47:
260:
496:, which allows for neatly packaged bottles of factor IX concentrates. With the rise of factor IX concentrates it became easier for people to get treatment at home. Although these advances in medicine had a significant positive impact on the treatment of haemophilia, there were many complications that came with it. By the early 1980s, scientists discovered that the medicines they had created were transferring blood-borne
1531:
788:
189:
exfoliation of primary dentition, or prolonged bleeding after an invasive procedure/tooth extraction; In severe haemophilia, there may be spontaneous bleeding from the oral tissues (e.g. soft palate, tongue, buccal mucosa), lips and gingiva, with ecchymoses. In rare cases, haemarthrosis (bleeding into joint space) of the temporomandibular joint (TMJ) may be observed.
492:, requiring large amounts of FFP to treat an actual bleeding episode, which resulted in the person requiring hospitalization. By the mid-1960s scientists found a way to get a larger amount of factor IX from FFP. By the late 1960s, pharmaceutical scientists found methods to separate the factor IX from
192:
Patients with haemophilia will experience many episodes of oral bleeding over their lifetime. Average 29.1 bleeding events per year are serious enough to require factor replacement in F VIII-deficient patients which 9% involved oral structures. Children with severe haemophilia have significant lower
155:
Most individuals who have
Hemophilia B and experience symptoms are men. The prevalence of Hemophilia B in the population is about one in 40,000; Hemophilia B represents about 15% of patients with hemophilia. Many women carriers of the disease have no symptoms. However, an estimated 10-25% of women
188:
Patients with bleeding disorders show a higher incidence of periodontal disease as well as dental caries, concerning the fear of bleeding which leads to a lack of oral hygiene and oral health care. The most prominent oral manifestation of a mild haemophilia B would be gingival bleeding during
1337:
Nathwani, Amit C.; Reiss, Ulreke M.; Tuddenham, Edward G.D.; Rosales, Cecilia; Chowdary, Pratima; McIntosh, Jenny; Della Peruta, Marco; Lheriteau, Elsa; Patel, Nishal; Raj, Deepak; Riddell, Anne; Pie, Jun; Rangarajan, Savita; Bevan, David; Recht, Michael; Shen, Yu-Min; Halka, Kathleen G.;
387:
Surgical treatment, including a simple dental extraction, must be planned to minimize the risk of bleeding, excessive bruising, or haematoma formation. Soft vacuum-formed splints can be used to provide local protection following a dental extraction or prolonged post-extraction bleed.
417:
1338:
Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Allay, James; Kay, Mark A.; Ng, Catherine Y.C.; Zhou, Junfang; Cancio, Maria; Morton, Christopher L.; Gray, John T.; Srivastava, Deokumar; Nienhuis, Arthur W.; Davidoff, Andrew M. (20 November 2014).
508:, the virus that causes AIDS. With the rise of these deadly viruses, scientists had to find improved methods for screening the blood products they received from donors. In 1982, scientists made a breakthrough in medicine and were able to clone factor IX
202:
476:
in the period during which blood was not routinely screened for this virus. He became an active worker for the
Canadian Hemophilia Society and campaigned for transfusion safety ever since getting infected, but developed
1426:
1411:
526:
In 2009, an analysis of genetic markers revealed that haemophilia B was the blood disease affecting many
European royal families of the United Kingdom, Germany, Russia and Spain: so-called "Royal Disease".
424:
Stephen
Christmas (12 February 1947 – 20 December 1993) was the first patient described to have Christmas disease (or Haemophilia B) in 1952 by a group of British doctors. Christmas was born to a
444:. The family returned to London in 1952 to visit their relatives, and during the trip Stephen was admitted to hospital. A sample of his blood was sent to the Oxford Haemophilia Centre in
988:
Chowdary, Pratima; Shapiro, Susan; Makris, Mike; Evans, Gillian; Boyce, Sara; Talks, Kate; Dolan, Gerard; Reiss, Ulrike; Phillips, Mark; Riddell, Anne; Peralta, Maria R. (2022-07-21).
408:(FIX) protein, normal levels of the protein were observed with low doses of the therapy but immunosuppression was necessitated to decrease the risk of vector-related immune responses.
274:
Factor IX deficiency can cause interference of the coagulation cascade, thereby causing spontaneous haemorrhage when there is trauma. Factor IX when activated activates
512:. With this new development it decreased the risk of the many viruses. Although the new factor was created, it was not available for haemophilia B patients until 1997.
1577:
973:
Andrew Brewer, Maria Elvira Correa (May 2006). "Guildelines for Dental
Treatment of Patients with Inherited Bleeding Disorders" (PDF). Treatment of Hemophilia.
