What are the causes of elevated Prothrombin Time (PT), International Normalized Ratio (INR), and Partial Thromboplastin Time (PTT) in a patient with menorrhagia?

Causes of Elevated PT/INR and PTT in Patients with Menorrhagia

In a patient presenting with menorrhagia and elevated PT/INR and PTT, you should immediately investigate for inherited bleeding disorders (particularly von Willebrand disease), acquired coagulopathies (liver disease, DIC, consumptive coagulopathy), and anticoagulant medications, as these represent the most life-threatening and treatable causes.

Primary Diagnostic Categories

Inherited Bleeding Disorders

• Von Willebrand disease is the most common inherited coagulation disorder causing menorrhagia, affecting approximately 20% of women with menorrhagia once pelvic abnormalities are excluded 1, 2.
• Factor VIII, Factor IX, Factor XI deficiencies can present with menorrhagia and abnormal coagulation studies 2.
• Platelet function disorders (Bernard-Soulier syndrome, Glanzmann thrombasthenia) may present with menorrhagia and can affect coagulation testing 3.

Acquired Coagulopathies Affecting Both PT/INR and PTT

Consumptive Coagulopathy:

• Disseminated intravascular coagulation (DIC) causes consumption of coagulation factors, leading to elevated PT/INR and PTT, with fibrinogen typically <1 g/L in severe cases 4.
• Adenomyosis can activate both coagulation and fibrinolysis systems during menstruation, particularly in patients with uterine volume ≥100 cubic centimeters, potentially causing both thrombosis risk and worsening menorrhagia 5.

Liver Disease:

• Hepatic dysfunction impairs synthesis of vitamin K-dependent factors (II, VII, IX, X) measured by PT/INR and other coagulation factors, causing elevation of both tests 4.
• Liver disease produces dysfunctional fibrinogen (dysfibrinogenemia) and should be anticipated to cause clinically significant coagulopathy 4.

Dilutional Coagulopathy:

• If the patient has experienced massive hemorrhage from menorrhagia, volume replacement with crystalloid and insufficient fresh frozen plasma can cause dilutional reduction of platelets, fibrinogen, and coagulation factors 4.

Anticoagulant Medications

Direct Effects on Both PT/INR and PTT:

• Unfractionated heparin prolongs both aPTT (primary monitoring parameter) and PT/INR 6.
• Direct thrombin inhibitors (argatroban, bivalirudin, dabigatran) prolong both aPTT and PT/INR 6.
• Warfarin therapy elevates PT/INR primarily, but can also increase aPTT even in the absence of heparin 7.

Essential Diagnostic Workup

Initial Laboratory Assessment

• Obtain complete blood count with peripheral smear, PT/INR, aPTT, fibrinogen level, and platelet count as the essential coagulation panel 6.
• Measure von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo), and Factor VIII levels in all patients with menorrhagia and abnormal coagulation studies 3.
• Check liver function tests (transaminases) and renal function (creatinine) to identify hepatic or renal dysfunction 3.
• Fibrinogen level is more sensitive than PT and aPTT for detecting developing dilutional or consumptive coagulopathy, with levels <1 g/L insufficient in massive hemorrhage 4.

Advanced Testing When Indicated

• Perform platelet aggregation studies by lumiaggregometer if there is history of nose and gum bleeding in addition to menorrhagia 3.
• Consider thromboelastography (TEG) or rotational thromboelastometry (ROTEM) when available to characterize coagulopathy comprehensively, particularly if massive bleeding is present 6.
• Measure D-dimer, thrombin-antithrombin complex (TAT), and soluble fibrin (SF) if DIC or consumptive coagulopathy is suspected 5.

Critical Clinical Context

History and Physical Examination Priorities

• Document bleeding history beyond menorrhagia: epistaxis, gum bleeding, easy bruising, prolonged bleeding from minor cuts, excessive bleeding with dental procedures or surgery 1, 2.
• Obtain detailed family history of bleeding disorders and parental consanguinity 3.
• Assess for medication use including warfarin, heparin, direct oral anticoagulants, NSAIDs, and antiplatelet agents 7.
• Evaluate for signs of liver disease (jaundice, hepatomegaly, spider angiomata) or systemic illness 4.

Age-Related Considerations

• In adolescents without bleeding history other than menorrhagia, absent family history of bleeding, and no parental consanguinity, menorrhagia may be dysfunctional and transient in approximately 50% of cases, allowing detailed coagulation assays to be postponed 3.
• External factors including age, phase of menstrual cycle, and hormonal therapy can influence coagulation factor levels 2.

Common Pitfalls to Avoid

• Do not rely solely on PT/INR and aPTT to guide management, as these tests monitor only the initiation phase of blood coagulation (first 4% of thrombin production) and can appear normal while overall coagulation remains abnormal 6.
• Do not use INR as a general predictor of bleeding risk in patients not on vitamin K antagonist therapy, as it was designed and validated specifically for monitoring warfarin therapy 6, 8.
• Recognize that PT/INR and aPTT can be confounded in coagulopathic states, potentially leading to inappropriate anticoagulant dosing if these tests are being used to monitor therapy 9.
• In pregnancy-related menorrhagia, use PT ratio and aPTT ratio ≥1.5 as the coagulopathy threshold rather than absolute values, as coagulation factors increase toward term 6.

Management Implications

• Patients with menorrhagia and identified bleeding disorders require specific treatments: hormonal therapy, tranexamic acid, or desmopressin depending on the underlying disorder 1, 2.
• Women with bleeding disorders are susceptible to hemorrhagic complications with invasive procedures and require prophylactic treatment 1.
• If consumptive or dilutional coagulopathy is present, target fibrinogen >1.5 g/L and platelet count >75 × 10⁹/L in the context of ongoing hemorrhage 4.
• All patients with menorrhagia and coagulation abnormalities should be co-managed by both gynecologists and hematologists 3.