In this episode, I’ll discuss the treatment of intracranial hemorrhage after thrombolytic therapy.
Background
Alteplase, reteplase, and tenectaplase are fibrin-selective plasminogen activators. They convert plasminogen to plasmin, which then degrades fibrin and results in fibrinolysis. Massive pulmonary embolism, acute ischemic stroke, and myocardial infarction are three common indications for thrombolytic therapy.
One of the most feared complications from thrombolytic therapy is intracranial hemorrhage. When used for pulmonary embolism or myocardial infarction, the risk of intracranial bleeding from a thrombolytic is less than 1%. However, when used for acute ischemic stroke the risk of intracranial bleeding from a thrombolytic is as much as 7%. The 3-month mortality rate from symptomatic intracranial hemorrhage after thrombolytics is as high as 61%.
Timeframe
Although the plasma half-lives of thrombolytics are very short, they have a longer terminal half-life and can suppress fibrinogen levels for days. Therefore guidelines recommend attempting to reverse thrombolytic therapy if intracranial hemorrhage occurs within 24 hours of administration.
One study of 128 patients found that a low fibrinogen level (below 150 mg/dL) was the sole factor associated with hematoma expansion.
The easiest way to administer a large amount of fibrinogen is with cryoprecipiate. An initial dose of 10 units is suggested in the case of intracranial hemorrhage. Fresh frozen plasma (FFP) also contains fibrinogen, but it is much more dilute when compared with cryoprecipitate.
There is not sufficient data to determine whether treatment with cryoprecipitate affects outcomes in patients with intracranial hemorrhage from thrombolytics. Cryoprecipitate is only known to achieve the surrogate endpoint of increasing fibrinogen levels.
There is also not sufficient data to suggest that platelet transfusion or antifibrinolytic agents such as aminocaproic acid or tranexamic acid affect outcomes in patients with intracranial hemorrhage from thrombolytics.
Guidelines
(1) We recommend discontinuing thrombolytic agents when intracranial hemorrhage is present or suspected. (Good Practice statement)
(2) We suggest using cryoprecipitate (10 units initial dose) in patients with thrombolytic agent-related symptomatic intracranial hemorrhage who have received a thrombolytic agent in the previous 24 h. (Conditional recommendation, low-quality evidence)
(3) In cases where cryoprecipitate is contraindicated or not available in a timely manner, we suggest using an antifibrinolytic agent (tranexamic acid 10–15 mg/kg IV over 20 min or e-aminocaproic acid 4–5 g IV) as an alternative to cryoprecipitate. (Conditional recommendation, very low-quality evidence)
(4) We suggest checking fibrinogen levels after administration of reversal agents. If the fibrinogen is less than 150 mg/dL, we suggest administration of additional cryoprecipitate. (Conditional recommendation, very low-quality evidence)
(5) It is unclear if platelet transfusion is useful and we cannot offer a recommendation at this time.
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