What Is Antithrombin?
Antithrombin is a glycoprotein enzyme produced by the liver and released in the blood vessels, which binds with the natural anticoagulant heparin resulting in the inactivation of the clotting factor. Antithrombin is composed of 432 amino acid molecules. The significant role of antithrombin in hemostasis is to inhibit the clotting factors in plasma at the site of the injury to regulate the process of coagulation cascade pathways.
What Does Antithrombin Do?
The main function of antithrombin is to provide a counter mechanism for clot formation. It acts as an inhibitory component for thrombin formation along with factor IXa and Xa inhibition.
What Is the Mechanism of the Antithrombin?
The Antithrombin complex has two specific binding sites — reactive center loop and Heparin-binding site. The endothelium produces a glycosaminoglycan called Heparin sulfate, a natural anticoagulant with negative charges on the surface and a high affinity to bind with the antithrombin by the heparin-binding site. Conversely, the reactive center loop inactivates specific clotting factors like thrombin, factor IX (Christmas factor), and factor X (Stuart Prower factor). Antithrombin regulates clot formation and prevents clots from becoming more prominent so that the clot can not form emboli.
What Is Antithrombin Deficiency?
The deficiency of antithrombin refers to the inherited blood clotting disorder, which leads to a genetic mutation of a gene making antithrombin either deficient or defective. This causes excessive clot formation, which can lodge into the small vessels that nourish different organs and tissues, causing strokes. This could also be acquired. The deficiency of antithrombin can increase the risk of circulating blood clots, leading to other systemic disorders like thrombosis, thromboembolism, and complications in a hypercoagulation state. Antithrombin deficiency is also known as AT, Antithrombin III, AT III, heparin cofactor I, thrombin inhibitor I, and thrombophilia.
In the case of genetically transmitted antithrombin deficiency, the individual can be affected by single-gene mutations from either parent, called— Heterozygote. Similarly, Homozygote is a team used to describe an individual who inherited two mutant genes from both parents. Although the disorder is rare, it can affect males and females equally.
What Happens in Antithrombin III Deficiency?
Antithrombin III deficiency causes blood clots more than usual. This is an inherited condition. This is caused when the person receives an abnormal gene copy from one of the parents. This results in reduced levels of antithrombin III protein.
What Are the Causes of Antithrombin Deficiency?
Antithrombin deficiency causes can be hereditary or acquired.
The Hereditary Antithrombin Deficiency: Hereditary deficiency of antithrombin deficiency is an autosomal dominant disorder caused by the mutation in the SERINC1 gene, primarily responsible for antithrombin deficiency. This mutation makes the gene either defective or deficient. Hereditary antithrombin deficiency is of two types -
1. Type I - Quantitative Defect - In type I, antithrombin protein production is insufficient.
2. Type II - Qualitative Defect - In type II, the production of antithrombin protein is sufficient, but the mutation leads to defective protein synthesis, which does not work correctly.
The Acquired Antithrombin Deficiency: Acquired antithrombin deficiency is more common than hereditary antithrombin deficiency, but the risk of clot formation is less. It can be caused by other underlying disorders or ongoing therapy. It can be associated with -
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Impaired production of the antithrombin protein due to liver disease.
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Nephrotic syndrome because of protein loss.
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Disseminated intravascular coagulation leads to the secretion of both coagulation and anticoagulant.
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Vitamin K antagonists.
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Asparaginase.
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Heparin Insensitivity.
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Widespread tumors.
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Malnutrition, especially protein-energy malnutrition.
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Kwashiorkor (a serious type of malnutrition caused by insufficient protein and other nutrient requirements).
What Are the Signs and Symptoms of Antithrombin Deficiency?
The patient suffering from antithrombin deficiency shows the following signs and symptoms -
Venous Thromboembolism: In antithrombin deficiency, there is a high chance of forming a blood clot called– a thrombus that circulates in the bloodstream. The thrombus can travel within the deep veins and adhere to the walls of the blood vessels, forming a thrombus; this usually happens in the deep veins of the legs — causing deep vein thrombosis.
Pulmonary Embolism: Antithrombin deficiency causes blood clot formation in the deep veins of the legs. The blood clot (thrombus) can break off and form an embolus that flows into the blood vessels and can reach the body's other organs, like the lungs, and stick to the walls of the blood capillaries, which can block the blood flow. The blockage to the blood flow in the lungs because of the blood clot is called pulmonary embolism.
Arterial Thromboembolism: Arterial thromboembolism is quite rare. This is because the thrombus adhesion in the walls of the arterial blood vessels results in the blockage of the blood flow called arterial thromboembolism.
Heparin Insensitivity: In antithrombin deficiency, if the patient is insensitive to Heparin, the chances of clot formation are higher, which can adhere to the walls of the blood vessels.
How to Diagnose Antithrombin Deficiency?
Antithrombin deficiency can be diagnosed by recording history and performing some tests.
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Past medical and family history is essential for the diagnosis of the disorder. The history of deep vein thrombosis can be related to antithrombin deficiency.
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A repetitive blood test is needed to examine the value of thrombin in the blood.
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Testing partial prothrombin time before and after Heparin administration.
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Diagnosis can be confirmed with the functional assay for plasma antithrombin activity called the antithrombin-heparin cofactor assay. This test measures the ability of Heparin to inhibit thrombin or factor Xa.
What Are the Risk Factors Due to the Deficiency of Antithrombin?
The deficiency of antithrombin causes some risk factors -
- Antithrombin deficiency can lead to strokes due to clot formation.
- Due to the clot, insufficient oxygen supply causes organ ischemia.
- The heart pumps blood at a pace; if the lump is stuck in the wall of the vessels, the speed gets disturbed.
What Is the Treatment for Antithrombin Deficiency?
The treatment modalities for antithrombin deficiency are as follows -
Oral Medication: Indication of oral medicine involving blood thinner.
Anticoagulant Therapy: In anticoagulant therapy, a direct thrombin inhibitor is inserted.
Prophylactic Anticoagulation: In prophylactic anticoagulation, blood thinners are used during surgery or by injecting the concentration of the factor that inhibits thrombin.
Secondary Prophylaxis: In secondary prevention, blood thinners like Warfarin, low molecular weight Heparin, and 2-DOAC direct factors XA inhibitors such as Rivaroxaban.
Replacement Antithrombin Therapy: Antithrombin replacement can be done through recombinant antithrombin or plasma transfusion.
Conclusion -
Antithrombin deficiency is a rare blood disorder. If an individual is diagnosed with antithrombin deficiency, there is a good outcome if they are physically active and can stay on anticoagulant medication.
