What is the best treatment approach for a patient with segmental pulmonary embolism (PE) without heart strain, presenting with multiple small intracranial bleeds?

Management of Segmental PE Without Heart Strain in Patients with Multiple Small Intracranial Bleeds

Anticoagulation with unfractionated heparin (UFH) is the recommended treatment for this patient, as thrombolysis is absolutely contraindicated due to the intracranial hemorrhages, and UFH offers the advantage of rapid reversibility if bleeding complications occur. 1

Thrombolysis is Absolutely Contraindicated

• Multiple small intracranial bleeds represent an absolute contraindication to systemic thrombolysis, regardless of PE severity. 1
• The 2019 ESC guidelines explicitly list "history of hemorrhagic stroke or stroke of unknown origin" and "central nervous system neoplasm" as absolute contraindications, with recent head injury in the previous 3 weeks also contraindicated. 1
• Even in massive PE with hemodynamic instability, the presence of intracranial hemorrhage would preclude thrombolytic therapy due to the 1.7-2.2% risk of intracranial hemorrhage with thrombolysis, which would be catastrophic in a patient with existing bleeds. 1
• Since this patient has segmental PE without heart strain (low-risk PE), thrombolysis would not be indicated even in the absence of bleeding contraindications. 1

Anticoagulation Strategy

Initiate unfractionated heparin immediately rather than low-molecular-weight heparin (LMWH), despite LMWH being preferred for most PE patients. 2

Rationale for UFH Over LMWH:

• UFH can be rapidly reversed with protamine sulfate if intracranial bleeding worsens, providing a critical safety advantage in this high-risk scenario. 2
• The ability to monitor anticoagulation intensity with aPTT allows for precise titration in patients at extreme bleeding risk. 2
• UFH should be dosed with an 80 U/kg IV bolus followed by 18 U/kg/hour continuous infusion, targeting aPTT of 1.5-2.5 times control. 2

Evidence Supporting Anticoagulation Despite ICH:

• A retrospective neurosurgical series of 37 patients with PE demonstrated that heparin therapy can be used safely without intracranial or intraspinal bleeding in neurosurgical patients, including those with recent intracranial pathology. 3
• The mortality rate of untreated PE (59.4% in the neurosurgical series) far exceeds the bleeding risk when anticoagulation is carefully monitored. 3

Monitoring Requirements

Close neurological monitoring is mandatory to detect any expansion of intracranial hemorrhages:

• Serial neurological examinations every 2-4 hours initially. 2
• Consider repeat head CT at 24-48 hours to assess stability of intracranial bleeds before continuing anticoagulation. 2
• Continuous monitoring of aPTT to maintain therapeutic range without excessive anticoagulation. 2
• Monitor platelet count if UFH is continued beyond 5 days due to risk of heparin-induced thrombocytopenia. 2

Alternative Interventions if Anticoagulation Fails or is Truly Contraindicated

If the patient deteriorates hemodynamically or intracranial bleeding worsens on anticoagulation, consider:

IVC Filter Placement:

• IVC filters should be considered for patients at high risk of further emboli in whom anticoagulation is contraindicated. 1
• This provides mechanical protection against recurrent PE while the intracranial bleeds stabilize. 1
• Filter insertion should only be undertaken by an experienced interventional radiologist. 1

Catheter-Directed Interventions (if hemodynamic deterioration occurs):

• Ultrasound-assisted catheter-directed thrombolysis (U-ACDT) uses significantly lower doses of thrombolytic agents compared to systemic therapy, potentially reducing bleeding risk. 4, 5
• Case series have demonstrated successful use of U-ACDT in patients with "extreme bleeding risk" and contraindications to systemic thrombolysis, though this remains investigational. 5
• The SEATTLE II trial showed that catheter-directed low-dose fibrinolysis minimizes intracranial bleeding risk compared to systemic full-dose therapy. 4
• However, this should only be considered if the patient develops hemodynamic instability, as the current presentation is segmental PE without heart strain. 5

Inhaled Nitric Oxide (iNO):

• iNO is a selective pulmonary vasodilator that can improve hemodynamics in massive PE when thrombolysis is contraindicated. 6
• A case report demonstrated successful use in a patient with recent ICH who developed massive PE, showing immediate improvement in blood pressure. 6
• This represents a temporizing measure to stabilize hemodynamics while definitive therapy is arranged. 6

Critical Pitfalls to Avoid

• Do not delay anticoagulation while awaiting repeat imaging of the brain, as untreated PE carries higher mortality risk than the bleeding risk with careful anticoagulation. 2, 3
• Never use LMWH in this scenario despite its general superiority, as the inability to rapidly reverse it makes UFH the safer choice. 2
• Do not use fixed-dose UFH; weight-based dosing with aPTT monitoring is essential. 2
• Avoid thrombolysis entirely, even if the patient deteriorates hemodynamically—pursue mechanical interventions or catheter-directed approaches instead. 1, 5
• Do not withhold all treatment based on bleeding risk alone, as the 2020 ASH guidelines note that even patients with submassive PE have low 30-day mortality (around 1-2%) with anticoagulation alone. 1

Transition to Oral Anticoagulation

• Once the intracranial bleeds are confirmed stable on repeat imaging (typically after 5-7 days), transition to oral anticoagulation can be considered. 2
• Warfarin should be started only after PE is confirmed and intracranial bleeds are stable, overlapping with UFH for at least 5 days AND until INR reaches 2.0-3.0 for at least 24 hours. 2
• Target INR is 2.0-3.0, with initial warfarin dosing of 5 mg daily in most patients (lower in elderly). 2
• Direct oral anticoagulants (DOACs) may be considered as an alternative to warfarin once bleeding risk has diminished, though warfarin offers the advantage of reversibility with vitamin K. 1