2437:
484:
In the 1950s and 1960s, with newfound technology and gradual advances in medicine, pharmaceutical scientists found a way to take the factor IX from
146:, the first patient described with haemophilia B. In addition, the first report of its identification was published in the Christmas edition of the
365:
should be avoided once the diagnosis is made since they can exacerbate a bleeding episode. Any surgical procedure should be done with concomitant
940:
765:
2493:
2357:
1570:
672:
2393:
2204:
909:
488:(FFP) and give it to those with haemophilia B. Though they found a way to treat the disease, the FFP contained only a small amount of
2253:
1563:
2548:
441:
2700:
2582:
1694:
375:(Hemgenix) was approved for medical use in the United States in November 2022. It is the first gene therapy approved by the US
2815:
2619:
2362:
2338:
821:
651:
1099:
Giangrande PL (June 2003). "Six characters in search of an author: the history of the nomenclature of coagulation factors".
2695:
2273:
2538:
1869:
1852:
1441:
19:
This article is about the bleeding disorder with factor IX deficiency. For the disorder with factor VIII deficiency, see
1196:
297:
provide a binding site for both cofactors. This complex (in the coagulation pathway) will eventually activate factor X.
2328:
244:– where patients experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty.
2572:
2398:
950:
2614:
2543:
2478:
2197:
1931:
1883:
2324:
546:
521:
2705:
2647:
2227:
1650:
816:
Glick, Michael (2015). Burket's Oral
Medicine. USA: People's Medical Publishing House. pp. 473, 475, 481, 482.
2508:
2729:
2243:
1937:
1923:
201:
1546:
1284:
Franchini, Massimo; Frattini, Francesco; Crestani, Silvia; Sissa, Cinzia; Bonfanti, Carlo (1 January 2013).
2248:
1911:
1874:
1744:
771:
376:
357:
Treatment is given intermittently, when there is significant bleeding. It includes intravenous infusion of
347:
2785:
2710:
2604:
2258:
2190:
2064:
1640:
551:
138:
Haemophilia B was first recognized as a distinct disease entity in 1952. It is also known by the eponym
2780:
2367:
2019:
1864:
1687:
460:, which is normally decreased in classic hemophilia, but a different protein, which received the name
440:, Canada, with his family, and was there at the age of two years that hemophilia was diagnosed at the
2740:
2600:
2483:
2263:
2135:
1706:
372:
2775:
2442:
2105:
2095:
1848:
1677:
1452:
2820:
2745:
2669:
2459:
2388:
1888:
1514:
1045:
702:
680:
148:
917:
883:
2760:
2609:
2567:
2517:
2469:
2411:
2009:
1984:
1942:
453:
401:
339:
1492:
131:, and resulting in a deficiency of factor IX. It is less common than factor VIII deficiency (
2592:
2424:
2004:
1994:
1812:
193:
prevalence of dental caries and lower plaque scores compared with matched, healthy controls.
2810:
2380:
2306:
2278:
1760:
1655:
1645:
1235:
247:
This lack of protein attachment to the DNA was thereby turning off the gene that produces
8:
2577:
2288:
2125:
1999:
1989:
1785:
1665:
1430:
485:
1536:
1239:
156:
carriers have mild symptoms; in rare cases, women may have moderate or severe symptoms.
2750:
2450:
2348:
1807:
1765:
1739:
1612:
1372:
1339:
1320:
1285:
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1027:
731:
706:
318:
75:
55:
1435:
2642:
2333:
2316:
2014:
1790:
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1463:
1377:
1359:
1325:
1307:
1265:
1253:
1167:
1159:
1116:
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1031:
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1011:
946:
817:
736:
647:
616:
469:
229:
143:
93:
63:
1503:
1128:
2755:
2629:
2120:
1840:
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1635:
1367:
1351:
1315:
1297:
1243:
1155:
1151:
1108:
1001:
726:
718:
607:
Konkle, Barbara A.; Josephson, Neil C.; Nakaya
Fletcher, Shelley (1 January 1993).
461:
437:
1142:
Schramm, Wolfgang (November 2014). "The history of haemophilia – a short review".
580:
2690:
2637:
2513:
2429:
2235:
2145:
1954:
1795:
1660:
1457:
805:"Hemophilia A" (PDF). College of Dental Hygienists of Ontario. September 2, 2015.
366:
225:
221:
2770:
2685:
2558:
2523:
2455:
2155:
1857:
1800:
1682:
449:
433:
425:
1468:
866:
608:
2804:
2765:
2528:
2488:
2416:
2403:
2296:
2268:
2165:
1977:
1967:
1724:
1363:
1311:
1177:
1163:
1015:
792:
541:
536:
400:
candidate for haemophilia B called FLT180 were announced, it works using an
331:
305:
The diagnosis for haemophilia B can be done via the following tests/methods:
177:
132:
20:
1898:
1420:
1248:
1223:
722:
2375:
1607:
1381:
1329:
1257:
1171:
1120:
1069:
1023:
740:
620:
493:
397:
217:
recessive trait, which explains why males are affected in greater numbers.
210:
1355:
1006:
989:
330:
The differential diagnosis for this inherited condition is the following:
2213:
2150:
2115:
2090:
1962:
1770:
1602:
1591:
1487:
1340:"Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B"
457:
309:
290:
268:
120:
68:
46:
1403:
1184:(Subscription may be required or content may be available in libraries.)
