What to do with a patient with suspected Deep Vein Thrombosis (DVT) and high risk of Pulmonary Embolism (PE) who is also presenting with leukocytosis and has an increased Prothrombin Time/International Normalized Ratio (PT/INR)?

Management of Elevated PT/INR in Suspected DVT/PE with High PE Risk and Leukocytosis

In a patient with suspected DVT/PE at high risk for PE who presents with an elevated PT/INR, you should immediately initiate parenteral anticoagulation while simultaneously investigating the cause of the coagulopathy, as the mortality benefit of preventing PE progression outweighs bleeding risk in most cases. 1

Immediate Anticoagulation Strategy

Start anticoagulation immediately without waiting for imaging confirmation when clinical suspicion is high, even with elevated PT/INR. 1, 2 The British Thoracic Society explicitly recommends that heparin should be given to patients with intermediate or high clinical probability before imaging. 1

Choice of Anticoagulant with Elevated PT/INR

• Unfractionated heparin (UFH) is the preferred initial agent when rapid reversal of effect may be needed, which is critical in patients with baseline coagulopathy. 1

• Administer UFH as an initial bolus of 80 U/kg followed by continuous IV infusion at 18 U/kg/hour, adjusting to maintain aPTT prolongation corresponding to plasma heparin levels of 0.3-0.7 IU/mL anti-factor Xa activity. 1

• Avoid LMWH and fondaparinux initially in patients with elevated PT/INR because these agents cannot be rapidly reversed and dosing adjustments are more difficult to titrate. 1

Investigating the Elevated PT/INR

While anticoagulation proceeds, urgently determine the cause of the elevated PT/INR:

• If the patient is on warfarin: The elevated INR may represent therapeutic or supratherapeutic dosing. Continue anticoagulation but hold warfarin temporarily and monitor INR closely. 1

• If NOT on warfarin: Consider liver dysfunction (suggested by leukocytosis if infectious), vitamin K deficiency, consumptive coagulopathy (DIC), or inherited coagulation factor deficiencies. 1

• Leukocytosis context: The concurrent leukocytosis raises concern for sepsis-associated coagulopathy or underlying malignancy. Check liver function tests, complete coagulation panel (including fibrinogen and D-dimer), and blood cultures. 1

Diagnostic Imaging Timeline

• Perform imaging within 1 hour if massive PE is suspected (hemodynamic instability, shock, hypotension). 1

• Perform imaging ideally within 24 hours for non-massive PE. 1

• CTPA is the recommended initial imaging modality for non-massive PE. 1

• In patients with coexisting clinical DVT, leg ultrasound as the initial imaging test is often sufficient to confirm VTE. 1

Special Considerations for Bleeding Risk

The elevated PT/INR does NOT constitute an absolute contraindication to anticoagulation unless there is active bleeding or severe coagulopathy (INR >3.0-4.0 with bleeding manifestations). 3, 4

• If active bleeding is present, consider temporary IVC filter placement while holding anticoagulation, with plans to resume anticoagulation once hemostasis is achieved (typically within 7-14 days). 3

• If severe coagulopathy without bleeding exists, consider fresh frozen plasma to partially correct INR while maintaining therapeutic anticoagulation with UFH. 1

Transition to Oral Anticoagulation

• Do not commence oral anticoagulation until VTE has been reliably confirmed. 1

• Once VTE is confirmed and PT/INR etiology is clarified, overlap UFH with warfarin for at least 5 days and until INR is ≥2.0 for at least 24 hours. 1, 2

• Target INR should be 2.0-3.0 when warfarin is used. 1

• If the patient has underlying liver disease or other causes of baseline elevated PT/INR, consider using a DOAC (apixaban, rivaroxaban, edoxaban, or dabigatran) instead of warfarin once acute phase is complete, as these do not require INR monitoring. 1, 5

Common Pitfalls to Avoid

• Do not delay anticoagulation while investigating the elevated PT/INR unless there is active bleeding or INR >4.0 with high bleeding risk. 1, 2

• Do not use LMWH as first-line therapy in patients with coagulopathy requiring potential rapid reversal. 1

• Do not assume elevated PT/INR alone is sufficient reason to withhold anticoagulation—the risk of fatal PE typically exceeds bleeding risk in high-probability cases. 1, 2

• Do not forget to investigate underlying causes of both the leukocytosis and coagulopathy, as sepsis, malignancy, or liver disease may fundamentally alter management. 1