How should purpura fulminans be managed?

Management of Purpura Fulminans

For acute purpura fulminans, immediately administer protein C replacement (as concentrate or fresh-frozen plasma) combined with anticoagulation, along with aggressive fluid resuscitation (up to 60 ml/kg isotonic crystalloid in three sequential 20 ml/kg boluses) and broad-spectrum antibiotics (cefotaxime) within the first hour of recognition. 1

Immediate Resuscitation and Stabilization

Fluid Management

• Give three sequential intravenous boluses of 20 ml/kg isotonic crystalloid or colloid, reassessing after each dose, up to a total of 60 ml/kg 1
• If shock persists after 60 ml/kg, immediately consult intensive care for inotropic support and mechanical ventilation 1
• Monitor for fluid overload; when large plasma volumes are required, use concomitant diuretics or continuous renal-replacement therapy to avoid >10% fluid overload 1

Antibiotic Therapy

• Administer intravenous cefotaxime within the first hour for patients older than 3 months 1
• For infants younger than 3 months, add ampicillin (or amoxicillin) to cefotaxime for Listeria coverage 1
• Continue antibiotics for 7 days if clinical improvement occurs 1
• The most common causative organisms are Neisseria meningitidis, Hemophilus influenzae, and Streptococcus pneumoniae 2

Corticosteroid Administration

• Start hydrocortisone at 50 mg/m² per day (may increase up to 50 mg/kg/day for refractory shock), as approximately 25% of pediatric patients with septic shock and purpura have absolute adrenal insufficiency 1
• If bacterial meningitis is present, administer dexamethasone 0.15 mg/kg every 6 hours within 24 hours of the first antibiotic dose, continued for 4 days 1
• For meningococcal septicemia without meningitis, steroids are not recommended except in shock resistant to inotropes 1

Protein C Replacement and Anticoagulation Strategy

Acute Phase Management

The cornerstone of treatment is immediate protein C replacement combined with anticoagulation, which is superior to anticoagulation alone and reduces mortality from 5% to 0% in congenital cases. 3, 4

• Administer protein C concentrate or fresh-frozen plasma immediately upon recognition of acute exacerbation 3, 4, 1
• Fresh-frozen plasma supplies protein C, antithrombin III, and other anticoagulant proteins that reverse thrombotic microangiopathy 1
• Infuse plasma until coagulation tests (PT/PTT) normalize and purpuric lesions stop progressing 1
• Combine anticoagulation with protein C replacement rather than using anticoagulation alone, as this lowers the intensity of anticoagulation needed and reduces bleeding risk from 14% to 0% 3, 4, 1

Critical Warfarin Warning

• Do NOT start warfarin acutely without protein C coverage, as rapid protein C depletion can paradoxically worsen skin necrosis 1
• If warfarin is unavoidable, begin with a low dose under therapeutic parenteral anticoagulation and titrate gradually over at least one week 1

Transfusion Support

Red Blood Cell Transfusion

• During active resuscitation, target hemoglobin of 10 g/dL if central venous oxygen saturation is below 70% 1
• After stabilization, a lower hemoglobin target of 7 g/dL is acceptable 1

Platelet Transfusion

• Do NOT transfuse platelets for isolated thrombocytopenia without active bleeding, as this provides no benefit in vasculitic-type purpura 1

Congenital Purpura Fulminans (Homozygous Protein C Deficiency)

Long-Term Management Options

For congenital purpura fulminans, protein C replacement is superior to anticoagulation alone for long-term management, with zero mortality compared to 5% mortality with anticoagulation alone. 3

The American Society of Hematology recommends three management strategies based on resources and patient factors 3:

1. Protein C replacement alone (preferred): Superior long-term effectiveness without bleeding risk of anticoagulation, but expensive and increasingly difficult as children grow 3

2. Combined protein C replacement with reduced-intensity anticoagulation: When full protein C replacement is not feasible due to cost, this approach reduces the required anticoagulation intensity and consequently reduces bleeding risk 3, 4

3. Liver transplantation: Curative option that should be considered early before progressive organ damage occurs, though it carries significant acute and chronic risks 3

Historical Outcomes with Anticoagulation Alone

• Mortality: 5% 3, 4
• Pulmonary embolism: 38% 3, 4
• Major bleeding: 14% 3, 4
• Skin necrosis: 14% 3, 4

Surgical Management

Timing and Indications

• Evaluate for compartment syndrome early in the presentation 2
• Prompt surgical consultation and debridement may decrease mortality 2
• Surgical debridement of necrotic areas is essential once demarcation occurs 5
• There appears to be higher mortality in patients who did not undergo surgical intervention 2

Monitoring and Escalation

Clinical Assessment

• Document the extent of purpuric involvement (body-surface-area) and lesion progression daily 1
• After each 20 ml/kg fluid bolus, evaluate for persistent shock signs; repeat boluses only if shock persists 1
• Obtain serum cortisol level at the time hydrocortisone is empirically started 1

Laboratory Monitoring

• Thrombocytopenia, decreased coagulation factors, presence of fibrinogen split products, and fragmented erythrocytes in blood smear confirm the diagnosis 5
• Monitor PT/PTT to guide plasma infusion therapy 1

Escalation Triggers

• Need for repeated fluid boluses or evidence of circulatory failure mandates immediate intensive-care consultation and prompt initiation of inotropic support 1

Prognosis and Outcomes

• Death from combined adrenal insufficiency and septic shock can occur within 8 hours of presentation 1
• Overall mortality rate is 30-43% despite treatment 5, 2
• The vast majority of patients are under age 7, though the disease can occur in adults 2
• Survivors are usually left with severe scarring and tissue loss 6
• Patients who survive past the first 24-72 hours often die from complications of unchecked thrombosis rather than from shock 6

Common Pitfalls

• Delaying protein C replacement while waiting for definitive diagnosis—start immediately when purpura fulminans is suspected 1, 6
• Starting warfarin without adequate protein C coverage, which worsens skin necrosis 1
• Transfusing platelets for isolated thrombocytopenia without bleeding 1
• Failing to recognize adrenal insufficiency in approximately 25% of pediatric cases 1
• Delaying surgical consultation for compartment syndrome evaluation 2
• Inadequate fluid resuscitation in the first hour—up to 60 ml/kg may be required 1