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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

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
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

Recent clinical studies

Etiology

Johnsen JM, Fletcher SN, Dove A, McCracken H, Martin BK, Kircher M, Josephson NC, Shendure J, Ruuska SE, Valentino LA, Pierce GF, Watson C, Cheng D, Recht M, Konkle BA
J Thromb Haemost 2022 Sep;20(9):2022-2034. Epub 2022 Jul 17 doi: 10.1111/jth.15805. PMID: 35770352
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
Moreno MM, Cuesta-Barriuso R
Blood Coagul Fibrinolysis 2019 Mar;30(2):55-57. doi: 10.1097/MBC.0000000000000783. PMID: 30507712
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

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
van Galen KPM, d'Oiron R, James P, Abdul-Kadir R, Kouides PA, Kulkarni R, Mahlangu JN, Othman M, Peyvandi F, Rotellini D, Winikoff R, Sidonio RF
J Thromb Haemost 2021 Aug;19(8):1883-1887. doi: 10.1111/jth.15397. PMID: 34327828Free PMC Article
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
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
Blair HA
Drugs 2019 Oct;79(15):1697-1707. doi: 10.1007/s40265-019-01200-2. PMID: 31542880

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
Koc B, Zulfikar B
J Pediatr Hematol Oncol 2021 Jan;43(1):e29-e32. doi: 10.1097/MPH.0000000000001868. PMID: 32569036
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
Berntorp E, Shapiro AD
Lancet 2012 Apr 14;379(9824):1447-56. Epub 2012 Mar 27 doi: 10.1016/S0140-6736(11)61139-2. PMID: 22456059

Clinical prediction guides

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
Makris M, Oldenburg J, Mauser-Bunschoten EP, Peerlinck K, Castaman G, Fijnvandraat K; subcommittee on Factor VIII, Factor IX and Rare Bleeding Disorders
J Thromb Haemost 2018 Dec;16(12):2530-2533. Epub 2018 Nov 15 doi: 10.1111/jth.14315. PMID: 30430726
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
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
Martinoli C, Della Casa Alberighi O, Di Minno G, Graziano E, Molinari AC, Pasta G, Russo G, Santagostino E, Tagliaferri A, Tagliafico A, Morfini M
Thromb Haemost 2013 Jun;109(6):1170-9. Epub 2013 Apr 4 doi: 10.1160/TH12-11-0874. PMID: 23571706

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
Fairfax A, Brehaut J, Colman I, Sikora L, Kazakova A, Chakraborty P, Potter BK; Canadian Inherited Metabolic Diseases Research Network
BMC Pediatr 2019 Jul 1;19(1):215. doi: 10.1186/s12887-019-1587-3. PMID: 31262261Free PMC Article
Strike K, Mulder K, Michael R
Cochrane Database Syst Rev 2016 Dec 19;12(12):CD011180. doi: 10.1002/14651858.CD011180.pub2. PMID: 27992070Free PMC Article

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