How should I manage a patient presenting with purpura fulminans?

Management of Purpura Fulminans

Purpura fulminans is a hematologic and dermatologic emergency requiring immediate aggressive resuscitation, early antibiotic administration within 1 hour, and protein C replacement therapy to prevent death from microvascular thrombosis and multi-organ failure. 1, 2

Immediate Recognition and Resuscitation (First Hour)

Fluid Resuscitation

• Administer rapid intravenous fluid boluses of 20 ml/kg isotonic crystalloid or colloid, up to 60 ml/kg total (given as three 20 ml/kg boluses with reassessment after each) 1
• Fluid resuscitation often exceeds 60 ml/kg, and early consultation with intensive care is mandatory for inotropic and ventilatory support 1
• Approximately 25% of children with septic shock and purpura have absolute adrenal insufficiency; initiate hydrocortisone 50 mg/m²/24h (up to 50 mg/kg/day may be required for refractory shock) 1

Antibiotic Therapy

• Administer intravenous cefotaxime within 1 hour of recognition for children >3 months 1
• For infants <3 months, use cefotaxime plus ampicillin or amoxicillin to cover Listeria 1
• Continue antibiotics for 7 days assuming satisfactory clinical progress 1
• Death from absolute adrenal insufficiency and septic shock occurs within 8 hours of presentation 1

Protein C Replacement: The Critical Intervention

Acute Management

Protein C replacement is the primary intervention for purpura fulminans, as acquired protein C deficiency is the central mechanism responsible for uncontrolled microvascular thrombosis. 3, 2

• Administer protein C concentrate or fresh-frozen plasma immediately for acute exacerbations 1, 4
• Fresh-frozen plasma contains protein C, antithrombin III, and other anticoagulant proteins that reverse thrombotic microangiopathies 1
• Infuse plasma with the goal of correcting prolonged PT/PTT and halting purpura progression 1
• Large plasma volumes require concomitant diuretics, continuous renal replacement therapy, or plasma exchange to prevent >10% fluid overload 1

Rationale for Protein C Priority

• The fundamental pathologic lesion in purpura fulminans is failure of the anticoagulant protein C pathway, leading to uncontrolled microvascular clotting 2
• Patients who survive past 24-72 hours often die from complications of unchecked thrombosis rather than shock 2
• Protein C replacement provides both anticoagulant and anti-inflammatory cytoprotective effects vital for survival in sepsis 3, 2

Anticoagulation Strategy

When to Anticoagulate

• For congenital purpura fulminans (homozygous protein C deficiency), use anticoagulation plus protein C replacement rather than anticoagulation alone in acute settings 1, 4
• This combination reduces the required intensity of anticoagulation and consequently reduces bleeding risk 1, 4

Critical Pitfall to Avoid

• Do NOT initiate warfarin acutely without protein C coverage, as vitamin K antagonists paradoxically worsen skin necrosis during initiation due to rapid depletion of protein C 4
• If warfarin must be used, start at low dose under coverage of therapeutic parenteral anticoagulation, with gradual increases over ≥1 week 4

Transfusion Support

Hemoglobin Targets

• Target hemoglobin 10 g/dL during resuscitation if superior vena cava oxygen saturation <70% 1
• After stabilization and recovery from shock, a lower target of 7.0 g/dL is reasonable 1

Platelet Transfusion

• Do NOT transfuse platelets for isolated thrombocytopenia without active bleeding, as this is not indicated in vasculitic processes 5

Specific Clinical Scenarios

Congenital Purpura Fulminans (Homozygous Protein C Deficiency)

• Long-term management: Protein C replacement is superior to anticoagulation alone, offering better effectiveness without bleeding risks 1, 4
• When cost prohibits full protein C replacement, use combined protein C replacement with reduced-intensity anticoagulation 1, 4
• Consider liver transplantation early (before progressive organ damage) as it is curative, though it carries significant acute and chronic risks 1, 4
• Historical outcomes with anticoagulation alone: 5% mortality, 38% pulmonary embolism, 14% bleeding, 14% skin necrosis 1

Meningococcal Purpura Fulminans

• Maintain aggressive resuscitation even when early hemodynamic parameters appear stable, as purpura can develop impressively over minutes despite stable vital signs 3
• Necropsy studies show microvascular thrombosis limited to dermis, not visceral organs, in some cases 3
• Mortality rate remains 30-40% despite optimal treatment 6

Monitoring and Escalation

What to Monitor

• Reassess after each 20 ml/kg fluid bolus for signs of persistent shock 1
• Document body surface area involvement and progression of purpuric lesions daily 5
• Obtain serum cortisol level at time of empiric hydrocortisone administration 1

When to Escalate

• Evidence of circulatory failure and need for repeated fluid boluses mandates immediate intensive care consultation 1
• Inotropic support is often required and should not be delayed 1
• Surgical debridement of necrotic areas is necessary after stabilization 6

Corticosteroid Use

• Steroids are NOT recommended for meningococcal septicemia except in inotrope-resistant shock 1
• For bacterial meningitis of unknown etiology or confirmed meningococcal meningitis, administer dexamethasone 0.15 mg/kg every 6 hours with or within 24 hours of first antibiotic dose, continued for 4 days 1