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Thrombophilia due to thrombin defect(THPH1)

MedGen UID:
463623
Concept ID:
C3160733
Finding
Synonyms: Factor V R2 Mutation Thrombophilia; Prothrombin-Related Thrombophilia; Prothrombin-Related Thrombophilia (Factor II); THPH1; THROMBOPHILIA DUE TO FACTOR 2 DEFECT; Thrombosis susceptibility
 
Genes (locations): F13A1 (6p25.1); F2 (11p11.2); HABP2 (10q25.3); MTHFR (1p36.22)
Related genes: PROS1, PROC, F5, SERPINC1
 
Monarch Initiative: MONDO:0008559
OMIM®: 188050

Disease characteristics

Excerpted from the GeneReview: Prothrombin Thrombophilia
Prothrombin thrombophilia is characterized by venous thromboembolism (VTE) manifest most commonly in adults as deep-vein thrombosis (DVT) in the legs or pulmonary embolism. The clinical expression of prothrombin thrombophilia is variable; many individuals heterozygous or homozygous for the 20210G>A F2 variant never develop thrombosis, and while most heterozygotes who develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years. The relative risk for DVT in adults heterozygous for the 20210G>A variant is two- to fivefold increased; in children, the relative risk for thrombosis is three- to fourfold increased. Heterozygosity for 20210G>A has at most a modest effect on recurrence risk after a first episode. Although prothrombin thrombophilia may increase the risk for pregnancy loss, its association with preeclampsia and other complications of pregnancy such as intrauterine growth restriction and placental abruption remains controversial. Factors that predispose to thrombosis in prothrombin thrombophilia include: the number of 20210G>A alleles; presence of coexisting genetic abnormalities including factor V Leiden; and acquired thrombophilic disorders (e.g., antiphospholipid antibodies). Circumstantial risk factors for thrombosis include pregnancy and oral contraceptive use. Some evidence suggests that the risk for VTE in 20210G>A heterozygotes increases after air travel. [from GeneReviews]
Authors:
Jody L Kujovich   view full author information

Additional description

From MedlinePlus Genetics
Prothrombin thrombophilia is a disorder that increases the risk of developing blood clots. Thrombophilia is the term used to describe an increased tendency to form blood clots. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss. People with thrombophilia can develop clots when they are not needed. These clots can block normal blood flow and cause harm.

People who have prothrombin thrombophilia have a higher-than-average risk of developing a type of clot called a deep vein thrombosis, which typically occurs in the blood vessels of the arms or legs. People with prothrombin thrombophilia also have an increased risk of developing a pulmonary embolism, which is a clot that travels through the bloodstream and lodges in the lungs.

Research suggests that pregnancy loss may be somewhat more likely in people with prothrombin thrombophilia than in those who do not have the condition. Some researchers have suggested that prothrombin thrombophilia may also increase the risk of other complications during pregnancy, though this remains controversial.

While many people with prothrombin thrombophilia will never have clotting issues, several factors increase a person's risk of blood clots. Some risk factors that contribute to the development of harmful blood clots include surgery, injury or trauma, air travel, obesity, and a family history of blood clots. Additional risk factors include pregnancy, using contraceptives such as birth control pills or patches that contain estrogen, and receiving post-menopausal hormone replacement therapy. The combination of prothrombin thrombophilia and other clotting disorders may also increase a person's risk.  https://medlineplus.gov/genetics/condition/prothrombin-thrombophilia

Clinical features

From HPO
Pulmonary embolism
MedGen UID:
11027
Concept ID:
C0034065
Pathologic Function
An embolus (that is, an abnormal particle circulating in the blood) located in the pulmonary artery and thereby blocking blood circulation to the lung. Usually the embolus is a blood clot that has developed in an extremity (for instance, a deep venous thrombosis), detached, and traveled through the circulation before becoming trapped in the pulmonary artery.
Thromboembolism
MedGen UID:
21532
Concept ID:
C0040038
Pathologic Function
The formation of a blood clot inside a blood vessel that subsequently travels through the blood stream from the site where it formed to another location in the body, generally leading to vascular occlusion at the distant site.
Deep venous thrombosis
MedGen UID:
57448
Concept ID:
C0149871
Disease or Syndrome
Formation of a blot clot in a deep vein. The clot often blocks blood flow, causing swelling and pain. The deep veins of the leg are most often affected.
Cerebral venous thrombosis
MedGen UID:
57743
Concept ID:
C0151945
Disease or Syndrome
Formation of a blood clot (thrombus) inside a cerebral vein, causing the obstruction of blood flow.
Recurrent thrombophlebitis
MedGen UID:
763064
Concept ID:
C3550150
Finding
Repeated episodes of inflammation of a vein associated with venous thrombosis (blood clot formation within the vein).

