Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments.

Computer vision quantitation of erythrocyte shape abnormalities provides diagnostic, prognostic, and mechanistic insight.

Examination of red blood cell (RBC) morphology in peripheral blood smears can help diagnose hematologic diseases, even in resource-limited settings, but this analysis remains subjective and semiquantitative with low throughput. Prior attempts to develop automated tools have been hampered by their poor reproducibility and limited clinical validation. Here, we present a novel, open-source machine-learning approach (denoted as RBC-diff) to quantify abnormal RBCs in peripheral smear images and generate an RBC morphology differential.

Pathway-driven rare germline variants associated with transplant-associated thrombotic microangiopathy (TA-TMA).

The significance of rare germline mutations in transplant-associated thrombotic microangiopathy (TA-TMA) is not well studied. We performed a genetic association study in 100 adult TA-TMA patients vs. 98 post-transplant controls after matching by race, sex, and year.

Emergency transfusion with whole blood versus packed red blood cells: A study of 1400 patients.

Background: Low-titer group O whole blood (LTOWB) is increasingly used for emergency transfusion. We studied whether initial release of LTOWB compared with packed red blood cells (pRBCs) reduced overall blood requirements for patients needing emergency transfusion. Secondary outcomes examined included survival and non-lethal adverse clinical outcomes.

Retrospective analysis of outcomes in patients with acute hypertriglyceridemic pancreatitis treated without therapeutic plasma exchange.

Background: Therapeutic plasma exchange (TPE) is often used to decrease serum triglyceride levels in hypertriglyceridemic pancreatitis (HTGP), although there is a lack of high-quality data directly attributing improved clinical outcomes to TPE. There are currently no large studies evaluating the treatment of HTGP without TPE.

Study Design And Methods: This study retrospectively analyzes clinical and laboratory outcomes of 115 encounters at Massachusetts General Hospital (MGH) wherein a HTGP patient was treated without TPE and compares these outcomes to those of HTGP patients in the literature treated with TPE.

Management of hemostatic complications in acute leukemia: Guidance from the SSC of the ISTH.

Patients with acute leukemia frequently develop thrombocytopenia and hemostatic complications caused by coagulopathy. Coagulopathy complicates the management of these patients and can lead to significant morbidity and mortality. This guidance document aims to review and provide guidance on the management of hemostatic complications in adult patients with acute leukemia, addressing four main issues, including platelet transfusion, disseminated intravascular coagulation, L-asparaginase-related hypofibrinogenemia, and the use of antifibrinolytic agents.

Non-Alloimmune Mechanisms of Thrombocytopenia and Refractoriness to Platelet Transfusion.

Refractoriness to platelet transfusion is a common clinical problem encountered by the transfusion medicine specialist. It is well recognized that most causes of refractoriness to platelet transfusion are not a consequence of alloimmunization to human leukocyte, platelet-specific, or ABO antigens, but are a consequence of platelet sequestration and consumption. This review summarizes the clinical factors that result in platelet refractoriness and highlights recent data describing novel biological mechanisms that contribute to this clinical problem.

Deaths and complications associated with the management of acute immune thrombotic thrombocytopenic purpura.

Background: The introduction of therapeutic plasma exchange (TPE) dramatically decreased mortality in patients with immune thrombotic thrombocytopenic purpura (iTTP). However, there are few modern descriptions of residual causes of death from iTTP and complications associated with TPE.

Study Design And Methods: This was a retrospective study in a multi-institutional cohort of 109 patients with iTTP between 2004 and 2017.

Severe CD4+ T-cell lymphopenia is not observed in frequent plateletpheresis donors collected on the Fenwal Amicus.

Background: In a recent study, we determined that 30% of frequent plateletpheresis donors collected using the Trima Accel Automated Blood Collection System (Terumo BCT) had a CD4+ T-cell count below 200 cells/μL. Whether CD4+ T-cell lymphopenia is associated with donation using other plateletpheresis instruments is unknown.

Study Design And Methods: We obtained blood samples from 30 current frequent Fenwal Amicus plateletpheresis donors.

Utilizing a PLASMIC score-based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative.

