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Unfractionated heparin (UFH) was uncovered in 1916, has been used as an anticoagulant since 1935, and has been listed in the World Health Organization's Model List of Essential Medicines. Despite the availability of many other anticoagulants, the use of heparin (either low molecular weight heparin [LMWH] or UFH) is still substantial. Heparin has pleotropic effects including anticoagulant and several nonanticoagulant properties such as antiproliferative, anti-inflammatory activity, and anticomplement effects. Although UFH has been widely replaced by LMWH, UFH is still the preferred anticoagulant of choice for patients undergoing cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, and patients with high-risk mechanical cardiac valves requiring temporary bridging with a parenteral anticoagulant. UFH is a highly negatively charged molecule and binds many positively charged molecules, hence has unpredictable pharmacokinetics, and variable anticoagulant effect on an individual patient basis. Therefore, anticoagulant effects of UFH may not be proportional to the dose of UFH given to any individual patient. In this review, we discuss the anticoagulant and nonanticoagulant activities of UFH, differences between UFH and LMWH, when to use UFH, different methods of monitoring the anticoagulant effects of UFH (including activated partial thromboplastin time, heparin anti-Xa activity level, and activated clotting time), while discussing pros and cons related to each method and comparison of clinical outcomes in patients treated with UFH monitored with different methods based on available evidence. [ABSTRACT FROM AUTHOR]

This article compares heparin-induced thrombocytopenia with thrombosis (HITT) in COVID-19 patients to vaccine-induced immune thrombocytopenia and thrombosis (VITT) in the United Kingdom. HITT is caused by antibodies binding to heparin-platelet factor 4 (PF4), while VITT is associated with adenoviral vector-based COVID-19 vaccines. The incidence of HITT in COVID-19 patients was 0.43%, while the estimated incidence of VITT was approximately 7 to 10 cases per million persons receiving the ChAdOx1 CoV-19 vaccine. The two conditions have differences in the sites of thrombosis, pathogenic antibodies, and management. Mortality rates were similar between the two conditions. Further research is needed to understand the antigens and immune complexes involved in these conditions. [Extracted from the article]

The article in the British Journal of Haematology offers guidelines for healthcare professionals in the UK regarding the measurement of non-coumarin anticoagulants and their effects on laboratory assays. It includes a comprehensive table of licensed anticoagulants, their measurement methods, and potential laboratory tests. The document stresses the importance of monitoring direct oral anticoagulants (DOACs) in specific situations, such as renal impairment or suspected overdose, and discusses the challenges and variability in monitoring unfractionated heparin (UFH) therapy. The text provides detailed information on monitoring various anti-coagulant therapies, highlighting the significance of using specific assays for accurate monitoring and addressing potential adverse events associated with these medications. [Extracted from the article]

The article outlines the British Society for Haematology's guidelines for investigating and managing antiphospholipid syndrome (APS), an autoimmune disease linked to thrombosis and pregnancy complications. Diagnosis requires clinical events and detection of antiphospholipid antibodies on multiple occasions. It covers the pathophysiology, clinical signs, and lab tests for APS, with specific recommendations for managing patients in different scenarios, like surgery or pregnancy. The guidance stresses accurate testing, tailored treatment plans, and a holistic approach considering individual risks and needs. [Extracted from the article]

This article provides guidelines for assessing and managing bleeding risk before invasive procedures. It recommends individualized assessment and decision-making based on the specific procedure and patient characteristics. The article discusses the management of anticoagulant and antiplatelet therapy, the limitations of routine coagulation testing, and the potential use of global haemostatic and platelet function testing to predict bleeding risk. It also addresses the use of plasma products and platelet transfusions in the ICU, emphasizing the lack of evidence supporting their prophylactic use. The article highlights the importance of operator and procedural factors in reducing the risk of complications during procedures. [Extracted from the article]

This article provides guidelines for the diagnosis and management of heparin-induced thrombocytopenia (HIT), a condition characterized by low platelet count caused by an immune response to heparin. It discusses different types of HIT, the incidence of the condition, and the presentation and assessment of HIT. The article also provides recommendations for platelet monitoring and laboratory diagnosis of HIT, as well as management strategies including the use of alternative anticoagulants and therapies such as intravenous immunoglobulin and plasma exchange. The recommendations are evidence-based and aim to assist healthcare professionals in managing HIT. [Extracted from the article]

