From the Guidelines
Purpura fulminans is a life-threatening condition that requires immediate treatment, including addressing the underlying cause, aggressive fluid resuscitation, broad-spectrum antibiotics, and blood product support, with protein C concentrate and heparin therapy considered in specific cases, as recommended by the American Society of Hematology 2018 guidelines 1.
Diagnosis and Treatment
Purpura fulminans is characterized by rapidly progressive skin necrosis and disseminated intravascular coagulation (DIC), with diagnosis primarily based on clinical presentation and laboratory evidence of DIC, including thrombocytopenia, prolonged coagulation times, decreased fibrinogen, and elevated D-dimer levels.
- Key symptoms and signs include:
- Sudden appearance of purpuric skin lesions
- Hemorrhagic necrosis
- Laboratory evidence of DIC
Management and Investigations
Treatment must be initiated immediately and includes:
- Addressing the underlying cause (typically severe infection, particularly meningococcemia)
- Aggressive fluid resuscitation
- Prompt administration of broad-spectrum antibiotics, such as ceftriaxone 2g IV every 12 hours plus vancomycin 15-20 mg/kg IV every 8-12 hours until the pathogen is identified
- Blood product support, including:
- Fresh frozen plasma (10-15 mL/kg)
- Cryoprecipitate to maintain fibrinogen above 100 mg/dL
- Platelet transfusions to keep counts above 50,000/μL
Protein C Replacement and Anticoagulation
Protein C concentrate (50-100 IU/kg initially, followed by 50 IU/kg every 6 hours) should be administered if available, particularly in cases of congenital protein C deficiency, as recommended by the American Society of Hematology 2018 guidelines 1.
- Heparin therapy may be considered at 10-15 units/kg/hour without a loading dose
- The use of anticoagulation plus protein C replacement is suggested in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency, as it may reduce the required intensity of anticoagulation and the bleeding risk 1
Surgical Consultation and Liver Transplantation
Surgical consultation is necessary for potential debridement of necrotic tissue and possible amputations.
- Liver transplantation may be considered in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency, as it is curative of protein C deficiency, but has its own acute and chronic risks and burden of care 1
From the Research
Symptoms and Signs
- Purpura fulminans is characterized by skin necrosis and disseminated intravascular coagulation 2, 3, 4, 5
- Patients often present with acute onset of progressive cutaneous hemorrhage and necrosis 5
- Presence of purpura, particularly when generalized, is an important predictor of a poor outcome following meningococcal infection 5
Diagnosis
- Diagnosis of purpura fulminans involves recognition of skin necrosis and disseminated intravascular coagulation 2, 3, 4
- Laboratory features of the disease include evidence of disseminated intravascular coagulation and deficiency of natural anticoagulants such as protein C and protein S 3, 4
- Histopathologic hallmarks of acute infectious purpura fulminans are dermal vascular thrombosis and secondary hemorrhagic necrosis 5
Treatment and Management
- Treatment of purpura fulminans involves treatment of the underlying infection, aggressive anticoagulation, and robust transfusion support aimed at correcting acquired deficiencies in natural anticoagulant proteins 3
- Management strategies require accurate identification of the underlying cause 4
- Protein C replacement therapy offers a safe, effective treatment for thromboembolic complications of severe congenital protein C deficiency and secondary prophylaxis for recurrent disseminated intravascular coagulation, purpura fulminans, and thromboembolic events 6
- Early referral to a burn center with a multidisciplinary team is recommended for the best outcomes in patients with severe purpura fulminans 2
Investigations
- Investigations for purpura fulminans include laboratory tests to diagnose disseminated intravascular coagulation and deficiency of natural anticoagulants such as protein C and protein S 3, 4
- Histopathologic examination of skin lesions can help confirm the diagnosis 5
Causes and Pathogenesis
- Purpura fulminans can occur as a complication of severe bacterial or viral infections 3, 5
- The disease is associated with an extremely high mortality rate, and patients often die of overwhelming multisystemic thrombosis rather than septic shock 3
- Severe acquired deficiency of protein C and dysfunction of the protein C-thrombomodulin pathway as well as other systems that exert a negative regulatory effect on coagulation have been implicated in the pathogenesis of purpura fulminans 3
- The disturbance in the balance of anticoagulant and procoagulant activities of endothelial cells is triggered by endotoxin and mediated by cytokines, leading to the consumption of proteins C and S and antithrombin III 5