How should an intermediate‑high risk pulmonary embolism (PE) be managed in a patient with a recent (1‑week‑old) intracranial hemorrhage (ICH)?

Management of Intermediate-High Risk PE with Recent Intracranial Hemorrhage

In a patient with intermediate-high risk pulmonary embolism and a 1-week-old intracranial hemorrhage, systemic thrombolysis is absolutely contraindicated; initiate therapeutic anticoagulation with unfractionated heparin (UFH) immediately, consider catheter-directed interventions or surgical embolectomy if hemodynamic deterioration occurs, and use mechanical prophylaxis with intermittent pneumatic compression devices until anticoagulation is established. 1, 2, 3

Absolute Contraindication to Thrombolysis

• Recent intracranial hemorrhage within the past 6 months is an absolute contraindication to systemic thrombolysis. 1
• The ESC guidelines explicitly list "history of haemorrhagic stroke or stroke of unknown origin" as an absolute contraindication to fibrinolytic therapy for PE. 1
• Even in intermediate-high risk PE, where thrombolysis reduces hemodynamic decompensation, the PEITHO trial demonstrated a 2% incidence of hemorrhagic stroke with thrombolysis versus 0.2% with placebo—this risk is unacceptably elevated in patients with recent ICH. 1
• At 1 week post-ICH, the hemorrhage is still in the acute phase and thrombolysis would carry catastrophic bleeding risk. 1, 3

Immediate Anticoagulation Strategy

Start therapeutic anticoagulation with UFH immediately despite the recent ICH, as the mortality risk from untreated intermediate-high risk PE outweighs the hemorrhage expansion risk at 1 week. 1, 3, 4

• UFH is preferred over LMWH because it allows for rapid reversal with protamine sulfate if hemorrhage expansion occurs, and its short half-life provides better control in this high-risk scenario. 1
• The AHA/ASA guidelines support initiating prophylactic-dose anticoagulation at 24-48 hours post-ICH when hemorrhage is stable; at 1 week, therapeutic anticoagulation becomes reasonable given the life-threatening nature of intermediate-high risk PE. 2, 3
• A case report demonstrated successful management of massive PE 18 days post-ICH using UFH followed by rivaroxaban without recurrent hemorrhage, supporting this approach. 4

UFH Dosing Protocol

• Administer UFH as an 80 units/kg bolus followed by 18 units/kg/hour infusion, targeting aPTT of 1.5-2.5 times control (approximately 50-70 seconds). 4, 5
• Monitor aPTT every 6 hours initially, then every 24 hours once therapeutic range is achieved. 5
• Obtain urgent repeat head CT before initiating anticoagulation to document hemorrhage stability—any expansion is a contraindication. 2, 3

Mechanical Circulatory Support and Adjunctive Measures

If hemodynamic instability develops despite anticoagulation, proceed immediately to catheter-directed interventions or surgical embolectomy rather than systemic thrombolysis. 1

• Surgical pulmonary embolectomy is the recommended therapeutic alternative when thrombolysis is absolutely contraindicated in high-risk PE, and this applies to intermediate-high risk patients with deterioration. 1
• Catheter-directed thrombus aspiration or fragmentation can be performed without systemic thrombolytics and has been successfully used in patients with recent ICH. 5, 6
• Ultrasound-assisted catheter-directed thrombolysis uses only 10-25% of the systemic fibrinolytic dose, but even this carries ICH risk and should be avoided at 1 week post-hemorrhage. 7

Inhaled Nitric Oxide as Bridge Therapy

• If the patient develops hemodynamic instability while awaiting definitive intervention, inhaled nitric oxide (20-40 ppm) can be used as a selective pulmonary vasodilator to reduce right ventricular afterload and improve systemic hemodynamics. 6
• A case report demonstrated successful use of iNO in a patient with massive PE 8 days post-ICH, allowing stabilization for subsequent mechanical thrombectomy. 6

Mechanical Prophylaxis

Initiate intermittent pneumatic compression (IPC) devices immediately on both lower extremities. 2, 3

• IPC devices provide VTE protection without increasing bleeding risk and should be used continuously until therapeutic anticoagulation is established. 2
• Do not use graduated compression stockings alone—they are significantly less effective than IPC devices and multiple trials show they are ineffective for VTE prevention in ICH patients. 2, 3

Monitoring and Transition Strategy

• Obtain repeat head CT at 24-48 hours after initiating anticoagulation to assess for hemorrhage expansion. 2, 3
• If hemorrhage remains stable on UFH for 48-72 hours, consider transitioning to a NOAC (apixaban or rivaroxaban) rather than warfarin, as DOACs have lower intracranial hemorrhage risk. 3, 4
• Continue therapeutic anticoagulation for at least 3 months for the PE, with ongoing reassessment of bleeding risk. 4

Critical Pitfalls to Avoid

• Never administer systemic thrombolysis in this scenario, even if the patient deteriorates hemodynamically—proceed directly to mechanical interventions. 1, 3
• Do not delay anticoagulation beyond what is necessary to document hemorrhage stability on imaging—untreated intermediate-high risk PE carries significant mortality risk. 3, 4
• Avoid LMWH as the initial anticoagulant because it cannot be rapidly reversed if hemorrhage expansion occurs. 1
• Do not rely on prophylactic-dose anticoagulation for intermediate-high risk PE—therapeutic dosing is required given the presence of RV dysfunction. 1

Risk Stratification Context

• Intermediate-high risk PE is defined by the presence of both RV dysfunction (on echocardiography or CT) and elevated cardiac biomarkers (troponin), with preserved blood pressure. 1
• These patients have a 30-day mortality risk of approximately 3-15% without thrombolysis, compared to <1% in low-risk PE. 1
• The recent ICH fundamentally alters the risk-benefit calculation, making anticoagulation plus mechanical backup the safest strategy. 3, 4