Professional guidelines

PubMed

O'Leary JG, Greenberg CS, Patton HM, Caldwell SH
Gastroenterology 2019 Jul;157(1):34-43.e1. Epub 2019 Apr 12 doi: 10.1053/j.gastro.2019.03.070. PMID: 30986390
Meeks SL, Abshire TC
Haemophilia 2008 Nov;14(6):1159-63. doi: 10.1111/j.1365-2516.2008.01832.x. PMID: 19141155
Haverkate F, Samama M
Thromb Haemost 1995 Jan;73(1):151-61. PMID: 7740487

Recent clinical studies

Etiology

Chowdary P
Exp Physiol 2022 Jul;107(7):749-758. Epub 2022 Jun 22 doi: 10.1113/EP089404. PMID: 35733235Free PMC Article
O'Leary JG, Greenberg CS, Patton HM, Caldwell SH
Gastroenterology 2019 Jul;157(1):34-43.e1. Epub 2019 Apr 12 doi: 10.1053/j.gastro.2019.03.070. PMID: 30986390
Coelho MC, Santos CV, Vieira Neto L, Gadelha MR
Eur J Endocrinol 2015 Oct;173(4):M11-21. Epub 2015 May 13 doi: 10.1530/EJE-15-0198. PMID: 25971647
Falanga A, Marchetti M
Hematology Am Soc Hematol Educ Program 2012;2012:571-81. doi: 10.1182/asheducation-2012.1.571. PMID: 23233637
Cunningham MT, Brandt JT, Laposata M, Olson JD
Arch Pathol Lab Med 2002 Apr;126(4):499-505. doi: 10.5858/2002-126-0499-LDOD. PMID: 11900586

Diagnosis

Gausman JN, Marlar RA
Methods Mol Biol 2017;1646:161-167. doi: 10.1007/978-1-4939-7196-1_13. PMID: 28804827
Hepner M, Karlaftis V
Methods Mol Biol 2013;992:373-81. doi: 10.1007/978-1-62703-339-8_30. PMID: 23546730
Hepner M, Karlaftis V
Methods Mol Biol 2013;992:355-64. doi: 10.1007/978-1-62703-339-8_28. PMID: 23546728
Tripodi A
Pol Arch Med Wewn 2008 Jul-Aug;118(7-8):445-8. PMID: 18714742
Rosing J, Tans G
Int J Biochem Cell Biol 1997 Oct;29(10):1123-6. doi: 10.1016/s1357-2725(97)00040-x. PMID: 9438374

Therapy

Chowdary P
Exp Physiol 2022 Jul;107(7):749-758. Epub 2022 Jun 22 doi: 10.1113/EP089404. PMID: 35733235Free PMC Article
O'Leary JG, Greenberg CS, Patton HM, Caldwell SH
Gastroenterology 2019 Jul;157(1):34-43.e1. Epub 2019 Apr 12 doi: 10.1053/j.gastro.2019.03.070. PMID: 30986390
Coelho MC, Santos CV, Vieira Neto L, Gadelha MR
Eur J Endocrinol 2015 Oct;173(4):M11-21. Epub 2015 May 13 doi: 10.1530/EJE-15-0198. PMID: 25971647
Falanga A, Marchetti M
Hematology Am Soc Hematol Educ Program 2012;2012:571-81. doi: 10.1182/asheducation-2012.1.571. PMID: 23233637
Francis JL, Biggerstaff J, Amirkhosravi A
Semin Thromb Hemost 1998;24(2):93-109. doi: 10.1055/s-2007-995829. PMID: 9579631

Prognosis

Wada H, Matsumoto T, Yamashita Y, Hatada T
Clin Chim Acta 2014 Sep 25;436:130-4. Epub 2014 Apr 30 doi: 10.1016/j.cca.2014.04.020. PMID: 24792730
Owczarek D, Cibor D, Głowacki MK, Rodacki T, Mach T
World J Gastroenterol 2014 Jan 7;20(1):53-63. doi: 10.3748/wjg.v20.i1.53. PMID: 24415858Free PMC Article
Falanga A, Marchetti M
Hematology Am Soc Hematol Educ Program 2012;2012:571-81. doi: 10.1182/asheducation-2012.1.571. PMID: 23233637
ten Cate H
Crit Care Med 2000 Sep;28(9 Suppl):S9-11. doi: 10.1097/00003246-200009001-00003. PMID: 11007190
Dahlbäck B
Thromb Haemost 1995 Jul;74(1):139-48. PMID: 8578447

Clinical prediction guides

Wada H, Shiraki K, Matsumoto T, Shimpo H, Shimaoka M
Ann Lab Med 2023 Nov 1;43(6):531-538. Epub 2023 Jun 30 doi: 10.3343/alm.2023.43.6.531. PMID: 37387486Free PMC Article
O'Leary JG, Greenberg CS, Patton HM, Caldwell SH
Gastroenterology 2019 Jul;157(1):34-43.e1. Epub 2019 Apr 12 doi: 10.1053/j.gastro.2019.03.070. PMID: 30986390
Wada H, Matsumoto T, Yamashita Y, Hatada T
Clin Chim Acta 2014 Sep 25;436:130-4. Epub 2014 Apr 30 doi: 10.1016/j.cca.2014.04.020. PMID: 24792730
Owczarek D, Cibor D, Głowacki MK, Rodacki T, Mach T
World J Gastroenterol 2014 Jan 7;20(1):53-63. doi: 10.3748/wjg.v20.i1.53. PMID: 24415858Free PMC Article
Falanga A, Marchetti M
Hematology Am Soc Hematol Educ Program 2012;2012:571-81. doi: 10.1182/asheducation-2012.1.571. PMID: 23233637

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