What laboratory tests are indicated for a patient presenting with bleeding?

Laboratory Workup for Bleeding Patients

For any patient presenting with bleeding, immediately order a complete blood count with platelets and peripheral smear, PT/INR, aPTT, and fibrinogen level as your first-line tests. 1, 2, 3

First-Line Laboratory Tests (Order These Initially)

Essential Coagulation Studies

• Complete blood count (CBC) with platelets and peripheral blood smear to evaluate for thrombocytopenia and abnormal platelet morphology 1, 3
• Prothrombin time (PT/INR) to assess the extrinsic coagulation pathway 1, 3
• Activated partial thromboplastin time (aPTT) to evaluate the intrinsic coagulation pathway 1, 3
• Fibrinogen level (Clauss method) to assess for fibrinogen disorders 1, 2

Von Willebrand Disease Screening

• Von Willebrand factor antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and Factor VIII coagulant activity should be included in first-line testing for 84% of bleeding evaluations, as these establish VWD diagnosis, type, and severity 4, 1, 3

Additional First-Line Tests

• ABO blood group testing, as blood type O patients have 60-70% lower VWF levels than type AB 4, 5
• Iron studies to evaluate for chronic blood loss 4
• Thyroid function testing if clinically indicated, as hyperthyroidism elevates VWF levels 4, 5

Critical Pitfall to Avoid

Do not rely solely on PT and aPTT to rule out bleeding disorders—this approach will completely miss von Willebrand disease and mild platelet function disorders. 1, 3 Normal PT/aPTT does not exclude bleeding disorders, as some have variable expression 2

Second-Line Testing (If First-Line Tests Are Normal But Bleeding History Is Convincing)

Coagulation Factor Assays

• Intrinsic pathway factors: FVIII, FIX, and FXI assays 4
• Extrinsic pathway factors: FII, FV, FVII, and FX assays 4, 2
• Factor XIII activity, which is frequently overlooked but clinically important 2

Platelet Function Testing

• Light transmission aggregometry with multiple agonists (ADP, collagen, epinephrine, ristocetin, arachidonic acid) for patients with mucocutaneous bleeding 4, 2
• Platelet flow cytometry to evaluate platelet surface glycoproteins and activation markers 2
• PFA-100/200 testing as an alternative platelet function screen 4

Specialized VWD Testing

• VWF multimer analysis should be performed if the ratio of VWF:RCo to VWF:Ag is below 0.5-0.7, or if initial VWD testing shows abnormal results 1, 2, 3
• This detects subtle structural abnormalities in VWF not apparent in routine testing 2

Advanced Testing

• Fibrinolysis assays to evaluate for hyperfibrinolysis 4
• Thrombin generation assay (TGA) or thromboelastography (TEG/ROTEM) for global hemostatic assessment 4
• Genetic testing for rare bleeding disorders if other testing remains inconclusive 4, 2

Interpretation Algorithm

If Platelet Count Alone Is Low

• Consider peripheral platelet destruction, immune thrombocytopenia, or bone marrow production abnormality 5, 6

If aPTT Alone Is Prolonged

• Mild prolongation with moderate Factor VIII decrease: Suspect von Willebrand disease or hemophilia A carrier state 5
• Marked prolongation with very low Factor VIII (<3%): Consider acquired Factor VIII inhibitor or severe (type 3) von Willebrand disease 5
• With definite bleeding history: One of the hemophilia states is present 6

If PT Alone Is Abnormal

• Indicates abnormal reduction in vitamin K-dependent clotting factors (II, VII, IX, X) or Factor V 6

If Both PT and aPTT Are Normal But Bleeding Persists

• Proceed immediately to VWF testing and platelet function studies, as 75% of clinicians formally register patients with convincing bleeding history despite normal basic coagulation tests 4, 1

Special Considerations for Pediatric Patients

For children with easy bruising, additionally test:

• Serum calcium, phosphorus, and alkaline phosphatase for bone metabolism disorders 1
• Parathyroid hormone and 25-hydroxy-vitamin D 1
• Serum copper and ceruloplasmin 1
• Consider non-hematologic causes including connective tissue disorders, medication effects, and non-accidental trauma 1

Documentation and Follow-Up

Use a structured bleeding assessment tool (ISTH-BAT or Pediatric Bleeding Questionnaire) to quantify bleeding severity, as 80% of specialists use these instruments and they influence the extent of testing ordered 4, 1