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| {{More citations needed|date=June 2008}} | | {{Short description|A genetic disorder affecting blood clotting}} |
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| | name = Antithrombin III deficiency
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| '''Antithrombin III deficiency''' (abbreviated '''ATIII deficiency''') is a [[wikt:deficiency|deficiency]] of [[antithrombin|antithrombin III]]. This deficiency may be inherited or acquired.<ref name=":0">{{cite journal | vauthors = Găman AM, Găman GD | title = Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature | journal = Current Health Sciences Journal | volume = 40 | issue = 2 | pages = 141–3 | date = 2014 | pmid = 25729597 | pmc = 4340457 | doi = 10.12865/CHSJ.40.02.12 }}</ref> It is a [[rare disease|rare]] [[hereditary disorder]] that generally comes to light when a patient suffers recurrent venous [[thrombosis]] and [[pulmonary embolism]], and repetitive intrauterine fetal death (IUFD).<ref>{{cite book | editor-first = Robert J | editor-last = Kurman | name-list-format = vanc | title = Blaustein's Pathology of the Female Genital Tract | edition = Fifth | year = 2002 | chapter = Chapter 23: Diseases of the Placenta | pages = 1136–7 }}</ref> Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to [[venous thrombosis]].<ref>{{cite journal | vauthors = Khor B, Van Cott EM | title = Laboratory tests for antithrombin deficiency | journal = American Journal of Hematology | volume = 85 | issue = 12 | pages = 947–50 | date = December 2010 | pmid = 21108326 | doi = 10.1002/ajh.21893 }}</ref> Inheritance is usually [[autosomal]] [[Dominance (genetics)|dominant]], though a few [[recessive]] cases have been noted.<ref>{{OMIM|107300}}</ref> The disorder was first described by Egeberg in 1965.<ref name="pmid14347873">{{cite journal | vauthors = Egeberg O | title = Inherited antithrombin deficiency causing thrombophilia | journal = Thrombosis et Diathesis Haemorrhagica | volume = 13 | issue = | pages = 516–30 | date = June 1965 | pmid = 14347873 | doi = | url = }}</ref> The causes of acquired antithrombin deficiency are easier to find than the hereditary deficiency.<ref name="Khor_2010">{{cite journal | vauthors = Khor B, Van Cott EM | title = Laboratory tests for antithrombin deficiency | journal = American Journal of Hematology | volume = 85 | issue = 12 | pages = 947–50 | date = December 2010 | pmid = 21108326 | doi = 10.1002/ajh.21893 | url = }}</ref>
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| This disease is affecting one in thousand people annually. It is type of multifactorial disease where both genetics and environment affect the pro[[Coagulation|coagulant]] 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.<ref name="pmid18574041">{{cite journal | vauthors = Dahlbäck B | title = Advances in understanding pathogenic mechanisms of thrombophilic disorders | journal = Blood | volume = 112 | issue = 1 | pages = 19–27 | date = July 2008 | pmid = 18574041 | doi = 10.1182/blood-2008-01-077909 }}</ref> The deficiency may be caused by adhesion of [[platelet]]s with immobilised fibrinogen.<ref name="pmid17040572">{{cite journal | vauthors = Loncar R, Kalina U, Stoldt V, Thomas V, Scharf RE, Vodovnik A | title = Antithrombin significantly influences platelet adhesion onto immobilized fibrinogen in an in-vitro system simulating low flow | journal = Thrombosis Journal | volume = 4 | issue = | pages = 19 | date = October 2006 | pmid = 17040572 | pmc = 1618384 | doi = 10.1186/1477-9560-4-19 }}</ref>
| | '''Antithrombin III deficiency''' is a [[genetic disorder]] that affects the body's ability to regulate blood clotting. It is characterized by a deficiency in [[antithrombin]], a protein that helps prevent abnormal blood clot formation. This condition can lead to an increased risk of [[thrombosis]], which is the formation of blood clots within blood vessels. |
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| The patients are treated with [[anticoagulant]]s or, more rarely, with antithrombin concentrate.
