Laboratory Evaluation for Heavy Menstrual Bleeding

Initial Mandatory Tests

Pregnancy testing (beta‑hCG) should be performed in every reproductive‑age individual presenting with abnormal uterine bleeding to rule out pregnancy‑related hemorrhage (American College of Obstetricians and Gynecologists recommendation) [5][6].
A complete blood count (CBC) is required to detect anemia from blood loss and to evaluate platelet count abnormalities (thrombocytopenia or thrombocytosis) that may contribute to bleeding (American Society of Hematology guidance) [3][4]7.
Prothrombin time (PT) and activated partial thromboplastin time (PTT) should be obtained to screen for coagulation factor deficiencies; these tests do not assess von Willebrand disease (American Society of Hematology guidance) [3][4]7.

Order the three VWD assays together as the initial evaluation:
- VWF antigen (VWF:Ag) – quantifies von Willebrand factor protein.
- VWF ristocetin cofactor activity (VWF:RCo) – measures functional activity of VWF.
- Factor VIII coagulant activity (FVIII) – reflects VWF‑mediated stabilization of factor VIII.
The combined results establish the presence, type, and severity of VWD when abnormal (American Society of Hematology guidance) [3][4]7.
VWD affects up to 1 % of the general population and is responsible for heavy menstrual bleeding in roughly 90 % of affected women (American Society of Hematology epidemiologic data) [1][2].

Guidelines advise obtaining VWD studies at the initial presentation, but recognize that acute bleeding episodes can transiently elevate VWF and FVIII levels, potentially obscuring a diagnosis (American Society of Hematology recommendation) [1][2].

Thyroid‑stimulating hormone (TSH) testing is recommended because thyroid dysfunction can cause anovulatory bleeding and alter coagulation (American Academy of Family Physicians guidance) 8.
Serum prolactin measurement should be considered, as hyperprolactinemia may lead to anovulation and abnormal uterine bleeding (American Academy of Family Physicians guidance) 8.

Utilize a validated bleeding assessment tool; approximately 80 % of clinicians managing bleeding disorders report routine use (International Society on Thrombosis and Haemostasis survey) [9][10].
A personal or family history of bleeding symptoms should trigger referral to a hematology specialist (American Society of Hematology recommendation) 1.

If initial VWD results are markedly low or the VWF:RCo/VWF:Ag ratio falls below 0.5–0.7, proceed with specialized assays such as multimer analysis to determine VWD subtype (American Society of Hematology recommendation) [3][4]7.
These advanced studies are technically complex and should be coordinated with a hematologist (American Society of Hematology recommendation) [1][2].

Signs of anemia (e.g., pallor, tachycardia) are important adjuncts to laboratory evaluation (American Society of Hematology guidance) 4.
Bleeding stigmata—including ecchymoses, hematomas, and petechiae—should be recorded (American Society of Hematology guidance) 4.
Evidence of liver disease (e.g., jaundice, splenomegaly) may affect coagulation and warrants documentation (American Society of Hematology guidance) 7.
Features of connective‑tissue disorders (joint/skin laxity, telangiectasia) can be associated with bleeding diatheses (American Society of Hematology guidance) 4.
A focused gynecologic exam for anatomic lesions or cervical pathology should be performed after excluding pregnancy (American Society of Hematology guidance) [3][4]7.

Do not rely on bleeding time or platelet function analyzer (PFA‑100) for routine VWD screening, as evidence does not support adequate sensitivity or specificity (American Society of Hematology consensus) [3][4]7.
PT and PTT are universally endorsed as baseline hemostatic tests for unexplained bleeding; however, VWD‑specific testing remains essential when clinical suspicion is present (International Society on Thrombosis and Haemostasis consensus) [9][10].