In a middle-aged female taking oral contraceptives (OCs) who develops a bilateral pulmonary embolism with hypotension, would you consider starting intravenous (IV) heparin or tissue plasminogen activator (tPA) first?

Thrombolytic Therapy (tPA) Should Be Initiated First in This High-Risk Patient

In a middle-aged female with bilateral pulmonary embolism and hypotension, thrombolytic therapy (tPA or streptokinase) should be started immediately, as hemodynamic instability is the primary indication for thrombolysis and is associated with high mortality without rapid clot dissolution. 1, 2

Clinical Reasoning

Hypotension Defines High-Risk PE Requiring Thrombolysis

• Hemodynamic instability, particularly hypotension, is the primary indication for thrombolytic therapy in pulmonary embolism 1
• Thrombolysis is indicated primarily in patients who are hemodynamically unstable, as these patients have the most to gain from rapid clot dissolution 1, 3
• The condition of hypotensive patients with right ventricular overload from acute PE is typically made worse by fluid challenges; immediate thrombolysis is the standard of care for any patient with significant hypoxemia or hypotension due to proven PE 2
• Bilateral PE with hypotension represents massive pulmonary embolism with high mortality risk without aggressive intervention 2

Thrombolytic Agents and Dosing

For rtPA (recombinant tissue plasminogen activator):

• Administer 100 mg over 2 hours intravenously 1
• Alternative dosing: 0.6 mg/kg bolus over 15 minutes (maximum 50 mg) has been shown equally effective with similar bleeding risk 1
• rtPA accelerates normalization of pulmonary artery pressure and pulmonary perfusion much more rapidly than heparin alone 1

For streptokinase (alternative if rtPA unavailable):

• Initial dose: 250,000 units over 20 minutes 1
• Maintenance: 100,000 units/hour for 24 hours 1
• Must administer hydrocortisone concurrently to prevent further circulatory instability and reduce allergic reactions 1, 3
• Hypotension during streptokinase infusion is common and rate-related; slower infusion may reduce severity 3

Heparin Management During Thrombolysis

• Stop heparin before initiating thrombolytic therapy 1
• After thrombolysis is complete, resume heparin at maintenance dose of 1,280 IU/hour (or 18 IU/kg/hour) as continuous infusion once aPTT is less than twice the upper limit of normal 1, 4
• Target aPTT: 1.5-2.5 times control (45-75 seconds) 1, 4, 5

Practical Algorithm

Immediate Actions (First 15 Minutes)

1. Confirm diagnosis and assess hemodynamic status - hypotension (SBP <90 mmHg) mandates thrombolysis 1, 3
2. Screen for absolute contraindications to thrombolysis:
   • Recent hemorrhage 1
   • Recent stroke 1
   • Current gastrointestinal bleeding 1
3. If no absolute contraindications exist, initiate thrombolytic therapy immediately 1, 2

Thrombolytic Administration

• Preferred agent: rtPA 100 mg IV over 2 hours 1
• If using streptokinase, give hydrocortisone first, then 250,000 units over 20 minutes followed by 100,000 units/hour 1, 3
• Monitor blood pressure every 5 minutes during first 20 minutes of infusion 3
• Thrombolysis can be effective up to 14 days after the embolic event 1

Post-Thrombolysis Management

• Resume heparin after thrombolysis when aPTT <2× upper limit of normal 1
• Weight-adjusted heparin dosing: 18 IU/kg/hour continuous infusion 4, 5
• Monitor aPTT 4-6 hours after starting heparin, then after dose adjustments 4, 5
• Continue heparin for at least 5 days while overlapping with warfarin 4, 5

Critical Caveats

Oral Contraceptive Context

• Oral contraceptives are a recognized risk factor for venous thromboembolism, though classified as a minor risk factor 1
• This patient requires specialist advice regarding future contraception after recovery 1
• The contraceptive should be discontinued immediately 6, 7

Bleeding Risk Considerations

• Major bleeding with heparin occurs in approximately 10% of high-risk patients versus 1% in low-risk patients 1
• Thrombolysis carries higher bleeding risk than heparin alone, but mortality benefit in hemodynamically unstable PE outweighs this risk 1, 2
• The risk-benefit ratio strongly favors thrombolysis in hypotensive patients with massive PE 1

Alternative if Thrombolysis Fails

• Surgical embolectomy should be considered if patient fails to respond to thrombolytic therapy within the first hour 1
• Emergency thoracotomy or femorofemoral cardiopulmonary bypass may be necessary for full cardiac arrest from PE 2

Supportive Care

• Avoid aggressive fluid resuscitation - hypotension may be relieved by preload reduction or gentle diuresis 2
• Pressor agents of choice if needed: norepinephrine, isoproterenol, or epinephrine 2
• Standard CPR is ineffective when pulmonary circulation is obstructed by thrombus 2