1046:"Novel gene therapy could reduce bleeding risk for haemophilia patients"
2140:
1734:
1716:
1509:
1302:
343:
279:
169:
2182:
2085:
2049:
1672:
1498:
990:"Phase 1–2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B"
501:
489:
465:
405:
358:
335:
294:
248:
173:
128:
707:"Christmas disease: a condition previously mistaken for haemophilia"
701:
Biggs R, Douglas AS, MacFarlane RG, Dacie JV, Pitney WR, Merskey C,
271:, which can be either spontaneously or in response to mild trauma.
2100:
2054:
2039:
1729:
1587:
766:"FDA Approves First Gene Therapy to Treat Adults with Hemophilia B"
275:
259:
233:
214:
165:
124:
2059:
910:"Factor IX Deficiency: Background, Pathophysiology, Epidemiology"
791:
This article incorporates text from this source, which is in the
1446:
884:"Hemophilia B: Practice Essentials, Background, Pathophysiology"
123:
disorder causing easy bruising and bleeding due to an inherited
2044:
1415:
1224:"Genotype Analysis Identifies the Cause of the "Royal Disease""
835:
445:
429:
416:
362:
289:
Factor IX becomes active eventually in coagulation by cofactor
283:
1283:
606:
2661:
1336:
497:
673:"Haemophilia B (Factor IX Deficiency) information | Patient"
2657:
2498:
1286:"Treatment of hemophilia B: focus on recombinant factor IX"
700:
509:
478:
987:
646:(19th ed.). Philadelphia: Saunders. pp. 1700–1.
267:
Factor IX deficiency leads to an increased propensity for
240:
of people with a rare and unusual form of haemophilia B –
505:
473:
237:
1585:
1197:"Case Closed: Famous Royals Suffered From Hemophilia"
1393:
977:: 9 – via World Federation of Hemophilia (WFH).
760:
758:
756:
754:
752:
750:
2802:
1222:Evgeny I. Rogaev; et al. (8 October 2009).
1221:
581:"Hemophilia B: MedlinePlus Medical Encyclopedia"
2404:Danon disease/glycogen storage disease Type IIb
1070:"Transformational therapy cures haemophilia B"
747:
432:. He was the son of film and television actor
2509:Color blindness (red and green, but not blue)
2494:Alpha-thalassemia mental retardation syndrome
2198:
1571:
1194:
1098:
2394:Glucose-6-phosphate dehydrogenase deficiency
836:"OMIM Entry - # 306900 - HEMOPHILIA B; HEMB"
16:Genetic X-linked recessive bleeding disorder
2205:
2191:
1578:
1564:
916:. Medscape. 24 August 2016. Archived from
98:Bleeding scores, Coagulation factor assays
45:
2254:X-linked severe combined immunodeficiency
1371:
1319:
1301:
1247:
1005:
730:
325:
641:
456:discovered that he was not deficient in
415:
382:
258:
200:
2648:X-linked nephrogenic diabetes insipidus
2573:Hypohidrotic ectodermal dysplasia (EDA)
1832:
1141:
2803:
2583:X-linked endothelial corneal dystrophy
2226:
2212:
861:
859:
857:
855:
602:
600:
515:
2728:
2727:
2539:Charcot–Marie–Tooth disease (CMTX2-3)
2363:Ornithine transcarbamylase deficiency
2339:X-linked adrenal hypoplasia congenita
2225:
2186:
1559:
1094:
1092:
1090:
878:
876:
667:
665:
663:
635:
575:
573:
571:
569:
567:
251:, which prevents excessive bleeding.
209:The factor IX gene is located on the
159:
2274:X-linked lymphoproliferative disease
2244:Chronic granulomatous disease (CYBB)
938:
2620:Emery–Dreifuss muscular dystrophy 1
852:
597:
13:
2329:Spinal and bulbar muscular atrophy
1277:
1087:
873:
660:
564:
254:
54:This condition is inherited in an
14:
2832:
2399:Pyruvate dehydrogenase deficiency
1389:
945:. London: Springer. p. 416.
2479:X-linked intellectual disability
1932:platelet storage pool deficiency
1884:Heparin-induced thrombocytopenia
1529:
1195:Michael Price (8 October 2009).
1113:10.1046/j.1365-2141.2003.04333.x
786:
183:
2325:Androgen insensitivity syndrome
1344:New England Journal of Medicine
1215:
1188:
1135:
1062:
1038:
994:New England Journal of Medicine
981:
966:
932:
902:
547:Haemophilia in European royalty
522:Haemophilia in European royalty
40:Hemophilia B, Christmas disease
2701:Simpson–Golabi–Behmel syndrome
1651:Activated protein C resistance
1290:Biologics: Targets and Therapy
1156:10.1016/j.thromres.2013.10.020
828:
809:
798:
694:
404:(AAV) to restore the clotting
1:
2670:AMELX Amelogenesis imperfecta
2610:Centronuclear myopathy (MTM1)
2307:X-linked sideroblastic anemia
679:. 3 July 2014. Archived from
644:Nelson textbook of pediatrics
557:
470:blood and plasma transfusions
379:(FDA) to treat Hemophilia B.
