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Hereditary factor XI deficiency disease

MedGen UID:
8770
Concept ID:
C0015523
Disease or Syndrome
Synonyms: Congenital factor XI deficiency; Plasma thromboplastin antecedent deficiency; PTA deficiency; Rosenthal syndrome
SNOMED CT: Thromboplastin antecedent deficiency (49762007); Hereditary factor XI deficiency disease (49762007); Hemophilia C (49762007); Congenital factor XI deficiency disease (49762007); Plasma thromboplastin antecedent deficiency (49762007); PTA deficiency (49762007); Rosenthal's disease (49762007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): F11 (4q35.2)
 
Monarch Initiative: MONDO:0012897
OMIM®: 612416
Orphanet: ORPHA329

Definition

Factor XI deficiency is an autosomal bleeding disorder characterized by reduced levels of factor XI in plasma (less than 15 IU/dL). Bleeding occurs mainly after trauma or surgery. On the basis of the concordance or discordance of F11 antigen and activity, the disorder is classified into the more frequent cross-reactive negative (CRM-) and the rarer CRM positive (CRM+) (summary by Duga and Salomon, 2009). [from OMIM]

Additional description

From MedlinePlus Genetics
Factor XI deficiency is a disorder that can cause abnormal bleeding due to a shortage (deficiency) of the factor XI protein, which is involved in blood clotting. This condition is classified as either partial or severe based on the degree of deficiency of the factor XI protein. However, regardless of the severity of the protein deficiency, most affected individuals have relatively mild bleeding problems, and some people with this disorder have few if any symptoms. The most common feature of factor XI deficiency is prolonged bleeding after trauma or surgery, especially involving the inside of the mouth and nose (oral and nasal cavities) or the urinary tract. If the bleeding is left untreated after surgery, solid swellings consisting of congealed blood (hematomas) can develop in the surgical area.

Other signs and symptoms of this disorder can include frequent nosebleeds, easy bruising, bleeding under the skin, and bleeding of the gums. Women with this disorder can have heavy or prolonged menstrual bleeding (menorrhagia) or prolonged bleeding after childbirth. In contrast to some other bleeding disorders, spontaneous bleeding into the urine (hematuria), gastrointestinal tract, or skull cavity are not common in factor XI deficiency, although they can occur in severely affected individuals. Bleeding into the muscles or joints, which can cause long-term disability in other bleeding disorders, generally does not occur in this condition.  https://medlineplus.gov/genetics/condition/factor-xi-deficiency

Clinical features

From HPO
Prolonged partial thromboplastin time
MedGen UID:
66815
Concept ID:
C0240671
Finding
Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms.
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Reduced factor XI activity
MedGen UID:
1368629
Concept ID:
C4317093
Finding
Decreased activity of coagulation factor XI. Factor XI, also known as plasma thromboplastin antecedent, is a serine proteinase that activates factor IX.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary factor XI deficiency disease
Follow this link to review classifications for Hereditary factor XI deficiency disease in Orphanet.

Professional guidelines

PubMed

Barg AA, Livnat T, Kenet G
Blood 2024 Apr 11;143(15):1455-1464. doi: 10.1182/blood.2023020721. PMID: 38194679
Davies J, Kadir R
Semin Thromb Hemost 2016 Oct;42(7):732-740. Epub 2016 Oct 3 doi: 10.1055/s-0036-1587685. PMID: 27699729
Bauer KA
Am J Manag Care 2015 Mar;21(6 Suppl):S112-22. PMID: 26168206

Recent clinical studies

Etiology

Bentounes NK, Melicine S, Martin AC, Smadja DM, Gendron N
J Med Vasc 2023 Apr;48(2):69-80. Epub 2023 May 5 doi: 10.1016/j.jdmv.2023.04.002. PMID: 37422330
Harrington J, Piccini JP, Alexander JH, Granger CB, Patel MR
J Am Coll Cardiol 2023 Feb 28;81(8):771-779. doi: 10.1016/j.jacc.2022.11.057. PMID: 36813377
De Caterina R, Prisco D, Eikelboom JW
Eur Heart J 2023 Jan 21;44(4):280-292. doi: 10.1093/eurheartj/ehac464. PMID: 36263776
Huang Q, Wu D, Zhao J, Yan Z, Chen L, Guo S, Wang D, Yuan C, Wang Y, Liu X, Xing J
EMBO J 2022 Jun 1;41(11):e110324. Epub 2022 Apr 22 doi: 10.15252/embj.2021110324. PMID: 35451091Free PMC Article
Lewandowska MD, Connors JM
Hematol Oncol Clin North Am 2021 Dec;35(6):1157-1169. Epub 2021 Sep 15 doi: 10.1016/j.hoc.2021.07.012. PMID: 34535287

Diagnosis

Lu Z, Mao W, Yang H, Santiago-O'Farrill JM, Rask PJ, Mondal J, Chen H, Ivan C, Liu X, Liu CG, Xi Y, Masuda K, Carrami EM, Chen M, Tang Y, Pang L, Lakomy DS, Calin GA, Liang H, Ahmed AA, Vankayalapati H, Bast RC Jr
J Clin Invest 2022 Jun 1;132(11) doi: 10.1172/JCI146471. PMID: 35642638Free PMC Article
Lewandowska MD, Connors JM
Hematol Oncol Clin North Am 2021 Dec;35(6):1157-1169. Epub 2021 Sep 15 doi: 10.1016/j.hoc.2021.07.012. PMID: 34535287
Gando S, Levi M, Toh CH
Nat Rev Dis Primers 2016 Jun 2;2:16037. doi: 10.1038/nrdp.2016.37. PMID: 27250996
Duga S, Salomon O
Semin Thromb Hemost 2009 Jun;35(4):416-25. Epub 2009 Jul 13 doi: 10.1055/s-0029-1225764. PMID: 19598070
Gomez K, Bolton-Maggs P
Haemophilia 2008 Nov;14(6):1183-9. Epub 2008 Feb 27 doi: 10.1111/j.1365-2516.2008.01667.x. PMID: 18312365

Therapy

Bentounes NK, Melicine S, Martin AC, Smadja DM, Gendron N
J Med Vasc 2023 Apr;48(2):69-80. Epub 2023 May 5 doi: 10.1016/j.jdmv.2023.04.002. PMID: 37422330
Harrington J, Piccini JP, Alexander JH, Granger CB, Patel MR
J Am Coll Cardiol 2023 Feb 28;81(8):771-779. doi: 10.1016/j.jacc.2022.11.057. PMID: 36813377
De Caterina R, Prisco D, Eikelboom JW
Eur Heart J 2023 Jan 21;44(4):280-292. doi: 10.1093/eurheartj/ehac464. PMID: 36263776
Gando S, Levi M, Toh CH
Nat Rev Dis Primers 2016 Jun 2;2:16037. doi: 10.1038/nrdp.2016.37. PMID: 27250996
Phillippe HM, Hornsby LB, Treadway S, Armstrong EM, Bellone JM
J Pharm Pract 2014 Jun;27(3):227-33. Epub 2014 Apr 16 doi: 10.1177/0897190014530390. PMID: 24739277

Prognosis

Han Z, Zhang Z, Yang X, Li Z, Sang S, Islam MT, Guo AA, Li Z, Wang X, Wang J, Zhang T, Sun Z, Yu L, Wang W, Xiong W, Li G, Jiang Y
J Immunother Cancer 2024 May 15;12(5) doi: 10.1136/jitc-2024-008927. PMID: 38749538Free PMC Article
Dhaha Y, El Borgi W, Elmahmoudi H, Achour M, Fekih Salem S, Ben Lakhal F, Meddeb B, Gouider E
Tunis Med 2022 Janvier;100(1):60-65. PMID: 35822334Free PMC Article
Gando S, Levi M, Toh CH
Nat Rev Dis Primers 2016 Jun 2;2:16037. doi: 10.1038/nrdp.2016.37. PMID: 27250996
Peyvandi F, Bolton-Maggs PH, Batorova A, De Moerloose P
Haemophilia 2012 Jul;18 Suppl 4:148-53. doi: 10.1111/j.1365-2516.2012.02841.x. PMID: 22726099
Gomez K, Bolton-Maggs P
Haemophilia 2008 Nov;14(6):1183-9. Epub 2008 Feb 27 doi: 10.1111/j.1365-2516.2008.01667.x. PMID: 18312365

Clinical prediction guides

Ding J, Xu M, Du W, Fang ZQ, Xu H, Liu JJ, Song P, Xu C, Li ZW, Yue ZS, Ling YW, Duan JL, Tao KS, He F, Wang L
Int J Biol Sci 2023;19(6):1941-1954. Epub 2023 Mar 27 doi: 10.7150/ijbs.80122. PMID: 37063432Free PMC Article
Harrington J, Piccini JP, Alexander JH, Granger CB, Patel MR
J Am Coll Cardiol 2023 Feb 28;81(8):771-779. doi: 10.1016/j.jacc.2022.11.057. PMID: 36813377
Huang Q, Wu D, Zhao J, Yan Z, Chen L, Guo S, Wang D, Yuan C, Wang Y, Liu X, Xing J
EMBO J 2022 Jun 1;41(11):e110324. Epub 2022 Apr 22 doi: 10.15252/embj.2021110324. PMID: 35451091Free PMC Article
Gando S, Levi M, Toh CH
Nat Rev Dis Primers 2016 Jun 2;2:16037. doi: 10.1038/nrdp.2016.37. PMID: 27250996
Duga S, Salomon O
Semin Thromb Hemost 2009 Jun;35(4):416-25. Epub 2009 Jul 13 doi: 10.1055/s-0029-1225764. PMID: 19598070

Recent systematic reviews

Li Z, Wei X, Shao Z, Liu H, Bai S
BMC Oral Health 2023 Oct 19;23(1):768. doi: 10.1186/s12903-023-03422-z. PMID: 37858104Free PMC Article
Zhang Z, Fang T, Lv Y
World J Surg Oncol 2022 Nov 14;20(1):361. doi: 10.1186/s12957-022-02825-6. PMID: 36372891Free PMC Article
Kulkarni BP, Nair SB, Vijapurkar M, Mota L, Shanbhag S, Ali S, Shetty SD, Ghosh K
PLoS One 2014;9(9):e108683. Epub 2014 Oct 2 doi: 10.1371/journal.pone.0108683. PMID: 25275492Free PMC Article
Qu Y, Nie X, Yang Z, Yin H, Pang Y, Dong P, Zhan S
Southeast Asian J Trop Med Public Health 2014 Mar;45(2):455-66. PMID: 24968688
Sotiriadis A, Makrigiannakis A, Stefos T, Paraskevaidis E, Kalantaridou SN
Obstet Gynecol 2007 May;109(5):1146-55. doi: 10.1097/01.AOG.0000260873.94196.d6. PMID: 17470597

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