Haemophilia - Knowledge (XXG)

1105:"About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is unfortunately subject, and had been the source not only of great solicitude, but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted. (...) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation." 636:

haemophiliac. In contrast, for a female to inherit the disease, she must receive two deficient X-chromosomes, one from her mother and the other from her father (who must therefore be a haemophiliac himself). Hence, haemophilia is expressed far more commonly among males than females, while females, who must have two deficient X-chromosomes in order to have haemophilia, are far more likely to be silent carriers, survive childhood and to submit each of her genetic children to an at least 50% risk of receiving the deficient gene. However, it is possible for female carriers to become mild haemophiliacs due to

450: 598: 1200: 1140:, a Philadelphian physician, wrote an account about "a hemorrhagic disposition existing in certain families" in which he called the affected males "bleeders". He recognised that the disorder was hereditary and that it affected mostly males and was passed down by healthy females. His paper was the second paper to describe important characteristics of an X-linked genetic disorder (the first paper being a description of 6017: 71: 6047: 6057: 6037: 6027: 843: 589:

eliminate excessive blood may be more likely to easily rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis. In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in cartilage and bone destruction.

1185:, a doctor from Buenos Aires, found haemophilia A and haemophilia B to be separate diseases by doing a lab test. This test was done by transferring the blood of one haemophiliac to another haemophiliac. The fact that this corrected the clotting problem showed that there was more than one form of haemophilia. 964:

cyclophosphamide and cyclosporine are used and are proven effective for those who did not respond to the steroid treatments. In rare cases a third route or treatment is used, high doses of intravenous immunoglobulin or immunosorbent that works to help control bleeding instead of battling the auto-antibodies.

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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

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Clotting factors are either given preventively or on-demand. Preventive use involves the infusion of clotting factor on a regular schedule in order to keep clotting levels sufficiently high to prevent spontaneous bleeding episodes. On-demand (or episodic) treatment involves treating bleeding episodes

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vary with severity. In general symptoms are internal or external bleeding episodes, which are called "bleeds". People with more severe haemophilia experience more severe and more frequent bleeds, while people with mild haemophilia usually experience more minor symptoms except after surgery or serious

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may reduce symptoms to those that a person with mild or moderate haemophilia might have. The best results have been found in haemophilia B. In 2016 early stage human research was ongoing with a few sites recruiting participants. In 2017 a gene therapy trial on nine people with haemophilia A reported

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If a male has the disease and has children with a female who is not a carrier, his daughters will be carriers of haemophilia. His sons, however, will not be affected with the disease. The disease is X-linked and the father cannot pass haemophilia through the Y-chromosome. Males with the disorder are

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of this genetic disposition. However, the Y-chromosome in the male has no gene for factors VIII or IX. If the genes responsible for production of factor VIII or factor IX present on a male's X-chromosome are deficient there is no equivalent on the Y-chromosome to cancel it out, so the deficient gene

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Haemophilic arthropathy is characterised by chronic proliferative synovitis and cartilage destruction. If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans. The hypertrophied and fragile synovial lining while attempting to

406:. Human embryos in research can be regarded as the technical object/process. Missing blood clotting factors are replaced to treat haemophilia. This may be done on a regular basis or during bleeding episodes. Replacement may take place at home or in hospital. The clotting factors are made either from 1062:

varies with severity and adequate treatment. People with severe haemophilia who do not receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years. By the

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Haemophilia can be diagnosed before, during or after birth if there is a family history of the condition. Several options are available to parents. If there is no family history of haemophilia, it is usually only diagnosed when a child begins to walk or crawl. Affected children may experience joint

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supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related haemorrhage may be more cost effective than waiting until the fixed age to begin. Most haemophiliacs in third world countries have

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products) have been available and have been widely used in wealthier western countries. While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world. In many cases, factor products of

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In June 2023, the FDA approved the first gene therapy treatment for Hemophilia A, called Roctavian. It was only approved for patients with severe cases, but it has been shown to reduce yearly bleeding episodes by 50%. It works similarly to Hemgenix, being administered by intravenous infusion that

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Haemophilia frequency is about 1 instance in every 10,000 births (or 1 in 5,000 male births) for haemophilia A and 1 in 50,000 births for haemophilia B. About 18,000 people in the United States have haemophilia. Each year in the US, about 400 babies are born with the disorder. Haemophilia usually

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There are numerous different mutations which cause each type of haemophilia. Due to differences in changes to the genes involved, people with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those

