APC resistance

In around five to eight percent of the population, APC resistance is the most common laboratory risk factor for venous thrombosis and pulmonary embolism. In women, this can also be associated with a tendency to abortion

Our content is pharmaceutically and medically tested

What is APC resistance?

In most cases, the APC resistance is based on a genetic variant of the coagulation factor V (read: factor five). The Factor V Leiden variant is a genetic modification of the Ges, which is "responsible" for the coagulation factor V. A point mutation in the gene changes factor V and its binding sites for activated protein C (APC). Activated protein C (APC) is a blood coagulation inhibitor - see also the separate box below: The blood coagulation cascade.

Resistance to the anticoagulant APC therefore increases the tendency to clot. This increased tendency to blood clots is a risk factor, for example thrombosis in the deep leg and pelvic veins, pulmonary embolism or inflammation of the veins on the body surface. The APC resistance thus represents a risk factor for the development of a thrombosis, but mostly several risk factors that favor the development of a thrombosis (such as immobility, long sitting, smoking, pill) are decisive.

People who have the modified gene on one of their chromosomes have a three to four-fold increased risk of thrombosis. People who have the altered gene on both chromosomes have a 60 to 80-fold increased risk of thrombosis.

The APC resistance was discovered by the Swedish doctor Björn Dahlbeck. The genetic defect was discovered in the Dutch city of Leiden, which is why the factor V Leiden variant was named.

The blood coagulation cascade

If the vascular wall is injured, for example due to a cut, blood coagulation begins in parallel on different levels.

  • immediate repair mechanisms for hemostasis

Damage to the vascular wall releases the so-called von Willebrand factor (vWF), which leads to the adhesion of blood platelets (thrombocytes). These now activated thrombocytes seal the defective area on the one hand and lead to the release of various messenger substances, which among other things lead to a narrowing of the blood vessel and to a further accumulation and clumping of platelets (platelet plug, white thrombus).

  • Onset of blood clotting

Two different systems are activated during blood clotting. The "exogenous" and the "endogenous" system. The "exogenous" system is set in motion by factors that are released when the tissue is damaged. The endogenous system is activated by the exposed connective tissue fibers (collagen fibers). Both systems activate other factors that are important for blood clotting. So factor X (ten) becomes activated factor X, i.e. Xa. This in turn is necessary to activate prothrombin (factor II, two) to IIa, which then activates fibrinogen (factor I, one) to fibrin (Ia). This is why one speaks of a blood coagulation cascade, since it practically runs through and a factor through its activation is important to get the next step in motion. The fibrin consists of fibers, similar to a felt, and blood cells, which then lead to the final seal (called a mixed or red thrombus) of the vessel.

Sophisticated system between thrombus formation and dissolution:

In the course of the wound healing - and so that the affected vessel remains open - the plug must of course be dissolved again. This is ensured by another system in the blood which, together with the coagulation, forms a finely tuned, constantly active balance: fibrinolysis. An important substance in it that dissolves the thrombus is plasmin. There are also other substances that "control" individual coagulation factors in order to avoid excessive coagulation.

What happens now with a factor V Leiden variant or APC resistance?

The activated factor V (five) is a cofactor for the above-mentioned factor Xa and is therefore important for the blood coagulation cascade. Factor V is activated via factor Xa or IIa. The activated protein C and protein S inhibit factor Va - this is important to keep blood clotting in balance. Due to the gene mutation on factor Va, it can only be inactivated slowly by activated protein C (APC) and the coagulation cascade continues with (somewhat) increased activity.

Diagnosis: How is a factor V Leiden variant and APC resistance determined?

Suspected APC resistance and a factor V Leiden variant can be checked using special laboratory tests.

The doctor will recommend testing for possible APC resistance, especially if

  • Thromboses occur without an external cause
  • younger patients have a thrombosis
  • Family thrombosis is common
  • Thromboses occur in unusual places
  • Spontaneous abortions occurred

Therapy: How is a Factor V Leiden variant and APC resistance treated?

A cure for the Factor V Leiden variant is not possible. However, risk factors that favor the development of thrombosis can be minimized.

This includes the following measures:

Smoking should be taboo. Taking birth control pills is associated with an increased risk of thrombosis. The benefit and risk should be carefully weighed against each other. In risky situations such as long-haul flights, thrombosis prophylaxis with compression stockings is recommended, and additional prevention (prophylaxis) with heparin injections into the subcutaneous tissue to thin the blood is also possible.

In the case of spontaneous or frequently recurring thromboses, the doctor also prescribes permanent treatment with anticoagulant drugs.

Prof. Dr. Michael Spannagl

© Thomas Corner / Berlin

Our advisory expert:

Professor Dr. Michael Spannagl works as a hemostaseologist at the Ludwig Maximilian University (LMU) in Munich and is well known in specialist circles for his work in the fields of hemostasis, intensive therapy and laboratory medicine. He is responsible for experimental and clinical studies on anticoagulation, therapy of hemophilia and management of blood components. He is a member of several committees (DIN, ISO, CEN) for the development of standards for medical laboratory diagnostics and for quality management. He was guideline coordinator and deputy chairman of the Society for Thrombosis and Haemostasis Research (GTH) and is chairman of the board of the Society for the Promotion of Quality Assurance in Medical Laboratories (INSTAND e.V.) and a member of the Blood Working Group of the Federal Ministry of Health (BMG). He is the author and co-author of over 250 publications (articles and book chapters). As a member of the commission of the German Medical Association, he co-authored the guidelines on "Therapy with blood components and plasma derivatives" and the guidelines on "Prophylaxis and therapy of venous thromboembolism (VTE)". In addition, Prof. Spannagl is an active member of numerous national and international scientific societies for hemostasis, transplant and laboratory medicine as well as for standardization and quality management in medical laboratories.

Important NOTE:
This article contains general information only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor. Unfortunately, our experts cannot answer individual questions.

blood Vessels Veins