AC after undergoing liver transplant. Conclusion: The differential diagnosis of TCP and MAHA in patients with liver injury includes hepatic dysfunction, DIC and TMA. In the current cohort, 89% of evaluable patients met criteria for overt DIC per ISTH criteria. Due to a low ADMTS13:AC, 40% of patients underwent a trial of PEX with 37.5% demonstrating improvement in MAHA that was not sustained upon discontinuation of PEX due to persistent liver dysfunction. Six-month mortality was 75% and use of PEX did not affect mortality. Given the high mortality, further studies evaluating which patients with TMA and liver injury are more likely to benefit from therapies typically used to treat TTP are necessary.

Challenges and Management of Thrombotic Thrombocytopenic Purpura During Pregnancy: A Case Report

Challenges and Management of Thrombotic Thrombocytopenic Purpura During Pregnancy: A Case Report

A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies.

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services.

A safe and effective use of caplacizumab in pregnancy-related acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is not uncommonly seen in pregnancy, either with the first episode or with the exacerbation of known disease. The management of TTP in pregnancy can be challenging if there is refractoriness to the use of therapeutic plasma exchange (TPE) and high-dose corticosteroids. Caplacizumab, a vWF-directed humanized antibody fragment, is approved for the treatment of acquired TTP but there is sparse data on its use in pregnant patients. Antenatal and peripartum haemorrhage is a theoretical concern with the use of the medication in the obstetric population. However, as options for treatment of TTP in the patients who have refractory disease are significantly limited, off-label use of caplacizumab to achieve disease control and prevent maternofetal morbidity and mortality is a reasonable consideration. This article described the successful use of caplacizumab in a pregnant patient with acquired TTP and the associated favourable outcome. The patient suffered an exacerbation following initial TPE and became refractory to both plasma exchange and high-dose corticosteroids. Off-label use of caplacizumab resulted in hematologic recovery and successful delivery of a healthy neonate. This case represents a contribution to the sparse literature on the use of this effective medication in an often-challenging clinical situation.

Systemic sclerosis sine scleroderma presenting as renal crisis, a case report and review of the literature

Systemic sclerosis sine scleroderma is a rare subset of systemic sclerosis with isolated organ involvement. Scleroderma renal crisis is a severe manifestation of systemic sclerosis characterized by malignant hypertension, oligo/anuric renal failure, and thrombotic microangiopathy. We present a case of a 55-year-old male with uncontrolled hypertension who presented with hematospermia and was found to have acute renal failure, microangiopathic hemolytic anemia, concerning thrombotic microangiopathy. Empiric management for thrombotic thrombocytopenic purpura (TTP) with plasma exchange and corticosteroids yielded a paradoxical response, ultimately leading to the diagnosis of systemic sclerosis sine scleroderma presenting as scleroderma renal crisis (SRC) after serological confirmation. Given the morbidity and mortality associated with scleroderma renal crisis, it should be increasingly considered as a differential for thrombotic microangiopathy even without outward manifestations of systemic sclerosis. Additionally, the empiric management of TTP can include the use of corticosteroids which can exacerbate SRC, an early clinical clue in the diagnosis of this disease.

Therapeutic modalities in thrombotic thrombocytopenic purpura management among Jehovah’s Witness patients: A review of reported cases

IntroductionDevout members of the Jehovah’s Witness faith flatly refuse transfusions of white blood cells, red blood cells, platelets, and plasma. The latter agent is a mainstay in the treatment of thrombotic thrombocytopenic purpura (TTP). Alternative treatment options for Jehovah’s Witness patients are needed and reviewed herein. MethodsCases of TTP treatment among Jehovah’s Witnesses were obtained from the published literature. Key baseline and clinical data were extracted and summarized. ResultsA total of 13 reports spanning a 23-year period and 15 TTP episodes were identified. Median (IQR) age was 45.5 (29.0–57.5) and 12/13 (93%) patients were female. Neurologic symptoms were present in 7/15 (47%) episodes at presentation. Disease confirmation with ADAMTS13 testing was present in 11/15 (73%) of episodes. Corticosteroids and rituximab were employed in 13/15 (87%) and 12/15 (80%) of cases, respectively, with apheresis-based therapy employed in 9/15 (60%) episodes. For eligible cases, caplacizumab was used in 4/5 (80%) episodes; average time to platelet response was shortest in these cases. Sources of exogenous ADAMTS13 accepted by patients in this series included cryo-poor plasma, FVIII concentrate, and cryoprecipitate. Conclusions: Successful management of TTP within the boundaries of the Jehovah’s Witness faith is possible.

