Q) What are the indications for treatment of hemorrhagic transformation after alteplase administration? 

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A) According to 2017 AHA guideline indications for treatment are 

 

1) Symptomatic ICH (sICH) ≤ 24 h or with hypofibrinogenemia

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2) Asymptomatic ICH, the use of reversal agents for any asymptomatic parenchymal hematoma (PH) occurring ≤ 24 h may be considered, particularly in the setting of ongoing coagulopathy.

 

     There are several definitions of sICH but ECASS II definition has the highest interrater agreement. There are 3 radiographic classifications of postthrombolysis ICH, but the most familiar one is ECASS criteria. PH-2 was found to be associated with increased risk of early neurological deterioration and approaching 50% mortality. The clinical relevance of HI-1, HI-2 and PH-1 is less clear.

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     The pathophysiology of postthrombolytic hemorrhagic transformation has multiple interconnected pathological processes including alteplase-associated coagulopathy, blood-brain barrier disruption and reperfusion injury. Alteplase itself has a half life about 4 minutes, but it does not only affect fibrin but fibrinogen as well. It causes a prominent fibrinogen turnover “early fibrinogen degradation coagulopathy.” Some of the fibrinogen degradation products have anticoagulant properties acting as antithrombin or attenuating fibrin polymerization and platelet activation. Fibrinogen depletion within hours of thrombolysis was paralleled by a significant increase in a PTT, and INR.

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     Once sICH is diagnosed, we should send fibrinogen level stat and immediately transfusing 10U of cryoprecipitate and give more if needed to achieve fibrinogen

level ≥ 150 mg/dl. (10 U cryoprecipitate increases fibrinogen by nearly 50 mg/dl. 

 

     The degree of alteplase related coagulopathy is associated with fibrinogen level.

A decrease in fibrinogen level by ≥ 200 mg/dl from baseline ≤ 6 h of alteplase infusion or fibrinogen level < 200 mg/dl at 2 hours after alteplase administration increase risk of ICH. Fibrinogen level < 150 mg/dl at the time of sICH has been associated with hematoma expansion.

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     The use of platelet transfusion, PCC, FFP, and vitamin K in most patients with sICH are controversial except certain conditions. Please see the following table. For antifibrinolytic agents, there are limited data on the safety and efficacy. These agents, however, may be considered in all patients with sICH, particularly in patients who decline blood products.

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     The blood pressure goal after hemorrhagic transformation depends on recanalization status and the severity of hemorrhage. We have to balance between ischemic risk and risk of hemorrhagic expansion.

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References

1. Yaghi S, Willey JZ, Cucchiara B, et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2017;48(12):e343-e361.

2. Yaghi S, Eisenberger A, Willey JZ. Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment. JAMA Neurol. 2014;71:1181–1185.

3. Vandelli L, Marietta M, Gambini M, Cavazzuti M, Trenti T, Cenci MA, Casoni F, Bigliardi G, Pentore R, Nichelli P, Zini A. Fibrinogen decrease after intravenous thrombolysis in ischemic stroke patients is a risk factor for intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2015;24:394–400.

4. Matosevic B, Knoflach M, Werner P, Pechlaner R, Zangerle A, Ruecker M,        Kirchmayr M, Willeit J, Kiechl S. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology. 2013;80:1216–1224.