How to assess bleeding risk in a patient on anticoagulation (Anti-Coagulant) therapy, such as warfarin or direct oral anticoagulants (DOACs) like apixaban (Apixaban) or rivaroxaban (Rivaroxaban)?

Assessing Bleeding Risk in Patients on Anticoagulation

Use a standardized risk stratification approach that evaluates both patient-specific bleeding risk factors and procedural bleeding risk when assessing patients on warfarin or DOACs like apixaban or rivaroxaban. 1

Patient-Specific Bleeding Risk Factors

High-Risk Clinical Features

Assess for the following patient characteristics that significantly increase bleeding risk:

• Serious comorbid diseases: Cerebrovascular disease, kidney disease (especially CKD stage 4/5), heart disease, and liver disease are independent risk factors for major bleeding 2, 3
• Advanced age: Older patients have elevated bleeding risk on anticoagulation 2
• Renal function: Calculate creatinine clearance (CrCl) as it directly impacts DOAC half-life and bleeding risk—patients with CrCl <30 mL/min have substantially prolonged drug half-lives (dabigatran: 27-30 hours vs. 13 hours with normal function) 1
• Concurrent medications: Antiplatelet agents (aspirin, clopidogrel), NSAIDs, and drugs that inhibit both P-gp and CYP3A4 (ketoconazole, itraconazole, ritonavir) significantly increase bleeding risk 1, 4

Timing-Related Risk

• Early treatment period: The risk for major bleeding during the first month of warfarin therapy is approximately 10 times higher than after the first year of therapy 2
• First 90 days of DOAC therapy: Bleeding incidence is 3.0%/year during initial 90 days compared to 1.2%/year afterwards (relative risk 2.5) 5

Procedural/Surgical Bleeding Risk Classification

Classify planned procedures using standardized categories to determine whether anticoagulation interruption is necessary 1:

• Low bleeding risk procedures: Continue anticoagulation without interruption
• High bleeding risk procedures: Withhold DOACs for 1-2 days (low bleeding risk) to 2-4 days (high bleeding risk) based on CrCl 1
• Critical site procedures: Include intracranial, intraspinal, intraocular, pericardial, intra-abdominal, retroperitoneal, intra-articular, or intramuscular with compartment syndrome risk 1

Laboratory Assessment

For Warfarin

• PT/INR measurement: Use INR to guide perioperative and bleeding management; therapeutic range is typically INR 2.0-3.0 for most indications 1, 2

For DOACs

When bleeding occurs or urgent procedures are needed, measure anticoagulant activity 1:

For dabigatran:

• Preferred: Dilute thrombin time, ecarin clotting time, or ecarin chromogenic assay
• Rapid exclusion: Normal thrombin time (TT) excludes clinically relevant dabigatran levels
• Qualitative: Prolonged aPTT suggests on-therapy or above-therapy levels, but normal aPTT does not exclude therapeutic levels

For apixaban, rivaroxaban, edoxaban:

• Preferred: Chromogenic anti-FXa assay calibrated with the specific drug
• Consider reversal if DOAC level >50 ng/mL with serious bleeding or >30 ng/mL with high-risk invasive procedure 1

Comparative Bleeding Risk Between Anticoagulants

Evidence-Based Risk Hierarchy

Based on recent head-to-head studies:

• Apixaban: Lowest major bleeding risk among DOACs and warfarin 6, 3, 7
• Rivaroxaban: Higher major bleeding risk than apixaban (HR 1.69), particularly gastrointestinal bleeding (HR 1.22 vs. apixaban) 6, 3, 7
• Warfarin: Highest bleeding risk—major bleeding HR 1.85 vs. apixaban, including intracranial bleeding (HR 2.15) and gastrointestinal bleeding (HR 1.86) 3

Specific Bleeding Patterns

• Gastrointestinal bleeding: Most common site during anticoagulation; rivaroxaban > warfarin > apixaban 4, 6, 3
• Intracranial hemorrhage: Rare but frequently fatal; warfarin has highest risk, rivaroxaban lower than apixaban (HR 0.86) 2, 6
• Soft tissue and urinary tract: Common bleeding sites requiring diagnostic evaluation even when anticoagulation is therapeutic 2

Clinical Bleeding Classification

Major Bleeding Criteria

Classify as major bleeding if ANY of the following are present 1, 8:

• Bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intra-abdominal, retroperitoneal, intra-articular, intramuscular with compartment syndrome)
• Hemodynamic instability
• Hemoglobin decrease ≥2 g/dL
• Transfusion requirement ≥2 units of packed RBCs

Critical caveat: Patients with cardiovascular disease (angina, MI, heart failure, peripheral artery disease) are more likely to die from hemoglobin drops than patients without CV disease 1

Non-Major Bleeding

Any bleeding not meeting major criteria; manage with local hemostatic measures and continued anticoagulation in most cases 9

Quantifying Baseline Bleeding Rates

Expected Bleeding Frequencies

During heparin therapy 2:

• Fatal bleeding: 0.05% per day
• Major bleeding: 0.8% per day
• Any bleeding: 2.0% per day

During warfarin therapy 2:

• Fatal bleeding: 0.6% per year
• Major bleeding: 3.0% per year
• Any bleeding: 9.6% per year

During DOAC therapy 4, 5:

• Major bleeding: 0.6-1.8% per year (varies by agent and indication)
• Lower rates with apixaban compared to warfarin or rivaroxaban

Common Pitfalls to Avoid

• Do not rely on ACCP bleeding risk score: This score has poor predictive value (c-statistic 0.50-0.56) and cannot reliably guide extended treatment decisions 5
• Do not assume normal aPTT excludes dabigatran effect: Insensitive aPTT reagents may show normal results despite therapeutic dabigatran levels 1
• Do not use fresh frozen plasma for DOAC reversal: FFP does not reverse DOAC anticoagulant effects to any appreciable degree 1
• Avoid bridging with heparin for DOACs: Bridging significantly increases major bleeding (6.5% vs. 1.8% for dabigatran, 2.7% vs. 0.5% for rivaroxaban) without reducing thromboembolism 1
• Evaluate GI bleeding and hematuria even when INR is elevated: Approximately one-third of cases reveal previously unknown lesions requiring treatment 2