What is the treatment for Purpura fulminans (a rare blood disorder) complicated by sepsis (systemic inflammatory response syndrome)?

From the Guidelines

Purpura fulminans complicated by sepsis requires immediate aggressive treatment with broad-spectrum antibiotics, fluid resuscitation, vasopressor support, and correction of coagulation abnormalities, with protein C replacement being a crucial component, as suggested by the American Society of Hematology 2018 guidelines 1. The treatment approach should prioritize the management of sepsis and the correction of coagulation abnormalities.

• Broad-spectrum antibiotics, such as vancomycin (15-20 mg/kg IV every 8-12 hours) and a carbapenem like meropenem (1g IV every 8 hours) or piperacillin-tazobactam (4.5g IV every 6 hours), should be initiated promptly to target the most likely pathogens.
• Fluid resuscitation and vasopressor support are essential for managing septic shock.
• Coagulation abnormalities should be addressed with fresh frozen plasma (10-15 mL/kg), cryoprecipitate, and platelet transfusions as needed.
• Protein C concentrate (50-100 IU/kg initially, followed by 50 IU/kg every 6 hours) should be administered if available, particularly in cases associated with meningococcal infection or if severe protein C deficiency is present, as it has been shown to be superior to anticoagulation alone in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency 1.
• Surgical consultation is necessary for potential debridement of necrotic tissue, and some patients may require amputation of affected limbs.
• Continuous renal replacement therapy may be needed for acute kidney injury, as large volumes of plasma can lead to fluid overload, and diuretics, continuous renal replacement therapy, or plasma exchange may be required to prevent this complication 1. The pathophysiology of purpura fulminans involves bacterial endotoxins triggering massive inflammatory responses and consumption of coagulation factors, particularly protein C, leading to microvascular thrombosis and tissue necrosis.
• Early recognition and aggressive multidisciplinary management in an intensive care setting are essential for improving survival and reducing long-term morbidity.

From the Research

Treatment Approaches for Purpura Fulminans Complicated by Sepsis

The treatment for Purpura fulminans (PF) complicated by sepsis involves several approaches, including:

• Repletion of natural circulating anticoagulants, such as protein C, to control microvascular clotting and promote cytoprotective effects 2
• Use of therapeutic anticoagulation to prevent further thrombosis and tissue damage 2
• Optimization of transfusion support to manage coagulopathy and prevent bleeding complications 2
• Administration of activated protein C (APC) to improve coagulopathy and reduce mortality 3, 4
• Treatment of underlying sepsis with antibiotics and supportive care to prevent multi-organ failure 5, 6

Specific Interventions

Specific interventions that may be recommended for the treatment of PF complicated by sepsis include:

• Early recognition and timely institution of therapy to prevent significant morbidity and mortality 5
• Avoidance of delayed diagnosis and treatment, as waiting for a skin biopsy result can delay the diagnosis and result in significant morbidity and mortality 5
• Use of hyperbaric oxygen therapy and IVIG, although their benefits are still questionable 5
• Consideration of the use of drotrecogin alfa (activated) in septic patients at high risk of death, although it is associated with an increased risk of serious bleeding 4

Management of Coagulopathy

Management of coagulopathy is critical in the treatment of PF complicated by sepsis, and may involve:

• Treatment with protein C concentrate to increase activated protein C plasma levels and decrease d-dimer levels 4
• Use of APC to improve coagulopathy and reduce mortality 3, 4
• Optimization of transfusion support to manage coagulopathy and prevent bleeding complications 2