What is the role of hematology in determining the cause of pulmonary embolism (PE)?

Role of Hematology in Determining the Cause of Pulmonary Embolism

Hematology consultation should be reserved for patients with unprovoked PE, recurrent VTE, unusual site thrombosis, or those with a strong family history of thrombosis to evaluate for underlying thrombophilia. 1

Initial Diagnostic Approach for PE

The diagnosis of pulmonary embolism follows a structured approach:

1. Clinical probability assessment:

   • Evaluate symptoms (dyspnea, chest pain, hemoptysis, syncope)
   • Assess risk factors (immobilization, surgery, trauma, previous DVT/PE, malignancy)
   • Use validated clinical prediction tools (Wells score or revised Geneva score) 2

2. Initial testing:

   • D-dimer testing (for low/intermediate probability cases)
   • CT pulmonary angiography (CTPA) as first-line imaging test
   • Echocardiography (essential in suspected high-risk PE)
   • Lower limb compression ultrasound when appropriate 2, 1

When Hematology Consultation Is Indicated

Hematology consultation is not routinely needed for all PE cases but is valuable in specific scenarios:

Indications for Thrombophilia Testing and Hematology Referral:

• Unprovoked PE (no identifiable risk factors)
• Recurrent venous thromboembolism
• Thrombosis at unusual sites
• Strong family history of thrombosis
• PE in young patients (<40 years) without risk factors
• Pregnancy-associated thrombosis
• Warfarin-induced skin necrosis 1, 3

Timing of Thrombophilia Testing:

• Not during acute thrombosis - acute thrombosis affects many test results
• Not while on anticoagulation therapy - especially warfarin which affects protein C and S levels
• Optimal timing: 2-4 weeks after completing anticoagulation therapy 3

Thrombophilia Evaluation Components

When indicated, hematology evaluation may include testing for:

1. Hereditary thrombophilias:

   • Factor V Leiden mutation
   • Prothrombin gene mutation (G20210A)
   • Protein C deficiency
   • Protein S deficiency
   • Antithrombin deficiency

2. Acquired thrombophilias:

   • Antiphospholipid syndrome (lupus anticoagulant, anticardiolipin antibodies, anti-β2 glycoprotein I)
   • Paroxysmal nocturnal hemoglobinuria
   • Myeloproliferative neoplasms 3

Important Considerations and Pitfalls

• Avoid routine thrombophilia testing in patients with provoked PE (e.g., after surgery, immobilization)
• Testing during acute thrombosis or anticoagulation can lead to false results
• Thrombophilia testing rarely changes immediate management of the acute PE event
• Family testing should be considered only when results would influence clinical decisions (e.g., female relatives considering estrogen therapy or pregnancy) 3
• Multidisciplinary approach involving hematology as part of a PE response team (PERT) is recommended for complex cases 1

Clinical Impact of Hematology Evaluation

The identification of an underlying thrombophilia may impact:

• Duration of anticoagulation therapy - indefinite anticoagulation may be recommended for certain thrombophilias with high recurrence risk
• Family screening - particularly relevant for hereditary thrombophilias
• Management of special situations - pregnancy, surgery, or hormonal therapy in patients with known thrombophilias 3

Hematology consultation should be considered as part of a comprehensive approach to PE management, particularly in cases where the cause is not readily apparent and where identification of an underlying thrombophilia would impact long-term management decisions.