The PLASMIC score is a recently described clinical scoring algorithm that rapidly assesses the probability of severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency among patients presenting with microangiopathic haemolytic anaemia. Using a large multi-institutional cohort, we explored whether an approach utilizing the PLASMIC score to risk-stratify patients with suspected immune thrombotic thrombocytopenic purpura (iTTP) could lead to significant cost savings. Our consortium consists of institutions with an unrestricted approach to ADAMTS13 testing (Group A) and those that require pre-approval by the transfusion medicine service (Group B).

Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura.

Patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) often experience life-threatening relapses of the disease, and rituximab (RTX) can be used to mitigate relapse risk. However, the predictors of relapse in iTTP and the magnitude and duration of effect of RTX remain key unanswered questions. Using a multi-institutional cohort of consecutive adult patients with iTTP, we used survival analysis to compare relapse rates between patients who received RTX during the index presentation with acute iTTP and those who did not.

Routine Solid Phase Multiplex Anti-HLA Antibody Tests Predict Platelet Refractoriness.

Objectives: No validated screening methods identify patients at risk for human leukocyte antigen (HLA) alloimmune-mediated platelet refractoriness (alloPR). We determined if bead-based HLA antibody tests could predict risk of developing HLA alloPR.

Methods: Hematopoietic progenitor cell transplant patients screened for HLA antibodies without prior refractoriness were identified.

Red blood cell alloantibodies are associated with increased alloimmunization against human leukocyte antigens.

Background: Alloantibodies recognizing human leukocyte antigens (HLA) can cause immune-mediated refractoriness to platelet transfusion. An association between HLA alloimmunization and red blood cell (RBC) alloimmunization has been suggested but remains uncertain.

Study Design And Methods: We tested for HLA alloantibodies in 660 patients with and without RBC alloantibodies.

Clinical features and outcomes in patients with thrombotic microangiopathy not associated with severe ADAMTS13 deficiency.

Background: The a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity assay has become important in distinguishing autoimmune thrombotic thrombocytopenic purpura from other forms of thrombotic microangiopathy (TMA). Although the significance of severe deficiency in ADAMTS13 (activity levels 10% or less) has been well defined, little data are available on the clinical importance of mild to moderate deficiency (activity levels 11%-70%) among patients with TMA.

Study Design And Methods: We conducted a retrospective study using the Harvard TMA Research Collaborative Registry.

Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study.

Background: Among the syndromes characterised by thrombotic microangiopathy, thrombotic thrombocytopenic purpura is distinguished by a severe deficiency in the ADAMTS13 enzyme. Patients with this disorder need urgent treatment with plasma exchange. Because ADAMTS13 activity testing typically requires prolonged turnaround times and might be unavailable in resource-poor settings, a method to rapidly assess the likelihood of severe ADAMTS13 deficiency is needed.

Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score-matched study.

Background: Therapeutic plasma exchange (TPE) is a proven treatment for thrombotic thrombocytopenic purpura (TTP) characterized by severe ADAMTS13 deficiency, but the efficacy of TPE in suspected TTP with an ADAMTS13 activity level of more than 10% remains controversial.

Study Design And Methods: We conducted a propensity score (PS)-matched study of 186 adult patients included in the Harvard Thrombotic Microangiopathy (TMA) Research Collaborative registry who presented with TMA suggestive of TTP but an ADAMTS13 activity level of more than 10%.

Results: Before matching, patients treated with TPE (n = 71) differed from untreated patients (n = 115) by several clinical measures.

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.

The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation.

Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency.

Background: Collection of hematopoietic progenitor cells by apheresis (HPC-A) requires separation of cells by density. Previous studies highlighted the challenges of HPC-A collection from patients with abnormal red blood cells (RBCs). TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting.

Reduced Albumin Dosing During Large-Volume Paracentesis Is Not Associated with Adverse Clinical Outcomes.

Background: LVP is used to manage diuretic-resistant ascites in cirrhotic patients. Albumin administration prevents complications including acute kidney injury and paracentesis-induced circulatory dysfunction, but the optimal dose is unclear.

Aim: We sought to assess adherence to guidelines enacted in July 2011 at our center for reducing the albumin dose administered at large-volume paracentesis (LVP) and evaluate the cost and rate of complications of LVPs before and after guideline enactment.