Introduction: Thrombosis and bleeding are major complications in patients supported with left ventricular assist devices (LVADs). We aimed to assess the incidence of bleeding and thrombosis in patients supported with a HeartWare left ventricular assist device (HVAD), their predictive factors and their impact on mortality. Methods: A single centre retrospective observational study of patients supported with HVAD over 5 years from January 2015 to October 2020. Results: A total 139 patients (median age 52.5, 72.1% male) were included for analysis. The probability of 1-year survival was 73.1%. Advanced age (>60 years) and EuroSCORE II score (>20%) were independently associated with reduced survival. Major bleeding and thrombosis occurred in 46.8% and 35.3% respectively. Secondary mechanical circulatory support (MCS) increased likelihood of experiencing major bleeding (HR: 2.76, 95%1.65–4.62, p < 0.0001) whilst patients receiving aspirin were protected from bleeding and thrombosis (HR: 0.34 95% CI 0.19–0.58, p < 0.001). Pre-operative anaemia (HR: 3.02, 95% CI: 1.6–5.7, p = 0.014) and use of a secondary MCS device (HR: 2.78, 95% CI: 1.2–6.3, p = 0.001) were associated with an increased risk of thrombosis. Patients with any major bleeding (with or without thrombosis) had a 7.68-fold (95% CI 3.5–16.8) increased risk of death compared to those without. In contrast, 'thrombosis only' patients had 4.23-fold (95% CI 1.8–10.2) increased risk of death compared to those without thrombosis. The risk of mortality was increased in patients with any thrombosis and the risk of death was highest in patients with major bleeding and thrombosis (HR: 16.49 [95% CI 7.7–35.3]). Conclusions: Major bleeding and thrombosis significantly increase the 1-year mortality. Optimal perioperative haemostasis and anticoagulation remains crucial in patients supported with HVAD. [ABSTRACT FROM AUTHOR]

The article responds to a letter regarding the interpretation of findings from a meta-analysis comparing vitamin K antagonist (VKA)/warfarin with direct-acting oral anticoagulants (DOACs) in patients with thrombotic anti-phospholipid syndrome (APS). The authors caution against the use of DOACs for arterial thrombosis in APS patients and recommend VKA/warfarin as the first-line treatment for recurrent venous thromboembolism (VTE). They acknowledge the limitations of subgroup analyses and emphasize the importance of individual patient factors in treatment decisions. The recommendations are based on existing evidence and may change with future research developments. [Extracted from the article]

Post‐discharge thromboprophylaxis in patients admitted with COVID‐19 remains controversial. We aimed to determine the impact of thromboprophylaxis on hospital acquired thrombosis (HAT) in patients (≥18 years) discharged following admission for COVID‐19 in an observational study across 26 NHS Trusts in the UK (01.04.2020–31.12.2021). Overall, 8895 patients were included to the study: 971 patients were discharged with thromboprophylaxis and propensity score matched (PSM) with a desired ratio of 1:1, from patients discharged without thromboprophylaxis. Patients with heparin induced thrombocytopenia, major bleeding during admission and pregnant women were excluded. As expected from 1:1 PSM, no difference was observed in parameters between the two groups, including duration of hospital stay, except the thromboprophylaxis group had a significantly higher proportion who had received therapeutic dose anticoagulation during admission. There were no differences in the laboratory parameters especially D‐dimers between the two groups at admission or discharge. Median duration of thromboprophylaxis following discharge from hospital was 4 weeks (1–8 weeks). No difference was found in HAT in patients discharged with TP versus no TP (1.3% vs. 0.92%, p = 0.52). Increasing age and smoking significantly increased the risk of HAT. Many patients in both cohorts had raised D‐dimer at discharge but D‐dimer was not associated with increased risk of HAT. [ABSTRACT FROM AUTHOR]

