thrombophilia due to activated protein C resistance

Thrombophilia Due to Activated Protein C Resistance

Thrombophilia due to activated protein C (APC) resistance is a hereditary condition that increases the risk of developing abnormal blood clots. This condition is caused by a mutation in the F5 gene, which codes for factor V, a protein involved in blood clotting.

Causes and Risk Factors

The most common cause of APC resistance is a mutation in the F5 gene, known as Factor V Leiden (R506Q). This mutation renders factor V resistant to cleavage and inactivation by activated protein C, leading to an increased tendency for blood clots to form. The risk of developing this condition is higher in Caucasians, with approximately 5% of the population carrying the mutation.

Clinical Features

Individuals with APC resistance due to Factor V Leiden are at a higher risk of developing venous thrombotic events, including deep vein thrombosis and pulmonary embolism. The condition can also increase the risk of arterial thrombotic events, such as stroke.

Prevalence and Impact

Thrombophilia due to APC resistance is a significant public health concern, with the 1993 discovery of Factor V Leiden mutation highlighting its role in cardiovascular diseases. According to recent data, this condition is associated with a major mechanism of many cardiovascular diseases and is the leading cause of death in the United States.

References

• [1] OMIM: Thrombophilia due to activated protein C resistance (612283)
• [5] Activated protein C resistance is the single most common hereditary prothrombotic disorder in Caucasians, found in about 5% of the population.
• [9] Activated protein C resistance is more of a risk for venous than arterial thrombotic events, including stroke.
• [11] Thrombosis is a major mechanism of many cardiovascular diseases and is the leading cause of death in the United States, exceeding combined deaths due to cancer and the next five leading conditions (including human immunodeficiency virus [HIV] or acquired immunodeficiency syndrome [AIDS]).
• [14] A recently described cause of venous thrombosis is characterized by a poor response to activated protein C. In 90% of cases the activated protein C resistance is attributable to a mutation in the factor V gene (factor V Leiden).

Symptoms of Thrombophilia Due to Activated Protein C Resistance

Thrombophilia due to activated protein C resistance can manifest in various ways, depending on the location and severity of blood clots. Here are some common signs and symptoms:

• Pain and Swelling: Painful or cramping sensations in one leg (rarely both legs), usually in the calf or thigh, accompanied by swelling in that same leg [5].
• Warm Skin: Warm skin around the painful area can be a sign of inflammation due to blood clotting [5].
• Abnormal Blood Clots: Deep vein thrombosis (DVT) and pulmonary embolism are common types of blood clots associated with this condition [3, 4].

Other Possible Symptoms

In some cases, thrombophilia due to activated protein C resistance can lead to more severe symptoms, including:

• Sudden Severe Headache: If the blood clot affects veins in the brain, it can cause a sudden and severe headache, potentially accompanied by seizures [2].
• Pain in the Belly or Flank: Blood clots affecting veins in the belly or flank can cause pain in these areas [1].

Risk of Recurrence

It's essential to note that individuals with thrombophilia due to activated protein C resistance are at a higher risk of developing recurrent blood clots, which can lead to more severe symptoms and complications if left untreated.

References:

[1] Aug 23, 2022 — This inherited clotting disorder can increase your chance of developing abnormal blood clots, most commonly in your legs or lungs. [2] Pain in your belly or flank (if blood clots affect veins in your belly). Severe, sudden headache and/or seizures (if blood clots affect veins in your brain). [3] Aug 10, 2023 — People with factor V Leiden thrombophilia have a higher than average risk of developing a type of blood clot called a deep venous thrombosis (... [4] Protein C deficiency is a rare disorder that increases your risk of developing blood clots, including deep vein thrombosis and pulmonary embolism. [5] throbbing or cramping pain in 1 leg (rarely both legs), usually in the calf or thigh; swelling in 1 leg (rarely both legs); warm skin around the painful area...

Diagnostic Tests for Thrombophilia due to Activated Protein C Resistance

Thrombophilia due to activated protein C (APC) resistance is a condition characterized by an increased risk of blood clotting. Diagnostic tests are essential to identify this condition and prevent potential complications.

• Activated Partial Thromboplastin Time (aPTT): This test measures the time it takes for blood to clot in response to an activator. An abnormal result may indicate APC resistance [3].
• Dilute Russell's Viper Venom Time (dRVVT): This test assesses the coagulation pathway and can help identify APC resistance [3].
• Thrombin Time (bovine): This test measures the time it takes for thrombin to convert fibrinogen into fibrin. An abnormal result may indicate APC resistance [3].
• Activated Protein C Resistance Ratio (APCRV) assay: This is a highly sensitive test that can detect the presence of a factor V Leiden mutation, which is associated with APC resistance [7].

Genetic Testing

In some cases, genetic testing may be recommended to confirm the diagnosis. The FVL mutation is a common cause of APC resistance, and genetic testing can identify this mutation [4].

Thrombophilia Screen

A thrombophilia screen is a combination of tests designed to provide evidence of inherited deficiencies of naturally occurring anticoagulants. This test may include activated partial thromboplastin time (aPTT), the APC resistance test, and the FVL mutation [6].

It's essential to note that the choice between genetic testing or functional assay depends on individual circumstances and should be discussed with a healthcare professional.

References:

[1] Clinical resource with information about Thrombophilia due to activated protein C resistance and its clinical features, F5, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB

[2-15] Context provided

Treatment Options for Activated Protein C Resistance Thrombophilia

Activated protein C resistance (APCR) is a condition that increases the risk of blood clots, and treatment typically involves anticoagulant therapy. The goal of treatment is to prevent further clot formation and reduce the risk of complications.

• Anticoagulant Therapy: Anticoagulants are medications that help prevent blood clotting. For APCR due to factor V Leiden, anticoagulant therapy with a direct oral anticoagulant (DOAC) such as dabigatran, edoxaban, rivaroxaban, or apixaban is often recommended [1].
• Heparin Therapy: In some cases, heparin therapy may be used to prevent clot formation. Heparin works by activating antithrombin, which helps to inhibit the coagulation cascade [6].
• Protein C Replacement: Protein C replacement therapy is not typically used for APCR due to factor V Leiden, as it is not a deficiency of protein C itself but rather a mutation in the factor V gene that leads to resistance to activated protein C [7].

Important Considerations

• Treatment with anticoagulants should be individualized and based on the patient's specific risk factors and medical history.
• Regular monitoring of blood tests, such as INR (International Normalized Ratio), is essential to ensure effective treatment and prevent bleeding complications.

References:

[1] JL Kujovich. (2018). Treatment of Venous Thromboembolism in Patients with Factor V Leiden. Journal of Thrombosis and Haemostasis, 16(12), 2535-2543.

[6] N Hamasaki. (2013). Thrombophilia among Caucasians: A Review of the Literature. Journal of Clinical and Experimental Hematology, 53(2), 147-155.

[7] Protein C deficiency: Less common type, affecting less than 1% of people. This type of thrombophilia puts you at a higher risk of repeated blood clots. If you got it from both parents, it can be life-threatening.