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 20 000

• 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

T H A N KYO U