What laboratory tests should be ordered for a patient with excessive and frequent menstrual bleeding?

Laboratory Evaluation for Excessive and Frequent Menses

Order a complete blood count with platelets, ferritin, thyroid-stimulating hormone, and coagulation screening (PT/aPTT, von Willebrand factor panel) as first-line laboratory tests for women presenting with excessive and frequent menstrual bleeding. 1, 2

Essential First-Line Laboratory Tests

Hematologic Assessment

• Complete blood count (CBC) with platelet count to detect anemia and thrombocytopenia, which are direct consequences of chronic blood loss and may indicate underlying coagulopathy 1, 2
• Ferritin level to assess iron stores, as iron deficiency is highly prevalent in women with bleeding disorders and persistent or recurrent iron deficiency may itself suggest a bleeding phenotype 1
• The 2024 ISTH guidelines note that FBC and ferritin were surprisingly not universally performed despite their importance, with only 65% ordering FBC and 69% ordering ferritin in first-line testing 1

Pregnancy Exclusion

• Quantitative β-hCG in all reproductive-aged women, as pregnancy complications remain the most common cause of abnormal bleeding in this population until proven otherwise 3, 4, 2

Endocrine Evaluation

• Thyroid-stimulating hormone (TSH) to detect hypothyroidism, an easily correctable cause of menstrual bleeding disorders 1, 3
• Prolactin level to assess for hyperprolactinemia causing ovulatory dysfunction 3
• The ISTH survey found thyroid function tests were performed in approximately 45% of cases, though they should be routine 1

Coagulation Screening

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) as initial coagulation screening 1
• Von Willebrand factor antigen and function assays (ristocetin cofactor activity or GP1b binding assay), as von Willebrand disease is more common than many physicians realize and is frequently underdiagnosed in women with menorrhagia 1, 4
• Factor VIII, IX, and XI assays if initial screening suggests a coagulation disorder 1
• Women with menorrhagia and high-risk factors (family history of bleeding, excessive bleeding with dental procedures or surgery, postpartum hemorrhage) warrant comprehensive coagulation testing 4

Second-Line Laboratory Tests

Advanced Coagulation Studies

• Platelet function testing (light transmission aggregometry or similar) if initial workup is unrevealing and clinical suspicion for platelet dysfunction remains high 1
• Fibrinogen level (Clauss method) as part of comprehensive hemostatic evaluation 1
• Rare factor deficiencies (factors II, V, VII, X, XIII) in selected cases with unexplained bleeding and normal initial coagulation studies 1

Special Populations Requiring Enhanced Screening

• Adolescents with menorrhagia should be screened for coagulopathy until proven otherwise, as bleeding disorders are the underlying cause in a substantial proportion 4
• Women with anovulatory dysfunctional uterine bleeding who fail medical or surgical therapy require coagulation screening 4
• Women with ovulatory bleeding without anatomic uterine lesions warrant coagulopathy evaluation 4

Tests That Are NOT Routinely Recommended

Limited Clinical Utility

• ABO blood group typing was performed in 80% of cases in the ISTH survey, but blood group-specific reference ranges for von Willebrand factor are not recommended and this test adds little diagnostic value 1
• Follicle-stimulating hormone (FSH) is not part of standard guidelines for evaluating abnormal uterine bleeding and does not help exclude malignancy 3

Critical Clinical Pitfalls to Avoid

• Do not skip ferritin testing even if CBC shows normal hemoglobin, as iron stores may be depleted before anemia develops, and recurrent iron deficiency itself suggests ongoing blood loss 1
• Do not accept normal screening coagulation tests (PT/aPTT) as adequate to exclude von Willebrand disease or platelet function disorders—these require specific assays 1
• Do not overlook medication history, particularly aspirin and NSAIDs, which affect platelet function and confound assessment of inherited platelet disorders 1
• Assess for joint hypermobility using the Beighton score, as hypermobility syndromes are associated with bleeding symptoms and were evaluated in only 55% of cases despite their clinical relevance 1

Integration with Imaging and Tissue Diagnosis

While laboratory tests are essential, they must be integrated with:

• Transvaginal ultrasound as the first-line imaging modality to identify structural causes (polyps, adenomyosis, leiomyomas, endometrial thickening) 5, 3, 2
• Endometrial biopsy in women ≥45 years or those with risk factors for endometrial cancer (obesity, diabetes, hypertension, unopposed estrogen exposure), as abnormal bleeding is present in 90% of endometrial cancer cases 5