What drug reverses the action of streptokinase (thrombolytic agent) in a patient with massive hematemesis (severe bleeding) following streptokinase infusion for acute ST elevation myocardial infarction (heart attack)?

Management of Streptokinase-Induced Bleeding in STEMI

Aminocaproic acid is the drug of choice to reverse the action of streptokinase in a patient with massive hematemesis following streptokinase infusion for acute ST-elevation myocardial infarction. 1

Mechanism of Action and Rationale

Streptokinase is a non-fibrin-specific thrombolytic agent that works by binding to plasminogen, creating a complex that converts other plasminogen molecules to plasmin, which degrades fibrin clots. When bleeding complications occur, the following considerations apply:

• Aminocaproic acid works as an antifibrinolytic agent by competitively inhibiting plasminogen activation, thereby preventing the breakdown of fibrin clots and stopping the ongoing fibrinolytic effect of streptokinase.

• Factor VIII concentrate (Option A) would not effectively reverse streptokinase action as streptokinase works through the plasminogen-plasmin system, not through factor VIII pathways.

• Protamine (Option C) is specifically used to reverse the anticoagulant effects of heparin, not fibrinolytic agents like streptokinase.

• Vitamin K (Option D) is used to reverse the effects of warfarin by promoting synthesis of clotting factors II, VII, IX, and X, but has no effect on the fibrinolytic system activated by streptokinase.

Management Algorithm for Streptokinase-Induced Bleeding

1. Immediately discontinue streptokinase infusion when massive hematemesis is identified

2. Administer aminocaproic acid:

   • Initial dose: 4-5 g IV over 1 hour
   • Followed by continuous infusion of 1 g/hour for 8 hours or until bleeding is controlled

3. Supportive measures:

   • Volume resuscitation with crystalloids and blood products as needed
   • Maintain hemodynamic stability
   • Consider platelet transfusion if platelet count is low
   • Fresh frozen plasma may be given to replenish clotting factors

4. Monitor for:

   • Ongoing bleeding
   • Hemodynamic parameters
   • Hemoglobin/hematocrit levels
   • Coagulation parameters

Important Clinical Considerations

• Streptokinase has a longer half-life (approximately 23 minutes) compared to other fibrinolytic agents, making reversal particularly important in cases of severe bleeding 2.

• Prior exposure to streptokinase (within 6 months) is an absolute contraindication to its use due to risk of allergic reactions, as streptokinase antibodies persist for at least 10 years 3.

• The European Society of Cardiology and American College of Cardiology guidelines recommend against readministering streptokinase to patients previously exposed due to risk of allergic reactions and reduced efficacy 2, 3.

• In cases where streptokinase was administered with adjunctive anticoagulation (heparin, enoxaparin, or fondaparinux), consider also reversing these agents if bleeding persists after aminocaproic acid administration 2.

Pitfalls to Avoid

• Do not delay treatment: Massive hematemesis following thrombolytic therapy represents a life-threatening emergency requiring immediate intervention.

• Do not confuse anticoagulant reversal with fibrinolytic reversal: Different agents are needed for different classes of medications (protamine for heparin, vitamin K for warfarin, aminocaproic acid for fibrinolytics).

• Do not readminister streptokinase: If further thrombolytic therapy is needed after bleeding is controlled, a non-immunogenic fibrinolytic agent should be considered 2.

• Do not overlook potential mechanical causes of bleeding: Urgent endoscopy may be needed to identify and potentially treat the source of hematemesis once the patient is stabilized.