What are the differential diagnoses and initial tests for a 25-year-old patient presenting with purpura (discoloration of the skin) all over the body, bilateral periorbital ecchymosis (bruising around the eyes), and severe thrombocytopenia (low platelet count)?

Severe Thrombocytopenia with Purpura and Periorbital Ecchymosis: Differential Diagnoses and Diagnostic Workup

This 25-year-old patient with severe thrombocytopenia (15,000/μL), diffuse purpura, and bilateral periorbital ecchymosis requires immediate evaluation for life-threatening causes including immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), drug-induced thrombocytopenia, and heparin-induced thrombocytopenia (HIT), with urgent hospitalization given the high risk of serious bleeding at platelet counts <20,000/μL. 1, 2

Key Clinical Context

The bilateral periorbital ecchymosis ("raccoon eyes") is particularly concerning and suggests:

• Severe thrombocytopenia with spontaneous bleeding into soft tissues 3
• Possible underlying systemic process beyond simple ITP
• Risk of progression to life-threatening hemorrhage including intracranial bleeding (ICH risk ~1.5% in adults with ITP) 2

Primary Differential Diagnoses

1. Immune Thrombocytopenic Purpura (ITP)

• Most likely diagnosis in a young adult with isolated severe thrombocytopenia and purpura 1, 4
• Typically presents with platelet counts between 30,000-70,000/μL, though can be lower 1
• Characterized by mucocutaneous bleeding (petechiae, purpura, ecchymosis) without systemic illness 3
• Splenomegaly argues AGAINST ITP (present in <3% of cases) 1

2. Drug-Induced Thrombocytopenia

• Common culprits include quinidine, heparin, sulfonamides, sulfonylureas, dipyridamole, salicylates 1
• Also consider GPIIb-IIIa inhibitors (cause early profound thrombocytopenia) 1
• Alcohol and chronic liver disease can cause thrombocytopenia 1

3. Thrombotic Thrombocytopenic Purpura (TTP)

• Critical to exclude given thrombocytopenia with potential thrombotic complications 1
• Classic pentad: thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, renal dysfunction, fever
• Requires urgent plasma exchange if suspected 1

4. Heparin-Induced Thrombocytopenia (HIT)

• Only if recent heparin exposure (within 3 months) 1
• Typically occurs 5-14 days after heparin initiation 1
• Platelet count rarely drops below 20,000/μL in HIT (argues against this diagnosis here) 1
• Paradoxically associated with thrombosis rather than bleeding 1

5. Viral-Induced ITP

• CMV, HIV, and other viral infections can trigger severe thrombocytopenia 5
• Consider recent viral illness history 5

6. Evans Syndrome

• Combination of autoimmune hemolytic anemia and immune thrombocytopenia 6
• Check for signs of anemia (pallor, fatigue, jaundice) 6

Essential Immediate Laboratory Tests

First-Line Tests (Order Immediately)

Complete Blood Count with Peripheral Blood Smear 1, 4, 3

• Confirms true thrombocytopenia vs. pseudothrombocytopenia (platelet clumping)
• Examine red blood cell morphology for schistocytes (suggests TTP, DIC, or other microangiopathy) 4, 7
• Assess white blood cell morphology (abnormalities suggest alternative diagnoses like leukemia) 4
• Look for normal-sized or slightly larger platelets with normal RBC/WBC morphology (supports ITP) 4
• If pseudothrombocytopenia suspected, repeat in heparin or sodium citrate tube 3

Coagulation Studies 3

• PT/INR and aPTT to exclude DIC or coagulation factor deficiencies
• Normal coagulation studies support ITP diagnosis

Comprehensive Metabolic Panel 3

• Renal function (creatinine, BUN) - elevated suggests TTP or HIT with thrombosis
• Liver function tests (AST, ALT, bilirubin) - exclude liver disease causing thrombocytopenia 1
• Lactate dehydrogenase (LDH) - markedly elevated in TTP due to hemolysis

Reticulocyte Count and Haptoglobin 6

• Assess for hemolysis (Evans syndrome, TTP)
• Low haptoglobin and elevated reticulocytes suggest hemolytic process

Direct Antiglobulin Test (Coombs Test) 6

• Positive in Evans syndrome (autoimmune hemolytic anemia component)
• Helps distinguish Evans syndrome from isolated ITP

Second-Line Tests (Based on Clinical Context)

HIV Antibody Testing 4

• Mandatory in patients with risk factors for HIV
• HIV-associated ITP has different management considerations

Viral Serologies 5

• CMV IgM/IgG if recent viral illness or immunocompromised
• Hepatitis B and C serologies
• EBV serologies in appropriate clinical context

Antiphospholipid Antibodies 7

• Lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I
• Important if thrombosis present alongside thrombocytopenia

Antinuclear Antibodies (ANA) 7

• Screen for underlying autoimmune disease (SLE)

Pregnancy Test (if applicable) 1

• Exclude gestational thrombocytopenia, preeclampsia, HELLP syndrome

Tests to AVOID (Not Helpful for Diagnosis)

The American Society of Hematology explicitly recommends AGAINST: 1

• Platelet-associated IgG assay (inappropriate and unnecessary)
• Platelet antigen-specific antibody assay (unnecessary)
• Serum complement levels (unnecessary)
• Platelet survival studies (unnecessary)

Imaging Studies

Abdominal Ultrasound or CT 4

• ONLY if splenomegaly suspected on physical examination
• Splenomegaly argues against ITP diagnosis 1

Head CT (Non-Contrast) 2

• If any neurologic symptoms present (headache, altered mental status, focal deficits)
• ICH is the most feared complication of severe thrombocytopenia

Critical Management Considerations

Immediate Hospitalization Required 1, 2

• Platelet count 15,000/μL with bleeding manifestations mandates admission
• High risk of serious bleeding at counts <20,000/μL 1, 2

Treatment Threshold Met 1, 4

• Withholding treatment is inappropriate for platelet counts <20,000/μL regardless of symptoms 1
• This patient has both severe thrombocytopenia AND bleeding manifestations

Initial Treatment Options (if ITP confirmed) 1, 4

• High-dose glucocorticoids (prednisone 1-4 mg/kg/day or methylprednisolone 30 mg/kg/day IV) 1
• Intravenous immunoglobulin (IVIg) for rapid platelet recovery 1
• Combination therapy for life-threatening bleeding 2
• Platelet transfusion reserved for active life-threatening hemorrhage 4, 2

Critical Pitfalls to Avoid

Do NOT assume ITP without excluding other causes 1, 3

• TTP requires urgent plasma exchange, not steroids
• HIT requires immediate heparin cessation and alternative anticoagulation
• Drug-induced thrombocytopenia requires stopping offending agent

Do NOT delay peripheral smear examination 4, 3

• Schistocytes indicate microangiopathic process requiring different management
• Pseudothrombocytopenia leads to unnecessary treatment

Do NOT order unnecessary antibody tests 1

• Platelet antibody testing does not change management and delays treatment

Do NOT transfuse platelets prophylactically in ITP 8, 4

• Reserve for active life-threatening bleeding only
• Prophylactic transfusion provides no benefit and risks alloimmunization 8