What are the next steps and possible differential diagnoses (DDs) for a patient with easy bruising and a normal platelet count on Complete Blood Count (CBC)?

Easy Bruising with Normal Platelet Count: Next Steps and Differential Diagnoses

In a patient with easy bruising and a normal platelet count, you must proceed with PT, aPTT, and fibrinogen testing, while recognizing that von Willebrand disease and platelet function disorders are the most likely diagnoses—neither of which are reliably detected by standard PT/aPTT screening. 1, 2, 3

Immediate Next Steps in Laboratory Evaluation

Essential Initial Tests

• PT (Prothrombin Time) and aPTT (Activated Partial Thromboplastin Time) should be ordered immediately, as these detect most factor deficiencies but critically miss von Willebrand disease and Factor XIII deficiency 1, 2
• Fibrinogen level must be added if PT or aPTT are abnormal to detect fibrinogen defects 2, 3, 4
• Peripheral blood smear should be reviewed to assess platelet morphology and identify altered platelet size/structure that may suggest specific inherited platelet function disorders 1, 3

Critical Clinical History Elements

Before ordering specialized tests, obtain specific bleeding history details:

• Significant bleeding after surgery or dental extractions, which strongly suggests an underlying bleeding disorder 3, 4
• Epistaxis requiring medical intervention (not just minor nosebleeds) 1, 3
• Menorrhagia in females, a hallmark of von Willebrand disease 1
• Joint hemorrhages or deep hematomas, which suggest coagulation factor deficiencies rather than platelet disorders 5, 6
• Family history of bleeding disorders, particularly important as this may indicate hereditary conditions 1, 3, 4

Medication Review

Document all medications that affect bleeding tendency:

• Anticoagulants, antiplatelet agents (including aspirin), NSAIDs, corticosteroids, and alternative therapies, as these affect both bleeding risk and coagulation test interpretation 2, 3, 4

Most Likely Differential Diagnoses

Primary Considerations with Normal Platelet Count

Von Willebrand Disease (VWD)

• Most common inherited bleeding disorder with prevalence of approximately 1 in 1000 people 2
• Presents with mucocutaneous bleeding and easy bruising 2
• Not reliably detected by PT/aPTT screening—requires specific VWD testing 1, 2, 4
• Initial VWD testing includes: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and Factor VIII coagulant activity 1
• If VWF:RCo is low or the ratio of VWF:RCo to VWF:Ag is below 0.5-0.7, specialized testing including multimer analysis is indicated 1

Inherited Platelet Function Disorders (IPFD)

• Can present with normal platelet count but abnormal platelet function 1, 2
• Require specialized testing including light transmission aggregometry (LTA) with epinephrine, ADP, collagen, arachidonic acid, and ristocetin 1
• Platelet granule release defects (delta-storage pool disease, alpha-granule deficiency) cause easy bruising with normal counts 1
• Flow cytometry to assess major platelet surface glycoproteins (GPIIb/IIIa, GPIb/IX) may identify specific disorders like Glanzmann thrombasthenia or Bernard-Soulier syndrome 1

Factor XIII Deficiency

• Not detected by standard PT/aPTT screening but causes significant bruising 2, 4
• Requires specific Factor XIII assay for diagnosis 2

Secondary Considerations

Mild Hemophilia (Factor VIII or IX Deficiency)

• Can cause significant bleeding even with mild deficiencies 2
• May not prolong aPTT if factor levels are >30-40% 2

Connective Tissue Disorders

• Ehlers-Danlos syndrome causes easy bruising due to capillary and perivascular connective tissue fragility 7
• Haematological studies are typically normal except for abnormal Hess test (capillary fragility test) 7
• Look for joint hypermobility, skin hyperextensibility, and tissue fragility on physical examination 1, 7

Vitamin K Deficiency

• Presents with prolonged PT and possibly aPTT 2
• Consider in patients with malabsorption, poor nutrition, or antibiotic use 2

Medication-Induced Platelet Dysfunction

• Even with normal platelet count, aspirin and NSAIDs impair platelet function 2, 8

Algorithmic Approach Based on Initial Test Results

If PT and aPTT are Normal

• High likelihood of von Willebrand disease or platelet function disorder 1, 2, 5
• Proceed with VWD-specific testing (VWF:Ag, VWF:RCo, Factor VIII) 1
• Consider referral to hematology for platelet function testing if VWD testing is normal but clinical suspicion remains high 3, 4

If aPTT is Prolonged with Normal PT

• Indicates intrinsic pathway defect 5, 6
• Perform mixing study to differentiate factor deficiency from inhibitor 1, 5
• If mixing study corrects, evaluate for Factor VIII, IX, XI, or XII deficiency 5

If PT is Prolonged with Normal aPTT

• Suggests Factor VII deficiency or early vitamin K deficiency 5, 6
• Consider vitamin K challenge 5

If Both PT and aPTT are Prolonged

• Evaluate for liver disease, vitamin K deficiency, or disseminated intravascular coagulation (DIC) 1, 5

Critical Pitfalls to Avoid

• Do not assume normal PT/aPTT rules out bleeding disorders—these tests miss von Willebrand disease, Factor XIII deficiency, and all platelet function disorders 2, 3, 4
• Do not dismiss a normal platelet count as excluding platelet disorders—platelet function defects require specialized testing beyond CBC 2, 3
• Do not overlook medication effects, particularly NSAIDs and aspirin, which impair platelet function despite normal screening tests 2, 3, 4
• Do not ignore a decreasing platelet trend even if still in normal range—this may indicate ongoing consumption as in subclinical DIC 1

When to Refer to Hematology

Referral is indicated when:

• Initial laboratory evaluation indicates a bleeding disorder 3, 4
• High clinical suspicion remains despite normal PT/aPTT/platelet count 3, 4, 5
• Specialized testing (platelet function studies, VWD multimer analysis, Factor XIII assay) is needed 1, 3
• Complex cases require expert interpretation 3, 4