A Study on the Safety of Tranexamic Acid for the Chronic Subdural Hematoma Population

Chronic subdural hematomas are a common problem faced by neurosurgery with an annual
incidence of 13.5/100,00 persons per year and up to 58/100,000 in the over 65 years old
population. Their treatment is often complicated by recurrence with rates reported as high
as 33%. Currently there is no good strategy to help avoid this problem, which adds
significantly to patient morbidity. The pathogenesis of this problem is believed to be
related to the propensity of the associated neo-membranes to bleed. It has been shown with
labeled red blood cells that bleeding continues to occur into the hematoma cavity. It has
also been shown that there are high levels of tissue plasminogen activator in the outer
membrane of chronic subdural hematomas. It has been found that ratio of tissue plasminogen
activator to plasminogen activator inhibitor contributed to the pathogenesis. It has also
been shown that chronic subdural hematomas have high levels of fibrin degradation products
which in addition to marking the breakdown of fibrin are themselves antihemostatic by
enhancing tissue plasminogen activator activity, having an antithrombin affect and
inhibiting platelet aggregation and fibrin polymerization. Essentially, a scenario of
ongoing hemorrhage and repeated clot formation and hyperfibrinolysis leads to the expansion
and recurrence of chronic subdural hematomas.

Given the importance of plasmin and hyperfibrinolysis in the pathophysiology of chronic
subdural hematomas, interrupting its action and the vicious cycle it propagates seems an
ideal therapeutic target. Tranexamic acid is a synthetic lysine amino acid derivative. It
binds to the fibrin binding sites on plasmin or plasminogen and prevents its interaction and
degradation of fibrin. This effect on the neo-membranes of chronic subdural hematomas should
prevent rebleeding and the reaccumulation of the subdural hematoma.

Tranexamic acid has been shown to be safe and effective in reducing blood loss and
transfusions in a number of types of surgery, reduced mortality and need for urgent surgery
in patients with GI bleeding, and reduced bleeding associated with menorrhagia and
pregnancy. Adverse effects are generally mild. Thought there is a theoretical increased risk
of thromboembolic complications, multiple randomized controlled trials have not shown an
increased risk. Furthermore, in a study of over 3000 gynecologic patients using tranexamic
acid, there were no thromboembolic complications. This is likely because tranexamic acid has
been shown to not have an effect on plasminogen in the vein wall.

Inclusion Criteria:

- all patients undergoing intervention for chronic subdural hematoma (cSDH) including
drainage

- cSDH will be defined as hematoma on CT imaging that is predominantly iso- to
hypodense to brain

- 18-85 years of age

Exclusion Criteria:

- cSDH not requiring surgical drainage

- patients undergoing bedside twist drill craniostomy

- medically unstable for surgery

- patients requiring long-term anticoagulation (unable to stay off for less than 30
days)

- patients not expected to survive to the completion of followup

- patients comatose prior to the initiation of treatment

- history of thromboembolic problem including stroke, myocardial infarction, deep vein
thrombosis and/or pulmonary embolism

- pregnant

- minor

- allergy/sensitivity to tranexamic acid

- irreversible coagulopathy

- known clotting disorder

- bilateral hematomas with both requiring drainage

- incarcerated

- any patient not judged suitable for the study by the investigators

- women who are taking combination hormonal contraception