176:), and bleeding into joints (
2816:X-linked recessive disorders
2696:Smith–Fineman–Myers syndrome
2544:Pelizaeus–Merzbacher disease
2438:Purine–pyrimidine metabolism
1745:Trousseau sign of malignancy
772:Food and Drug Administration
468:). Stephen was dependent on
377:Food and Drug Administration
361:and/or blood transfusions.
352:
300:
263:Coagulation (FIX is on left)
7:
2786:Craniofrontonasal dysplasia
2711:Nasodigitoacoustic syndrome
2259:X-linked agammaglobulinemia
2065:Nonthrombocytopenic purpura
1641:Antithrombin III deficiency
530:
391:
196:
10:
2837:
2781:Orofaciodigital syndrome 1
2615:Conradi–Hünermann syndrome
2368:Oculocerebrorenal syndrome
2020:Congenital afibrinogenemia
1924:Glanzmann's thrombasthenia
1688:Essential thrombocythaemia
890:. Medscape. 24 August 2016
519:
481:and died from it in 1993.
442:Hospital for Sick Children
411:
396:In July 2022 results of a
168:, urinary tract bleeding (
18:
2741:X-linked hypophosphatemia
2736:
2723:
2678:
2656:
2628:
2601:Becker muscular dystrophy
2591:
2557:
2468:
2347:
2315:
2287:
2264:Hyper-IgM syndrome type 1
2234:
2221:
2136:Gastrointestinal bleeding
2075:
2032:
1953:
1938:Hermansky–Pudlak syndrome
1897:
1839:
1825:
1753:
1715:
1707:Antiphospholipid syndrome
1628:
1621:
1598:
1478:
1397:
642:Kliegman, Robert (2011).
464:in his honour (and later
373:Etranacogene dezaparvovec
213:(Xq27.1-q27.2). It is an
102:
92:
84:
74:
62:
53:
44:
36:
31:
2706:Mohr–Tranebjærg syndrome
2249:Wiskott–Aldrich syndrome
2106:Subconjunctival bleeding
2096:Intracranial haemorrhage
1912:Bernard–Soulier syndrome
1875:Upshaw–Schulman syndrome
1849:Thrombocytopenic purpura
1678:Sticky platelet syndrome
552:von Willebrand's disease
472:, and was infected with
348:Bernard–Soulier syndrome
232:were preventing two key
228:showed that two sets of
2746:Focal dermal hypoplasia
2460:Occipital horn syndrome
2389:Carbohydrate metabolism
1249:10.1126/science.1180660
723:10.1136/bmj.2.4799.1378
149:British Medical Journal
2761:Incontinentia pigmenti
2568:Dyskeratosis congenita
2412:Lipid storage disorder
2334:KAL1 Kallmann syndrome
2010:Factor XIII deficiency
1990:Hypoprothrombinemia/II
1985:von Willebrand disease
1943:Gray platelet syndrome
454:Robert Gwyn Macfarlane
421:
402:adeno-associated virus
340:von Willebrand disease
326:Differential diagnosis
264:
236:from attaching to the
206:
164:Symptoms include easy
2484:Coffin–Lowry syndrome
2425:Mucopolysaccharidosis
2005:Factor XII deficiency
1995:Factor VII deficiency
1813:Renal vein thrombosis
1356:10.1056/NEJMoa1407309
1270:subscription required
1201:ScienceNOW Daily News
1007:10.1056/NEJMoa2119913
942:Diagnostic hematology
939:Beck, Norman (2009).
419:
383:Dental considerations
262:
204:
106:Factor IX concentrate
2776:Lujan–Fryns syndrome
2443:Lesch–Nyhan syndrome
2381:Adrenoleukodystrophy
2279:Properdin deficiency
1761:Deep vein thrombosis
1656:Protein S deficiency
1646:Protein C deficiency
293:(specifically IXa).
242:haemophilia B Leyden
88:Factor IX deficiency
2578:X-linked ichthyosis
2126:Pulmonary haematoma
2000:Factor X deficiency
1889:May–Hegglin anomaly
1666:Prothrombin G20210A
1240:2009Sci...326..817R
1144:Thrombosis Research
516:Society and culture
486:fresh frozen plasma
2751:Fragile X syndrome
2561:and related tissue
2228:X-linked recessive
2033:Signs and symptoms
1808:Pulmonary embolism
1613:Bleeding diathesis
1479:External resources
1303:10.2147/BTT.S31582
776:. 22 November 2022
436:. He emigrated to
422:
319:Coagulation factor
265:
249:clotting factor IX
207:
160:Signs and symptoms
56:X-linked recessive
2798:
2797:
2794:
2793:
2730:X-linked dominant
2719:
2718:
2679:No primary system
2180:
2179:
2176:
2175:
2028:
2027:
2015:Dysfibrinogenemia
1899:Platelet function
1821:
1820:
1700:Purpura fulminans
1524:
1523:
1350:(21): 1994–2004.
1176: – via
920:on 6 October 2016
822:978-1-60795-188-9
717:(4799): 1378–82.
