Mild bleeding disorders caused by platelet defects
| ISRCTN | ISRCTN77951167 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77951167 |
| IRAS number | 76061 |
| Secondary identifying numbers | 9858, IRAS 76061 |
- Submission date
- 21/03/2011
- Registration date
- 28/04/2011
- Last edited
- 17/04/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Haematological Disorders
Plain English summary of protocol
Background and study aims
This study aims to understand why certain patients bleed excessively. We look at the following groups of patients:
1. Patients with mild bleeding who have been seen by a blood specialist who feels their symptoms could be due to a problem in the platelets (clinically diagnosed platelet defects)
2. Patients who have unexpectedly heavy periods with no obvious cause
3. Patients with lifelong low platelet counts in the blood with no known cause
For these populations we suspect that there may be a problem in small cells in the blood, known as platelets, but we are not certain that this is the case. This study is using new and more specialist tests in an attempt to confirm that there is a problem in platelets in these groups and to use this information to help identify the gene or genes that cause this problem.
Who can participate?
Patients aged under 85 with a platelet disorder of unknown cause
What does the study involve?
Participants are asked questions about their medical history and complete a bleeding questionnaire. Participants are also asked to give a sample of blood (between 10–50 ml). The blood sample is usually be taken at a local Haematology Clinic, ideally early in the day so that the analyses can be carried out on the same day. Depending on the results of the tests, participants may be asked to give blood on up to three further occasions. This is to carry out different types of tests on the platelets and therefore find out more information on the problem. This can be taken either during a ‘regular’ visit to the Haematology Clinic/surgery or through a specific appointment. There is a minimum of one month between the dates that the blood is taken and no upper time limit on the gap between the donations. The blood samples are sent to research laboratories in Birmingham and/or Sheffield for analysis of the platelets. A frozen sample is also kept for a maximum of 10 years, which may be used to look for gene defects that could cause the platelet problem or changes in blood proteins that may increase your chance of bleeding. The sample is destroyed at this time, or earlier if requested. The sample may be kept for this length of time in the event that we are unable to find a problem with your genes in the first set of investigations. It is possible that, as we gain more knowledge, the sample is investigated at later times to find a gene defect that may be the cause of the bleeding problem.
What are the possible benefits and risks of participating?
The study will generate important information on possible defects in the platelets and may also identify the genes that are responsible for the defects. The identification of a defect in your platelets may influence clinical treatment. If a gene defect is found, it will be possible to investigate whether one or more members of the participant’s family have the same gene defect, should they wish.
Where is the study run from?
University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
December 2010 to February 2027
Who is funding the study?
1. British Heart Foundation (UK)
2. Wellcome Trust (UK)
Who is the main contact?
Prof Neil Morgan
N.V.Morgan@bham.ac.uk
Contact information
Scientific
Institute of Cardiovascular Sciences
College of Medical and Dental Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0001-6433-5692 |
|---|---|
| Phone | +44 (0)121 414 6820 |
| N.V.Morgan@bham.ac.uk |
Study information
| Study design | Non-randomised observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a patient information sheet |
| Scientific title | Mild bleeding disorders caused by platelet defects: a non-randomised observational study |
| Study acronym | Genotyping and platelet phenotyping (GAPP) |
| Study objectives | It is becoming increasingly recognised that platelet function disorders are heavily under-diagnosed and therefore under-researched. Several factors have contributed to this including: 1. The absence of a 'gold standard' point-of-care assay of platelet function 2. The generally asymptomatic presentation of patients with mild defects in platelet function who only exhibit symptoms of excessive bleeding when subject to an appropriate challenge such as surgery or severe injury 3. The considerable redundancy in the pathways underlying platelet activation such that a single gene defect may not be sufficient to give rise to excessive bleeding (but may become clinically important under challenging conditions) 4. The limited amount of mRNA that can be recovered from the anucleate platelet which severely hampers many standard approaches in molecular biology including the use of