Purpura fulminans

Purpura fulminans
Other names	purpura gangrenosa[1]: 825
Specialty	Hematology

Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.^[2][3]

Causes

Purpura fulminans is caused by defects in the protein C anticoagulant pathway. Identification of the cause of purpura fulminans often depends on the patient's age and circumstances of presentation.^[2]

Congenital protein C deficiency

Acquired protein C deficiency is caused by either depletion of available protein C in plasma or decreased protein C synthesis (caused by administration of vitamin K antagonists, severe liver failure or complications of prematurity).^[7]

Severe acute sepsis

Purpura fulminans is a presenting feature of severe acute sepsis, such as

In some cases, a combination of sepsis and a partial congenital defect in the protein C anticoagulant pathway initiates purpura fulminans.[8]

Unknown

In rare instances, purpura fulminans is an autoimmune manifestation against protein C or

Regardless of the underlying cause of purpura fulminans, the mechanism of disease is similar with deficiency in protein C concentration or decrease in protein C activity which promotes blood clotting (thrombosis).^[10]

In cases of severe sepsis, there is widespread activation of the acute systemic

The depletion of anticoagulant and anti-inflammatory proteins, in particular, protein C and its co-factor, protein S, may also promote thrombus formation, inhibit fibrinolysis and lead to further activation of the inflammatory pathways.^[14][15]

Diagnosis

Early purpura fulminans lesions look similar to traumatic skin bleeds or

The distribution of purpura fulminans lesions may be different according to the underlying pathogenesis.[2] Purpura fulminans in severe sepsis typically develops in the distal extremities and progresses proximally or appears as a generalised or diffuse rash affecting the whole body surface.^[16] In cases of severe inheritable protein C deficiency, purpura fulminans with disseminated intravascular coagulation manifests within a few hours or days after birth.^[7][17]

Laboratory investigations

The cardinal features of purpura investigations are the same as those of disseminated intravascular coagulation: prolonged plasma clotting times, thrombocytopenia, reduced plasma fibrinogen concentration, increased plasma fibrin-degradation products and occasionally microangiopathic haemolysis.^[2]

Prevention

For people who have severe congenital protein C deficiency, protein C replacement therapies are available, which is indicated and approved for use in the United States and Europe for the prevention of purpura fulminans. Protein C replacement is often in combination with anticoagulation therapy of injectable low molecular weight heparin or oral warfarin.^{[18][19][20][21][22]} Before initiating warfarin therapy, a few days of therapeutic heparin may be administered to prevent warfarin necrosis and other progressive or recurrent thrombotic complications.^[7][22]

Complications of prevention

The amount of fresh frozen plasma required to reverse disseminated intravascular coagulation associated with purpura fulminans may lead to complications of fluid overload and death, especially in neonates,^[7] such as transfusion-related acute lung injury. Exposure to multiple plasma donors over time increases the cumulative risk for transfusion-associated viral infection and allergic reaction to donor proteins found in fresh frozen plasma.^[7]

Allergic reactions and

Concomitant warfarin therapy in subjects with congenital protein C deficiency is associated with an increased risk of warfarin skin necrosis.^[7]

Treatment

Early stage sepsis-associated purpura fulminans may be reversible with quick therapeutic intervention.^[2][7] Treatment is mainly removing the underlying cause and degree of clotting abnormalities and with supportive treatment (antibiotics, volume expansion, tissue oxygenation, etc.). Thus, treatment includes aggressive management of the septic state.^{[citation needed]}

Purpura fulminans with disseminated intravascular coagulation should be urgently treated with fresh frozen plasma (10–20 mL/kg every 8–12 hours) and/or protein C concentrate to replace pro-coagulant and anticoagulant plasma proteins that have been depleted by the disseminated intravascular coagulation process.^[2][3][4][7]

Protein C in plasma in the steady state has a half life of 6- to 10-hour, therefore, patients with severe protein C deficiency and presenting with purpura fulminans can be treated acutely with an initial bolus of protein C concentrate 100 IU/kg followed by 50 IU /kg every 6 hours.

Established soft tissue necrosis may require surgical removal of the dead tissue, fasciotomy, amputation or reconstructive surgery.^[2]

Prognosis

Purpura fulminans lesions, once established, often progress within 24 to 48 hours to full-thickness skin necrosis or soft-tissue necrosis. Once purpura fulminans lesions progress to full-thickness skin necrosis, healing takes between 4–8 weeks and leaves large scars.^[2]

Without treatment, necrotic soft tissue may become gangrenous, leading to loss of limbs.

Purpura fulminans secondary to severe infection is self-limiting.[2] In cases of homozygous protein C deficiency, episodes of purpura fulminans and other thrombotic events are recurrent.^[4] Moreover, infant survival due to maintenance replacement therapy is often associated with intellectual disability or visual impairment.^[2][23] For post-infection purpura fulminans, new lesions will occur while neutralising autoantibodies are present (1–2 weeks after presentation).^[9]

A multi-disciplinary care team is usually required for rehabilitation after purpura fulminans.^[2]

Epidemiology

Purpura fulminans is rare and most commonly occurs in babies and small children

Due to the rarity of purpura fulminans and its occurrence in vulnerable patient groups like children research on the condition is very limited and evidence based knowledge is scarce. ^[citation needed]

History

Purpura fulminans was first described by Guelliot in 1884.^[28]

References