What initial laboratory tests should be ordered for a patient presenting with vaginal bleeding?

Initial Laboratory Testing for Vaginal Bleeding

Order a complete blood count (CBC) with platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and von Willebrand disease (VWD) screening panel (VWF antigen, VWF ristocetin cofactor activity, and Factor VIII) as your initial laboratory workup for patients presenting with vaginal bleeding. 1, 2

Essential First-Line Tests

Hematologic Assessment

• CBC with platelet count and peripheral smear is performed by 100% of hematology specialists to detect anemia from blood loss, thrombocytopenia, and abnormal platelet morphology that may indicate an underlying bleeding disorder 1, 2, 3
• Hemoglobin and hematocrit quantify the degree of blood loss and guide transfusion decisions 4, 3
• Iron studies (ferritin, serum iron, total iron-binding capacity) should be obtained to identify chronic blood loss and iron deficiency anemia 1, 2

Coagulation Screening

• PT/INR assesses the extrinsic coagulation pathway and is essential for detecting factor VII deficiency or liver disease 1, 2
• aPTT evaluates the intrinsic pathway and may be prolonged when Factor VIII is markedly reduced, though it is often normal in mild VWD 4, 1
• Fibrinogen level (Clauss method) rules out primary fibrinogen disorders 2

Von Willebrand Disease Screening Panel

This is critical because VWD is the most common inherited bleeding disorder, affecting up to 1% of the population, and menorrhagia is a hallmark presentation in women. 4, 5

The three mandatory tests that must be ordered simultaneously include:

• VWF antigen (VWF:Ag) measures the quantity of VWF protein (normal range 50-200 IU/dL) 1, 6
• VWF ristocetin cofactor activity (VWF:RCo) assesses VWF functional ability to bind platelets (normal range 50-200 IU/dL) 1, 6
• Factor VIII coagulant activity (FVIII) evaluates FVIII levels, which are carried and stabilized by VWF (normal range 50-200 IU/dL) 1, 6

These three tests are included in 84% of initial bleeding workups and should be ordered together as the initial evaluation panel when bleeding is suspected. 1, 2

Additional Essential Tests

Pregnancy-Related

• Quantitative hCG (beta-hCG) is mandatory because abnormal uterine bleeding in reproductive-age women must be considered a complication of pregnancy (threatened abortion, ectopic pregnancy, trophoblastic disease) until proven otherwise 5, 3

Blood Type

• ABO blood group testing is recommended because type O patients have 25-30% lower VWF levels than type AB, which affects interpretation of VWD screening results 1, 2

Additional Screening Based on Clinical Context

• Thyroid function tests (TSH) when hypothyroidism is suspected, as it can cause menorrhagia 5, 7
• Liver function tests if cirrhosis or hepatic dysfunction is suspected 5, 7
• Renal function (BUN, creatinine) particularly in elderly patients, as renal insufficiency impairs platelet function 4, 2

Critical Pre-Analytical Considerations for VWD Testing

Timing and patient factors significantly affect VWF levels and can lead to false-negative results:

• Avoid testing during acute illness, pregnancy, systemic inflammation, or within 48 hours of strenuous exercise, as these conditions falsely elevate VWF levels by 25-50% 1, 6
• Minimize patient stress during venipuncture, as stress increases VWF levels 1, 6
• Oral contraceptives and estrogen therapy elevate VWF and FVIII levels 4, 6

Sample handling is crucial:

• Blood samples must be transported at room temperature 1, 6
• Plasma should be separated promptly at room temperature 1, 6
• If testing will be delayed beyond 2 hours, samples must be frozen at or below -40°C 1, 6

Interpretation Thresholds

VWD Diagnosis

• VWF:RCo <30 IU/dL indicates definitive VWD 1
• VWF:RCo 30-50 IU/dL with supportive clinical/family history suggests likely VWD and warrants hematology referral 1, 2
• VWF:RCo/VWF:Ag ratio <0.5-0.7 suggests Type 2 (qualitative) VWD rather than Type 1 (quantitative deficiency) and requires VWF multimer analysis 1, 6

When to Order Second-Line Testing

If first-line tests are normal but bleeding history remains convincing, proceed to:

• Intrinsic pathway factors (FVIII, FIX, FXI assays) 2
• Extrinsic pathway factors (FII, FV, FVII, FX assays) 2
• Factor XIII activity (frequently overlooked but clinically important for delayed bleeding) 2
• Light transmission aggregometry with multiple agonists (ADP, collagen, epinephrine, ristocetin, arachidonic acid) to detect inherited platelet function defects 1, 2

Common Pitfalls to Avoid

• Never rely on a single test – no single laboratory test can screen for all forms of bleeding disorders 6
• Do not order VWF multimer analysis as initial screening – this complex, costly test should be reserved for reflex testing when initial VWD results are abnormal 1, 6
• Avoid bleeding time and PFA-100/200 as routine screening tools – conflicting data on sensitivity and specificity mean these are not recommended for initial evaluation 1, 6
• Do not forget to consider medication effects – anticoagulants (warfarin, heparin), antiplatelet agents (aspirin, clopidogrel, NSAIDs), and supplements alter coagulation and must be documented 2, 7

When to Refer to Hematology

Immediate referral to a hemostasis specialist is indicated for:

• Abnormal initial VWD assay results requiring subtyping 1, 2
• Strong bleeding history with repeatedly normal laboratory tests (possible bleeding disorder of unknown cause) 1, 2
• VWF:RCo between 30-50 IU/dL with supporting clinical or family evidence 1, 2
• Adolescents with menorrhagia, as coagulopathy (particularly VWD) should be assumed until proven otherwise 5
• Women with ovulatory dysfunctional uterine bleeding without anatomic lesion who fail medical or surgical therapy 5