microarrays. The Birmingham Platelet Group has an approach to gene mapping of platelet disorders based on initial evaluation of clinical and laboratory phenotypes of patients with clinically diagnosed bleeding disorders and subsequent targeted gene sequencing. In this project, we intend to investigate populations of patients enriched for bleeding to test the hypothesis that a proportion of patients who present with excessive bleeding have a previously unrecognised impairment in platelet function which may explain their propensity to bleed in conditions which would not normally be associated with severe bleeding. The proposed research will use a combination of platelet phenotyping and targeted gene sequencing approach to identify candidate mutations underlying platelet dysfunction. The effect of a small number of missense mutations on protein function will be investigated through expression studies in immortalised cell lines. |
| Ethics approval(s) | West Midlands Research Ethics Committee, original approval date 10/08/2006, substantial amendment AM 2/1 approved on 06/12/2010 |
| Health condition(s) or problem(s) studied | Non-malignant haematology |
| Intervention | Assessment of bleeding history 1. By medical questionnaire 2. Assessment: Laboratory testing for defect, extended aggregometry, flow cytometry, protein expression studies and DNA sequencing for platelet genes |
| Intervention type | Other |
| Primary outcome measure | Identification of defects: End of project 2016, aim to identify on a molecular basis platelet defects which cause bleeding |
| Secondary outcome measures | No secondary outcome measures |
| Overall study start date | 31/12/2010 |
| Completion date | 28/02/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 0 Years |
| Upper age limit | 85 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1200; UK Sample Size: 1200 |
| Key inclusion criteria | 1. Patients, aged 0 - 85 years, either sex 2. Diagnosed with a platelet disorder of unknown cause 3. Willing to participate and able to provide informed consent |
| Key exclusion criteria | 1. Patients taking drugs that are known to influence platelet function, including nonsteroidal anti-inflammatory drugs (NSAIDs) including COX-2 selective anti-inflammatory drugs), aspirin, clopidogrel, dipyridamole, warfarin or acenocoumarol within 7 days of enrolment 2. Patients having undergone a major surgical procedure within 1 month of enrolment 3. Patients with chronic renal failure requiring dialysis 4. Patients with a platelet count outside the 100 000 to 450 000/µL range 5. Patients with severe anaemia (haemoglobin < 8g/dl) |
| Date of first enrolment | 31/12/2010 |
| Date of final enrolment | 28/02/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Edgbaston
Birmingham
B15 2TT
United Kingdom
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Website | http://www.birmingham.ac.uk/index.aspx |
|---|---|
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Private sector organisation / International organizations
- Location
- United Kingdom
Government organisation / National government
- Alternative name(s)
- Institutos Nacionales de la Salud, US National Institutes of Health, NIH
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | To be confirmed at a later date |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to the danger of it being identifiable. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2013 | Yes | No | |
| Results article | results | 20/02/2014 | Yes | No | |
| Results article | results | 01/05/2014 | Yes | No | |
| Results article | results | 01/04/2015 | Yes | No | |
| Results article | results | 01/04/2015 | Yes | No | |
| Results article | results | 01/09/2015 | Yes | No | |
| Results article | results | 01/10/2017 | Yes | No |
Editorial Notes
17/04/2024: The following changes were made:
1. The study settings Hospital and University/medical school/dental school replaced Other.
2. The recruitment end date was changed from 30/09/2020 to 28/02/2027.
3. The overall study end date was changed from 30/09/2020 to 28/02/2027.
4. IRAS number added.
31/03/2023: The following changes have been made:
1. The trial website has been added.
2. The target number of participants has been changed from 800 to 1200.
23/10/2020: The following changes were made to the trial record:
1. The recruitment end date and overall trial end date were changed from 30/09/2020 to 01/04/2024.
2. The intention to publish date was changed from 30/09/2021 to 01/04/2025.
3. National Institutes of Health was added as a funder.
20/02/2019: Internal review.
19/02/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2018 to 30/09/2020.
2. The overall trial end date was changed from 01/12/2018 to 30/09/2020.
3. The intention to publish date was added.
03/08/2017: Publication references added.
07/07/2016: Publication references added.
06/07/2016: The following changes were made to the trial record:
1. The plain English summary was added.
2. The overall trial end date was changed from 31/12/2016 to 01/12/2018.
