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Severe hemophilia A

MedGen UID:
543973
Concept ID:
C0272322
Disease or Syndrome
Synonym: HEMOPHILIA A, SEVERE
SNOMED CT: Severe hereditary factor VIII deficiency disease (16872008); Severe hemophilia A (16872008)
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.
 
Monarch Initiative: MONDO:0015719
OMIM®: 300841
Orphanet: ORPHA169802

Definition

Severe disease manifests factor VIII activity of less than 1%, except in the U.K. and Italy, where severe disease includes factor VIII activity levels of less than 2% [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSevere hemophilia A
Follow this link to review classifications for Severe hemophilia A in Orphanet.

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
Cho S, Perry AM, Cheng AM, Wang C, Rico JF
Adv Pediatr 2022 Aug;69(1):133-147. Epub 2022 Jun 21 doi: 10.1016/j.yapd.2022.03.009. PMID: 35985706
Valentino LA, Khair K
Expert Rev Hematol 2020 Jul;13(7):731-743. Epub 2020 Jun 23 doi: 10.1080/17474086.2020.1775576. PMID: 32573295

Recent clinical studies

Etiology

Malec L, Peyvandi F, Chan AKC, Königs C, Zulfikar B, Yuan H, Simpson M, Álvarez Román MT, Carcao M, Staber JM, Dunn AL, Chou SC, d'Oiron R, Albisetti M, Demissie M, Santagostino E, Yarramaneni A, Wong N, Abad-Franch L, Gunawardena S, Fijnvandraat K; XTEND-Kids Trial Group
N Engl J Med 2024 Jul 18;391(3):235-246. doi: 10.1056/NEJMoa2312611. PMID: 39018533
Mahlangu J, Kaczmarek R, von Drygalski A, Shapiro S, Chou SC, Ozelo MC, Kenet G, Peyvandi F, Wang M, Madan B, Key NS, Laffan M, Dunn AL, Mason J, Quon DV, Symington E, Leavitt AD, Oldenburg J, Chambost H, Reding MT, Jayaram K, Yu H, Mahajan R, Chavele KM, Reddy DB, Henshaw J, Robinson TM, Wong WY, Pipe SW; GENEr8-1 Trial Group
N Engl J Med 2023 Feb 23;388(8):694-705. doi: 10.1056/NEJMoa2211075. PMID: 36812433
von Drygalski A, Chowdary P, Kulkarni R, Susen S, Konkle BA, Oldenburg J, Matino D, Klamroth R, Weyand AC, Jimenez-Yuste V, Nogami K, Poloskey S, Winding B, Willemze A, Knobe K; XTEND-1 Trial Group
N Engl J Med 2023 Jan 26;388(4):310-318. doi: 10.1056/NEJMoa2209226. PMID: 36720133
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
Winter WE, Flax SD, Harris NS
Lab Med 2017 Nov 8;48(4):295-313. doi: 10.1093/labmed/lmx050. PMID: 29126301

Diagnosis

Hamedani NS, Donners AAMT, van Luin M, Gasper S, Rühl H, Klein C, Albert T, El Amrani M, Pötzsch B, Oldenburg J, Müller J
J Thromb Haemost 2023 Dec;21(12):3490-3500. Epub 2023 Sep 21 doi: 10.1016/j.jtha.2023.09.011. PMID: 37741510
Lim MY, Buckner TW
Curr Opin Hematol 2020 Sep;27(5):295-301. doi: 10.1097/MOH.0000000000000600. PMID: 32701616
Valentino LA, Khair K
Expert Rev Hematol 2020 Jul;13(7):731-743. Epub 2020 Jun 23 doi: 10.1080/17474086.2020.1775576. PMID: 32573295
Tabibian S, Motlagh H, Naderi M, Dorgalaleh A
Blood Coagul Fibrinolysis 2018 Jan;29(1):1-11. doi: 10.1097/MBC.0000000000000660. PMID: 28901996
Winter WE, Flax SD, Harris NS
Lab Med 2017 Nov 8;48(4):295-313. doi: 10.1093/labmed/lmx050. PMID: 29126301

Therapy

De Wolf D, Singh K, Chuah MK, VandenDriessche T
Hum Gene Ther 2023 Sep;34(17-18):782-792. doi: 10.1089/hum.2023.112. PMID: 37672530
Mahlangu J, Kaczmarek R, von Drygalski A, Shapiro S, Chou SC, Ozelo MC, Kenet G, Peyvandi F, Wang M, Madan B, Key NS, Laffan M, Dunn AL, Mason J, Quon DV, Symington E, Leavitt AD, Oldenburg J, Chambost H, Reding MT, Jayaram K, Yu H, Mahajan R, Chavele KM, Reddy DB, Henshaw J, Robinson TM, Wong WY, Pipe SW; GENEr8-1 Trial Group
N Engl J Med 2023 Feb 23;388(8):694-705. doi: 10.1056/NEJMoa2211075. PMID: 36812433
von Drygalski A, Chowdary P, Kulkarni R, Susen S, Konkle BA, Oldenburg J, Matino D, Klamroth R, Weyand AC, Jimenez-Yuste V, Nogami K, Poloskey S, Winding B, Willemze A, Knobe K; XTEND-1 Trial Group
N Engl J Med 2023 Jan 26;388(4):310-318. doi: 10.1056/NEJMoa2209226. PMID: 36720133
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
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

