Essentials
An international collaboration provides a consensus for clinical definitions.
This concerns thrombotic microangiopathies and thrombotic thrombocytopenic purpura (TTP).
The consensus ...defines diagnosis, disease monitoring and response to treatment.
Requirements for ADAMTS‐13 are given.
Summary
Background
Thrombotic thrombocytopenic purpura (TTP) and hemolytic–uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic microangiopathy (TMA) is a broad pathophysiologic process that leads to microangiopathic hemolytic anemia and thrombocytopenia, and involves capillary and small‐vessel platelet aggregates. The most common cause is disseminated intravascular coagulation, which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia, including cancer, infection, transplantation, drug use, autoimmune disease, and pre‐eclampsia and hemolysis, elevated liver enzymes and low platelet count syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiologies and treatment pathways.
Objectives
To present a consensus document from an International Working Group on TTP and associated thrombotic microangiopathies (TMAs).
Methods
The International Working Group has proposed definitions and terminology based on published information and consensus‐based recommendations.
Conclusion
The consensus aims to aid clinical decisions, but also future studies and trials, utilizing standardized definitions. It presents a classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune‐mediated TTP.
Abstract Background About 5% of civilian trauma requires massive transfusion. Protocolized resuscitation with blood products to achieve high plasma:RBC ratio has been advocated to improve survival. ...Our objectives were to measure compliance to our institutional MTP, to identify quality assurance activities that could improve protocol compliance and to determine if protocol compliance was related to patient outcome. Methods The investigators determined 13 compliance criteria based upon our institutional protocol. We measured compliance in 72 consecutive MTP activations between January 2010 and September 2011 at a Level I trauma centre. Data elements were retrospectively retrieved from blood bank, trauma registry and clinical records. Patients were stratified into three groups based on compliance level, and mortality differences were compared. Results Average compliance for the cohort ( n = 72) was 66%. The most common cause of non-compliance was failure to send a complete haemorrhage panel from the trauma bay (96%). Failure to monitoring blood work every 30 min occurred in 89% of cases. Delay in activation and deactivation occurred in 50% and 50% respectively. Non-compliance to protocol-based administration of blood products happened in 47%. The cohort was stratified into three groups based on compliance, A: <60%, B: 60–80% and C: >80% (low, moderate and high compliance groups). There was no statistical significance with regard to median age, median ISS, ED SBP, ED GCS and AIS of the head/spine, chest and abdomen. The mortality rates in each group were 62%, 50% and 10% in the low, moderate and high compliance groups respectively. Mortality differences were compared using adjusted logistic regression. The OR for mortality between Groups A and B = 1.1 95% CI 0.258–4.687 ( P = 0.899) while the OR for mortality between Groups C and B = 0.02 95% CI <0.001–0.855 ( P = 0.041). Conclusions Measures should be directed towards provider and system factors to improve compliance. In this study, there was an association between survival and higher level of compliance.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are ...prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.
Background: Massive transfusion protocols (MTP) are widely used to rapidly deliver blood products to bleeding trauma patients. Every minute delay in blood product administration in bleeding trauma ...patients is associated with a 5% increased odds of death. In-situ simulation (ISS) is simulation that takes place in the actual clinical work environment. We used ISS as a novel, prospective and iterative quality improvement (QI) approach to identify and improve MTP steps that impact time to blood delivery (TTBD) during actual trauma resuscitations. Aim Statement: To reduce the TTBD for bleeding trauma patients by 20% over a 12-month ISS-based QI initiative. Measures & Design: We conducted twelve high-fidelity, interprofessional ISS sessions at a Level-1 trauma center in Toronto, Canada. We used clinician video review as well as extensive stakeholder involvement, including with nurses, porters, blood bank and human factors experts, to develop Plan-Do-Study-Act (PDSA) cycles for MTP improvement. Our three major PDSA cycles revolved around: 1) decreasing MTP activation time; 2) reducing the unpredictable and inefficient transport times for the blood itself; and 3) improving the notification of blood product arrival in the trauma bay. Each PDSA cycle was iteratively tested with ISS prior to implementation into clinical care. Outcome measure was the mean TTBD for trauma patients requiring MTP (in minutes, standard deviation SD). Process measures included time to MTP activation and porter transport times. Balancing measures included stakeholder satisfaction. Evaluation/Results: Our baseline TTBD for MTP patients was 11.58min (n = 41, SD 6.8). There were 54 trauma patients that had MTP during the ISS-based QI initiative, and their mean TTBD was 10.44min (SD 6.1). The TTBD after the QI initiative was 9.12min, sustained over 1 year (n = 50, SD 5.3; 21.2% relative reduction, p < 0.05). A run chart did not show special cause variation chronologically related to our interventions. Patients in each group were similar in demographic data, trauma characteristics and injury severity score. Discussion/Impact: We achieved a 21.2% reduction in TTBD for trauma patients requiring MTP with an ISS-based QI initiative. ISS represents a novel approach to the identification and iterative testing of process improvements within trauma care. This methodology can and should be included in QI projects in order to safely test and improve processes of care before they impact real patients.
Among patients with thrombotic thrombocytopenic purpura, the addition of caplacizumab, an anti–von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, to daily plasma ...exchange resulted in faster platelet recovery, fewer TTP-related deaths, and fewer recurrences and thromboembolic events.
Background:
Massive hemorrhage protocols (MHPs) streamline the complex logistics required for prompt care of the bleeding patient, but their uptake has been variable and few regions have a system to ...measure outcomes from these events.
Aim Statement:
We aim to implement a standardized MHP with uniform quality improvement (QI) metrics to increase uptake of evidence-based MHPs across 150-hospitals in Ontario between 2017 and 2021.
Measures & Design:
We performed ongoing PDSA cycles; 1) stakeholder analysis by surveying the Ontario Regional Blood Coordinating Network (ORBCoN), 2) problem characterization and Ishikawa analysis for key QI metrics based on areas of MHP variability in 150 Ontario hospitals using a web-based survey, 3) creation of a consensus MHP via a modified Delphi process, 4) problem characterization at ORBCoN for the design of a freely available toolkit for provincial implementation by expert working groups, 5) design of 8 key QI metrics by a modified Delphi process, and 6) identification of process measures for QI data collection by implementation metrics.
Evaluation/Results:
PDSA1-2; 150-hospitals were surveyed. 33% of hospitals lacked MHPs, mostly in smaller sites. Major areas for QI were related to activation criteria, hemostatic agents, protocolized hypothermia management, variable MHP naming, QI metrics and serial blood work requirements. PDSA3; 3 Delphi rounds were held to reach 100% expert consensus for 42 statements and 8 CQI metrics. Major areas for modification were protocol name, laboratory resuscitation targets, cooler configurations, and role of factor VIIa. PDSA4; adaptable toolkit is under development by the steering committee and expert working groups. Implementation is scheduled for Spring 2020. PDSA5; the 8 CQI metrics are: TXA administration < 1 h, RBC transfusion < 15 min, call to transfer for definitive care < 60 min, temp >35°C at end of protocol, Hgb kept between 60-110g/L, transition to group-specific RBC by 90 min, appropriate activation defined by ≥6 units RBC in the first 24 hours, and any blood component wastage.
Discussion/Impact:
MHP uptake, content, and tracking is variable. A standardized MHP that is adaptable to diverse settings decreases complexity, improves use of evidence-based practices, and provides a platform for continuous QI. PDSA6 will occur after implementation; we will complete an implementation survey, and design a pilot and feasibility study for prospective tracking of patient outcomes using existing prospectively collected inter-hospital and provincial databases.
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