Description, Causes and Risk Factors:
A severe and rapidly fatal form of purpura hemorrhagica, occurring especially in children, with hypotension, fever, and disseminated intravascular coagulation, usually following an infectious illness.
Neonatal purpura fulminans describes a clinicopathological entity of dermal microvascular thrombosis associated with disseminated intravascular coagulation (DIC) and perivascular hemorrhage, occurring in the Newborn period. The clinical presentation is that of acute DIC and hemorrhagic necrosis of the skin. This is a rare condition, but it is often fatal if it is not treated early and effectively. Therefore early recognition with prompt investigation and treatment is of paramount importance.
Purpura fulminans was ?rst described in a neonate in 1962 and the etiology was presumed an inherited disorder as three siblings had similar skin lesions. It was only in 1983 that a possible link between the clinical ?ndings of purpura fulminans and protein C de?ciency was described in a child, and soon after this the ?rst child with con?rmed homozygous protein C de?ciency was successfully treated with protein C replacement therapy. The ?rst association of homozygous protein S de?ciency and purpura fulminans was reported in 1990. There are both congenital and acquired causes of neonatal purpura fulminans. Inherited causes are due to a homozygous protein C or S de?ciency; compound heterozygosity and co-inheritance with other inherited thrombophilias have been described. Acquired causes are more common and often associated with severe infection causing a consumptive coagulopathy and a relative de?ciency of protein C and/or S.
Protein C is a vitamin K-dependent coagulation protein that is synthesized in the liver. Plasma protein C is activated by complex formation with thrombin bound to an endothelial cell surface receptor, thrombomodulin (TM). TM and endothelial protein C receptor (EPCR) are both expressed on endothelial cells and regulate the protein C pathway. Thrombin binds TM and acts as a catalyst for the activation of protein C by thrombin. EPCR binds to protein C and enhances the activation of protein C by thrombin-TM complexes by 10-fold. Activated protein C (APC) inactivates factor (F) Va and (F) VIIIa by limited proteolysis, resulting in a down regulation of thrombin generation. APC activity is enhanced by protein S. Therefore, protein C or S de?ciency predisposes to a decreased capacity to reduce thrombin generation and a hypercoagulable state.
Neonatal purpura fulminans, whether caused by congenital or acquired de?ciencies of protein C or S, remains a life-threatening condition. Fortunately it is a rare disorder. Early recognition of the clinical symptoms, prompt diagnosis and judicious replacement therapy decreases both the Morbidity & Mortality associated with this condition. Every effort should be made to increase awareness of this rarely diagnosed condition and its treatment, so that affected infants and their families will derive maximum bene?t, even if replacement therapy with protein C concentrate is not widely available.
The mortality rate has recently been significantly reduced in purpura fulminans, largely because of more widespread use of therapeutic heparinization in these patients and aggressive replacement of platelets and coagulation factors.
Clinically, patients with purpura fulminanspresent with painful, erythematous macular lesions, and ecchymoses. These lesions evolve into painful indurated, well-demarcated purple papules with erythematous borders. Finally, they progress to necrosis with the formation of bullae and vesicles.
Diagnosis is based on clinical findings. Neonatal purpura fulminans occurs usually in patients with a deficiency of protein C. Protein C deficiency is usually inherited in an autosomal dominant manner, with heterozygous carriers often remaining asymptomatic until later in life, when they become very susceptible to venous thromboembolism. Autosomal recessive protein C deficiency, which is caused by homozygous or compound heterozygous mutations in protein C, is less common and usually leads to a more severe form of the disease, with onset of thrombotic manifestations at birth.
Within the first 72 hours after birth, purpuric lesions usually appear on the surface of the skin. The skin lesions soon enlarge and become vesiculated, producing hemorrhagic bullae with subsequent necrosis and black eschar formation. The margins of the lesions become erythematous and indurated. Thrombocytopenia is often evident. The patient may later develop signs of a urinary tract infection (UTI).
Laboratory investigations that should be performed include a full blood count, PT, PTT, fibrinogen and fibrin degradation products. Whole blood and plasma supply both procoagulant and anticoagulant factors (protein C and S and antithrombin III) and rapid improvement in skin necrosis has been reported after their use.Massive quantities may be needed to replace losses into infarcted skin.
Prompt excision of necrotic tissue and wound closure is recommended. Patients who survive are often left with difficult wounds involving underlying muscle and bone, and a significant number of patients who survive multiple organ failure may need major amputations.Escharotomies and/or fasciotomies may be indicated.Fasciotomies should be considered early in patients with tense limbs and distal ischemia, and should be performed on a clinical basis rather than on the basis of raised compartment pressures.
Management of DIC should be based on the clinical and associated laboratory ?ndings. The platelet count should be maintained > 50,000 ×109/L and the ?brinogen level >1 g/L. If the etiology is secondary to severe infection, appropriate intravenous antibiotics should be administered.
If the infant has the classical signs of purpura fulminans, blood samples of the infant and parents should be drawn into citrated tubes for antigen and activity levels of protein C and protein S, before replacement therapy is commenced. There is no protein S concentrate available. Fresh frozen plasma (FFP) or cryoprecipitate is used as replacement therapy. The mainstay of management of severe acquired, transient de?ciencies of protein C or S is aggressive treatment of the underlying cause, although replacement therapy has been used in such cases.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
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