What are the potential causes of prolonged International Normalized Ratio (INR) in a medically free female of reproductive age presenting with heavy menorrhagia?

Causes of Prolonged INR in a Medically Free Female with Heavy Menorrhagia

In a previously healthy woman presenting with heavy menorrhagia and prolonged INR, the most likely causes are acquired vitamin K deficiency (from dietary insufficiency or malabsorption), an underlying inherited bleeding disorder (particularly von Willebrand disease), or occult liver disease. 1, 2

Primary Diagnostic Considerations

Acquired Vitamin K Deficiency

• Vitamin K deficiency is a documented cause of severe menorrhagia with markedly elevated INR (>5.0) in otherwise healthy young women 1
• Look specifically for: inadequate dietary intake over weeks to months, consumption of high-energy drinks that may displace nutritious foods, fat malabsorption conditions, or prolonged antibiotic use affecting gut flora 1
• Laboratory pattern shows: prolonged PT/INR with prolonged aPTT, and reduced levels of factors II, VII, IX, and X (vitamin K-dependent factors) 1
• This responds rapidly to parenteral vitamin K administration, which can be both diagnostic and therapeutic 1

Inherited Bleeding Disorders

• Von Willebrand disease and other inherited bleeding disorders are present in 10-20% of adult women with objectively documented menorrhagia, and even higher (up to 20%) in adolescents presenting with heavy bleeding 2
• Essential workup includes: factor VIII level, von Willebrand factor antigen, von Willebrand factor functional assay (ristocetin cofactor activity), and complete coagulation factor assay 2
• Critical timing consideration: testing should ideally be performed BEFORE starting oral contraceptive therapy, as hormones artificially increase factor VIII and vWF levels, potentially masking the diagnosis 2
• Family history of bleeding (easy bruising, prolonged bleeding after dental procedures, postpartum hemorrhage) is a key historical feature 2

Occult Liver Disease

• Liver disease causes prolonged INR through decreased synthesis of clotting factors I, II, V, VII, and X 3, 4
• Even early or subclinical liver disease can manifest with coagulopathy before other signs become apparent 3
• Look for: subtle signs of chronic liver disease, alcohol use history, viral hepatitis risk factors, autoimmune markers, or metabolic liver disease 3
• The INR in liver disease reflects true synthetic dysfunction, unlike the reversible deficiency seen with vitamin K deficiency 4

Secondary Considerations

Consumptive Coagulopathy

• While less common in an outpatient setting, consumptive coagulopathy can occur with massive hemorrhage and is particularly associated with obstetric bleeding 4
• The fibrinogen level is more sensitive than PT/aPTT for detecting developing consumptive coagulopathy, with levels below 1.0 g/L being insufficient 4
• This would be accompanied by thrombocytopenia and elevated D-dimer 4

Lupus Anticoagulant

• Can cause prolonged PT/INR, though typically causes only slight PT prolongation 5, 3
• Consider if there is history of recurrent pregnancy loss, thrombotic events, or other autoimmune features 5

Critical Laboratory Evaluation Algorithm

Initial testing should include:

• Complete blood count with platelet count (to assess for thrombocytopenia and anemia severity) 2
• PT/INR and aPTT (to characterize the coagulopathy pattern) 2
• Fibrinogen level (more sensitive for consumptive coagulopathy than PT/aPTT) 4
• Ferritin (to assess iron stores from chronic blood loss) 2

Second-tier testing based on initial results:

• If both PT and aPTT prolonged: vitamin K level, factors II, VII, IX, X assay, and liver function tests 1
• If isolated PT prolongation: factor VII assay and liver function tests 5
• Von Willebrand disease workup: factor VIII, vWF antigen, vWF activity (ristocetin cofactor) 2
• Mixing study if lupus anticoagulant suspected 5

Common Pitfalls to Avoid

• Do not assume the INR elevation is causing the menorrhagia—the bleeding disorder may be causing both the menorrhagia AND the prolonged INR 2
• Do not start hormonal therapy before completing the coagulation workup, as it will artificially normalize factor VIII and vWF levels 2
• Do not use INR as a general screening test for bleeding risk in non-warfarin patients—it was designed and validated only for monitoring vitamin K antagonist therapy 5, 3
• Do not overlook dietary history, including fad diets, energy drink consumption, or eating disorders that may lead to vitamin K deficiency 1

Immediate Management Considerations

• If INR is markedly elevated (>5.0), administer parenteral vitamin K 5-10 mg while awaiting definitive diagnosis 1
• Correct severe anemia with iron supplementation or transfusion if hemodynamically significant 2
• Platelet count below 50 × 10⁹/L is strongly associated with hemorrhagic complications; target should be >75 × 10⁹/L in active bleeding 4
• Consider tranexamic acid (antifibrinolytic) as first-line medical therapy for menorrhagia while diagnostic workup proceeds 2, 6