Catherine Bagot

Pregnancy loss and thrombophilia: the elusive link

Recurrent pregnancy loss (RPL) affects 1% pregnancies and is multi‐factorial in origin. The role of the acquired thrombophilia antiphospholipid syndrome (APS) as a common and potentially treatable cause of RPL is well established but this is less so for inherited thrombophilia. In obstetric APS the combination of aspirin and heparin has improved outcomes. By analogy, the use of low molecular weight heparin (LMWH) has become commonplace in women with inherited thrombophilia and also those with unexplained miscarriage to help safeguard the pregnancy. This review will examine the pathophysiological role of thrombophilia in pregnancy loss, and the evidence for anticoagulant‐based intervention. The limited data supporting the use of heparin for women with RPL and inherited thrombophilia suggests adoption of a more cautious and judicious approach in this setting.

Perioperative myocardial infarction in a patient receiving low-dose prothrombin complex concentrates

Perioperative myocardial infarction in a patient receiving low-dose prothrombin complex concentrates -

Correlating prothrombin time with plasma rivaroxaban level

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Extrinsic venous compression: A sufficient explanation for venous thromboembolism due to massive fibroids?

Extrinsic venous compression: A sufficient explanation for venous thromboembolism due to massive fibroids? -

Establishing a reference range for thrombin generation using a standard plasma significantly improves assay precision.

BACKGROUND Thrombin generation is a global coagulation assay which appears to be an effective method for assessing the potential for an individuals plasma to coagulate. However for this assay to become accepted in routine clinical practice it requires standardization. OBJECTIVES To establish a reference range for the NIBSC reference plasma (TGT-RP) which can then become an internal quality control (IQC) for thrombin generation assays. PATIENTS/METHODS Thrombin generation was measured in TGT-RP in 153 independent experiments using 4 assay conditions; 1 pM tissue factor (TF) or 5 pM TF +/- thrombomodulin (TM). A target value +/- 2 SD was calculated to provide an acceptance range under the 4 conditions. A plasma sample from a healthy volunteer was subsequently tested in 11 separate experiments using the TGT-RP for (i) normalisation and (ii) exclusion of experimental results when the TGT-RP results did not fall within the established acceptance range. RESULTS An acceptance range was established for TGT-RP for the 4 assay conditions. Normalisation of all results from a healthy volunteer reduced inter-assay variability significantly (ETP: p=0.0003; Peak: p=0.001). Exclusion of results from the volunteer when concurrently run TGT-RP results fell outside the acceptance range reduced inter-assay variability significantly when reporting raw data (ETP: p=0.001; Peak: p=0.004). However normalisation of this data had no beneficial effect (ETP: p=0.126; Peak: p=0.232). CONCLUSIONS Our work represents further progress in the standardization of thrombin generation techniques with the establishment of an IQC reference range. Using an IQC reduces inter-assay variability, whilst allowing reporting of raw data and ensures production of accurate and reproducible data.

A United Kingdom Immune Thrombocytopenia (ITP) Forum review of practice: thrombopoietin receptor agonists

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Autologous 111In-labelled platelet scan as a predictor of splenectomy outcome in ITP

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Trial protocol: a multicentre randomised trial of first-line treatment pathways for newly diagnosed immune thrombocytopenia: standard steroid treatment versus combined steroid and mycophenolate. The FLIGHT trial

Introduction Immune thrombocytopenia (ITP) is an autoimmune condition that may cause thrombocytopenia-related bleeding. Current first-line ITP treatment is with high-dose corticosteroids but frequent side effects, heterogeneous responses and high relapse rates are significant problems with only 20% remaining in sustained remission with this approach. Mycophenolate mofetil (MMF) is often used as the next treatment with efficacy in 50%–80% of patients and good tolerability but can take up to 2 months to work. Objective To test the hypothesis that MMF combined with corticosteroid is a more effective first-line treatment for immune thrombocytopenia (ITP) than current standard of corticosteroid alone. Methods and analysis Design Multicentre, UK-based, open-label, randomised controlled trial. Setting Haematology departments in secondary care. Participants We plan to recruit 120 patients >16 years old with a diagnosis of ITP and a platelet count <30x109/L who require first-line treatment. Patients will be followed up for a minimum of 12 months following randomisation. Primary outcome Time from randomisation to treatment failure defined as platelets <30x109/L and a need for second-line treatment. Secondary outcomes Side effects, bleeding events, remission rates, time to relapse, time to next therapy, cumulative corticosteroid dose, rescue therapy, splenectomy, socioeconomic costs, patient-reported outcomes (quality of life, fatigue, impact of bleeding, care costs). Analysis The sample size of 120 achieves a 91.5% power to detect a doubling of the median time to treatment failure from 5 to 10 months. This will be expressed as an HR with 95% CI, median time to event if more than 50% have had an event and illustrated with Kaplan-Meier curves. Cost-effectiveness will be based on the first 12 months from diagnosis. Ethics and dissemination Ethical approval from NRES Committee South West (IRAS number 225959). EudraCT Number: 2017-001171-23. Results will be submitted for publication in peer-reviewed journals. Trial registration number NCT03156452

Normal pregnancy is associated with an increase in thrombin generation from the very early stages of the first trimester

BACKGROUND Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. METHODS We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n=22). Blood samples were taken just prior to conception and repeated five times during very early pregnancy, up to Day 59 estimated gestation. RESULTS Mean Endogenous Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI) increased significantly from pre-pregnancy to Day 43 gestation (p=0.024-0.0004). This change persisted to Day 59 gestation. The mean of the percentage change from baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI increased significantly from pre-pregnancy to Day 32 gestation (p=0.0351-<0.0001) with the mean increase from baseline persisting to Day 59 gestation. CONCLUSION Thrombin generation increases significantly during the very early stages of normal pregnancy when compared to the pre-pregnancy state. The increased risk of venous thrombosis therefore likely begins very early in a womans pregnancy, suggesting that women considered clinically to be at high thrombotic risk should start thromboprophylaxis as early as possible after a positive pregnancy test.

Handbook of Venous Thromboembolism

Venous thromboembolism (VTE) is associated with high morbidity and mortality both in and out of the hospital setting, and is one of the commonest reasons for hospital attendances and admissions. Designed as a practical resource, the Handbook of Venous Thromboembolism covers the practical aspects of venous thromboembolism management in short and easily followed algorithms and tables. This important text helps physicians keep up-to-date with the latest recommendations for treating venous thromboembolism in clinic-oriented settings. Experts in fields such as the radiological diagnosis of pulmonary embolism and thrombophilia testing, give a succinct summary of the investigation, diagnosis and treatment of venous thromboembolism and include evidence-based guidelines.