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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

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
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
Dahl OE
Thromb Haemost 1999 Aug;82(2):902-6. PMID: 10605801

Diagnosis

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
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;992:365-72. doi: 10.1007/978-1-62703-339-8_29. PMID: 23546729
Hepner M, Karlaftis V
Methods Mol Biol 2013;992:355-64. doi: 10.1007/978-1-62703-339-8_28. PMID: 23546728
Patnaik MM, Moll S
Haemophilia 2008 Nov;14(6):1229-39. doi: 10.1111/j.1365-2516.2008.01830.x. PMID: 19141163

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
Warkentin TE
Expert Opin Drug Saf 2014 Jan;13(1):25-43. Epub 2013 Aug 23 doi: 10.1517/14740338.2013.823946. PMID: 23971903
Francis JL, Biggerstaff J, Amirkhosravi A
Semin Thromb Hemost 1998;24(2):93-109. doi: 10.1055/s-2007-995829. PMID: 9579631

Prognosis

Abdelmaguid A, Roberts LN, Tugores L, Joslin JR, Hunt BJ, Parmar K, Nebres D, Naga SS, Khalil ES, Bramham K
J Thromb Haemost 2022 Apr;20(4):845-856. Epub 2022 Feb 3 doi: 10.1111/jth.15653. PMID: 35068080Free PMC Article
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
Mammen EF
Semin Thromb Hemost 1998;24(1):19-25. doi: 10.1055/s-2007-995819. PMID: 9515776

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
Carr ME
J Diabetes Complications 2001 Jan-Feb;15(1):44-54. doi: 10.1016/s1056-8727(00)00132-x. PMID: 11259926

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