653:978-1-4377-0755-7
230:genetic mutations
144:Stephen Christmas
140:Christmas disease
127:of the gene for
110:
109:
94:Diagnostic method
26:Medical condition
2828:
2756:Aicardi syndrome
2725:
2724:
2223:
2222:
2207:
2200:
2193:
2184:
2183:
2121:Haemopericardium
1841:Thrombocytopenia
1837:
1836:
1830:
1829:
1786:Lowenberg's sign
1636:Clotting factors
1626:
1625:
1580:
1573:
1566:
1557:
1556:
1533:
1532:
1395:
1394:
1385:
1375:
1333:
1323:
1305:
1271:
1269:
1251:
1219:
1213:
1212:
1210:
1208:
1192:
1186:
1185:
1182:
1175:
1139:
1133:
1132:
1096:
1085:
1084:
1082:
1081:
1066:
1060:
1059:
1057:
1056:
1042:
1036:
1035:
1009:
985:
979:
970:
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963:
961:
959:
936:
930:
929:
927:
925:
906:
900:
899:
897:
895:
880:
871:
870:
863:
850:
849:
847:
846:
832:
826:
813:
807:
802:
796:
790:
789:
785:
783:
781:
762:
745:
744:
734:
698:
692:
691:
689:
688:
669:
658:
657:
639:
633:
631:
629:
627:
604:
595:
594:
592:
591:
577:
462:Christmas factor
438:Toronto, Ontario
49:
29:
28:
2836:
2835:
2831:
2830:
2829:
2827:
2826:
2825:
2801:
2800:
2799:
2790:
2732:
2715:
2691:McLeod syndrome
2674:
2652:
2638:Alport syndrome
2624:
2587:
2553:
2514:Ocular albinism
2464:
2430:Hunter syndrome
2343:
2311:
2283:
2230:
2217:
2211:
2181:
2172:
2146:Haemoperitoneum
2071:
2024:
1955:Clotting factor
1949:
1893:
1817:
1766:Bancroft's sign
1749:
1740:Virchow's triad
1711:
1661:Factor V Leiden
1617:
1594:
1584:
1554:
1553:
1552:
1534:
1530:
1525:
1520:
1519:
1474:
1473:
1406:
1392:
1280:
1278:Further reading
1275:
1274:
1220:
1216:
1206:
1204:
1193:
1189:
1183:
1180:
1140:
1136:
1101:Br. J. Haematol
1097:
1088:
1079:
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1068:
1067:
1063:
1054:
1052:
1044:
1043:
1039:
986:
982:
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967:
957:
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953:
937:
933:
923:
921:
908:
907:
903:
893:
891:
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874:
865:
864:
853:
844:
842:
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829:
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803:
799:
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763:
748:
699:
695:
686:
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671:
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654:
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623:
605:
598:
589:
587:
585:medlineplus.gov
579:
578:
565:
560:
533:
524:
518:
414:
394:
385:
367:tranexamic acid
355:
328:
315:Bleeding scores
303:
257:
255:Pathophysiology
226:Merlin Crossley
222:George Brownlee
199:
186:
172:), nosebleeds (
162:
115:, also spelled
27:
24:
17:
12:
11:
5:
2834:
2824:
2823:
2821:Coagulopathies
2818:
2813:
2796:
2795:
2792:
2791:
2789:
2788:
2783:
2778:
2773:
2771:CHILD syndrome
2768:
2763:
2758:
2753:
2748:
2743:
2737:
2734:
2733:
2721:
2720:
2717:
2716:
2714:
2713:
2708:
2703:
2698:
2693:
2688:
2686:Barth syndrome
2682:
2680:
2676:
2675:
2673:
2672:
2666:
2664:
2654:
2653:
2651:
2650:
2645:
2643:Dent's disease
2640:
2634:
2632:
2626:
2625:
2623:
2622:
2617:
2612:
2607:
2597:
2595:
2589:
2588:
2586:
2585:
2580:
2575:
2570:
2564:
2562:
2555:
2554:
2552:
2551:
2546:
2541:
2532:
2531:
2526:
2524:Norrie disease
2521:
2511:
2506:Eye disorders:
2502:
2501:
2496:
2491:
2486:
2474:
2472:
2470:Nervous system
2466:
2465:
2463:
2462:
2456:Menkes disease
2446:
2445:
2433:
2432:
2420:
2419:
2407:
2406:
2401:
2396:
2384:
2383:
2371:
2370:
2365:
2353:
