What is the management approach for Purpura fulminans?

Management of Purpura Fulminans

For congenital purpura fulminans due to homozygous protein C deficiency, protein C replacement therapy is the primary treatment, while for acute infection-associated purpura fulminans, immediate protein C pathway restoration combined with therapeutic anticoagulation and aggressive supportive care is essential to prevent mortality and tissue loss. 1, 2, 3

Immediate Recognition and Diagnosis

Purpura fulminans is a hematological emergency characterized by skin necrosis, disseminated intravascular coagulation (DIC), and thrombotic occlusion of small and medium-sized blood vessels that can rapidly progress to multi-organ failure. 4 The condition presents with:

• Progressive cutaneous hemorrhage and necrosis with purpuric ecchymosis 4, 5
• Absent palpable pulses and sluggish capillary refill in involved extremities 6
• High fever (mean 104°F in pediatric cases) and potential altered mental status 6
• Severe thrombocytopenia and coagulopathy in end-stage sepsis 6

Critical distinction: Determine whether this is infection-associated (acute) versus congenital (protein C/S deficiency) purpura fulminans, as management differs significantly. 4, 3

Acute Infection-Associated Purpura Fulminans

Immediate Management (First 24-72 Hours)

The fundamental pathologic lesion is failure of the anticoagulant protein C pathway, leading to uncontrolled microvascular clotting and inadequate cytoprotective effects. 3 Therefore:

• Initiate therapeutic anticoagulation with intravenous heparin immediately to prevent subsequent small vessel thrombosis and limit ongoing tissue loss 6, 5
• Administer broad-spectrum intravenous antibiotics targeting likely pathogens (meningococcus most common) 6, 5
• Provide protein C replacement therapy if available (protein C concentrate or fresh-frozen plasma) to restore the anticoagulant pathway 2, 3
• Optimize transfusion support while avoiding interventions that may worsen thrombosis 3

The evidence strongly supports immediate heparinization as the mainstay of treatment alongside systemic support. 6 In a pediatric case series, all four survivors received intravenous heparin, with two experiencing complete resolution without tissue loss. 6

Supportive Care

• Aggressive hemodynamic support for septic shock 4, 3
• Correct coagulopathy with judicious use of blood products 3
• Do not transfuse platelets for isolated thrombocytopenia without active bleeding, as this is not indicated and may worsen thrombosis 7

Tissue Management

Conservative management of purpuric lesions is the treatment of choice until final demarcation occurs. 6 Early surgical intervention should be avoided:

• Allow clear demarcation of viable versus necrotic tissue over days to weeks 6
• Survivors often require multiple plastic reconstructive procedures after stabilization 6
• Document extent and progression with clinical photography 7

Congenital Purpura Fulminans (Homozygous Protein C Deficiency)

Acute Episode Management

For acute exacerbations, use anticoagulation plus protein C replacement rather than anticoagulation alone. 1, 2 This combination approach:

• Reduces the required intensity of anticoagulation 1, 2
• Consequently reduces bleeding risk 1, 2
• Provides immediate restoration of protein C levels 2

Protein C replacement can be administered as protein C concentrate or fresh-frozen plasma. 2

Long-Term Management Strategy

The American Society of Hematology 2018 guidelines provide a hierarchical approach: 1

Primary recommendation: Protein C replacement therapy alone rather than anticoagulation for long-term management, as it offers superior long-term effectiveness without the adverse bleeding risk of anticoagulation. 1, 2

Secondary option: Combined protein C replacement with anticoagulation when full protein C supplementation cannot be followed due to pragmatic or cost reasons. 1, 2

Tertiary consideration: Liver transplantation as a curative option, particularly as the child grows and protein C replacement becomes increasingly expensive and difficult to maintain. 1, 2

Evidence Supporting Protein C Replacement

Case series data demonstrate striking differences in outcomes: 1

• Children receiving protein C replacement or combined therapy: 0% mortality, 0% pulmonary embolus, 0% bleeding, 0% skin necrosis
• Children receiving anticoagulation alone: 5% mortality, 38% pulmonary embolus, 14% bleeding, 14% skin necrosis

Liver Transplantation Considerations

Liver transplantation should be discussed early before progressive organ damage has occurred. 1, 2 The procedure:

• Is curative of protein C deficiency with all transplanted patients achieving normal protein C levels 1
• Carries significant acute and chronic risks and burden of care 1
• Should be considered as children grow due to increasing cost and difficulty of protein C replacement 2
• Requires careful discussion of values and preferences with families 1

Critical Pitfalls to Avoid

Never initiate warfarin or vitamin K antagonists acutely without coverage, as they may paradoxically worsen skin necrosis during initiation due to rapid depletion of protein C before depleting procoagulant factors. 2 If warfarin must be used, start at low doses under coverage of therapeutic parenteral anticoagulants with gradual increases over 1 or more weeks. 2

Do not delay treatment waiting for definitive diagnosis, as patients who survive past 24-72 hours often die from complications of unchecked thrombosis rather than shock. 3

Avoid premature surgical debridement or amputation before clear demarcation of tissue viability. 6

Prognostic Indicators

Poor prognostic factors in acute infection-associated purpura fulminans include: 6

• Markedly depressed platelet counts at presentation
• Markedly depressed white blood cell counts
• Presence of generalized purpura (important predictor of poor outcome in meningococcemia) 5
• Altered mental status on initial examination 6

Survivors with mean platelet counts of 370,000 and mean WBC of 25,000 had better outcomes than those with severe cytopenias. 6