Protein C deficiency 25/12/2010 BY: MOHAMMED ALSAIDAN

Protein C deficiency AR, usually presents in the neonatal period with purpura fulminans (PF) severe disseminated intravascular coagulation (DIC) venous thromboembolism (VTE) Asymptomatic : 1 in 500 healthy individuals clinically significant : 1 in Most parents of infants with severe protein C deficiency are asymptomatic

Protein C Protein C is a vitamin K-dependent coagulation protein Synthesized in hepatocytes Activated after complex formation with thrombin on the endothelial cell receptor It cleaves critical sites in the activated procoagulant factors V and VIII, thus inactivating these enzymes

Protein C level Mild, moderate sever The mean level in a healthy term infant is 40 IU /dL lower limit of normal in infants of 25 IU /dL Later: approximately 60 IU/dL

Labs At the ontset of skin lesions: normal Coagulation studies elevated D-dimer undetectable plasma protein C activity Rapidly after onset of PF : thrombocytopenia hypofibrinogenaemia prolongation of the PT

Clinical features Foetal demise or die from DIC before diagnosis Most affected infants are congenitally blind from thrombosis into the developing vitreal vein Evidence of prenatal arterial ischaemic stroke on MRI Recurrent episodes of PF triggered by infection, trauma, and minor decreases anticoagulation

Protein C deficiency PF originates with red or purpuric lesions at pressure points Histologically, PF lesions consist of fibrin clots in small venules of the subcutaneous fat. Low INR  short-term bridging anticoagulation with low- molecular-weight heparin or protein C replacement with concentrate, to prevent VTE, DIC and PF

Protein C deficiency No anticoagulation required when plasma protein C concentrations above 50% around surgery and above 20% during baseline conditions Infants managed with intensive anticoagulation and/or protein C replacement have exhibited normal growth in longterm follow-up Some will have developmental delays and/or cognitive impairment

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