2351:
2345:
2344:
2342:
2341:
2336:
2331:
2321:
2319:
2313:
2312:
2310:
2309:
2304:
2299:
2293:
2291:
2285:
2284:
2282:
2281:
2276:
2271:
2266:
2261:
2256:
2251:
2246:
2240:
2238:
2232:
2231:
2219:
2218:
2210:
2209:
2202:
2195:
2187:
2178:
2177:
2174:
2173:
2171:
2170:
2169:
2168:
2160:
2159:
2158:
2156:Haematosalpinx
2153:
2148:
2143:
2138:
2130:
2129:
2128:
2123:
2118:
2110:
2109:
2108:
2103:
2098:
2093:
2088:
2079:
2077:
2073:
2072:
2070:
2069:
2068:
2067:
2057:
2052:
2047:
2042:
2036:
2034:
2030:
2029:
2026:
2025:
2023:
2022:
2017:
2012:
2007:
2002:
1997:
1992:
1987:
1982:
1981:
1980:
1975:
1970:
1959:
1957:
1951:
1950:
1948:
1947:
1946:
1945:
1940:
1928:
1927:
1926:
1916:
1915:
1914:
1903:
1901:
1895:
1894:
1892:
1891:
1886:
1880:
1879:
1878:
1877:
1872:
1862:
1861:
1860:
1858:Evans syndrome
1845:
1843:
1834:
1827:
1823:
1822:
1819:
1818:
1816:
1815:
1810:
1805:
1804:
1803:
1798:
1793:
1791:Peabody's sign
1788:
1783:
1778:
1773:
1768:
1757:
1755:
1751:
1750:
1748:
1747:
1742:
1737:
1732:
1727:
1721:
1719:
1713:
1712:
1710:
1709:
1704:
1703:
1702:
1692:
1691:
1690:
1685:
1683:Thrombocytosis
1680:
1670:
1669:
1668:
1663:
1658:
1653:
1648:
1643:
1632:
1630:
1623:
1619:
1618:
1616:
1615:
1610:
1605:
1599:
1596:
1595:
1583:
1582:
1575:
1568:
1560:
1535:
1528:
1527:
1526:
1522:
1521:
1518:
1517:
1506:
1495:
1483:
1482:
1480:
1476:
1475:
1472:
1471:
1460:
1449:
1438:
1423:
1407:
1402:
1401:
1399:
1398:Classification
1391:
1390:External links
1388:
1387:
1386:
1334:
1279:
1276:
1273:
1272:
1214:
1187:
1134:
1086:
1061:
1037:
1000:(3): 237–247.
980:
965:
951:
931:
901:
872:
851:
827:
808:
797:
746:
693:
659:
652:
634:
609:"Hemophilia B"
596:
562:
561:
559:
556:
555:
554:
549:
544:
539:
532:
529:
520:Main article:
517:
514:
450:Rosemary Biggs
434:Eric Christmas
413:
410:
393:
390:
384:
381:
354:
351:
346:disorders and
327:
324:
323:
322:
316:
313:
312:screening test
302:
299:
256:
253:
198:
195:
185:
182:
161:
158:
142:, named after
121:blood clotting
108:
107:
104:
100:
99:
96:
90:
89:
86:
82:
81:
78:
72:
71:
66:
60:
59:
51:
50:
42:
41:
38:
34:
33:
25:
15:
9:
6:
4:
3:
2:
2833:
2822:
2819:
2817:
2814:
2812:
2809:
2808:
2806:
2787:
2784:
2782:
2779:
2777:
2774:
2772:
2769:
2767:
2766:Rett syndrome
2764:
2762:
2759:
2757:
2754:
2752:
2749:
2747:
2744:
2742:
2739:
2738:
2735:
2731:
2726:
2722:
2712:
2709:
2707:
2704:
2702:
2699:
2697:
2694:
2692:
2689:
2687:
2684:
2683:
2681:
2677:
2671:
2668:
2667:
2665:
2663:
2659:
2655:
2649:
2646:
2644:
2641:
2639:
2636:
2635:
2633:
2631:
2627:
2621:
2618:
2616:
2613:
2611:
2608:
2606:
2602:
2599:
2598:
2596:
2594:
2593:Neuromuscular
2590:
2584:
2581:
2579:
2576:
2574:
2571:
2569:
2566:
2565:
2563:
2560:
2556:
2550:
2547:
2545:
2542:
2540:
2537:
2534:
2533:
2530:
2529:Choroideremia
2527:
2525:
2522:
2519:
2515:
2512:
2510:
2507:
2504:
2503:
2500:
2497:
2495:
2492:
2490:
2489:MASA syndrome
2487:
2485:
2482:
2480:
2476:
2475:
2473:
2471:
2467:
2461:
2457:
2454:
2452:
2448:
2447:
2444:
2441:
2439:
2435:
2434:
2431:
2428:
2426:
2422:
2421:
2418:
2417:Fabry disease
2414:
2413:
2409:
2408:
2405:
2402:
2400:
2397:
2395:
2392:
2390:
2386:
2385:
2382:
2379:
2377:
2373:
2372:
2369:
2366:
2364:
2361:
2359:
2355:
2354:
2352:
2350:
2346:
2340:
2337:
2335:
2332:
2330:
2326:
2323:
2322:
2320:
2318:
2314:
2308:
2305:
2303:
2302:Haemophilia B
2300:
2298:
2297:Haemophilia A
2295:
2294:
2292:
2290:
2286:
2280:
2277:
2275:
2272:
2270:
2267:
2265:
2262:
2260:
2257:
2255:
2252:
2250:
2247:
2245:
2242:
