BAT-X Study
Research type
Research Study
Full title
Bleeding Assessment Tool (BAT) in patients with X-Linked Agammaglobulinemia (XLA)
IRAS ID
282808
Contact name
PLR Nicolson
Contact email
Sponsor organisation
University of Birmingham
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
Abnormal blood clotting (thrombosis) plays a major role in numerous cardiovascular diseases such as heart attack and stroke. Medications that prevent thrombosis are effective in many clinical settings, however these treatments can also result in mild or severe bleeding. Therefore new medications that reduce the risk of thrombosis without causing bleeding are needed.
Recently inhibitors of Bruton’s tyrosine kinase (Btk) have been identified as a new potential medication to stop thrombosis. Btk is a protein present in platelets, the small cells that circulate in the blood and prevent bleeding but are also responsible for thrombosis causing heart attacks and strokes. Blocking Btk in platelets has been shown to reduce or prevent formation of clots on collagen and atherosclerotic plaque, the main triggers of thrombosis in patients. Btk inhibitors, such as ibrutinib, have been approved as treatments in several blood cancers. However, increased rates of minor and major bleeding in ibrutinib-treated patients have been reported. Bleeding in patients treated with ibrutinib and other Btk inhibitors has been attributed to their off-target effects; i.e. inhibiting the function of other important proteins.
X-linked agammaglobulinemia (XLA) is a rare hereditary disease affecting males' immune system. Patients with XLA lack functional Btk protein due to a genetic mutation. XLA patient platelets show reduced platelet activation to collagen.
This study aims to determine whether the absence of functional Btk protein in platelets causes bleeding through administration of a retrospective questionnaire to XLA patients at multiple centres across the UK. Findings will answer the question whether bleeding in patients treated with Btk inhibitors is due to their effect on Btk or off-target effects on other important proteins. Crucially this will give indication on the suitability of targeting platelet Btk as an anti-thrombotic therapy to prevent thrombosis, but crucially not causing bleeding.
Lay summary of study results: This study explored the bleeding tendencies in individuals with X-linked Agammaglobulinemia (XLA), a rare genetic condition that affects the immune system and blood clotting. XLA is caused by a mutation in the gene responsible for producing Bruton’s tyrosine kinase (Btk), a protein critical for the development of certain immune cells and the function of platelets, which are essential for blood clotting. Because people with XLA lack this protein, researchers wanted to understand if they were at higher risk of bleeding, especially as Btk is being studied as a target for new drugs to prevent blood clots.
The research involved 42 patients from across the UK. A special questionnaire called the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) was used to measure bleeding history. Most participants had normal bleeding scores, but about one-third showed slightly higher scores, indicating mild bleeding issues. Younger participants were more likely to have elevated scores, and in some cases, other health conditions or medications that affect bleeding might have contributed.
This study suggests that while XLA patients generally don’t experience severe bleeding, the absence of Btk may cause a mild increase in bleeding risk. These findings are important for developing safer blood-clot prevention drugs that target Btk without causing significant bleeding problems.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
21/SC/0049
Date of REC Opinion
9 Feb 2021
REC opinion
Favourable Opinion