What initial laboratory work‑up should hematology order for a non‑pregnant woman being evaluated?

Initial Laboratory Work-Up for Non-Pregnant Women in Hematology

For a non-pregnant woman being evaluated by hematology, order a complete blood count with differential and peripheral smear, PT/INR, aPTT, fibrinogen level, von Willebrand disease panel (VWF:Ag, VWF:RCo, FVIII), iron studies, and ABO blood typing as the essential first-line panel. 1, 2

Core First-Line Hematologic Panel

Complete Blood Count Assessment

• CBC with platelet count and peripheral blood smear is performed by 100% of hematology specialists and detects thrombocytopenia, anemia, abnormal platelet morphology, and other hematologic abnormalities. 2
• Hemoglobin and hematocrit quantify anemia severity and guide transfusion decisions. 1
• The peripheral smear identifies abnormal red cell morphologies that may indicate hemolysis, membranopathies, or other intrinsic red cell disorders. 3, 4

Coagulation Screening Tests

• PT/INR assesses the extrinsic coagulation pathway and detects factor VII deficiency or liver disease. 1, 5
• aPTT evaluates the intrinsic pathway; it may be prolonged with severe factor VIII deficiency but is often normal in mild von Willebrand disease. 1, 5
• Fibrinogen level (Clauss method) excludes primary fibrinogen disorders and should be included in the initial panel. 1, 2

Von Willebrand Disease Screening (Essential for Women)

• VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and Factor VIII activity (FVIII:C) must be ordered simultaneously, as this three-test panel is incorporated in 84% of initial bleeding work-ups and is the standard first-line evaluation. 1, 2, 5
• Normal reference ranges for all three tests are 50–200 IU/dL. 1, 5
• VWD affects up to 1% of the population, and menorrhagia is a common presenting symptom in women, making this screening particularly important in female patients. 1

Iron Studies and Blood Typing

• Iron studies (ferritin, serum iron, total iron-binding capacity) identify chronic blood loss and iron-deficiency anemia, which are common in women with menorrhagia. 1, 2
• ABO blood group typing is essential because individuals with blood type O have 25–30% lower VWF levels than those with type AB, directly affecting interpretation of VWD screening results. 1, 2, 5

Critical Pre-Analytical Considerations

Timing and Patient Factors

• Avoid testing during acute illness, pregnancy, systemic inflammation, or within 48 hours of strenuous exercise, as these conditions can falsely elevate VWF levels by 25–50%. 1, 5
• Minimize patient stress during venipuncture because stress also elevates VWF concentrations. 1, 5
• Document oral contraceptives and estrogen therapy, as these increase VWF and FVIII levels and affect result interpretation. 1

Sample Handling Requirements

• Transport blood specimens at room temperature. 1, 5
• Separate plasma promptly at room temperature. 1, 5
• If analysis is delayed beyond 2 hours, freeze samples at ≤ –40°C. 1, 5

Interpretation Thresholds for VWD Screening

• VWF:RCo < 30 IU/dL → definitive diagnosis of VWD. 1, 5
• VWF:RCo 30–50 IU/dL with compatible clinical or family history → probable VWD; refer to hematology specialist. 1, 5
• VWF:RCo / VWF:Ag ratio < 0.5–0.7 → suggests Type 2 (qualitative) VWD; requires VWF multimer analysis. 1, 5

Additional Laboratory Studies Based on Clinical Context

If Hemolysis Is Suspected

• Reticulocyte count serves as a useful screen for hemolysis or blood loss. 3, 6, 4
• Lactate dehydrogenase (LDH) is elevated in intravascular hemolysis. 3, 6
• Unconjugated bilirubin increases with hemolysis. 3, 6
• Haptoglobin is reduced in hemolytic conditions. 3, 6
• Direct antiglobulin test (Coombs) differentiates immune from nonimmune causes of hemolysis. 3, 6

If Bleeding History Is Significant

• Renal function tests (BUN, creatinine) are important, especially in older patients, since renal insufficiency can impair platelet function. 1, 2
• A comprehensive medication review including anticoagulants, antiplatelet agents, NSAIDs, and supplements is essential, as these alter coagulation results. 1, 2

Common Pitfalls to Avoid

• Do not rely on a single laboratory test; no single assay screens for all bleeding disorders. 1
• VWF multimer analysis should be reserved for reflex testing after abnormal initial VWD results, not for primary screening. 1, 5
• Bleeding time and PFA-100/200 are not recommended for routine screening due to limited sensitivity and specificity. 1, 5
• Do not order VWD testing during menstruation, acute illness, or recent exercise, as these falsely elevate results. 1, 5
• Always interpret ferritin in clinical context, as it is an acute phase reactant and may be falsely elevated in inflammatory states despite true iron deficiency. 7

When to Proceed to Second-Line Testing

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

• Intrinsic pathway factor assays (FVIII, FIX, FXI). 1, 2
• Extrinsic pathway factor assays (FII, FV, FVII, FX). 1, 2
• Factor XIII activity to evaluate for delayed bleeding disorders. 1, 2
• Light-transmission aggregometry with multiple agonists (ADP, collagen, epinephrine, ristocetin, arachidonic acid) to detect inherited platelet function defects. 1, 2

Indications for Immediate Hematology Specialist Referral

• Abnormal initial VWD assay results that require subtyping (e.g., low VWF:RCo with abnormal ratio). 1, 5
• Strong bleeding history with repeatedly normal laboratory studies, suggesting an occult bleeding disorder. 1, 2
• VWF:RCo values 30–50 IU/dL accompanied by supportive clinical or family evidence. 1, 5