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The coagulopathy of major haemorrhage: how does the aetiology of major bleeding affect the coagulation changes and how can haematological markers be best used to stratify risks of bleeding and need for transfusion therapy?

   Radcliffe Department of Medicine

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  Dr Nicola Curry  No more applications being accepted  Self-Funded PhD Students Only

About the Project

This is a 3 year DPhil project that is suitable for a clinician seeking to develop their research skills. The project is focussed on major haemorrhage and the associated clotting abnormalities. 

To date, much of the understanding around the pathophysiology of major haemorrhage coagulopathy has arisen from the field of trauma and the dramatic changes to major haemorrhage therapy that have taken place over the last 10 years have been driven by this knowledge. However, major bleeding occurs for many reasons – e.g. post-partum, gastrointestinal bleeding, during or after major surgery – and it is becoming increasingly clear that the coagulopathy that accompanies different types of major bleeding is dependent upon the cause of the bleeding. There is an observational study that is being piloted in Oxford that will be enrolling patients with (or at risk of) major bleeding, and which will be collecting haemostasis samples. The student will be involved in this project and samples will be used to explore differences between clotting parameters in different patient groups.

Many patients who suffer with major bleeding are young: traumatic injury mostly affects young men (average age 28 – 35 years) and post-partum bleeding affects young women. It can be very difficult clinically to pick up bleeding in these patients until they have bled sufficiently to lead to a rapid change to their haemodynamic status. This project aims to develop a ‘haemostasis chip’ that can be used as an additional biomarker for risk stratifying patients who are at risk of bleeding. 

This DPhil will focus on several aspects of major bleeding and clinical research. The main aims of this project are: 1) to investigate the main clotting differences between different groups of patients with major bleeding and how these differences alter a patient’s outcome; 2) to develop a ‘haemostasis Chip’ (a rapid ELISA chip) that will be used to screen patients at risk of bleeding and 3) to support an ongoing observational study where patients with three specific types of bleeding will be recruited.

This work is one part of an exciting programme of work at the Oxford Haemophilia and Thrombosis Centre which centres on improving the treatment and diagnosis of patients with major haemorrhage and associated coagulopathy. This DPhil is highly translational in nature and will be best suited to a clinician with an interest in haematology.

Laboratory description:

The student will be a member of a developing research team based at the Oxford Haemophilia and Thrombosis Centre (OHTC), which is due to move to the Nuffield Orthopaedic Centre in early 2022. The team includes four haemostasis consultants, with Nicola Curry as your lead supervisor. There are laboratory facilities within the OHTC where the student will be based. The clinical study which the student will be supporting will involve patients who are, in the main, admitted to the John Radcliffe Hospital, Oxford.

DPhil support for the student will be primarily given by Nicola Curry (supported by Prof. Simon Stanworth) and the laboratory and clinical work will be supported by Dr. Curry and a post-doctoral researcher. 

Research and Training Opportunities:

As a student of Oxford University, all generic training opportunities will be available (see below). Specific training for this post will involve:

Clinical research:

·      opportunities to work with the Systematic Review Initiative and develop systematic review skills

·      develop understanding and experience of research study development, including protocol writing; ethics applications; R&D and HRA processes; grant writing

·      experience of running clinical studies, including recruitment of participants to studies; data collection and subsequent data analysis (statistical courses are readily available)

Laboratory research:

·      experience of optimising haemostasis experiments and assays, including: clot lysis, thrombin generation, ELISAs, standard coagulation assays, fibrinogen specific assays

·      development of a specific assay – working with industry to optimise an ELISA chip

There are several established collaborations within OHTC which includes those with the cardiovascular laboratory in Oxford (Professor R. Choudhury) and with the haemostasis laboratory in Aberdeen (Dr. N Mutch). Opportunities for developing specific haemostasis laboratory techniques may be possible with these laboratories, during the period of this DPhil.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.


1 Survey evaluating clinical equipoise around platelet transfusion after head injury and traumatic intracranial haemorrhage (ICH) in patients on antiplatelet medications.
Ashton C. et al, (2021), Emerg Med J.
2 Fibrinogen Replacement Therapy for Traumatic Coagulopathy: Does the Fibrinogen Source Matter?
Morrow GB. et al, (2021), Int J Mol Sci, 22
3 Characterisation of a novel thrombomodulin c.1487delC,p.(Pro496Argfs*10) variant and evaluation of therapeutic strategies to manage the rare bleeding phenotype.
Morrow GB. et al, (2021), Thromb Res, 197, 100 - 108
4 Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.
Baksaas-Aasen K. et al, (2021), Intensive Care Med, 47, 49 - 59
5 A Delphi study to establish consensus on a definition of major bleeding in adult trauma.
Wong HS. et al, (2020), Transfusion, 60, 3028 - 3038
6 Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): Results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial
Curry N. et al, (2018), Critical Care, 22

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