2241:
2239:
2237:
2233:
2229:
2224:
2220:
2215:
2208:
2203:
2201:
2196:
2194:
2189:
2188:
2185:
2167:
2166:Haemarthrosis
2164:
2163:
2161:
2157:
2154:
2152:
2149:
2147:
2144:
2142:
2139:
2137:
2134:
2133:
2131:
2127:
2124:
2122:
2119:
2117:
2114:
2113:
2111:
2107:
2104:
2102:
2099:
2097:
2094:
2092:
2089:
2087:
2084:
2083:
2081:
2080:
2078:
2074:
2066:
2063:
2062:
2061:
2058:
2056:
2053:
2051:
2048:
2046:
2043:
2041:
2038:
2037:
2035:
2031:
2021:
2018:
2016:
2013:
2011:
2008:
2006:
2003:
2001:
1998:
1996:
1993:
1991:
1988:
1986:
1983:
1979:
1976:
1974:
1971:
1969:
1966:
1965:
1964:
1961:
1960:
1958:
1956:
1952:
1944:
1941:
1939:
1936:
1935:
1934:
1933:
1929:
1925:
1922:
1921:
1920:
1917:
1913:
1910:
1909:
1908:
1905:
1904:
1902:
1900:
1896:
1890:
1887:
1885:
1882:
1881:
1876:
1873:
1871:
1868:
1867:
1866:
1863:
1859:
1856:
1855:
1854:
1850:
1847:
1846:
1844:
1842:
1838:
1835:
1831:
1828:
1824:
1814:
1811:
1809:
1806:
1802:
1799:
1797:
1794:
1792:
1789:
1787:
1784:
1782:
1781:Louvel's sign
1779:
1777:
1776:Lisker's sign
1774:
1772:
1769:
1767:
1764:
1763:
1762:
1759:
1758:
1756:
1752:
1746:
1743:
1741:
1738:
1736:
1733:
1731:
1728:
1726:
1725:Thrombophilia
1723:
1722:
1720:
1718:
1714:
1708:
1705:
1701:
1698:
1697:
1696:
1693:
1689:
1686:
1684:
1681:
1679:
1676:
1675:
1674:
1671:
1667:
1664:
1662:
1659:
1657:
1654:
1652:
1649:
1647:
1644:
1642:
1639:
1638:
1637:
1634:
1633:
1631:
1627:
1624:
1620:
1614:
1611:
1609:
1606:
1604:
1601:
1600:
1597:
1593:
1589:
1586:Disorders of
1581:
1576:
1574:
1569:
1567:
1562:
1561:
1558:
1550:
1549:
1548:
1547:Haemophilia B
1542:
1538:
1516:
1515:Haemophilia B
1512:
1511:
1507:
1505:
1501:
1500:
1496:
1494:
1490:
1489:
1485:
1484:
1481:
1477:
1470:
1466:
1465:
1461:
1459:
1455:
1454:
1450:
1448:
1444:
1443:
1439:
1437:
1433:
1432:
1428:
1424:
1422:
1418:
1417:
1413:
1409:
1408:
1405:
1400:
1396:
1383:
1379:
1374:
1369:
1365:
1361:
1357:
1353:
1349:
1345:
1341:
1335:
1331:
1327:
1322:
1317:
1313:
1309:
1304:
1299:
1295:
1291:
1287:
1282:
1281:
1267:
1263:
1259:
1255:
1250:
1245:
1241:
1237:
1234:(5954): 817.
1233:
1229:
1225:
1218:
1202:
1198:
1191:
1179:
1178:ScienceDirect
1173:
1169:
1165:
1161:
1157:
1153:
1149:
1145:
1138:
1130:
1126:
1122:
1118:
1114:
1110:
1107:(5): 703–12.
1106:
1102:
1095:
1093:
1091:
1075:
1071:
1065:
1051:
1047:
1041:
1033:
1029:
1025:
1021:
1017:
1013:
1008:
1003:
999:
995:
991:
984:
978:
976:
969:
954:
952:9781848002951
948:
944:
943:
935:
919:
915:
911:
905:
889:
885:
879:
877:
868:
862:
860:
858:
856:
841:
837:
831:
825:
823:
819:
812:
806:
801:
794:
793:public domain
775:
773:
767:
761:
759:
757:
755:
753:
751:
742:
738:
733:
728:
724:
720:
716:
712:
708:
704:
697:
683:on 2024-02-26
682:
678:
674:
668:
666:
664:
655:
649:
645:
638:
622:
618:
614:
610:
603:
601:
586:
582:
576:
574:
572:
570:
568:
563:
553:
550:
548:
545:
543:
542:Haemophilia C
540:
538:
537:Haemophilia A
535:
534:
528:
523:
513:
511:
507:
503:
499:
495:
491:
487:
482:
480:
475:
471:
467:
463:
459:
455:
451:
447:
443:
439:
435:
431:
427:
418:
409:
407:
403:
399:
389:
380:
378:
374:
370:
368:
364:
360:
350:
349:
345:
341:
337:
333:
332:haemophilia A
320:
317:
314:
311:
308:
307:
306:
298:
296:
292:
287:
285:
281:
277:
272:
270:
261:
252:
250:
245:
243:
239:
235:
231:
227:
223:
218:
216:
212:
203:
194:
190:
184:Complications
181:
179:
178:haemarthrosis
175:
171:
167:
157:
153:
151:
150:
145:
141:
136:
134:
133:haemophilia A
130:
126:
122:
118:
114:
113:Haemophilia B
105:
101:
97:
95:
