What is Purpura Fulminans
Purpura fulminans is a life-threatening hematological emergency characterized by rapidly progressive skin necrosis, disseminated intravascular coagulation (DIC), and thrombotic occlusion of small and medium-sized blood vessels that can rapidly progress to multi-organ failure and death. 1, 2
Clinical Presentation and Pathophysiology
Purpura fulminans manifests as:
- Rapidly spreading purpuric skin lesions that progress to hemorrhagic necrosis and gangrene 3, 4
- Disseminated intravascular coagulation with consumption of clotting factors and platelets 2, 3
- Thrombotic occlusion of small and medium-sized blood vessels leading to tissue ischemia 1, 3
- Multi-organ failure if untreated, with patients often dying from overwhelming thrombosis rather than septic shock 1, 2
The fundamental pathologic defect is failure of the anticoagulant protein C pathway, leading to uncontrolled microvascular clotting and loss of protein C-mediated cytoprotective effects that are vital for survival in sepsis 1.
Three Distinct Etiologic Categories
1. Infection-Associated (Acute) Purpura Fulminans
- Most common form, complicating severe bacterial sepsis (particularly meningococcemia, pneumococcemia) and rarely viral infections 1, 2, 3
- Presents with high fever, hypotension, purpuric ecchymosis, and rapid progression over hours to days 4, 5
- Associated with severe acquired protein C deficiency during acute sepsis 2, 3
- Can be confused with Rocky Mountain spotted fever, which also presents with cutaneous necrosis and gangrene but has a longer prodrome with fever, headache, and myalgia before rash development 6
2. Congenital (Neonatal) Purpura Fulminans
- Presents in the newborn period as the most dramatic manifestation of homozygous protein C deficiency 6
- Results from inherited severe deficiency of natural anticoagulant proteins (protein C or protein S) 3
- Requires lifelong management with protein C replacement, anticoagulation, or liver transplantation 6, 7
3. Autoimmune (Post-Infectious) Purpura Fulminans
- Occurs as an autoimmune response to otherwise benign childhood infections (typically varicella, scarlet fever) 3
- Develops days to weeks after the initial infection 3
Mortality and Morbidity
- Extremely high mortality rate if not recognized and treated immediately 2, 3
- Patients who survive past 24-72 hours often die from complications of unchecked thrombosis rather than shock 1
- Survivors typically require multiple amputations of involved extremities and experience severe scarring in affected areas 1, 2, 5
- In one series, 24 amputations were performed on 12 patients who survived the acute phase 5
Critical Diagnostic Features
The diagnosis requires recognition of:
- Rapidly progressive purpuric skin lesions with necrosis 3, 4
- Laboratory evidence of DIC with thrombocytopenia, prolonged PT/PTT, low fibrinogen, elevated D-dimer 2, 3
- Severe acquired protein C deficiency (in infection-associated cases) or congenital deficiency (in neonatal cases) 1, 2, 3
- Clinical context of severe sepsis, newborn with family history, or recent childhood infection 3
Management Principles
Immediate treatment is essential and includes:
- Aggressive treatment of underlying infection with appropriate antimicrobials 2, 3
- Protein C replacement therapy (protein C concentrate or fresh-frozen plasma) to restore anticoagulant function 7, 8, 2
- Therapeutic anticoagulation to prevent further thrombosis 2, 3
- Robust transfusion support aimed at correcting acquired deficiencies in natural anticoagulant proteins 2
- Avoidance of vasopressors when possible, as adrenergic agents worsen ischemic changes 5
For congenital cases, protein C replacement is superior to anticoagulation alone for treating skin lesions, with non-necrotic lesions healing in a median of 4 days and necrotic lesions in a median of 11 days 7, 8.
Delayed surgical debridement (up to 3 weeks) is recommended to allow ischemic tissue to fully demarcate before amputation 5.