Antithrombin III deficiency

Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of antithrombin III. This deficiency may be inherited or acquired.[1] It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism, and repetitive intrauterine fetal death (IUFD).[2] Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to venous thrombosis.[3] Inheritance is usually autosomal dominant, though a few recessive cases have been noted.[4] The disorder was first described by Egeberg in 1965.[5] The causes of acquired antithrombin deficiency are easier to find than the hereditary deficiency.[6]

Antithrombin III deficiency
Other namesATIII deficiency
SpecialtyHematology 

This disease is affecting one in thousand people annually. It is type of multifactorial disease where both genetics and environment affect the procoagulant and anticoagulant forces, finally leading the ATIII deficiency. Various mutations in genes, such as deletion or addition of genes, for anticoagulant proteins such as protein C, antithrombin or protein S are one of the risk factors.[7] The deficiency may be caused by adhesion of platelets with immobilised fibrinogen.[8]

The patients are treated with anticoagulants or, more rarely, with antithrombin concentrate.

In kidney failure, especially nephrotic syndrome, antithrombin is lost in the urine, leading to a higher activity of Factor II and Factor X and in increased tendency to thrombosis.

Diagnosis

Different laboratory tests can be performed to investigate for antithrombin III deficiency. First, numerical analysis for antithrombin can be performed. A lower antithrombin III level increases the risk of venous thrombosis and pulmonary embolism.[1] Second, Anticardiolipin antibodies (immunoglobulin G [IgG] and IgM class) can be injected. Third, antigen activity and total tests for Protein C and Protein S can be checked to see if the genes of their proteins have been mutated.[9] Fourth, Prothrombin time (PT) and activated partial thromboplastin time (aPTT) can be calculated. Finally, Factor V Leiden test can also be performed in order to check blood clotting and adhesion of platelets.[10]

Once a patient develops the congenital antithrombin III deficiency, a sign of anticoagulation can be easily indicated.[11]

Image experiments can be studied to evaluate the antithrombin III deficiency. First of all, echocardiography is performed to all patients suffering from antithrombin III deficiency. These patients will be first go through the blood test to find a sign go arterial thrombus, then echocardiography can be tested.[12] Second, doppler ultrasonography is usually performed at the earlier stage than echocardiography to compress. It is used to find the resolution of an acute thrombus.[11] Finally, ventilation-perfusion scanning is test to check for images of pulmonary thrombosis.[11]

Management

Heparin enhances ATIII activity and neutralizes "activated serine protease coagulation factors."[13] Patients with ATIII deficiency requiring anticoagulant therapy with heparin will need higher doses of heparin. ATIII binds to thrombin and then forms the thrombin-anti thrombin complex or TAT complex. This is a major natural pathway of anticoagulation. This binding of thrombin to AT is greatly enhanced in the presence of heparin. Heparin does not affect vitamin K metabolism, so giving vitamin K1 (Phytonadione) will not reverse the effects of heparin.[14]

Heparin is used as "bridging" therapy when initiating a patient on warfarin in a hospital setting. It can be used in DVT prophylaxis and treatment, acute coronary syndromes, and ST-segment elevated MI.

See also

References
  1. Găman AM, Găman GD (2014). "Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature". Current Health Sciences Journal. 40 (2): 141–3. doi:10.12865/CHSJ.40.02.12. PMC 4340457. PMID 25729597.
  2. Kurman RJ, ed. (2002). "Chapter 23: Diseases of the Placenta". Blaustein's Pathology of the Female Genital Tract (Fifth ed.). pp. 1136–7.
  3. Khor B, Van Cott EM (December 2010). "Laboratory tests for antithrombin deficiency". American Journal of Hematology. 85 (12): 947–50. doi:10.1002/ajh.21893. PMID 21108326.
  4. Online Mendelian Inheritance in Man (OMIM) 107300
  5. Egeberg O (June 1965). "Inherited antithrombin deficiency causing thrombophilia". Thrombosis et Diathesis Haemorrhagica. 13: 516–30. doi:10.1055/s-0038-1656297. PMID 14347873.
  6. Khor B, Van Cott EM (December 2010). "Laboratory tests for antithrombin deficiency". American Journal of Hematology. 85 (12): 947–50. doi:10.1002/ajh.21893. PMID 21108326.
  7. Dahlbäck B (July 2008). "Advances in understanding pathogenic mechanisms of thrombophilic disorders". Blood. 112 (1): 19–27. doi:10.1182/blood-2008-01-077909. PMID 18574041.
  8. Loncar R, Kalina U, Stoldt V, Thomas V, Scharf RE, Vodovnik A (October 2006). "Antithrombin significantly influences platelet adhesion onto immobilized fibrinogen in an in-vitro system simulating low flow". Thrombosis Journal. 4: 19. doi:10.1186/1477-9560-4-19. PMC 1618384. PMID 17040572.
  9. Undas A, Brummel K, Musial J, Mann KG, Szczeklik A (October 2001). "Blood coagulation at the site of microvascular injury: effects of low-dose aspirin". Blood. 98 (8): 2423–31. doi:10.1182/blood.V98.8.2423. PMID 11588039.
  10. Jennings LK, Kotha J (December 2013). "The Utility of Platelet and Coagulation Testing of Antithrombotics: Fusing Science with Patient Care". Drug Development Research. 74 (8): 587–593. doi:10.1002/ddr.21119. PMC 3902984. PMID 24489427.
  11. Hassan Y (2 February 2018). "Antithrombin III Deficiency: Practice Essentials, Pathophysiology, Epidemiology". Medscape.
  12. Hayıroğlu Mİ, Keskin M, Dönmez C, Günay MB, Ünal Dayı Ş (December 2016). "Antithrombin III deficiency concomitant with atrial fibrillation causes thrombi in all chambers: 2D and 3D echocardiographic evaluation". Anatolian Journal of Cardiology. 16 (12): E21–E22. doi:10.14744/AnatolJCardiol.2016.7456. PMC 5324928. PMID 28005013.
  13. Edward F. Goljan (2011). Pathology. Mosby/Elsevier. p. 251. ISBN 9780323084383. Retrieved 24 August 2014.
  14. Basic and Clinical Pharmacology, Lange, 12th ed
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