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What is Severe Congenital Protein C Deficiency


Protein C deficiency can be caused by mutation of the protein C gene (congenital protein C deficiency) or as a result of other conditions (acquired protein C deficiency).1,2 The severity of the deficiency is determined by the remaining plasma activity of protein C.1

Severe Congenital Protein C Deficiency (SCPCD) is an autosomal recessive, rare disorder that leads to high initial mortality and long-term morbidity in survivors.1 In neonates, SCPCD can manifest, within hours after birth, as purpura fulminans with necrosis of the skin and venous thrombosis.1-3

Testing for SCPCD

Several laboratory tests can be conducted upon signs of purpura fulminans to confirm protein C deficiency:

Given possible confounding factors, severe congenital protein C deficiency is confirmed using multiple methods 3

  • Protein S assay 1 (low PC levels but normal Protein S levels are suggestive of SCPCD)
  • Protein C antigen5
  • Platelets 5,6
  • Fibrinogen 3,5
  • D-dimer5
  • Prothrombin time (PT) 3,5
  • Activated partial prothrombin time 3
  • Genetic analysis 3
  • Protein C level testing in parents 2 (Protein C activity assay and Protein C antigen)
  • PC testing in family members is recommended to determine if the deficiency is genetic and whether it is a homozygous or heterozygous mutation 3

The severity of protein C deficiency is based on protein C activity1

The mean plasma concentration of protein C in a healthy term infant is 40/IU dL, with a lower limit of normal of 25 IU/dL.1

Protein C concentration increases from birth until 6 months of age. Protein C concentration remains slightly low through childhood and achieves the adult range after puberty.1




Clinical diagnosis of purpura fulminans skin lesions is critical3

  • Visually identifying skin lesions:
    • Infants with SCPCD usually present within hours after birth with rapidly progressive purpura fulminans 3,1
  • Because purpura fulminans is a haematological emergency due to the rapidly progressive nature of the multi-organ thrombotic injury, consultation with a haematologist is recommended 2

SCPCD and its potential complications2

  • Purpura fulminans can lead to life-threatening complications:
  • Purpura fulminans can rapidly progress to organ failure as a result of necrosis and disseminated intravascular coagulation2
  • Rates of amputation in infants and children with purpura fulminans may be as high as 62%7

CEPROTIN® is indicated for prophylaxis and treatment of purpura fulminans coumarin-induced skin necrosis and venous thrombotic events in patients with severe congenital protein C deficiency.4

  1. Goldenberg N, Manco-Johnson M. Protein C deficiency. Haemophilia. 2008;14(6):1214–21.

  2. Chalmers E, et al. Purpura fulminans: recognition, diagnosis and management. Archives of Disease in Childhood. 2011;96(11):1066–71.

  3. Price VE, et al. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med. 2011;16(6):318–22.

  4. CEPROTIN® 500 IU Summary of Product Characteristics.

  5. Khor B, et al. Laboratory tests for protein C deficiency. Am J Hematol. 2010;85:440–2.

  6. Tairaku S, et al. Prenatal genetic testing for familial severe congenital protein C deficiency. Hum Genome Var. 2015;2:15017

  7. Gürgey A, et al. Outcome in Children With Purpura With Fulminans: Report on 16 Patients. Am J Hematol. 2005;80(1):20–5

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July 2023