What is the workup for a patient presenting with breakthrough bleeding?

Workup for Breakthrough Bleeding

Begin with a pregnancy test in all reproductive-age women, followed by focused history, physical examination with speculum exam, complete blood count, and transvaginal ultrasound as the primary imaging modality. 1

Immediate Initial Assessment

First-Line Testing

• Obtain urine or serum β-hCG immediately in all women of reproductive age, as pregnancy-related bleeding requires a completely different evaluation pathway 1
• Perform complete blood count (CBC) with platelet count to assess for anemia and thrombocytopenia 1
• Document the bleeding pattern: timing relative to menstrual cycle, duration, volume, and frequency 1

Critical History Elements

• Hormonal contraceptive use - combined oral contraceptives and progesterone-only pills commonly cause breakthrough bleeding 1, 2
• Anticoagulant or antiplatelet medications, which increase bleeding risk 1
• Personal bleeding history including easy bruising, nosebleeds, prolonged bleeding from minor cuts, and heavy bleeding after dental procedures or surgery 1
• Risk factors for endometrial cancer: obesity, diabetes, family history (particularly important in perimenopausal women) 3

Physical Examination

Speculum and Pelvic Examination

• Visualize the cervix and vagina for trauma, cervicitis, cervical polyps, lacerations, or masses 1
• Perform age-appropriate cervical cytology (typically ≥21 years) 1
• If cervical lesions are visualized, consider colposcopy with directed biopsy 1
• Assess uterine size and contour via bimanual exam - enlarged uterus suggests fibroids or adenomyosis 1
• Palpate for adnexal masses or tenderness 1

Systemic Examination

• Look for signs of bleeding disorders: ecchymoses, petechiae, hepatosplenomegaly, jaundice, joint hypermobility (Ehlers-Danlos), and telangiectasias 1

Laboratory Workup

Standard Coagulation Studies

• Prothrombin time (PT) to screen for factor VII deficiency and liver disease 1
• Activated partial thromboplastin time (PTT) to screen for factors VIII, IX, XI, XII deficiencies 1

Von Willebrand Disease Screening (if indicated)

• If strong mucocutaneous bleeding history is present, order: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII) 1
• Critical caveat: Ensure atraumatic blood draw at room temperature 1
• Be aware that VWF levels can be falsely elevated by acute stress, anxiety, recent exercise, inflammatory illness, pregnancy, estrogen/oral contraceptive use, and blood group O individuals have 25% lower baseline VWF levels 1

Imaging Studies

Primary Imaging

• Transvaginal ultrasound (TVUS) is the first-line imaging modality to evaluate: 3, 1
  • Endometrial thickness and appearance
  • Myometrium for leiomyomas (fibroids) and adenomyosis
  • Ovaries for masses or cysts
  • Cervical canal for polyps or structural abnormalities

Advanced Imaging (if needed)

• MRI of the pelvis without and with contrast if initial ultrasound is inconclusive or the endometrium cannot be fully visualized 3
• MRI is superior to ultrasound for diagnosing adenomyosis 3
• Sonohysterography should be performed if a polyp is suspected on the original ultrasound 3

Age-Specific Considerations

Perimenopausal Women (Critical)

• Endometrial biopsy is essential in perimenopausal women with breakthrough bleeding to rule out endometrial cancer or hyperplasia, even with normal imaging, due to high risk of malignancy in this age group 3
• The American College of Radiology emphasizes that endometrial cancer risk increases significantly in perimenopausal women 3
• Do not assume bleeding is simply due to perimenopause without thorough evaluation 3

Women on Hormonal Contraception

• Breakthrough bleeding typically subsides over time, with return to baseline within 3 months at higher estrogen doses (30 μg) but taking longer at lower doses (15-20 μg) 2
• Consider switching formulations if breakthrough bleeding persists beyond 3 cycles 4

Risk Stratification for Severe Bleeding

Hemodynamic Assessment

• Calculate shock index (heart rate ÷ systolic blood pressure) - a value >1 indicates unstable bleeding requiring urgent intervention 1
• Signs requiring urgent management: hemodynamic instability, severe anemia (hemoglobin <7 g/dL), active heavy bleeding requiring transfusion 1

When to Refer

• Refer to hematology if: abnormal coagulation studies, low VWF levels, or strong bleeding history with normal initial tests 1
• Refer to gynecology if: structural abnormalities requiring intervention, persistent bleeding despite medical management, or concern for malignancy 3

Common Pitfalls to Avoid

• Never skip pregnancy testing in reproductive-age women - this is the most critical first step 1
• Do not rely on imaging alone in perimenopausal women - endometrial biopsy is mandatory even with normal ultrasound 3
• Do not overlook coexisting pathologies such as adenomyosis when fibroids are identified 3
• Ensure proper technique when drawing blood for VWD studies to avoid false results 1