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Causes of protein C deficiency – key differences between Severe Congenital Protein C Deficiency and acquired protein C deficiency

Causes of Protein C Deficiency

Key differences between Severe Congenital and Acquired Protein C Deficiency

Making the distinction between congenital and acquired Protein C (PC) deficiency is often challenging particularly in the setting of acute thrombosis. Genetic testing is often useful in confirming the diagnosis of the patient in the long-term, but it is not always readily available.1,2 Because genetic testing takes time, the information below may be considered when diagnosing in the acute setting.


Severe Congenital PC Deficiency (SCPCD) is a rare, autosomal recessive disorder that mainly presents in neonates. One of the main symptoms is purpura fulminans. There are two genotypes that are associated with this disorder, homozygous and compound heterozygous.1

Homozygous pc DEFICIENCY


Furthermore, within each of the above genotypes of SCPCD, there exist two subtypes.
Type 1 – Reduction in both PC antigen concentration and activity3
Type 2 – Normal antigen concentration but with reduction in activity3

• In SCPCD, PC levels are nearly nonexistent [PC < 1 IU/dL].1

• Infants with SCPCD usually present within hours of birth with rapidly progressive purpura fulminans and Disseminated Intravascular Coagulation (DIC).1


Acquired PC deficiency is a result of the consumption of PC levels due to the some of the factors below:2

• Vitamin K deficiency also contributes to PC deficiency.Vitamin K is necessary for coagulation factors, as well as PC and protein S.4

• Liver disease, such as chronic hepatitis C, has also been demonstrated to be associated with PC deficiency.3,5

↑ Increased consumption of PC

• Sepsis/severe infection without overt DIC, e.g., Group B Streptococcus infection

• Overt DIC

• Antiphospholipid antibodies

• Cardiac bypass


↓ Decreased synthesis of PC

• Severe hepatic dysfunction

• Galactosemia

• Severe congenital heart disease

• Warfarin therapy

• Complications of prematurity


  1. Goldenberg N, Manco-Johnson M. Protein C Deficiency. Haemophilia. 2008;14(6):1214-1221.

  2. Price VE, et al. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med. 2011;16:318-322.

  3. Kottke-Marchant K, Comp P. Laboratory issues in diagnosing abnormalities of protein C, thrombomodulin, and endothelial cell protein C receptor. Arch Pathol Lab Med. 2002;126:1337–1348.

  4. Bovill EG, et al. Vitamin K1 metabolism and the production of des-carboxy prothrombin and protein C in the term and premature neonate. Blood. 1993;81(1):77–83.

  5. Saray A, et al. Protein C Deficiency in Chronic Hepatitis C: Correlation With Histological Extent of Liver Fibrosis. Clin Appl Thromb Hemost. 2017;23(1):72-77.

SCPCD - Key Management info  

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