Explore the vast range of titles available.

Introduction Patients with severe sepsis often present with concurrent coagulopathy, microcirculatory failure and evidence of vascular endothelial activation and damage. Given the critical role of the endothelium in balancing hemostasis, we investigated single-point associations between whole blood coagulopathy by thrombelastography (TEG) and plasma/serum markers of endothelial activation and damage in patients with severe sepsis. Methods A post-hoc multicenter prospective observational study in a subgroup of 184 patients from the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial. Study patients were admitted to two Danish intensive care units. Inclusion criteria were severe sepsis, pre-intervention whole blood TEG measurement and a plasma/serum research sample available from baseline (pre-intervention) for analysis of endothelial-derived biomarkers. Endothelial-derived biomarkers were measured in plasma/serum by enzyme-linked immunosorbent assay (syndecan-1, thrombomodulin, protein C (PC), tissue-type plasminogen activator and plasminogen activator inhibitor-1). Pre-intervention TEG, functional fibrinogen (FF) and laboratory and clinical data, including mortality, were retrieved from the trial database. Results Most patients presented with septic shock (86%) and pulmonary (60%) or abdominal (30%) focus of infection. The median (IQR) age was 67 years (59 to 75), and 55% were males. The median SOFA and SAPS II scores were 8 (6 to 10) and 56 (41 to 68), respectively, with 7-, 28- and 90-day mortality rates being 21%, 39% and 53%, respectively. Pre-intervention (before treatment with different fluids), TEG reaction (R)-time, angle and maximum amplitude (MA) and FF MA all correlated with syndecan-1, thrombomodulin and PC levels. By multivariate linear regression analyses, higher syndecan-1 and lower PC were independently associated with TEG and FF hypocoagulability at the same time-point: 100 ng/ml higher syndecan-1 predicted 0.64 minutes higher R-time (SE 0.25), 1.78 mm lower TEG MA (SE 0.87) and 0.84 mm lower FF MA (SE 0.42; all P <0.05), and 10% lower protein C predicted 1.24 mm lower TEG MA (SE 0.31). Conclusions In our cohort of patients with severe sepsis, higher circulating levels of biomarkers of mainly endothelial damage were independently associated with hypocoagulability assessed by TEG and FF. Endothelial damage is intimately linked to coagulopathy in severe sepsis. Trial registration Clinicaltrials.gov number: NCT00962156 . Registered 13 July 2009.

\"Over the last decades, major progress has been made in quality assurance of hemostatic laboratory assays. This book will be an indispensable part of every hemostasis laboratory, where, given its hands-on nature, it will rarely sit to get dusty on the shelves.\" -Frits R. Rosendaal, Leiden University Medical Center The hemostasis laboratory has a vital role in the diagnosis and management of patients with familial and acquired hemorrhagic and thrombotic disorders. Its role in the monitoring traditional anticoagulant therapy as well as therapy using new anticoagulants presents new challenges to the laboratory. Quality in Laboratory Hemostasis and Thrombosis not only addresses these important issues, but also covers international guidelines for testing, the development of international standard materials, management of hemostasis testing from the laboratory to the point of care as well as molecular genetic testing. Designed as a guide for all those working in hemostasis laboratories, this book details a quality program that, when put into place, will help to improve standards in testing. All of the authors are internationally recognised for their work in hemostasis and thrombosis. Using their experience, they provide information on standards, equipment and methods that will guide the development of a quality program to support all activities in the hemostasis laboratory.

Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially minimal abnormalities in prothrombin time and platelet count. Venous thromboembolism and arterial thrombosis are more frequent in CAC compared to SIC/DIC. Clinical and laboratory features of CAC overlap somewhat with a hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. We summarize the key characteristics of representative coagulopathies, discussing similarities and differences so as to define the unique character of CAC.

