Summary Previous studies in acquired haemophilia A have reported on cohorts of patients referred to specialist centres or were retrospective surveys of specialist centre experience. This may have resulted in the literature representing a more severe group of patients than seen in routine haematological practice. We report on a consecutive, unselected cohort of all patients in south and west Wales who presented with acquired haemophilia A between 1996 and 2002. There were 18 patients, an incidence of 1·34/million/year. Compared with previously reported cohorts our patients were older, with a median age of 70 years, and less likely to have an underlying diagnosis (27%). The bleeding phenotype was less severe, with only 27% having life or limb threatening bleeds and 41% required no haemostatic treatment. One patient died of bleeding, but three died of complications related to immunosuppression. Response to immunosuppression was high compared with other series, with 88% of treated patients attaining an undetectable inhibitor and normal factor VIII level. These data suggest that previously reported cohorts may represent more severely affected patients and, whilst guidelines for treatment based on these assumptions may be valid for severely affected patients, they may not be universally applicable.

Assessment of thrombin generation measured before and after cardiopulmonary bypass surgery and its association with post-operative bleeding.J Thromb Haemost 2011; 9: 282-92.Summary. Background: Bleeding after cardiopulmonary bypass (CPB) is a major cause of morbidity and mortality and consumes large amounts of blood. Identifying patients at increased risk of bleeding secondary to hemostatic impairment may improve clinical outcomes by allowing early intervention. Methods: This present study recruited 77 patients undergoing CPB and measured coagulation screens, coagulation factors, TEG Ò , Rotem Ò and thrombin generation (TG) before surgery and 30 min after heparin reversal. The tests were analyzed to investigate whether they identified patients at increased risk of excess bleeding (defined as > 1000 mL) in the first 24 h postoperatively. Results: Patients who bled > 1000 mL had a lower: platelet count (P < 0.02), factors (F)IX, X and XI (P < 0.005), endogenous thrombin potential (ETP) and an initial rate of TG (P < 0.02) and higher activated partial thromboplastin time (aPTT) (P < 0.001) than patients who bled < 1000 mL. Receiver operating characteristic (ROC) analysis was significant for post-operative TG and aPTT (P < 0.001). Furthermore, reduced pre-operative TG was associated with increased postoperative bleeding (P < 0.02). Pre-and postoperative TG were correlated (q = 0.7, P < 0.001). TEG Ò , Rotem Ò and prothrombin time (PT) at either time point were not associated with increased bleeding. Conclusion: These data suggest that pre-operative defects in the propagation phase of hemostasis are exacerbated during CPB, contributing to bleeding post-CPB. TG taken both pre-and postoperatively could potentially be used to identify patients at an increased risk of bleeding post-CPB.

SummaryPatients with haemophilia requires different amounts of FVIII to prevent and treat bleeds. We hypothesise that this is because FVIII has variable effects on individual patients' global haemostasis. Twelve patients with severe haemophilia A were infused with 50 IU/kg FVIII and thrombin generation in platelet rich (PRP) and platelet poor plasma (PPP) and velocity of changing clot elasticity were measured preinfusion and at nine subsequent time points over 72 h. Despite a close correlation between median FVIII and median initial rate of thrombin generation (R 2 0AE94), endogenous thrombin potential (ETP; R 2 0AE94) and peak thrombin (R 2 0AE91) in PPP, there was wide inter-patient variability at each time point. There was, however, a highly predictable intra-patient relationship between FVIII level and thrombin generation. Inter-patient variability was due to both differences in FVIII levels and the variable effect FVIII had on an individuals' thrombin generation. The utility of PRP was limited because, at low-FVIII levels, only rate of thrombin generation was measurable. At low-FVIII concentrations, the rate of thrombin generation in PPP was the most useful test whilst at higher levels ETP and peak thrombin could also be used.

This is the first study to report on the investigation and treatment of UBD. Future studies are needed to further our understanding of the bleeding phenotype and identify any underlying causes.

Background: COVIDTrach is a UK multi-centre prospective cohort study project evaluating the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation. It also examines the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure. Method: An invitation to participate was sent to all UK NHS departments involved in tracheostomy in mechanically ventilated patients with COVID-19. Data was entered prospectively and clinical outcomes updated over time via an online database (REDCap). Clinical variables were compared with clinical outcomes using multivariable regression analysis, with logistic regression used to develop a prediction model for mortality. Participants recorded whether any of the operators tested positive for SARS-CoV-2 within two weeks of the procedure. Findings: The cohort comprised 1605 tracheostomy cases from 126 UK hospitals. The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration requirement on the day of tracheostomy, PEEP setting, pyrexia, number of days of ventilation before tracheostomy, C-reactive protein and the use of anticoagulation and inotropic support independently predicticted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within two weeks following the procedure. Interpretation: Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical indicators that are predictive of mortality. Optimal timing of the procedure remains to be determined. Funding: The COVIDTrach project is supported by the Wellcome Trust UCL COVID-19 Rapid Response Award and the National Institute for Health Research.