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Hemophilia(HEMA)

MedGen UID:
146334
Concept ID:
C0684275
Disease or Syndrome
Synonym: HEMA
SNOMED CT: Hemophilia (90935002)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Related genes: F9, F8
 
Monarch Initiative: MONDO:0018660
Orphanet: ORPHA448

Definition

Hemophilia is a bleeding disorder that slows the blood clotting process. People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or even when there is no obvious injury (sometimes called spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not necessarily involve spontaneous bleeding, and the condition may not become apparent until abnormal bleeding occurs following surgery or a serious injury.

The major types of this condition are hemophilia A (also known as classic hemophilia or factor VIII deficiency) and hemophilia B (also known as Christmas disease or factor IX deficiency). Although the two types have very similar signs and symptoms, they are caused by variants (also known as mutations) in different genes. People with an unusual form of hemophilia B, known as hemophilia B Leyden, experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Franchini M, Mannucci PM
Semin Thromb Hemost 2022 Nov;48(8):904-910. Epub 2022 Sep 15 doi: 10.1055/s-0042-1756188. PMID: 36108649
Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, Carcao M, Mahlangu J, Ragni MV, Windyga J, Llinás A, Goddard NJ, Mohan R, Poonnoose PM, Feldman BM, Lewis SZ, van den Berg HM, Pierce GF; WFH Guidelines for the Management of Hemophilia panelists and co-authors
Haemophilia 2020 Aug;26 Suppl 6:1-158. Epub 2020 Aug 3 doi: 10.1111/hae.14046. PMID: 32744769
Tiede A, Collins P, Knoebl P, Teitel J, Kessler C, Shima M, Di Minno G, d'Oiron R, Salaj P, Jiménez-Yuste V, Huth-Kühne A, Giangrande P
Haematologica 2020 Jul;105(7):1791-1801. Epub 2020 May 7 doi: 10.3324/haematol.2019.230771. PMID: 32381574Free PMC Article

Recent clinical studies

Etiology

Gualtierotti R, Solimeno LP, Peyvandi F
J Thromb Haemost 2021 Sep;19(9):2112-2121. Epub 2021 Jul 27 doi: 10.1111/jth.15444. PMID: 34197690Free PMC Article
Pipe SW
Pediatr Blood Cancer 2018 Feb;65(2) Epub 2017 Oct 27 doi: 10.1002/pbc.26865. PMID: 29077262
Kruse-Jarres R, Kempton CL, Baudo F, Collins PW, Knoebl P, Leissinger CA, Tiede A, Kessler CM
Am J Hematol 2017 Jul;92(7):695-705. Epub 2017 Jun 5 doi: 10.1002/ajh.24777. PMID: 28470674
Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia
Haemophilia 2013 Jan;19(1):e1-47. Epub 2012 Jul 6 doi: 10.1111/j.1365-2516.2012.02909.x. PMID: 22776238
Vidler V
Br J Perioper Nurs 2004 Mar;14(3):110-3. doi: 10.1177/175045890401400302. PMID: 15060928

Diagnosis

Pai M
Hematol Oncol Clin North Am 2021 Dec;35(6):1131-1142. Epub 2021 Sep 15 doi: 10.1016/j.hoc.2021.07.007. PMID: 34535289
Dolan G, Benson G, Bowyer A, Eichler H, Hermans C, Jiménez-Yuste V, Ljung R, Pollard D, Santagostino E, Šalek SZ
Eur J Haematol 2021 Jun;106(6):762-773. Epub 2021 Mar 18 doi: 10.1111/ejh.13592. PMID: 33527471Free PMC Article
Kimura K, Kuriyama A, Kuninaga N, Sasaki A
Intern Med 2015;54(7):865. Epub 2015 Apr 1 doi: 10.2169/internalmedicine.54.3862. PMID: 25832961
Zimmerman B, Valentino LA
Pediatr Rev 2013 Jul;34(7):289-94; quiz 295. doi: 10.1542/pir.34-7-289. PMID: 23818083
Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia
Haemophilia 2013 Jan;19(1):e1-47. Epub 2012 Jul 6 doi: 10.1111/j.1365-2516.2012.02909.x. PMID: 22776238

Therapy

Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, Pipe SW, Madan B, Key NS, Pierce GF, O'Mahony B, Kaczmarek R, Henshaw J, Lawal A, Jayaram K, Huang M, Yang X, Wong WY, Kim B; GENEr8-1 Trial Group
N Engl J Med 2022 Mar 17;386(11):1013-1025. doi: 10.1056/NEJMoa2113708. PMID: 35294811
Okaygoun D, Oliveira DD, Soman S, Williams R
J Biomed Sci 2021 Sep 14;28(1):64. doi: 10.1186/s12929-021-00760-4. PMID: 34521404Free PMC Article
Leebeek FWG, Miesbach W
Blood 2021 Sep 16;138(11):923-931. doi: 10.1182/blood.2019003777. PMID: 34232980
Nathwani AC
Hematology Am Soc Hematol Educ Program 2019 Dec 6;2019(1):1-8. doi: 10.1182/hematology.2019000007. PMID: 31808868Free PMC Article
Nathwani AC, Davidoff AM, Tuddenham EGD
Hematol Oncol Clin North Am 2017 Oct;31(5):853-868. doi: 10.1016/j.hoc.2017.06.011. PMID: 28895852

