What is the initial workup for a patient presenting with irregular bleeding?

Initial Workup for Irregular Bleeding

Begin with pregnancy testing (urine or serum β-hCG), followed by transvaginal ultrasound as the primary imaging modality, combined with speculum examination to visualize the cervix and vagina, and initial hemostasis laboratory tests including CBC, PT, PTT, and consideration of von Willebrand disease screening in patients with strong bleeding history. 1, 2

Immediate First Steps

Exclude Pregnancy

• Obtain urine or serum β-hCG testing first in all reproductive-age women, as pregnancy-related bleeding requires a completely different evaluation pathway 1

Characterize the Bleeding Pattern

• Document timing relative to menstrual cycle (intermenstrual vs. heavy menstrual bleeding) 1
• Assess duration, volume, and frequency of bleeding episodes 1
• Determine if pattern suggests anovulatory (irregular, unpredictable) versus ovulatory (regular but heavy) bleeding 3

Obtain Targeted History

• Hormonal contraceptive use (can cause breakthrough bleeding) 1
• Anticoagulant or antiplatelet medications (increases bleeding risk) 1, 4
• Personal bleeding history: easy bruising, nosebleeds, prolonged bleeding from minor cuts, heavy bleeding after dental procedures or surgery 2
• Family history of bleeding disorders (von Willebrand disease, hemophilia carriers) or Lynch syndrome (endometrial cancer risk) 1, 5
• Thyroid symptoms (hypothyroidism/hyperthyroidism can cause menstrual irregularities) 3
• Signs of polycystic ovary syndrome: irregular cycles, hirsutism, acne 3
• Medications: antipsychotics, antiepileptics (can cause anovulation) 3

Physical Examination

Speculum Examination

• Visualize cervix and vagina for trauma, cervicitis, cervical polyps, lacerations, or masses 1, 2
• Perform cervical cytology if age-appropriate (typically ≥21 years) 1
• If cervical lesions visualized, consider colposcopy with directed biopsy 1

Bimanual and External Examination

• Assess uterine size and contour (enlarged suggests fibroids or adenomyosis) 1
• Palpate for adnexal masses or tenderness 1
• Inspect external genitalia for vulvar lesions 1
• Look for signs suggesting systemic causes: ecchymoses, petechiae, hepatosplenomegaly, jaundice, joint hypermobility (Ehlers-Danlos), telangiectasias 2

Initial Laboratory Testing

Basic Hemostasis Panel

Order these initial tests in all patients with irregular bleeding and concerning bleeding history: 2

• Complete blood count (CBC) with platelet count (assess for anemia, thrombocytopenia) 2
• Prothrombin time (PT) (screens for factor VII deficiency, liver disease) 2
• Activated partial thromboplastin time (PTT) (screens for factors VIII, IX, XI, XII deficiencies) 2

Von Willebrand Disease Screening

If mucocutaneous bleeding history is strong (heavy menstrual bleeding, easy bruising, nosebleeds, prolonged bleeding from minor trauma), order initial VWD assays with the initial visit: 2

• VWF antigen (VWF:Ag) 2
• VWF ristocetin cofactor activity (VWF:RCo) 2
• Factor VIII coagulant activity (FVIII) 2

Common pitfall: Von Willebrand disease is the most common inherited bleeding disorder (affects up to 1% of population) and is frequently missed in women with heavy menstrual bleeding. 2, 3

Additional Laboratory Tests Based on Clinical Suspicion

• Thyroid-stimulating hormone (TSH) if symptoms suggest thyroid dysfunction 3
• Prolactin level if galactorrhea or amenorrhea present 3
• Hemoglobin A1c if diabetes suspected 3
• Blood type and crossmatch if severe bleeding with hemodynamic instability 2
• Serum electrolytes, BUN, creatinine if severe bleeding 2

Imaging Studies

Transvaginal Ultrasound (Primary Imaging)

TVUS is the mainstay imaging modality and should be obtained in most patients with irregular bleeding: 1, 3

• Evaluates endometrial thickness and appearance (thickened endometrium >4mm postmenopausal or irregular appearance suggests pathology) 1
• Assesses myometrium for leiomyomas (fibroids) and adenomyosis 1
• Examines ovaries for masses or cysts (polycystic ovaries, ovarian tumors) 1
• Visualizes cervical canal for polyps or structural abnormalities 1

Alternative Imaging

• Saline infusion sonohysterography can better delineate endometrial polyps and submucosal fibroids 3
• MRI with diffusion-weighted imaging if TVUS inadequate or superior tissue characterization needed 1

Endometrial Sampling

Indications for Endometrial Biopsy

Endometrial sampling is indicated in the following scenarios: 1, 3

• Age ≥35 years with recurrent anovulation 3
• Age <35 years with risk factors for endometrial cancer: chronic anovulation (PCOS), obesity, family history of Lynch syndrome, prolonged unopposed estrogen exposure 1, 3
• Persistent unexplained bleeding despite medical management 1
• Excessive bleeding unresponsive to medical therapy 3

At age 18, endometrial sampling is generally NOT indicated unless specific risk factors are present. 1

Risk Stratification for Severe Bleeding

Assess Hemodynamic Stability

• Calculate shock index (heart rate ÷ systolic blood pressure): >1 indicates unstable bleeding requiring urgent intervention 2
• Oakland score can stratify lower GI bleeding severity (though developed for GI bleeding, principles apply to assessing bleeding severity) 2

Signs of Severe Bleeding Requiring Urgent Management

• Hemodynamic instability (tachycardia, hypotension, shock index >1) 2
• Severe anemia (hemoglobin <7 g/dL) 2
• Active heavy bleeding requiring transfusion 2

Critical Considerations

Conditions Affecting VWD Testing

If ordering von Willebrand studies, be aware these factors can falsely elevate VWF levels: 2

• Acute stress, anxiety, recent exercise (delay testing if possible) 2
• Acute or chronic inflammatory illness 2
• Pregnancy or estrogen/oral contraceptive use 2
• Blood group O individuals have 25% lower baseline VWF levels (adjust interpretation) 2
• Ensure atraumatic blood draw at room temperature 2

When to Refer

• Hematology referral if abnormal coagulation studies, low VWF levels, or strong bleeding history with normal initial tests 2
• Gynecology referral if structural abnormalities identified on imaging requiring intervention 3
• Gynecologic oncology referral if endometrial biopsy shows hyperplasia with atypia or adenocarcinoma 3