| | ==Pathophysiology== |
| | Antithrombin is a [[serine protease inhibitor]] (serpin) that plays a crucial role in the regulation of the [[coagulation cascade]]. It primarily inhibits [[thrombin]] and [[factor Xa]], which are key enzymes in the clotting process. In individuals with antithrombin III deficiency, the reduced levels or activity of antithrombin lead to an increased tendency for blood clot formation, as the inhibitory effect on thrombin and factor Xa is diminished. |
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| 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]].
| | ==Types== |
| | Antithrombin III deficiency can be classified into two main types: |
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| ==Diagnosis==
| | * '''Type I deficiency''': This is a quantitative deficiency where there is a reduced level of antithrombin in the blood. |
| 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.<ref name=":0" /> Second, [[Anti-cardiolipin antibodies|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.<ref>{{cite journal | vauthors = Undas A, Brummel K, Musial J, Mann KG, Szczeklik A | title = Blood coagulation at the site of microvascular injury: effects of low-dose aspirin | journal = Blood | volume = 98 | issue = 8 | pages = 2423–31 | date = October 2001 | pmid = 11588039 | doi = 10.1182/blood.V98.8.2423 }}</ref> 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.<ref name="pmid24489427">{{cite journal | vauthors = Jennings LK, Kotha J | title = The Utility of Platelet and Coagulation Testing of Antithrombotics: Fusing Science with Patient Care | journal = Drug Development Research | volume = 74 | issue = 8 | pages = 587–593 | date = December 2013 | pmid = 24489427 | pmc = 3902984 | doi = 10.1002/ddr.21119 }}</ref>
| | * '''Type II deficiency''': This is a qualitative deficiency where the level of antithrombin is normal, but its function is impaired. |
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| | ==Genetics== |
| | Antithrombin III deficiency is usually inherited in an [[autosomal dominant]] manner, meaning that a single copy of the mutated gene can cause the disorder. The gene responsible for antithrombin production is the [[SERPINC1]] gene, located on chromosome 1. Mutations in this gene can lead to either type I or type II deficiency. |
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| Once a patient develops the congenital antithrombin III deficiency, a sign of anticoagulation can be easily indicated.<ref name=":3">{{Cite journal|last=Hassan|first=Yaish | name-list-format = vanc |date=2 February 2018|title=Antithrombin III Deficiency: Practice Essentials, Pathophysiology, Epidemiology|url=https://emedicine.medscape.com/article/954688-overview|journal=Medscape|volume=|pages=|via=}}</ref>
| | ==Clinical Manifestations== |
| | Individuals with antithrombin III deficiency may experience recurrent episodes of [[venous thromboembolism]] (VTE), which includes conditions such as [[deep vein thrombosis]] (DVT) and [[pulmonary embolism]] (PE). Symptoms of DVT may include swelling, pain, and redness in the affected limb, while PE may present with shortness of breath, chest pain, and coughing up blood. |
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| 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.<ref>{{cite journal | vauthors = Hayıroğlu Mİ, Keskin M, Dönmez C, Günay MB, Ünal Dayı Ş | title = Antithrombin III deficiency concomitant with atrial fibrillation causes thrombi in all chambers: 2D and 3D echocardiographic evaluation | journal = Anatolian Journal of Cardiology | volume = 16 | issue = 12 | pages = E21–E22 | date = December 2016 | pmid = 28005013 | pmc = 5324928 | doi = 10.14744/AnatolJCardiol.2016.7456 }}</ref> 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.<ref name=":3" /> Finally, ventilation-perfusion scanning is test to check for images of pulmonary thrombosis.<ref name=":3" />
| | ==Diagnosis== |
| | Diagnosis of antithrombin III deficiency involves measuring the level and activity of antithrombin in the blood. A reduced level or activity suggests the presence of the deficiency. Genetic testing can also be performed to identify mutations in the SERPINC1 gene. |
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| ==Management== | | ==Management== |
| [[Heparin]] enhances ATIII activity and neutralizes "activated serine protease coagulation factors."<ref name="Goljan2011">{{cite book|title=Pathology|url=https://books.google.com/books?id=FvFCYgEACAAJ|access-date=24 August 2014|year=2011|publisher=Mosby/Elsevier|isbn=9780323084383|page=251|author=Edward F. Goljan|author-link = Edward F. Goljan}}</ref> 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.<ref>Basic and Clinical Pharmacology, Lange, 12th ed</ref> | | Management of antithrombin III deficiency focuses on preventing thrombotic events. This may include the use of [[anticoagulant]] medications such as [[heparin]] or [[warfarin]]. In some cases, antithrombin concentrates may be administered, especially during high-risk situations such as surgery or pregnancy. |
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| 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.