Prognosis

Goldenberg NA, Kittelson JM, Abshire TC, Bonaca M, Casella JF, Dale RA, Halperin JL, Hamblin F, Kessler CM, Manco-Johnson MJ, Sidonio RF, Spyropoulos AC, Steg PG, Turpie AGG, Schulman S; Kids-DOTT Trial Investigators and the ATLAS Group
JAMA 2022 Jan 11;327(2):129-137. doi: 10.1001/jama.2021.23182. PMID: 35015038Free PMC Article
Charlebois J, Rivard GÉ, St-Louis J
Transfus Apher Sci 2018 Dec;57(6):717-720. Epub 2018 Oct 30 doi: 10.1016/j.transci.2018.10.011. PMID: 30396835
Kruse-Jarres R, Kempton CL, Baudo F, Collins PW, Knoebl P, Leissinger CA, Tiede A, Kessler CM
Am J Hematol 2017 Jul;92(7):695-705. Epub 2017 Jun 5 doi: 10.1002/ajh.24777. PMID: 28470674
Byard RW
J Forensic Sci 2016 Sep;61(5):1244-9. Epub 2016 Jun 10 doi: 10.1111/1556-4029.13119. PMID: 27282512
Tuinenburg A, Mauser-Bunschoten EP, Verhaar MC, Biesma DH, Schutgens RE
J Thromb Haemost 2009 Feb;7(2):247-54. Epub 2008 Oct 18 doi: 10.1111/j.1538-7836.2008.03201.x. PMID: 18983484

Clinical prediction guides

Seidizadeh O, Baronciani L, Lillicrap D, Peyvandi F
J Thromb Haemost 2024 Aug;22(8):2115-2128. Epub 2024 May 16 doi: 10.1016/j.jtha.2024.05.006. PMID: 38762018Free PMC Article
Douxfils J, Adcock DM, Bates SM, Favaloro EJ, Gouin-Thibault I, Guillermo C, Kawai Y, Lindhoff-Last E, Kitchen S, Gosselin RC
Thromb Haemost 2021 Aug;121(8):1008-1020. Epub 2021 May 30 doi: 10.1055/a-1450-8178. [Epub ahead of print] PMID: 33742436
Kujovich JL
Obstet Gynecol Clin North Am 2016 Jun;43(2):247-64. Epub 2016 Mar 18 doi: 10.1016/j.ogc.2016.01.009. PMID: 27212091
Kim J, Huh R, Jaffer AK
Anesthesiol Clin 2016 Mar;34(1):101-25. doi: 10.1016/j.anclin.2015.10.010. PMID: 26927742
Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis
J Thromb Haemost 2014 Nov;12(11):1935-9. Epub 2014 Sep 3 doi: 10.1111/jth.12672. PMID: 25059285

Recent systematic reviews

Wallwork SB, Braithwaite FA, O'Keeffe M, Travers MJ, Summers SJ, Lange B, Hince DA, Costa LOP, Menezes Costa LDC, Chiera B, Moseley GL
CMAJ 2024 Jan 21;196(2):E29-E46. doi: 10.1503/cmaj.230542. PMID: 38253366Free PMC Article
Muniz RL, Camelo RM, Araújo MS, Barbosa MM, Guerra AA, Acurcio FA, Alvares-Teodoro J
Expert Rev Hematol 2023 Jul-Dec;16(12):1087-1097. Epub 2023 Dec 18 doi: 10.1080/17474086.2023.2293096. PMID: 38066708
Custodero C, Ciavarella A, Panza F, Gnocchi D, Lenato GM, Lee J, Mazzocca A, Sabbà C, Solfrizzi V
Geroscience 2022 Jun;44(3):1373-1392. Epub 2022 Apr 29 doi: 10.1007/s11357-022-00556-w. PMID: 35486344Free PMC Article
Yin R, Liu C
Blood Coagul Fibrinolysis 2022 Jan 1;33(1):1-7. doi: 10.1097/MBC.0000000000001076. PMID: 34412085
Parsa A, Azizbaig Mohajer M, Mirzaie M
Hip Int 2018 Sep;28(5):459-467. Epub 2018 Aug 20 doi: 10.1177/1120700018793777. PMID: 30124085

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