91:
87:
83:
80:Easy bruising
79:
77:
73:
70:
67:
65:
61:
57:
52:
48:
43:
39:
35:
32:Haemophilia B
30:
22:
21:haemophilia A
2535:
2505:
2477:
2449:
2436:
2423:
2410:
2387:
2376:Dyslipidemia
2374:
2356:
2301:
1972:
1930:
1918:
1906:
1796:Pratt's sign
1608:coagulopathy
1545:
1544:
1543:profile for
1540:
1508:
1497:
1486:
1462:
1451:
1440:
1425:
1410:
1347:
1343:
1293:
1289:
1231:
1227:
1217:
1205:. Retrieved
1200:
1190:
1147:
1143:
1137:
1104:
1100:
1078:. Retrieved
1076:. 2022-07-21
1073:
1064:
1053:. Retrieved
1050:ScienceDaily
1049:
1040:
997:
993:
983:
974:
972:
968:
956:. Retrieved
941:
934:
922:. Retrieved
918:the original
913:
904:
892:. Retrieved
887:
867:"Hemophilia"
843:. Retrieved
839:
830:
815:
811:
804:
800:
778:. Retrieved
769:
714:
710:
696:
685:. Retrieved
681:the original
676:
643:
637:
624:. Retrieved
612:
588:. Retrieved
584:
525:
483:
423:
398:gene therapy
395:
386:
371:
356:
338:deficiency,
329:
304:
288:
286:conversion.
278:which helps
273:
266:
246:
241:
219:
211:X chromosome
208:
205:X chromosome
191:
187:
163:
154:
147:
139:
137:
117:hemophilia B
116:
112:
111:
2811:Haemophilia
2289:Hematologic
2151:Haematocele
2116:Haemothorax
2091:Haemoptysis
1963:Haemophilia
1919:aggregation
1801:Rose's sign
1771:Homans sign
1603:Coagulation
1488:MedlinePlus
780:22 November
632:update 2014
613:GeneReviews
458:Factor VIII
310:Coagulation
291:factor VIII
269:haemorrhage
69:Haematology
37:Other names
2805:Categories
2358:Amino acid
2141:Haemobilia
1735:Thrombosis
1510:Patient UK
1464:DiseasesDB
1080:2022-08-03
1055:2022-08-03
845:2016-10-07
703:O'Brien JR
687:2016-04-21
590:2016-09-21
558:References
500:, such as
428:family in
344:fibrinogen
280:fibrinogen
170:haematuria
2349:Metabolic
2317:Endocrine
2216:disorders
2086:Epistaxis
2050:Haematoma
1673:Platelets
1504:emerg/240
1499:eMedicine
1364:0028-4793
1312:1177-5475
1296:: 33–38.
1266:206522975
1207:9 October
1164:1879-2472
1150:: S4–S9.
1032:250697905
1016:0028-4793
958:7 October
924:7 October
914:eMedicine
894:7 October
888:eMedicine
626:7 October
502:hepatitis
490:factor IX
466:Factor IX
420:Factor IX
406:factor IX
359:factor IX
353:Treatment
336:factor XI
301:Diagnosis
295:Platelets
220:In 1990,
174:epistaxis
129:factor IX
103:Treatment
64:Specialty
2630:Urologic
2605:Duchenne
2214:X-linked
2132:abdomen
2101:Hyphaema
2055:Petechia
2040:Bleeding
1907:adhesion
1833:By cause
1826:Bleeding
1730:Thrombus
1629:By cause
1622:Clotting
1592:clotting
1588:bleeding
1382:25409372
1330:23430394
1258:19815722
1172:24513149
1129:22694905
1121:12780784
1074:BBC News
1024:35857660
840:omim.org
741:12997790
711:Br Med J
705:(1952).
621:20301668
531:See also
448:, where
392:Research
276:factor X
234:proteins
215:X-linked
197:Genetics
166:bruising
125:mutation
76:Symptoms
2451:Mineral
2076:By site
2060:Purpura
1754:By site
1537:Scholia
1458:D002836
1373:4278802
1321:3575125
1236:Bibcode
1228:Science
732:2022306
677:Patient
498:viruses
426:British
412:History
119:, is a
58:manner.
2536:Other:
2236:Immune
2162:joint
2112:torso
2045:Bruise
1968:A/VIII
1539:has a
1493:000539
1447:306900
1380:
1370:
1362:
1328:
1318:
1310:
1264:
1256:
1203:. AAAS
1181:
1170:
1162:
1127:
1119:
1030:
1022:
1014:
949:
820:
739:
729:
650:
619:
504:, and
494:plasma
446:Oxford
430:London
363:NSAIDS
321:assays
284:fibrin
85:Causes
2662:tooth
2549:SMAX2
2082:head
1717:Clots
1541:topic
1436:286.1
1262:S2CID
1125:S2CID
1028:S2CID
774:(FDA)
770:U.S.
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