What is the cause and appropriate management of a nodule that develops at the site of a subcutaneous enoxaparin (Lovenox) injection?

Nodule After Lovenox (Enoxaparin) Injection

Primary Cause and Immediate Assessment

A nodule at the enoxaparin injection site is most commonly a benign subcutaneous hematoma or inflammatory reaction, but you must immediately assess for three serious complications: skin necrosis (with or without heparin-induced thrombocytopenia), expanding hematoma from arterial injection, or allergic vasculitis. 1, 2, 3

Benign vs. Serious: Key Distinguishing Features

Benign injection site reactions (most common):

• Small, firm nodule without skin color changes 4
• Mild ecchymosis or bruising 1, 5
• Resolves spontaneously within days to weeks 4
• No systemic symptoms 1

Serious complications requiring immediate action:

1. Skin necrosis (potentially life-threatening):

• Dark discoloration, purple-black appearance at injection site 1, 2
• Progressive expansion of necrotic area 1, 3
• May occur with or without thrombocytopenia 2, 3
• Can develop 5-14 days after starting therapy 6
• Mechanism: antibody-mediated reaction targeting platelet factor 4 (PF4) complexes causing microvascular thrombosis 6, 3

2. Expanding hematoma from arterial injection:

• Rapidly enlarging, tense mass 5
• Signs of hemorrhagic shock (hypotension, tachycardia) 5
• Severe pain disproportionate to examination 5

3. Allergic vasculitis:

• Urticarial rash extending beyond injection site 1
• Multiple lesions at distant sites 1

Immediate Management Algorithm

Step 1: Check Platelet Count Immediately

Order stat CBC with platelet count 6, 2

• If platelets dropped >50% from baseline (even if absolute count >150,000/μL): Suspect heparin-induced thrombocytopenia (HIT) 6
• If platelets <50,000/μL: High suspicion for HIT 6, 2
• Severe thrombocytopenia occurs in 0.5% of patients; profound thrombocytopenia (<20,000/μL) in 0.2% 6

Step 2: Assess Injection Site Characteristics

If skin necrosis present (dark, purple-black discoloration):

1. Immediately discontinue enoxaparin 2, 3
2. Switch to alternative anticoagulant: fondaparinux, argatroban, or bivalirudin 6
3. Never use warfarin alone initially—requires overlap with non-heparin anticoagulant until platelet recovery 6
4. Do not use any heparin product (including other LMWHs) if HIT suspected, as cross-reactivity occurs in up to 90% of cases 3
5. Monitor wound—most cases resolve with conservative management without surgical debridement 2, 3

If rapidly expanding hematoma:

1. Check vital signs for hemorrhagic shock 5
2. Reverse anticoagulation if hemodynamically unstable 5
3. Urgent vascular surgery consultation for possible embolization or surgical evacuation 5

If simple nodule/bruising without necrosis:

1. Continue enoxaparin if clinically indicated 4
2. Reassure patient this is common and benign 4, 1
3. Monitor platelet count once or twice weekly during first 14 days if unfractionated heparin was previously used 6

Risk Stratification for HIT

**Low risk (<0.1%):** Medical patients on prophylactic LMWH, obstetric patients, therapy >1 month 6

Intermediate risk (0.1-1%): Surgical patients on prophylactic LMWH, cancer patients, severe trauma 6

High risk: Cardiac or orthopedic surgery, recent heparin exposure within 3 months 6

• Enoxaparin has approximately 10-fold lower HIT risk compared to unfractionated heparin 6

Prevention Strategies

Proper injection technique:

• Inject into subcutaneous tissue of abdomen, avoiding muscle 4
• Rotate injection sites 4
• Do not aspirate or massage injection site 4
• Use proper needle angle (90 degrees for subcutaneous) 5

Avoid enoxaparin entirely in patients with:

• Previous heparin-induced thrombocytopenia 3
• Previous heparin-induced dermal necrosis 3
• Known antibodies to heparin-PF4 complexes 3

Common Pitfalls to Avoid

• Do not assume benign nodule if skin discoloration present—skin necrosis can be life-threatening and requires immediate drug discontinuation 1, 2
• Do not ignore platelet count decline of >50% even if absolute count remains normal—this is diagnostic criterion for HIT 6
• Do not switch to another LMWH if HIT suspected—cross-reactivity occurs, use non-heparin anticoagulant 6, 3
• Do not delay platelet monitoring in high-risk patients—check every 2-3 days during first 14 days 6
• Do not perform surgical debridement immediately—most necrotic lesions resolve with conservative management 2, 3