Prognosis

Verhagen MJA, Valke LLFG, Schols SEM
J Thromb Haemost 2022 Apr;20(4):794-805. Epub 2022 Jan 28 doi: 10.1111/jth.15640. PMID: 35034413Free PMC Article
Bawazir OA, Alharbi I
J Pediatr Hematol Oncol 2021 Jan;43(1):e33-e36. doi: 10.1097/MPH.0000000000001960. PMID: 33003145
Koc B, Zulfikar B
J Pediatr Hematol Oncol 2021 Jan;43(1):e29-e32. doi: 10.1097/MPH.0000000000001868. PMID: 32569036
Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, Laffan M, Russell CB, Li M, Pierce GF, Wong WY
N Engl J Med 2020 Jan 2;382(1):29-40. doi: 10.1056/NEJMoa1908490. PMID: 31893514
Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, Cohen A, Mathew P, Matsunaga A, Medeiros D, Nugent D, Thomas GA, Thompson AA, McRedmond K, Soucie JM, Austin H, Evatt BL
N Engl J Med 2007 Aug 9;357(6):535-44. doi: 10.1056/NEJMoa067659. PMID: 17687129

Clinical prediction guides

Madan B, Ozelo MC, Raheja P, Symington E, Quon DV, Leavitt AD, Pipe SW, Lowe G, Kenet G, Reding MT, Mason J, Wang M, von Drygalski A, Klamroth R, Shapiro S, Chambost H, Dunn AL, Oldenburg J, Chou SC, Peyvandi F, Millar CM, Osmond D, Yu H, Dashiell-Aje E, Robinson TM, Mahlangu J
J Thromb Haemost 2024 Jul;22(7):1880-1893. Epub 2024 Apr 12 doi: 10.1016/j.jtha.2024.04.001. PMID: 38614387
Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, Laffan M, Russell CB, Li M, Pierce GF, Wong WY
N Engl J Med 2020 Jan 2;382(1):29-40. doi: 10.1056/NEJMoa1908490. PMID: 31893514
Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, Germini F; Data and Demographics Committee of the World Federation of Hemophilia
Ann Intern Med 2019 Oct 15;171(8):540-546. Epub 2019 Sep 10 doi: 10.7326/M19-1208. PMID: 31499529
Tabibian S, Motlagh H, Naderi M, Dorgalaleh A
Blood Coagul Fibrinolysis 2018 Jan;29(1):1-11. doi: 10.1097/MBC.0000000000000660. PMID: 28901996
Mahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, Pabinger I, Hanabusa H, Gupta N, Kulkarni R, Fogarty P, Perry D, Shapiro A, Pasi KJ, Apte S, Nestorov I, Jiang H, Li S, Neelakantan S, Cristiano LM, Goyal J, Sommer JM, Dumont JA, Dodd N, Nugent K, Vigliani G, Luk A, Brennan A, Pierce GF; A-LONG Investigators
Blood 2014 Jan 16;123(3):317-25. Epub 2013 Nov 13 doi: 10.1182/blood-2013-10-529974. PMID: 24227821Free PMC Article

Recent systematic reviews

Thorat T, Neumann PJ, Chambers JD
J Manag Care Spec Pharm 2018 Jul;24(7):632-642. doi: 10.18553/jmcp.2018.24.7.632. PMID: 29952709Free PMC Article
Jiang L, Liu Y, Zhang L, Santoro C, Rodriguez A
Cochrane Database Syst Rev 2017 Jul 7;7(7):CD010810. doi: 10.1002/14651858.CD010810.pub3. PMID: 28685500Free PMC Article
Liu Y, Zhang L, Santoro C, Song J, Rodriguez A, Wang L
Cochrane Database Syst Rev 2015 Apr 4;(4):CD010810. doi: 10.1002/14651858.CD010810.pub2. PMID: 25841099
Di Minno MN, Ambrosino P, Franchini M, Coppola A, Di Minno G
Semin Thromb Hemost 2013 Oct;39(7):723-31. Epub 2013 Sep 10 doi: 10.1055/s-0033-1354422. PMID: 24022804
Eckhardt CL, van der Bom JG, van der Naald M, Peters M, Kamphuisen PW, Fijnvandraat K
J Thromb Haemost 2011 Oct;9(10):1948-58. doi: 10.1111/j.1538-7836.2011.04467.x. PMID: 21838755

Supplemental Content

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