Frontiers in pathophysiology and management of thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease in which platelet-rich microthrombi cause end-organ ischemia and damage. TTP is caused by markedly reduced ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Hereditary or congenital TTP (cTTP) is caused by ADAMTS13 gene mutations. In acquired or immune TTP (iTTP), ADAMTS13 activity is reduced by anti-ADAMTS13 autoantibodies. TTP is characterized by thrombocytopenia, hemolytic anemia, fever, renal dysfunction, and neuropsychiatric symptoms. Therapeutic plasma exchange (TPE) and immunosuppressive therapy are the mainstays of treatment. As untreated TTP has a high mortality rate, immediate initiation of TPE is recommended when TTP is suspected. Conventionally, corticosteroids have been used for immunosuppressive therapy. Current drug therapies include rituximab, an anti-CD20 antibody that is effective in newly diagnosed cases and refractory cases, as well as for relapse prevention, and caplacizumab, an anti- von Willebrand factor (VWF) nanobody that inhibits the binding of platelets to VWF and prevents microthrombi formation. Recombinant human ADAMTS13 is a promising treatment for cTTP. Although these therapeutic advances have improved the outcomes of TTP, early diagnosis and prompt initiation of appropriate therapy are necessary to achieve these outcomes.

A Real-World Analysis of Acquired Thrombotic Thrombocytopenic Purpura: Comparing Clinical Outcomes of Early Versus Late Responders to Plasma Exchange

INTRODUCTION: Acquired thrombotic thrombocytopenic purpura (TTP) is a rapidly fatal thrombotic microangiopathy mediated by autoantibodies targeting ADAMTS-13. The main pillars of acquired TTP management include therapeutic plasma exchange (PLEX) and immunosuppression with glucocorticoids and rituximab. PLEX is initiated in all patients with a presumptive clinical/confirmed diagnosis of TTP and is continued until platelet count recovery. The platelet response to PLEX is quite variable, with some patients having rapid recovery (early responders [ERs]) within 4-7 days, and others requiring a longer duration (late responders [LRs]) of PLEX. Although rapid platelet count recovery is reassuring to the treating physician, it is unclear whether there is a significant difference in outcomes between ERs and LRs to PLEX. We performed a single-center retrospective study of survival outcomes of ERs vs those of LRs with acquired TTP. METHODS: We performed a retrospective analysis of adult patients (≥18 years old) with acquired TTP who were treated at our institution between January 1, 2005, and May 1, 2020. Baseline demographic and clinical data and laboratory values at the time of diagnosis were collected. Patients were ERs if platelet recovery (platelet count >150,000/µL for 2 consecutive days) occurred within 7 days of starting PLEX, whereas LRs had delayed platelet recovery (≥7 days) after initiation of PLEX. Refractory disease was defined as recurrent thrombocytopenia (platelet count <150,000/µL) following an initial response between days 1 and 30 after last PLEX. Relapses were defined as thrombocytopenia and elevated LDH occurring >30 days after last PLEX. We analyzed survival outcomes and the relapse risk in ERs versus LRs. RESULTS: A total of 61 patients fulfilled the diagnostic criteria for acquired TTP (ER = 34 patients, LR = 27 patients). Patient demographics, laboratory studies, and treatment details are shown in Table 1. The mean age of ER and LR patients was 45 and 38 years, respectively. About 56% of patients in each group identified as Black. About 18% of ERs and 9% of LRs had a diagnosis of HIV. No statistically significant difference was noted in the baseline laboratory findings of the two groups. Involvement of ≥2 affected organ systems was seen in 79% of ERs and 93% of LRs (p=0.2757). All LRs (100%) and 88% of ERs had severe TTP at presentation (ADAMTS-13 level ≤10). The mean number of PLEX was 6.11 and 24.96 in ERs and LRs (p<0.0001), respectively. The mean number of PLEX to platelet recovery was 4.27 and 19.27 (p<0.0001). Glucocorticoids were given to 97% of ERs and 100% of LRs. First-line rituximab was given to 52% (n=14) of LRs, versus only 9% (n=3) of ERs (p=0.0004). About 15% of LRs went on to receive additional immunosuppressive agents, whereas no ERs did so (p=0.0336). The relapse rate among ERs and LRs was 55.56% and 44.44%, respectively (p > 0.9999). The 30-day mortality rate was 6% in ERs and 0% in LRs. Cardiovascular diseases were the common cause of early deaths. Overall survival (OS) at 6 months was 79% in ERs and 96% in LRs (p=0.0665). The OS at 1 year was 74% in ERs and 96% in LRs (p=0.03). The 2-year OS was available for 24 ER patients (83%) and LR 17 patients (89%) (p>0.9999). Among the 19 patients who received front-line rituximab, the OS at 1 year was 100%. CONCLUSIONS: More LRs than ERs received rituximab and glucocorticoids for immunosuppression as first-line therapy. LRs were found to have a statistically significant greater OS at 1 year. ERs were less likely to receive adequate immunosuppression than LRs. This may indicate that the time to response to PLEX should not be used as a surrogate for risk of relapse. Immunosuppression is the cornerstone of the management of acquired TTP, and first-line use of rituximab is critical in the reducing relapse rate and improving OS. Larger studies in the prospective setting are needed to evaluate the impact of duration of PLEX on OS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) - AN UPDATED REVIEW

Thrombotic thrombocytopenic purpura is a microangiopathic hemolytic amenia characterized by fever, neurological dysfunction, renal dysfunction, thrombocytopenia, hemolytic anemia. TTP can be inherited or acquired, caused due to ADAMTS13 enzyme malfunctioning. As the condition is medical emergency timely treatment is essential and vital plasma exchange and chemotherapy are used to control the activities of the enzymes. The present article describes the causes, risk factors, diagnosis and standard treatment for the management of TTP.