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| == See also ==
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| * [[Antithrombin]]
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| == References ==
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| {{reflist|32em}}
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| == External links == | | ==Prognosis== |
| {{Medical resources
| | With appropriate management, individuals with antithrombin III deficiency can lead normal lives. However, they remain at an increased risk for thrombotic events, and lifelong anticoagulation therapy may be necessary. |
| | DiseasesDB = 783
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| | ICD10 = {{ICD10|D|68|8|d|65}}
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| | ICD9 = {{ICD9|289.81}}
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| | ICDO =
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| | OMIM = 613118
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| | MedlinePlus =
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| | eMedicineSubj = ped
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| | eMedicineTopic = 119
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| | MeshID = D020152
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| }}
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| {{Diseases of megakaryocytes}}
| | ==Related pages== |
| {{Disorders of globin and globulin proteins}}
| | * [[Thrombophilia]] |
| | * [[Coagulation]] |
| | * [[Deep vein thrombosis]] |
| | * [[Pulmonary embolism]] |
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| [[Category:Serpinopathies]] | | [[Category:Genetic disorders]] |
| [[Category:Rare diseases]] | | [[Category:Hematology]] |
| [[Category:Coagulopathies]] | | [[Category:Coagulation system disorders]] |
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A genetic disorder affecting blood clotting
Antithrombin III deficiency is a genetic disorder that affects the body's ability to regulate blood clotting. It is characterized by a deficiency in antithrombin, a protein that helps prevent abnormal blood clot formation. This condition can lead to an increased risk of thrombosis, which is the formation of blood clots within blood vessels.
Pathophysiology
Antithrombin is a serine protease inhibitor (serpin) that plays a crucial role in the regulation of the coagulation cascade. It primarily inhibits thrombin and factor Xa, which are key enzymes in the clotting process. In individuals with antithrombin III deficiency, the reduced levels or activity of antithrombin lead to an increased tendency for blood clot formation, as the inhibitory effect on thrombin and factor Xa is diminished.
Types
Antithrombin III deficiency can be classified into two main types:
- Type I deficiency: This is a quantitative deficiency where there is a reduced level of antithrombin in the blood.
- Type II deficiency: This is a qualitative deficiency where the level of antithrombin is normal, but its function is impaired.
Genetics
Antithrombin III deficiency is usually inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene can cause the disorder. The gene responsible for antithrombin production is the SERPINC1 gene, located on chromosome 1. Mutations in this gene can lead to either type I or type II deficiency.
Clinical Manifestations
Individuals with antithrombin III deficiency may experience recurrent episodes of venous thromboembolism (VTE), which includes conditions such as deep vein thrombosis (DVT) and pulmonary embolism (PE). Symptoms of DVT may include swelling, pain, and redness in the affected limb, while PE may present with shortness of breath, chest pain, and coughing up blood.
Diagnosis
Diagnosis of antithrombin III deficiency involves measuring the level and activity of antithrombin in the blood. A reduced level or activity suggests the presence of the deficiency. Genetic testing can also be performed to identify mutations in the SERPINC1 gene.
Management
Management of antithrombin III deficiency focuses on preventing thrombotic events. This may include the use of anticoagulant medications such as heparin or warfarin. In some cases, antithrombin concentrates may be administered, especially during high-risk situations such as surgery or pregnancy.
Prognosis
With appropriate management, individuals with antithrombin III deficiency can lead normal lives. However, they remain at an increased risk for thrombotic events, and lifelong anticoagulation therapy may be necessary.
Related pages
