Protein C deficiency

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Protein C deficiency

Hematological system

Coagulation disorders


Vitamin K deficiency

Leukemoid reaction

Leukemoid reaction


Protein C deficiency


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USMLE® Step 1 questions

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High Yield Notes

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Protein C deficiency

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USMLE® Step 1 style questions USMLE

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A 52-year-old woman, para 4 gravida 2 aborta 2, comes to the clinic for a follow-up appointment after a hospitalization. Two weeks ago, she had an incident of acute, severe abdominal pain and bloody stools. She was diagnosed with portal vein thrombosis. She denies similar episodes in the past. Medical history is notable for Legg-Calvé-Perthes disease as a child. She does not smoke, drink excessive alcohol, or use illicit drugs. She had 2 spontaneous abortions in the first trimester, following 2 successful pregnancies. Family history is remarkable for DVT in her maternal uncle and colon cancer in her father. The physician suspects an inherited condition. Which of the following will prompt further evaluation in this patient?  

External References

First Aid



Protein C and S are two anticoagulation proteins that inactivate coagulation factors Va and VIIIa in the coagulation cascade. This means, they act like brakes on coagulation, limiting clot formation and preventing clots from growing too big. So, when either of these proteins is deficient, it leads to a hypercoagulable state, meaning a person is at increased risk of developing a clot that could block blood flow. The most common places for such clots to develop are in the deep veins of the legs and in the vessels that carry de-oxygenated blood through the lungs.

Normally, protein C and protein S are 2 of many proteins or enzymes that regulate the complex process called hemostasis. This is where a solid clot forms in the flowing, liquid blood to plug the defect in a damaged blood vessel. It has two steps; Primary hemostasis involves the formation of a platelet plug at the site of injury, and secondary hemostasis involves coagulation, where several clotting factors come into play to form a fibrin mesh over the platelet plug to reinforce it, and form the blood clot. The main role of protein C and protein S is to prevent excess coagulation, or fibrin formation, during secondary hemostasis.

Protein C and S prevent excess coagulation by interacting with several other proteins involved in a complex system of checks and balances. So, it starts with a protein called thrombomodulin, which is on endothelial cells that line our blood vessels, and together with thrombin, they form a complex that also includes protein C and protein S.

When protein S joins this complex, it activates the proteolytic site of protein C, which cleaves and inactivates active factor V, a cofactor for factor X in the common pathway, and factor VIII, a cofactor for factor IX in the intrinsic pathway. The factor V degradation product also binds to this complex and further enhances its ability to cleave more active factor V and active factor VIII. By inhibiting both the intrinsic and common pathway, less fibrin is produced and coagulation slows down dramatically.


Protein C deficiency is a rare genetic trait that results from a lack of functional protein C. Protein C is a naturally occurring anticoagulant that helps to prevent excessive blood clotting by inhibiting coagulation factors V and VIII. So, its deficiency will predispose people to thrombotic disease and an increased incidence of venous thromboembolism. Furthermore, people with protein C deficiency are at an increased risk of developing skin necrosis while on warfarin. Treatment for protein C deficiency typically involves anticoagulants to prevent the formation of blood clots. In some cases, replacement therapy with protein C concentrates may be used.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  3. "Harrison's Principles of Internal Medicine" McGraw-Hill Medical Publishing (2005)
  4. "Protein C deficiency" Haemophilia (2008)
  5. "Protein C and protein S deficiency - practical diagnostic issues" Adv Clin Exp Med (2013)
  6. "Protein S deficiency: a clinical perspective" Haemophilia (2008)

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