Thromboelastography (TEG) has been recommended to characterize post-traumatic coagulopathy, yet no study has evaluated the impact of pre-injury anticoagulation (AC) on TEG variables. We hypothesized patients on pre-injury AC have a greater incidence of coagulopathy on TEG compared to those without AC. This retrospective chart review evaluated all trauma patients admitted to an urban, level one trauma center from February 2011 to September 2014 who received a TEG within the first 24h. Patients were classified as receiving pre-injury AC or no AC if their documented medications prior to admission included warfarin, dabigatran, or anti-Xa (aXa) inhibitors (apixaban or rivaroxaban). The presence of coagulopathy on TEG or conventional assays was defined by exceeding local laboratory reference standards. A total of 54 patients were included (AC, n=27 [warfarin n=13, dabigatran n=6, aXa inhibitor n=8] vs. no AC, n=27). Baseline characteristics were similar between groups, including age (72±13years vs. 72±15; p=0.85), male gender (70% vs. 74%; p=0.76) and blunt mechanism of injury (100% vs. 100%; p=1). There was no difference in the number of patients determined to have coagulopathy on TEG (no AC 11% vs. AC 15%; p=0.99). Conventional tests, including the international normalized ratio (INR) and activated partial thromboplastin time (aPTT), identified coagulopathy in a high proportion of anti-coagulated patients (no AC 22% vs. AC 85%; p<0.01). TEG has limited clinical utility to evaluate the presence of pre-injury AC. Traditional markers of drug induced coagulopathy should guide reversal decisions.

The current diagnostic pathway for patients with a suspected inherited bleeding disorder is long, costly, resource intensive, emotionally draining for patients and often futile, as half of patients will remain without a diagnosis and be labelled 'bleeding disorder of unknown cause'. Advances in understanding the genetic basis of the inherited bleeding disorders, coupled with both increasing infrastructure for genetic/genomic testing and decreasing costs, have increased the feasibility of introducing genomic testing into the clinical diagnostic pathway as a potential solution to improve the care of these patients. Yet, there remain evidence gaps on the optimal integration of genomic analysis into the diagnostic pathway. Using a multicentre randomised-controlled trial design, we will evaluate an early genomic testing strategy for the diagnosis of newly referred patients with a suspected inherited bleeding disorder. Eligible participants will be randomised to early genomic testing diagnostic pathway (intervention) or standard diagnostic pathway (control) and will be followed for a 12-month period. Patients in the control group who remain undiagnosed at study end will be offered identical early genomic testing to ensure equitable access to the intervention. The study will follow a parallel fixed design with waitlist control group and a 1:1 allocation ratio. The study will be conducted at three tertiary care centres in Ontario, Canada, with a target sample size of 212 participants. Clinical utility will be evaluated via the primary outcome of diagnostic yield, as well as the secondary outcome of time to diagnosis. Additional secondary outcomes will allow for assessment of patient impact via health-related quality of life and patient burden measures, as well as evaluation of economic impact through a cost-effectiveness analysis and budget impact analysis. This investigator-initiated study was approved by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board through Clinical Trials Ontario (CTO-4909). Participant informed consent/assent is required. Findings will be disseminated through academic publications. ClinicalTrials.gov, NCT06736158.

PurposeThe modified Trauma-Induced Coagulopathy Clinical Score (mTICCS) presents a new scoring system for the early detection of the need for a massive transfusion (MT). This easily applicable score was validated in a large trauma cohort and proven comparable to more established complex scoring systems. However, the inter-rater reliability of the mTICCS has not yet been investigated.MethodsTherefore, a dataset of 15 randomly selected and severely injured patients (ISS ≥ 16) derived from the database of a level I trauma centre (2010–2015) was used. Moreover, 15 severely injured subjects that received MT were chosen from the same databank. A web-based survey was sent to medical professionals working in the field of trauma care asking them to evaluate each patient using the mTICCS.ResultsIn total, 16 raters (9 residents and 7 specialists) completed the survey. Ratings from 15 medical professionals could be evaluated and led to an ICC of 0.7587 (95% Bootstrap confidence interval (BCI) 0.7149–0.8283). A comparison of working experience specific ICC (n = 7 specialists, ICC: 0.7558, BCI: 0.7076–0.8270; n = 8 residents, ICC: 0.7634, BCI: 0.7183–0.8335) showed no significant difference between the two groups (p = 0.67).ConclusionIn summary, reliability values need to be considered when making clinical decisions based on scoring systems. Due to its easy applicability and its almost perfect inter-rater reliability, even with non-specialists, the mTICCS might therefore be a useful tool to predict the early need for MT in multiple trauma.

Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk. The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known. We conducted a retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia and we evaluated coagulation function using rotational thromboelastometry (ROTEM) on day of admission (T0) and 5 (T5) and 10 (T10) days after admission to ICU. Coagulation standard parameters were also evaluated. Forty patients were enrolled into the study. The ICU and the hospital mortality were 10% and 12.5%, respectively. On ICU admission, prothrombin time was slightly reduced and it increased significantly at T10 (T0 = 65.1 ± 9.8 vs T10 = 85.7 ± 1.5, p = 0.002), while activated partial thromboplastin time and fibrinogen values were higher at T0 than T10 (32.2 ± 2.9 vs 27.2 ± 2.1, p = 0.017 and 895.1 ± 110 vs 332.5 ± 50, p = 0.002, respectively); moreover, whole blood thromboelastometry profiles were consistent with hypercoagulability characterized by an acceleration of the propagation phase of blood clot formation [i.e., CFT below the lower limit in INTEM 16/40 patients (40%) and EXTEM 20/40 patients (50%)] and significant higher clot strength [MCF above the upper limit in INTEM 20/40 patients (50%), in EXTEM 28/40 patients (70%) and in FIBTEM 29/40 patients (72.5%)]; however, this hypercoagulable state persists in the first five days, but it decreases ten day after, without returning to normal values. No sign of secondary hyperfibrinolysis or sepsis induced coagulopathy (SIC) were found during the study period. In six patients (15%) a deep vein thrombosis and in 2 patients (5%) a thromboembolic event, were found; 12 patients (30%) had a catheter-related thrombosis. ROTEM analysis confirms that patients with severe COVID-19 pneumonia had a hypercoagulation state that persisted over time.

Normal haemostasis depends on an intricate balance between mechanisms of bleeding and mechanisms of thrombosis, and this balance can be altered after traumatic brain injury (TBI). Impaired haemostasis could exacerbate the primary insult with risk of initiation or aggravation of bleeding; anticoagulant use at the time of injury can also contribute to bleeding risk after TBI. Many patients with TBI have abnormalities on conventional coagulation tests at admission to the emergency department, and the presence of coagulopathy is associated with increased morbidity and mortality. Further blood testing often reveals a range of changes affecting platelet numbers and function, procoagulant or anticoagulant factors, fibrinolysis, and interactions between the coagulation system and the vascular endothelium, brain tissue, inflammatory mechanisms, and blood flow dynamics. However, the degree to which these coagulation abnormalities affect TBI outcomes and whether they are modifiable risk factors are not known. Although the main challenge for management is to address the risk of hypocoagulopathy with prolonged bleeding and progression of haemorrhagic lesions, the risk of hypercoagulopathy with an increased prothrombotic tendency also warrants consideration.

In this article, common abnormalities of blood coagulation leading to thrombosis or bleeding in the intensive care unit are reviewed. The definition of coagulopathy is “a condition in which the blood's ability to clot is impaired.” However, for some clinicians, the term also covers thrombotic states, and because of the complexity of the hemostatic pathways, the two conditions can exist simultaneously. Some practitioners would consider that mildly abnormal results on coagulation screening without bleeding can also indicate a coagulopathy. This review is confined to the original definition of coagulopathy as given above. Such states are common in patients in the intensive care unit (ICU) and require a clinicopathological approach to ensure that the correct diagnosis is made and the appropriate . . .

This study investigates the association between the treatment with heparin and mortality in patients admitted with Covid-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with Covid-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1447 had been discharged home from the hospitals, 201 were still admitted, and 126 had been transferred to hospitals not included in the study. Median follow up time was 8 (IQR 5–12) days. Heparin had been used in 1734 patients. Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI) 0.55 (0.37–0.82) p = 0.003. This association remained significant when saturation of oxygen < 90%, and temperature > 37 °C were added to de model with OR 0.54 (0.36–0.82) p = 0.003, and also when all the other drugs were included as covariates OR 0.42 (0.26–0.66) p < 0.001. The association between heparin and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized controlled trials to assess the causal effects of heparin in different therapeutic regimes are required.