Protein C Deficiency

Protein C deficiency is a blood clotting disorder that is usually related to abnormalities in the specific genes. People suffering from this condition are predisposed to the development of abnormal blood clots. It was first described in the year 1981.1

Protein c deficiency

Overview

Protein C is just like any other protein in our blood stream. However, its function is to prevent the blood from getting too much clotted up. We can say that Protein C is a type of "cop" or a "guard" that keeps a check on our clotting process. So, in case the levels of protein C are low, there will be a tendency of forming clots more easily in that person which is utterly abnormal.

On the other hand, if the levels of protein C are elevated it is relatively safe. This is because there doesn’t appear to be any increased bleeding tendency when the Protein C levels go up.2

Causes of Protein C Deficiency

Two major causes have been attributed to the low levels of protein C:

  • Inherited deficiency as a result of genetic abnormality or simply mutation
  • Acquired deficiency as a result of some other condition or disease

Types of Protein C Deficiency

In order to avoid being wrongly diagnosed as “inherited protein C deficiency” when the low value of this protein are detected in your blood, making the distinction between the inherited and the acquired (or temporary) deficiency is very important. It is firstly advisable to repeat the testing at a later time for confirming a low level of Protein C to check whether or not it was a temporary decrease due to certain conditions. Furthermore, testing of parents is necessary in order to help in the clarification in case the inherited type of Protein C deficiency is suspected.

Inherited Deficiency

Congenital or inherited form of protein C deficiency is a genetic disorder. So, it typically runs in families. This is has a rare occurrence as only 0.2 % of the general population are seen to have this deficiency from birth. This simply means that out of every 500 people, 1 person may have it.1 It affects men and women equally.

The Genetics behind Protein C deficiency simplified:

There is a dominant pattern of inheritance in case of Protein C deficiency. What this means is that there is a 50 % chance for a child to have the disorder in case one of the parents is suffering from this genetic condition. We all have two copies of protein C gene – one from father and one from mother.

  • Heterozygous Protein C deficiency: The person, who has 1 defective protein C gene inherited either from father or mother, is known as heterozygous for protein C deficiency.
  • Homozygous Protein C deficiency: The person, who has 2 defected protein C genes – one defective gene from father and other defective gene from mother, is known as homozygous for protein C deficiency.

    Homozygous deficiency is seen to occur as low as 1 in 1 million pregnancies.3 So, it is extremely rare. The fetus that is homozygous protein C deficient often doesn’t survive, which results in a miscarriage.2

Acquired Deficiency

Acquired protein C deficiency is a common type of protein C deficiency. We may find low levels of this protein in patients with the following conditions:

  • Patients on anticoagulant medication - Warfarin (Coumadin®)
  • Vitamin K deficiency
  • Liver failure (such as liver cirrhosis)
  • Fresh blood clots
  • Antibiotic therapy for a prolonged time in a person who had little food intake over many days
  • Surgical removal of the small intestine
  • Disseminated intravascular coagulation (DIC) - a generalized bleeding and clotting disorder usually associated with widespread infection in the blood stream
  • Widespread tumors (metastasis)
  • Severe infection even without DIC4, 5

When the acquired protein C deficiency takes place in adults, it does not increase their risk of blood clots. This is because of the fact that the conditions which cause temporary lowering of the protein C levels, also result in decrease of clotting proteins.

However, in children, when the levels of protein C are severely decreased as a result of infection, there occurs the increase in the risk of blood clots.4

Symptoms of Protein C deficiency

In many patients of protein C deficiency, there are usually no symptoms as well as no episodes of venous thromboembolism (i.e., the clot formation or movement of clots in veins). However, in some of them, there occurs:

Venous Thromboembolism (VTE)

  • Commonly it takes place in the legs and/or lungs.
  • The rarer sites include the brain and intestines.
  • It usually occurs after 20s and its rate increases as the person moves towards 50 years of age.

Warfarin-induced skin necrosis

  • WISN is rare complication of starting warfarin therapy.
  • It is a medical emergency.
  • Protein C levels fall faster than those of the vitamin K-dependent clotting factors.
  • So, a state of increased blood coagulation (thickening of blood) is achieved temporarily.
  • It presents with lesions on the skin usually at extremities, breast, torso and penis. When left unattended, the skin starts to become dead (necrotic) due to decreased blood flow to the skin.

Neonatal purpura fulminans

  • Protein C Deficiency, usually of the homozygous type, can also present immediate after the birth (i.e., in neonates).
  • There is diffuse purple discoloration of the skin due to the bleeding underneath, medically known as purpura.

Diagnosing Protein C Deficiency

"Protein C activity" or "functional protein C" is the best test to know whether or not a person has protein C deficiency.2 Patient’s blood is to be send to a larger medical institution or a specialized commercial laboratory for testing.

Two types of protein C tests are generally done:

  • Protein C antigen level determines how much of the protein is present in the blood
  • Protein C activity level (also called “functional test”) - determines whether or not the protein C that is present actually works

Genetic testing is not generally done in routine clinical practice. This is because there are over 160 different known defects or mutations that can occur on the protein C gene 4. Thus, genetic testing is only reserved for research studies.

If someone in your family is diagnosed with protein C deficiency, make sure that all other family members are tested for the same.

Treatment for Protein C Deficiency

Treatment of patients diagnosed with protein C deficiency depends on the risk of thromboembolic disease of each patient. Anticoagulation therapy – i.e., giving medications that decrease or prevent the clot formation, is started. This includes:

  • Heparin
  • Low-molecular-weight heparins
  • Warfarin

These medications are given for a period of 3-6 months. However, the patients that have had many episodes of clot formation and/or clot travelling through their veins (embolism), are put on long-term oral anticoagulation on warfarin. The only major risk associated with long term anticoagulation is massive bleeding (hemorrhage) which can be prevented if the warfarin use is properly monitored.

The patients, who are homozygous for protein C gene, can have a sudden death due to thrombus (or clot) formation. So, they are administered a source of protein C. This is done through the blood products like fresh frozen plasma (FFP). Also, a form of human protein C concentrates is available worldwide.

Warfarin-induced skin necrosis

  • Warfarin is immediately stopped
  • Vitamin K is quickly adminstered
  • Heparin is given in the therapeutic doses
  • Protein C is given to protein C deficient individuals

Neonatal purpura fulminans

  • Fresh frozen plasma is given
  • Next, Protein C concentrates are given intravenously
  • Life-long anticoagulation is needed
  • If sometimes the thrombosis occurs despite anticoagulation, Protein C can be used

If Protein C Deficiency is left untreated

The possible complications in case the Protein C deficiency is left untreated or mismanaged due to excessive anticoagulation include:

  • Complications of Venous Thromboembolism
  • Massive bleeding risk in case of bleeding from excessive anticoagulation
  • Increase in pregnancy losses (miscarriage) with inherited type of protein C deficiency
  • WISN and NPF, as discussed are serious or life-threatening emergencies

Prognosis for people with Protein C Deficiency

  • There is a 10 to 15 times increased risk of Venous Thromboembolism.5
  • After a known VTE event, the risk of getting VTE again may goes up to 60%.5 According to a recent study, the risk of getting another such episode was found to be 38% over 10 years.5
  • Protein C deficiency and Pregnancy – there is an increased risk of VTE in pregnant women with protein C deficiency However, the most events occur after delivery of baby.5
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