Protein C deficiency

General

Under the term Protein C deficiency one understands one congenital or acquired coagulation disorder, in which the coagulation is increased due to a lack of control on the part of the protein C and sometimes runs unchecked.
This goes with one increased risk of blood clots forming in the smallest blood vessels (Capillaries) hand in hand what to Lack of oxygen and the Tissue death can lead.
The consequences range from Redness over Skin necrosis up to Multiple organ failurewhich is fatal if left untreated.

Basics

The ability of human blood to clot in the event of injury or trauma is a vital property.
It prevents internal and external bleeding and runs as a if necessary complicated cascade with 13 so-called coagulation factors from.
However, so that the blood does not unintentionally coagulate in uninjured areas, it is subject to coagulation in various places precise controls. One of them contains the protein C. The protein C is a protein made in the liverwhich must be present in the blood in a certain amount.
Uninjured areas of the vessel activate protein C to form activated protein C (aPC), which in turn binds to another protein, protein S, and together with it inhibits coagulation factors 5 and 13.
Through this inhibition can the Cascade does not expire and a undisturbed blood flow in the intact vessel is guaranteed.
This system is the main body's own regulatory mechanism to inhibit coagulation.
If this protein C is present in insufficient concentration, the patient suffers from protein C deficiency.

Read more about the topic here: Blood clotting

causes

As mentioned above, a distinction is made between protein C deficiency congenital and acquired causes.
Of the congenital severe protein C deficiency is luckily one extremely rare disease with a statistical occurrence in the population of approx. 1: 30,000. One is responsible for the protein C deficiency Mutation in the protein C gene (PROC gene) on the DNA. This can also be passed on to children. This increases the risk for children of sick parents to also develop protein C deficiency.
A type 1 is differentiated from a type 2 based on the concentration in the blood and the ability to perform its tasks.
Of the Type 1 protein C deficiency is characterized by the fact that the protein is both limited in function and at the same time significantly reduced in the amount present in the blood (real protein C deficiency).
In contrast, the patient has with Type 2 protein C deficiency almost enough protein, but it cannot do its job (Protein C defect).
Both types can sometimes cause massive symptoms and even to be deadly.

On the other side are those acquired causeswhich can lead to a protein C deficiency. Here are primary other clinical pictures or health situations responsible for the deficiency, which then occurs secondary and can usually be eliminated by treating the underlying disease. Basically a decreased production or increased consumption of protein C to be responsible. Typical acquired causes are Liver disease, the place where protein C is formed, such as Cirrhosis of the liver, Liver fibrosis or one viral inflammation of the liver (hepatitis). Also Tumors that destroy liver tissue, can lead to protein C deficiency in the late stages.
In addition, caused a Treatment with anticoagulants how Marcumar a protein C deficiency, which is why it is essential when starting treatment with Marcumar given overlapping heparin for a few days must become. To form the protein C is Vitamin K necessary. Consequently, a vitamin K deficiency due to malnutrition or malnutrition also leads to an acquired protein C deficiency. An increased consumption, which leads to a deficiency in protein C, is part of the picture in particular sepsis. A sepsis is a severe clinical picturein which it becomes a Flood of blood and thus the body with bacterial pathogens.

Symptoms

The symptoms of protein C deficiency strongly depend on the activity of the protein and its concentration in the blood. The severity of the complaints is closely related to the measured values.
Slightly lowered values ​​are only clinically noticeable in rare cases.
In the severe form, both congenital and acquired, various symptoms come to the fore, which through Microthromboses in the smallest blood vessels in the skin and organs occurrence. First of all it comes to small, punctiform hemorrhages on the skin, which cannot be pushed away under pressure (Petechiae). In the further course these become flat and flow into one another. This appearance becomes technical Purpura fulminans called. As the capillaries that supply oxygen to the skin become more and more clogged with tiny blood clots, one continues to develop Death of skin (Skin necrosis), What Pain caused. These microthrombi are also found in all organs and thus cause the dire course that a protein C deficiency can lead to Multi-organ care, Amputations of body parts and untreated can also lead to death can.