Objective To establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) compared with a propensity-matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK. Methods This is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a predesigned standardized case record form. Adult patients (≥18 years) admitted between 1 April 2020 and 31 July 2020 were included. Results Overall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with SLE, RA or aPL syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia [240 (60.91%) vs 206 (52.28%), P  = 0.015], elevated LDH [150 (38.08%) vs 43 (10.92%), P  < 0.001] and raised creatinine [122 (30.96%) vs 86 (21.83%), P  = 0.01], respectively. A significantly higher proportion of patients with severe rheumatologic AD had elevated CRP [77 (96.25%) vs 70 (87.5%), P  = 0.044] and LDH [20 (25%) vs 6 (7.5%), P  = 0.021]. Patients with severe rheumatologic AD had significantly higher mortality [32/80 (40%)] compared with propensity matched cohort of patients without AD [20/80 (25%), P  = 0.043]. However, there was no difference in 180-day mortality between propensity-matched cohorts of patients with or without AD in general (P  = 0.47). Conclusions Patients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and elevated LDH were more frequent in patients with any AD while elevated CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Summary: Bleeding and thrombosis are major complications in patients supported with extracorporeal membrane oxygenation (ECMO). In this multicentre observational study of 152 consecutive patients (≥18 years) with severe COVID‐19 supported by veno‐venous (VV) ECMO in four UK commissioned centres during the first wave of the COVID‐19 pandemic (1 March to 31 May 2020), we assessed the incidence of major bleeding and thrombosis and their association with 180‐day mortality. Median age (range) was 47 years (23–65) and 75% were male. Overall, the 180‐day survival was 70·4% (107/152). The rate of major bleeding was 30·9% (47/152), of which intracranial bleeding (ICH) was 34% (16/47). There were 96 thrombotic events (63·1%) consisting of venous 44·7% [68/152 of which 66·2% were pulmonary embolism (PE)], arterial 18·6% (13/152) and ECMO circuit thrombosis 9·9% (15/152). In multivariate analysis, only raised lactate dehydrogenase (LDH) at the initiation of VV ECMO was associated with an increased risk of thrombosis [hazard ratio (HR) 1·92, 95% CI 1·21‐3·03]. Major bleeding and ICH were associated with 3·87‐fold (95% CI 2·10–7·23) and 5·97‐fold [95% confidence interval (CI) 2·36–15·04] increased risk of mortality and PE with a 2·00‐fold (95% CI1·09–3·56) risk of mortality. This highlights the difficult balancing act often encountered when managing coagulopathy in COVID‐19 patients supported with ECMO. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) could be life saving for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced severe respiratory failure not responding to optimal conventional management, including mechanical ventilation and proning. Thrombotic events in non-COVID-19 patients were distributed more evenly throughout the course of ECMO (prior, during and post-decannulation from ECMO) than for COVID-19 patients, in whom the majority of thromboses developed prior to or early in the course of ECMO (Supplementary Table S1, available in the online version only). Of the five non-COVID-19 patients who developed arterial thrombosis, three patients developed ischemic stroke and the other two patients each developed bowel, splenic, and renal infarcts. To summarize, thrombosis and major bleeding are frequent complications in both COVID-19 and non-COVID-19 patients supported with VV-ECMO. [Extracted from the article]

Summary: Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID‐19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID‐19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9‐fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93–1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58–1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID‐19 was admission to the Intensive‐Care Unit (ICU) (HR 1·98, 95% CI 1·37–2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding. [ABSTRACT FROM AUTHOR]

Despite its name, lupus anticoagulant (LAC) neither exclusively occurs in lupus nor induces anticoagulation. It is an antiphospholipid antibody found in 2%–4% of the population that promotes clot formation by targeting phospholipid-protein complexes in cell membranes. However, in vitro, LAC exhibits paradoxical effects, prolonging clotting times in phospholipid-dependent assays such as Activated Partial Thromboplastin Time (APTT). This unpredictability extends to point-of-care tests like Activated Clotting Time (ACT), which are frequently used to monitor anticoagulation during cardiac surgeries involving cardiopulmonary bypass (CPB). High doses of unfractionated heparin (UFH) are administered in these procedures, but the presence of LAC complicates ACT measurements, creating challenges for both anesthesiologists and surgeons. This case report highlights the clinical implications of LAC in perioperative management, underscoring the difficulties in ensuring adequate anticoagulation during CPB. [ABSTRACT FROM AUTHOR]