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Since a male receives his single X-chromosome from his mother, the son of a healthy female silently carrying the deficient gene will have a 50% chance of inheriting that gene from her and with it the disease; and if his mother is affected with haemophilia, he will have a 100% chance of being a

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may provide some benefit. Different treatments are used to help those with an acquired form of hemophilia in addition to the normal clotting factors. Often the most effective treatment is corticosteroids which remove the auto-antibodies in half of people. As a secondary route of treatment,

909:(infusions of 25 IU/kg body weight of Factor VIII every other day) in respect to its effect on the prevention of joint-diseases. When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on 2612:

Alesci RS, Goldmann G, Halimeh S, Holstein K, Königs C, Miesbach W, Pfrepper C, Olivieri M. Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey. Front Med (Lausanne). 2024 Feb 5;11:1347024. doi: 10.3389/fmed.2024.1347024. PMID: 38379557; PMCID:

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who studied his own family). Otto was able to trace the disease back to a woman who settled near Plymouth, New Hampshire, in 1720. The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John F. Hay, published an account in

826:. It is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors. Acquired haemophilia can be associated with cancers, autoimmune disorders and following childbirth. 1132:

noted cases of excessive bleeding among men in a village. Several similar references to the disease later known as hemophilia appear throughout historical writings, though no term for inherited abnormal bleeding tendencies existed until the nineteenth century.

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Gualtierotti R, Garagiola I, Mortarino M, Spena S, Romero-Lux O, Peyvandi F. Gender equity in hemophilia: need for healthcare, familial, and societal advocacy. Front Med (Lausanne). 2024 Apr 5;11:1345496. doi: 10.3389/fmed.2024.1345496. PMID: 38646558; PMCID:

1273:, died at age 19 from abdominal bleeding following a minor car accident in which he and his sister hit a wall while avoiding a cyclist. Neither appeared injured or sought immediate medical care and Gonzalo died two days later from internal bleeding. 1376:

In November 2022, the first gene therapy treatment for Hemophilia B was approved by the U.S. Food and Drug Administration, called Hemgenix. It is a single-dose treatment that gives the patient the genetic information required to produce Factor IX.

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Haemophilia A is a recessive X-linked genetic disorder resulting in a deficiency of functional clotting Factor VIII. Haemophilia B is also a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX. Haemophilia C is an

892:(FDA) approved an anti-haemophilic drug completely free of albumin, which made it the first anti-haemophilic drug in the US to use an entirely synthetic purification process. Since 1993 recombinant factor products (which are typically cultured in 679:, rather than inheriting it, because of a new mutation in one of their parents' gametes. Spontaneous mutations account for about 33% of all cases of haemophilia A. About 30% of cases of haemophilia B are the result of a spontaneous gene mutation. 640:(inactivation) of the X-chromosomes. Haemophiliac daughters are more common than they once were, as improved treatments for the disease have allowed more haemophiliac males to survive to adulthood and become parents. Adult females may experience 4503: 4484: 4465: 347:. Most commonly found in men, haemophilia can affect women too, though very rarely. A woman would need to inherit two affected X chromosomes to be affected, whereas a man would only need one X chromosome affected. It is possible for a new 719:

Genetic testing and counselling are available to help determine the risk of passing the condition onto a child. This may involve testing a sample of tissue or blood to look for signs of the genetic mutation that causes haemophilia.

489:. This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement. Bleeding into soft tissues such as 1078:. The second leading cause of death related to severe haemophilia complications is intracranial haemorrhage which today accounts for one third of all deaths of people with haemophilia. Two other major causes of death include 4413: 1254:, which worsened rather than lessened the problem. It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Tsarevich Alexei. 375:. Haemophilia A, B, and C prevent the intrinsic pathway from functioning properly; this clotting pathway is necessary when there is damage to the endothelium of a blood vessel. Acquired haemophilia is associated with 1335:

Tens of thousands worldwide were infected as a result of contaminated factor products including more than 10,000 people in the United States, 3,500 British, 1,400 Japanese, 700 Canadians, 250 Irish, and 115 Iraqis.

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Clotting factors are usually not needed in mild haemophilia. In moderate haemophilia clotting factors are typically only needed when bleeding occurs or to prevent bleeding with certain events. In severe haemophilia

3875:"AUTO CRASH FATAL TO SPANISH PRINCE; Don Gonzalo, 19, Succumbs to Hemophilia After Collision in Austrian Village. INFANTA BEATRIZ DRIVING Swerved Car to Avoid Hitting Bicyclist – Ex-King Present at Son's Bedside" 690:

then no more likely to pass on the gene to their children than carrier females, though all daughters they sire will be carriers and all sons they father will not have haemophilia (unless the mother is a carrier)

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Infection via the tainted factor products had mostly stopped by 1986 by which time viral inactivation methods had largely been put into place, although some products were shown to still be dangerous in 1987.

