What is the management for a patient on Eliquis (apixaban) with elevated PT and active bleeding?

Management of Bleeding on Apixaban with PT 17.3

Stop apixaban immediately, provide supportive care with volume resuscitation and local hemostatic measures, assess bleeding severity to determine if reversal agents are needed, and recognize that PT 17.3 (INR ~1.5) suggests clinically relevant apixaban levels but does NOT reliably quantify the degree of anticoagulation. 1, 2

Initial Assessment of Bleeding Severity

Classify the bleeding as major if ANY of the following criteria are met: 1, 2

• Bleeding at a critical site (intracranial, spinal, intraocular, pericardial, retroperitoneal, intra-articular, intramuscular with compartment syndrome risk) 1
• Hemodynamic instability (hypotension, tachycardia, signs of shock) 1
• Hemoglobin drop ≥2 g/dL or transfusion requirement ≥2 units RBCs 1

If none of these criteria are met, classify as nonmajor bleeding. 1

Understanding the PT 17.3 Result

Critical limitation: PT and aPTT are insensitive to apixaban and cannot be used to quantify drug levels or guide reversal decisions. 1, 2

• A prolonged PT suggests clinically important apixaban levels are present, but the degree of prolongation does NOT correlate linearly with drug concentration 1, 2, 3
• A normal PT does NOT exclude therapeutic or even supratherapeutic apixaban levels, as PT may remain normal at therapeutic concentrations depending on the reagent used 1, 2, 3
• The concentration needed to double PT ranges from 700-3900 μg/L (therapeutic range is typically 50-200 ng/mL), demonstrating poor sensitivity 3, 4
• Quantitative measurement requires anti-FXa assay calibrated specifically for apixaban or liquid chromatography-tandem mass spectrometry, but these are rarely available emergently 1, 2, 3

Management Algorithm Based on Bleeding Severity

For Life-Threatening or Critical Site Major Bleeding:

1. Stop apixaban immediately 1, 2

2. Administer reversal agent: 2

   • First-line: Andexanet alfa (specific reversal agent for apixaban) 2
     • Low-dose regimen: 400 mg IV bolus followed by 4 mg/min infusion × 120 minutes (if last dose ≤5 mg taken <8 hours prior) 2
     • High-dose regimen: 800 mg IV bolus followed by 8 mg/min infusion × 120 minutes (if last dose >5 mg taken <8 hours prior) 2
   • Alternative if andexanet alfa unavailable: 4-factor PCC at 50 IU/kg (clinical data shows 72.4% effective hemostasis) 2, 5

3. Provide supportive care: 1, 2

   • Volume resuscitation with crystalloids and blood products as needed 1
   • Local hemostatic measures and manual compression where applicable 1
   • Transfuse RBCs to maintain hemoglobin >7-8 g/dL (higher targets for cardiovascular disease) 1

4. Consider surgical/procedural intervention to control bleeding source 1, 2

5. Assess and manage comorbidities contributing to bleeding (thrombocytopenia, uremia, liver disease, concurrent antiplatelet therapy) 1

For Non-Life-Threatening Major Bleeding (No Critical Site):

1. Stop apixaban 1, 2

2. Provide local therapy/manual compression 1, 2

3. Supportive care and volume resuscitation 1, 2

4. Stop antiplatelet agents if applicable 1

5. Consider surgical/procedural management of bleeding source 1

6. Do NOT administer reversal agents unless bleeding progresses to life-threatening status 1

For Nonmajor Bleeding:

1. Consider continuing apixaban if there is an appropriate indication and bleeding is truly minor 1

2. Provide local therapy/manual compression 1

3. Assess risks/benefits of concomitant antiplatelet therapy 1

4. Verify appropriate dosing of apixaban (common cause of bleeding is inappropriate dosing) 6

Critical Pitfalls to Avoid

• Do NOT use vitamin K for apixaban reversal—it is completely ineffective for direct oral anticoagulants and only works for warfarin 2, 7
• Do NOT delay resuscitation while obtaining reversal agents; supportive care and local hemostatic measures should begin immediately 2
• Do NOT rely on normal PT/aPTT to exclude clinically significant apixaban levels 1, 2, 3
• Do NOT assume the PT 17.3 quantifies the degree of anticoagulation or guides reversal dosing 1, 2

Restarting Anticoagulation After Bleeding Control

Once bleeding is controlled and the patient is stable, consider restarting apixaban based on: 8, 2

Restart anticoagulation if ALL of the following are true: 8, 2

• Clinical indication for anticoagulation remains (e.g., atrial fibrillation with CHA₂DS₂-VASc ≥2, VTE treatment) 8
• Bleeding source has been identified and addressed 8, 2
• Patient is NOT at high risk of rebleeding 8, 2
• Bleeding did NOT occur at a critical site 2
• No planned surgical/invasive procedures 2

Timing: Apixaban can be resumed at least 6 hours after hemostasis is achieved, though the optimal timing depends on bleeding severity and thrombotic risk. 8

Delay or discontinue anticoagulation if: 2

• Bleeding occurred at a critical site (especially intracranial hemorrhage) 2
• High risk of rebleeding or death/disability with rebleeding 2
• Source of bleeding has not been identified 2
• Patient does not wish to restart anticoagulation 2

High-Risk Situations Requiring Extra Vigilance

• Advanced age (≥80 years), low body weight (≤60 kg), or renal impairment (CrCl 15-29 mL/min) may warrant dose reduction to 2.5 mg twice daily 7
• Severe renal impairment (CrCl <15 mL/min) is a relative contraindication to apixaban 8
• Drug-drug interactions with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) increase apixaban levels and bleeding risk 7
• Inappropriate dosing (either under- or overdosing) is a common cause of both thrombotic and bleeding complications 6