At the congenital protein C deficiency come in the newborn increased venous thrombosis before, i.e. blood clots in larger veins. Children have a higher risk of so-called atypical thrombosis in the brain or intestines.

diagnosis

The diagnosis of protein C deficiency is not so much a clinical one, but above all a diagnosis laboratory. After a normal blood collection can get the blood on Investigated the concentration of protein C and its activity become. First, the activity of the protein is measured in%, with the Normal range for adults between 70 and 140% measured by the average activity in healthy people.
From 20-25% to step severe symptoms who need treatment. In a further step you can use the Determine the number of protein C in the blood. This only makes sense if you have previously noticed a decreased activity or the patient suffers from symptoms that are compatible with a protein C deficiency. Here lies the Normal range at 2-6 mg / l for adults.
A protein C deficiency is diagnosed when the activity falls below 70%, whereupon a differentiation is made into type 1 (reduced) and type 2 (normal) based on the blood concentration.
In order to exclude and clarify acquired and reversible causes, the Status of the liver as well as possibly medication taken to be clarified. A vitamin K determination can also be useful.

therapy

The best direct therapy for severe protein C deficiency, which can also become noticeable for the first time in adulthood, consists in the administration of concentrated protein C over a infusion directly into the cycle. This directly corrects the deficiency and helps restore microcirculation in the capillaries.
This is before especially in newborns with congenital protein C deficiency the only way to prevent a fatal outcome.

The Administration of heparin, another coagulation inhibitor, is a quick measure to maintain an anticoagulant during the period of protein C deficiency.

That is at least as important Treatment of a potentially reversible primary cause. This includes having a Sepsis under control quickly or if the wrong medication is used, the substances that inhibit the formation of protein C are discontinued. Liver diseases must also be addressed as this is where protein C is formed.

Summary

At the Protein C deficiency it is a rare congenital or acquired disease that is associated with an increased tendency to form blood clots.

This tendency to thrombosis can lead to microthrombi and necrosis of the skin, occlusion of important arteries Liver damage, Gastric ulcers and strokes and, in untreated cases, to multiple organ failure and death of the patient. Protein C is a protein produced in the liver, which normally blocks the coagulation cascade with protein S and thus prevents unnecessary blood clotting and blood clot formation.
However, if there is a deficiency in Protein C or Protein S (for genetic or other reasons)please refer: Protein S Magel), this leads to uninhibited clot formation, which in turn comes with Thrombosis and Embolisms goes hand in hand.

Typical causes of an acquired protein C deficiency include cirrhosis of the liver Liver failure or blood poisoning (sepsis) in the context of untreated meningitis; the so-called Meningococcal sepsis. This leads to an enormous consumption and thus to a lack of anticoagulant enzymes such as protein C and S. A protein C deficiency can be life-threatening, especially in pregnant women.

Protein-C deficiency and pregnancy

Studies have shown that pregnant women are five times more at risk than non-pregnant women Thrombosis to have.

The reason for this is on the one hand the slower blood flow in the vessels of pregnant women and on the other hand the changed concentrations of blood clotting enzymes. Anticoagulant enzymes such as Protein C and protein S decrease, whereas those that promote blood clotting increase. Women who also have a genetic or acquired tendency to thrombosis experience thrombosis and embolism all the more frequently.
Pregnancy complications such as preeclampsia and HELLP syndrome can also result from protein C deficiency. These are two typical and feared diseases during pregnancy, the causes of which include is a bleeding disorder (e.g. protein C and S deficiency). In severe cases, these diseases can be accompanied by embolisms, childhood circulatory disorders and miscarriages, liver failure and death.

In order to prevent these complications, women at risk are recommended to wear compression stockings during and after pregnancy. Additional therapy with heparin injections is recommended for women who have already had a thrombosis or who have been diagnosed with a bleeding disorder.