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H. Are There Contraindications To Thrombolysis?

OBJECTIVE

Identify patients who have contraindications to thrombolytic therapy.

ANNOTATION

Patients with absolute contraindications to thrombolytic therapy should be considered for direct percutaneous revascularization. Relative contraindications are cautions only, where the relative risks and benefits must be weighted before administering the thrombolytic agent.

Absolute contraindications to thrombolysis, include the following:
  1. Previous hemorrhagic stroke at any time
  2. Other strokes or cerebrovascular events, within one year
  3. Known intracranial neoplasm
  4. Active internal bleeding (except menses)
  5. Suspected aortic dissection
  6. Acute pericarditis
Relative contraindications to thrombolysis, include the following:
  1. Severe, uncontrolled hypertension on presentation (i.e., blood pressure >180/110 mm Hg)
  2. Current use of anticoagulants in therapeutic doses
  3. Known bleeding problems
  4. Recent trauma (i.e., within 2 to 4 weeks) including head trauma or traumatic or prolonged (i.e., >10minutes) cardiopulmonary resuscitation (CPR)
  5. Recent major surgery (i.e., within 3 weeks)
  6. Non-compressible vascular punctures
  7. Recent internal bleeding (i.e., within 2 to 4 weeks)
  8. Prior exposure to streptokinase, if that agent is to be administered (i.e., 5 days to 2 years)
  9. Pregnancy
  10. Active peptic ulcer
  11. History of chronic, severe hypertension
  12. Age >75 years
  13. Stroke Risk Score > 4 risk factors:
    • Age >75 years
    • Female
    • African American descent
    • Prior stroke
    • Admission systolic blood pressure >160 mm Hg
    • Use of alteplase
    • Excessive anticoagulation (i.e., INR >4; APTT >24)
    • Below median weight (<65 kg for women; <80 kg for men)
  14. Cardiogenic shock (i.e., sustained systolic blood pressure <90 mmHg and evidence for end-organ hypoperfusion, such as cool extremities and urine output <30 cc/hr) and CHF
DISCUSSION

The most significant risk during the administration of thrombolytic agents is hemorrhage, the most catastrophic of which is intracranial hemorrhage. Intracranial hemorrhage carries a very high mortality rate. Although the risk of intracranial hemorrhage is <1% overall, it increases in select patient populations. In a retrospective cohort study of Medicare patients receiving thrombolytic agents from 1994-95, the rate of intracranial hemorrhage was associated with age >75 years, female gender, African American descent, prior stroke, admission systolic blood pressure >160 mmHg, use of alteplase, over-anticoagulation (INR >4; APTT >24), and low weight (i.e., <65 kg for women, <80 kg for men) (Brass et al., 2000). The risk of intracranial hemorrhage increased from .69% in patients with 0 to 1 risk factors, to 1.63% in patients with 3 risk factors, to 2.49% in patients with 4 risk factors.

Patients >age 75 years may actually have a survival disadvantage, if treated with thrombolytic agents. In a retrospective review of 7,864 thrombolytic-eligible, Medicare fee-for-service patients, aged 65 to 85 years, presenting with an AMI, thrombolysis was associated with a survival disadvantage, with a 30-day mortality hazard ratio of 1.38 (Thiemann et al., 2000).

Patients presenting with cardiogenic shock in the setting of an AMI have a high risk of death; from 50% to 80%. The use of thrombolytic agents has not been shown to affect this risk (Bates & Topol, 1991). In the SHOCK trial, 284 patients were randomized to either early revascularization or medical therapy, including thrombolysis. Intra-aortic balloon pumps (IABP) were encouraged in both groups. Though there was not a statistically significant mortality difference between groups at 30 days (46.7% in the revascularization group, 56.0% in the medical group, p=0.11), six-month mortality was significantly better in the revascularization group (50.3% versus 63.1%, p=0.027) (Hochman et al., 1999). Re-analysis of the SHOCK trial suggests that if direct percutaneous revascularization is not available, patients may be given thrombolytic agents with IABP support and immediately transferred to a center that can perform early revascularization (Sanborn et al., 2000).

EVIDENCE

Table 9. Absolute and Relative Contraindications to Thrombolysis
  Decision Criteria Sources of Evidence QE   R
1 Absolute contraindications to thrombolysis ACC/AHA AMI, 1996 III   E
2 Relative contraindications to thrombolysis ACC/AHA AMI, 1996 III   E
3 Relative contraindication: age >75 years Thiemann, 2000 II   D
4 Relative contraindication: stroke risk score >4 Brass, 2000 II   D
5 Relative contraindication: cardiogenic shock Bates, 1991
Hochman, 1999 		I   E

QE = Quality of Evidence; R = Recommendation (See Introduction.) *Note: This link will take you out of Module A.