What laboratory tests should be ordered for a patient with frequent nosebleeds?

Laboratory Testing for Frequent Nosebleeds

For patients with frequent nosebleeds, obtain a complete blood count (CBC) with platelets and peripheral smear, PT/INR, aPTT, fibrinogen level, von Willebrand factor antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), Factor VIII coagulant activity, ABO blood group, and iron studies as your first-line panel. 1

First-Line Laboratory Panel

The American Society of Hematology recommends a comprehensive initial workup that includes:

• CBC with platelets and peripheral smear to evaluate for thrombocytopenia and abnormal platelet morphology 1
• PT/INR to assess the extrinsic coagulation pathway 1, 2
• aPTT to evaluate the intrinsic coagulation pathway 1, 2
• Fibrinogen level (Clauss method) to assess for fibrinogen disorders and consumptive coagulopathies 1, 2
• Von Willebrand factor testing (VWF:Ag, VWF:RCo, and Factor VIII) should be included in first-line testing, as 84% of specialists include this panel in initial bleeding evaluations 1, 3
• ABO blood group because type O patients have 25-30% lower VWF levels than type AB, affecting interpretation of VWF assays 1, 3
• Iron studies (ferritin, serum iron, total iron-binding capacity) to evaluate for chronic blood loss 1, 2

Clinical Context That Guides Testing Decisions

Use a structured bleeding assessment tool to quantify bleeding severity, as 80% of specialists rely on these instruments to guide testing decisions. 1, 3 Key historical features include:

• Frequency and duration of epistaxis episodes (>30 minutes over 24 hours suggests severity) 4
• Bilateral versus unilateral bleeding (bilateral suggests systemic cause) 5
• History of hospitalization, blood transfusion, or >3 recent episodes 4
• Family history of recurrent nosebleeds 4
• Comorbid conditions (hypertension, cardiopulmonary disease, anemia, bleeding disorders, liver or kidney disease) 4
• Medication use, particularly anticoagulants or antiplatelet agents 4

When Laboratory Testing May Be Unnecessary

In pediatric patients, laboratory tests should be reserved for specific situations rather than routine use:

• Perform testing in cases with chronic disease history, bilateral bleeding, active bleeding at presentation, or nontraumatic epistaxis 5
• Avoid routine testing in children with unilateral, brief (<5 minutes), traumatic epistaxis without chronic disease 5
• Standardized bleeding questionnaires help determine which pediatric patients warrant hematologic testing 6

Second-Line Testing (When First-Line Tests Are Normal But Bleeding Persists)

If initial testing is normal but the bleeding history remains convincing:

• Intrinsic pathway factors (FVIII, FIX, FXI) if aPTT is normal 1, 2
• Extrinsic pathway factors (FII, FV, FVII, FX) if PT/INR is normal 1, 2
• Factor XIII activity, which is frequently overlooked but clinically important 1
• Light transmission aggregometry with multiple agonists (ADP, collagen, epinephrine, ristocetin, arachidonic acid) for suspected platelet function defects 1
• Platelet flow cytometry to evaluate platelet surface glycoproteins and activation markers 1
• VWF multimer analysis if VWF:RCo/VWF:Ag ratio is <0.5-0.7 or initial VWD testing shows abnormal results 1, 3

Critical Pre-Analytical Considerations

To ensure accurate results:

• Discontinue aspirin and NSAIDs for at least 7-10 days before platelet function testing 1
• Avoid testing during acute illness, pregnancy, recent exercise, or stress, as these elevate VWF and FVIII levels 3
• Ensure atraumatic blood draw and proper sample handling at room temperature 3
• Freeze samples at ≤-40°C if testing will be delayed beyond 2 hours 3

Interpretation Thresholds

• VWF:RCo <30 IU/dL indicates definitive von Willebrand disease 3
• VWF:RCo 30-50 IU/dL with supportive clinical/family history suggests likely VWD 3
• VWF:RCo/VWF:Ag ratio <0.5-0.7 suggests Type 2 (qualitative) VWD rather than Type 1 1, 3
• Factor activity <20% reliably correlates with bleeding risk 2
• Prolonged PT and/or aPTT that corrects with 50:50 mix indicates factor deficiency rather than inhibitor 2

When to Refer to a Hemostasis Specialist

Immediate referral is indicated for:

• Abnormal initial VWD assay results requiring subtyping 1, 3
• Strong bleeding history with repeatedly normal tests (bleeding disorder of unknown cause) 1
• Suspected acquired von Willebrand syndrome 3
• Need for specialized assays (VWF multimer analysis, genetic sequencing) 1, 3

Common Pitfalls to Avoid

• Do not rely on PT/aPTT alone as screening tests, as they miss many bleeding disorders including mild von Willebrand disease and platelet function defects 1, 3
• Do not order single tests in isolation—the complete panel is required to avoid misdiagnosis 3
• Do not forget to check INR control in patients taking coumarins, as inadequate control is common 7
• Remember that normal initial tests do not exclude bleeding disorders—repeat testing or second-line investigations may be necessary given the high coefficient of variation (10-30%) in VWF assays 1, 3