A new population pharmacokinetic model for recombinant factor IX-Fc fusion concentrate including young children with haemophilia B.

Aims: Recombinant factor IX Fc fusion protein (rFIX-Fc) is an extended half-life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged ≥12 years. The aim was to externally evaluate the predictive performance of the published rFIX-Fc population PK model for patients of all ages and develop a model that describes rFIX-Fc PK using real-world data.

Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.

Background: Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood.

Objectives: To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE.

Methods: Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.

Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial.

Objectives: Persistently impaired culprit artery flow (
Methods: In T-TIME (trial of low-dose adjunctive alTeplase during primary PCI), patients ≤6 hours from onset of ST-elevation myocardial infarction (STEMI) were randomised to placebo, alteplase 10 mg or alteplase 20 mg, administered by infusion into the culprit artery, pre-stenting.

Correction of international normalised ratio in major bleeding related to vitamin K antagonists is associated with better survival: A UK study.

Background: The association between international-normalised-ratio (INR) correction and mortality in patients with major bleeding on vitamin-K-antagonists (VKA) is important for evaluating the efficacy of reversal agents for oral anticoagulants.

Objectives: We evaluate if INR correction (defined as ≤1.3) following intervention in major bleeding on VKA is associated with better survival, and if there is a dose-response relationship between Vitamin K (VK) and INR correction.

History of the West of Scotland Haemophilia Centre, Glasgow, 1950-2019.

Over 70 years, the West of Scotland Haemophilia Centre in the UK has played a leading role in research, education and training. Its staff studied the natural history of haemophilias, their complications, and their treatment complications, pioneered the use of fibrinolytic inhibitors to reduce the risk of receiving a blood transfusion and developed national audit. Collaborations across Scotland with other haemophilia centres and the Scottish National Blood Transfusion Service progressed self-suffi ciency in NHS-produced factor concentrates, heat treatments to prevent HIV and hepatitis transmission, and finally, replacement of human by recombinant factor concentrates.

Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time.

Background: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.

Objectives: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.

Methods: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention.

Macroscopic hematuria as a risk factor for hypertension in ageing people with hemophilia and a family history of hypertension.

Ageing people with hemophilia (PWH) have a higher prevalence of hypertension than the general population. This study aimed to determine whether macroscopic hematuria was associated with hypertension in PWH in a post hoc analysis using data from a cross-sectional study conducted by the ADVANCE Working Group (the H3 study), which included PWH ≥ 40 years of age. Data from 16 contributing centers, located in 13 European countries and Israel, were analyzed using logistic regression models.

Hematuria in aging men with hemophilia: Association with factor prophylaxis.

Introduction: Macroscopic hematuria is considered a significant risk factor for urologic disease, and it is highly prevalent in people with hemophilia.

Aim: To determine whether prophylactic factor replacement therapy is associated with reduced occurrence of macroscopic hematuria in people with hemophilia in a post hoc analysis using data from a cross-sectional study conducted by the Age-Related Developments and Comobordities in Hemophilia (ADVANCE) Working Group that included males with hemophilia ≥40 years of age.

Methods: Data from 16 contributing centers, in 13 European countries and Israel, were analyzed using logistic regression.

Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction.

Background Impaired microcirculatory reperfusion worsens prognosis following acute ST-segment-elevation myocardial infarction. In the T-TIME (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low-dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio.

Haematological management of major bleeding associated with direct oral anticoagulants - UK experience.

The lack of antidotes for activated factor X-inhibitor direct oral anticoagulants (DOACs) means that management of bleeding consists largely of existing supportive therapies. This study aimed to: (i) examine the relative frequency of DOAC-related major bleeding in relation to DOAC prescriptions over the study period; (ii) describe the presentation and haematological management of DOAC-related major bleeding; and (iii) evaluate the association between the use of prothrombin-complex-concentrate (PCC) and in-hospital mortality. Over a 3-year period, 32 UK hospitals submitted data on haematological management of DOAC-related bleeding.

Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes.

Objective: To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction.

Design, Setting, And Participants: Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the United Kingdom within 6 hours of STEMI due to a proximal-mid-vessel occlusion of a major coronary artery were randomized in a 1:1:1 dose-ranging trial design.

British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism.

The following is a summary of the recommendations and good practice points for the BTS Guideline for the initial outpatient management of pulmonary embolism. Please refer to the full guideline for full information about each section.

Individual and monitoring centre influences upon anticoagulation control of AF patients on warfarin: A longitudinal multi-centre UK-based study.

Objectives: Time within therapeutic INR range (TTR) predicts benefits/risk of warfarin therapy. Identification of individual- and centre-related factors that influence TTR, and addressing them to improve anticoagulation control, are important. This study examined the impact of individual and centre-related factors upon long-term anticoagulation control in atrial fibrillation patients in seven UK-based monitoring services.

A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study).

The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization.

Is Cryotherapy a Genuine Rival to Robotic-assisted Partial Nephrectomy in the Management of Suspected Renal Malignancy? A Systematic Review and Meta-analysis.

We systematically reviewed the world literature and compare oncological outcomes, morbidity, renal function, and perioperative outcome between cryotherapy and robotic-assisted partial nephrectomy (RAPN) for suspected renal malignancy. There was a statistically significant difference in "recurrence rates" between the 2 techniques, favoring the RAPN cohort. There was no statistically significant difference in overall and ≥Clavien 3a complication rates between the 2 techniques.

A Joint Model for Vitamin K-Dependent Clotting Factors and Anticoagulation Proteins.

Background: Warfarin acts by inhibiting the reduction of vitamin K (VK) to its active form, thereby decreasing the production of VK-dependent coagulation proteins. The aim of this research is to develop a joint model for the VK-dependent clotting factors II, VII, IX and X, and the anticoagulation proteins, proteins C and S, during warfarin initiation.

Methods: Data from 18 patients with atrial fibrillation who had warfarin therapy initiated were available for analysis.

Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia.

The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP9) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in GP1BA have been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in GP1BB By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in GP1BB and macrothrombocytopenia.

Spontaneous sublingual haematoma in acquired haemophilia: case report.

Acquired haemophilia is a rare disease in which bleeding is more severe than in hereditary haemophilia and usually occurs in the soft tissues, the gastrointestinal tract, or the mucous membranes. There have been only a few presentations of spontaneous sublingual haematoma in acquired haemophilia, but prompt management of the airway and identification of the underlying cause was crucial in all.

An antithrombin replacement strategy during asparaginase therapy for acute lymphoblastic leukemia is associated with a reduction in thrombotic events.

Thrombosis is a well-recognized complication of asparaginase therapy for acute lymphoblastic leukemia (ALL), associated with the depletion of antithrombin (AT). Following a high incidence of thrombotic episodes during induction therapy for ALL in our tertiary referral center, we prospectively instituted a protocol of AT replacement. Forty-five consecutive adolescents and adults with ALL treated with asparaginase-containing phase I induction protocols were included in this observational study.

Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke.

Background And Purpose: We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage.

Methods: Venous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences.