Haemorrhage Post-Thrombolysis

OVERVIEW

• Haemorrhage is the most important complication of thrombolysis
• Intracerebral haemorrhage is especially important with approximately 0.5% risk following STEMI thrombolysis
• Given the short half-life of thrombolytic agents, by the time the diagnosis is made the biological effect of the drug may have abated
• 40% of patients with follow-up CT scans showed evidence of ICH expansion and ongoing bleeding, suggesting a window of opportunity for treatment
• bleeding following thrombolysis is complicated by numerous other agents that also contribute to a bleeding diathesis

RISK OF HAEMORRHAGE POST-THROMBOLYSIS

***To be completed

• what are the different bleeding rates after thrombolysis for STEMI, PE and stroke?

CONTRIBUTING AGENTS

Recommended anti-thrombotic agents for STEMI

• fibrinolytics
• Anti-platelet agents
  — BOTH Aspirin and Clopidogrel
• Anti-coagulant agents
  — ONE of: Heparin, LMWH, Fondaparinux, or Bivalirudin
• Usually not a IIb/IIIa inhibitor
  — Abciximab, Eptifibatide, or Tirofiban

DURATION OF BLEEDING DIATHESIS

***To be completed

• most likely <12 hours

MANAGEMENT

• Immediately stop ongoing infusion of thrombolytic drug, and stop all antiplatelet and anticoagulant therapies.
• Investigate according to site of haemorrhage (e.g. CT brain, CT abdo/pelvis)
• Obtain blood tests: FBC, coagulation profile; repeat q2h until bleeding controlled
• obtain cross match
• reverse fibrinolysis:
  — FFP 2 units q6h for 24h
  — cryoprecipitate 10 units
  — tranexamic acid 1g IV
  — ? role of prothrombinex and Factor 7
• reverse anti-platelet effects:
  — platelets 1 adult bag
  — DDAVP 0.3 microg/kg
• reverse anti-coagulant effects:
  — protamine 1 mg for every 100 U of unfractionated heparin given in the preceding 4 hours
  — protamine 1 mg for every 1 mg of enoxaparin (or 100 units of dalteparin) given in the preceding 8 hours
• consult appropriate teams e.g. haematology, neurosurgery, cardiology, general surgery

If intracerebral hemorrhage:

• outcome is likely poor, consider if palliation is appropriate
• BP control e.g. SBP <160 mmHg and MAP <110 mmHg
• control ICP:
  — elevate head to 30 degrees— target PaCO2 35-40 mmHg
  — mannitol or hypertonic saline
  — sedation +/- neuromuscular blockade
• consider surgical intervention for:
  — cerebellar ICH
  — lobar ICH with mass effect
  — ventricular drainage may be an option for intraventricular haemorrhage as blood is less likely to clot
• treat seizures (e.g. phenytoin loading 18 mg/kg IV), but do not give prophylaxis

FURTHER INFORMATION

• Goldstein et al (2010) found no cases in which patients developed fibrinogen levels of less than 100 mg/dL, suggesting that currently used tPA dosing regimens are unlikely to induce hypofibrinogenemia, and any benefit of such therapy may be limited.
• D-dimers produced by thrombolysis have a theoretical anti-platelet effect, but the clinical significance is uncertain.

References and Links

• Goldstein JN, Marrero M, Masrur S, Pervez M, Barrocas AM, Abdullah A, Oleinik A, Rosand J, Smith EE, Dzik WH, Schwamm LH. Management of thrombolysis-associated symptomatic intracerebral hemorrhage. Arch Neurol. 2010 Aug;67(8):965-9. doi: 10.1001/archneurol.2010.175. PubMed PMID: 20697046. [Free Fulltext]