Molecular Diagnosis Is Vital to the Accurate Classification and Management of Thrombotic Thrombocytopenic Purpura in Children.

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening hematologic disease, presenting a myriad of diagnostic and management challenges in children. Here, we provide a review of this disorder and discuss 2 exemplary cases of TTP occurring in adolescents, emphasizing the need for consideration of late-onset congenital TTP (cTTP). We demonstrate the importance of early confirmation of ADAMTS13 enzyme deficiency and the presence or absence of ADAMTS13 inhibitor in order to rapidly initiate the appropriate life-saving therapies. Ultimately, molecular testing is paramount to distinguishing between congenital and acquired immune-mediated TTP.

Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population

ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere. 150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies. Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups. TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.

Rituximab related non-infectious lung injury complicating treatment of severe TTP in pregnancy – literature review and case-report

Background: Thrombotic thrombocytopenic purpura (TTP) in pregnancy is a rare but potentially life-threatening condition. Management of severe, refractory TTP during pregnancy is challenging and includes multidisciplinary approach. The prognosis of cases with a variety of hematological and autoimmune diseases, including TTP has changed profoundly after the rituximab therapy was introduced into clinical practice. However, adverse pregnancy outcomes associated with biological agents should be kept in mind and the decision to treat should be weighed by measurement of potential risks vs benefits. Case report: We reported the first documented case of noninfectious lung toxicity in pregnancy related to rituximab use for TTP treatment. 26 y/o patient at 23 weeks gestation initially presented to ED secondary to numbness, headache, and slurred speech with negative brain imaging. Her laboratory findings revealed severe deficiency of platelets, hemoglobin and ADAMT13 activity. She underwent multiple therapeutic interventions including plasmapheresis, intravenous immunoglobulins (IVIG), prednisone, and eventually required more often hospitalizations. Ultimately, the decision was made to proceed with rituximab therapy. After the third infusion of rituximab, she developed non-infectious lung injury without evidence of SARS-CoV-2 or other infections, pulmonary edema, or pulmonary embolism. The maternal condition worsened acutely resulting in significant desaturation that required intubation and eventual emergent premature delivery at 31-weeks’ gestation via C-section. Conclusion: Rituximab therapy for TTP management in pregnancy may be associated with significant adverse maternal-fetal outcomes. Risks and benefits of treatment should be discussed with each patient and during multidisciplinary communications. Physicians should maintain high index of suspicion for non-infectious lung injury associated with rituximab treatment in order to be able to diagnose this complication early and start treatment to avoid severe mortality and morbidity.

Interpretation of Chinese guideline on the diagnosis and management of thrombotic thrombocytopenic purpura (2022)

Interpretation of Chinese guideline on the diagnosis and management of thrombotic thrombocytopenic purpura (2022)

Chinese guideline on the diagnosis and management of thrombotic thrombocytopenic purpura (2022)

Chinese guideline on the diagnosis and management of thrombotic thrombocytopenic purpura (2022)

Evaluation and Management of Thrombotic Thrombocytopenic Purpura in the Emergency Department.

Thrombotic thrombocytopenic purpura (TTP) is a dangerous condition that can be misdiagnosed in the emergency department. The purpose of this narrative review article is to provide a summary of the background, pathophysiology, diagnosis, and management of TTP, with a focus on emergency clinicians. TTP is a disorder with microangiopathic hemolytic anemia, severe thrombocytopenia, and multiorgan ischemic injury. It may be acquired or hereditary, and is caused by a reduced amount or function of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), which is an enzyme involved in cleaving von Willebrand factor. The classic presentation of TTP includes fever, neurologic abnormalities, thrombocytopenia with purpura, microangiopathic hemolytic anemia, and acute renal injury. However, < 7% of cases have all of these findings present. Testing should include a complete blood count, complete metabolic panel, blood smear, coagulation panel, fibrinogen, D-dimer, lactate dehydrogenase, ADAMTS13 level, troponin, human immunodeficiency virus assessment, urinalysis, pregnancy test as appropriate, and electrocardiogram. Management includes hematology consultation if available, plasma exchange and corticosteroids, and treatment of end-organ complications. All patients require admission for treatment and close monitoring. TTP is a potentially dangerous medical condition requiring rapid diagnosis and management. It is essential for emergency clinicians to know how to diagnose and treat this disorder.