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has a 50% chance of passing the faulty X-chromosome to her daughter, while an affected father will always pass on the affected gene to his daughters. A son cannot inherit the defective gene from his father.

308:. Those with a mild case of the disease may have symptoms only after an accident or during surgery. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term 747:

If haemophilia is suspected after a child has been born, a blood test can usually confirm the diagnosis. Blood from the umbilical cord can be tested at birth if there's a family history of haemophilia. A

4096: 433:, females are rarely severely affected. Some females with a nonfunctional gene on one of the X chromosomes may be mildly symptomatic. Haemophilia C occurs equally in both sexes and is mostly found in 3845: 4637: 1075: 1373:(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. 513:, and muscles may also occur. Children with mild haemophilia may not have noticeable symptoms for many years. Often, the first sign in very mild haemophiliacs is heavy bleeding from a 497:

is less severe but can lead to damage and requires treatment. Children with mild to moderate haemophilia may not have any signs or symptoms at birth, especially if they do not undergo

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1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years. Today with appropriate treatment, males with haemophilia typically have a near normal

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If a female gives birth to a haemophiliac son, either the female is a carrier for the blood disorder or the haemophilia was the result of a spontaneous mutation. Until modern direct

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Mishne Torah, laws of circumcision, chapter 1 law 18. It explicitly talks about multiple boys who have the same mother, regardless of whether or not they also have the same father.

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Tuddenham EG, Collins P, Yee TT (2012). "Clinical Manifestations and Therapy of Inherited and Acquired Hemophilia". In Marder VJ, Aird WC, Bennett S, Schulman S, White G (eds.).

521:. Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs. 881:

If a person becomes refractory to replacement coagulation factor as a result of high levels of circulating inhibitors, this may be partially overcome with recombinant human

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There is a small risk of these procedures causing problems such as miscarriage or premature labour, so the woman may discuss this with the doctor in charge of her care.

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It was claimed that Rasputin was successful at treating Tsarevich Alexei's haemophilia. At the time, a common treatment administered by professional doctors was to use

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Commercially produced factor concentrates such as "Advate", a recombinant Factor VIII, come as a white powder in a vial which must be mixed with sterile water prior to

874:(inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as 732:

chorionic villus sampling (CVS): a small sample of the placenta is removed from the womb and tested for the haemophilia gene, usually during weeks 11–14 of pregnancy

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Valentino LA, Hakobyan N, Rodriguez N, Hoots WK (November 2007). "Pathogenesis of haemophilic synovitis: experimental studies on blood-induced joint damage".

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Severe complications are much more common in cases of severe and moderate haemophilia. Complications may arise from the disease itself or from its treatment:

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Pool JG, Shannon AE (1965-12-30). "Production of High-Potency Concentrates of Antihemophilic Globulin in a Closed-Bag System: Assay in Vitro and in Vivo".

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infection. The plasma used to create the products was not screened or tested, nor had most of the products been subject to any form of viral inactivation.

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with 1–5% active factor have moderate haemophilia, and those with mild haemophilia have between 5% and 40% of normal levels of active clotting factor.

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Tribuzi, Susanna, Naccarato, Alessia, Pelagalli, Lorella, et al. Acquired Hemophilia A After Hepatic Yttrium-90 Radioembolization: A Case Report.

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occurs in males and less often in females. It is estimated that about 2,500 Canadians have haemophilia A, and about 500 Canadians have haemophilia B.

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is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a

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eMedicine from webMD. Dimitrios P Agaliotis, MD, PhD, FACP, Robert A Zaiden, MD, Fellow, and Saduman Ozturk, PA-C. Updated: 24 November 2009.

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also have a high rate of injuries, but have overall less contact and should be undertaken cautiously and only in consultation with a doctor.

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is often recommended two or three times a week and may continue for life. Rapid treatment of bleeding episodes decreases damage to the body.

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There is no long-term cure. Treatment and prevention of bleeding episodes is done primarily by replacing the missing blood clotting factors.

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Haemophilia A affects about 1 in 5,000–10,000, while haemophilia B affects about 1 in 40,000 males at birth. As haemophilia A and B are both

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for people with haemophilia as these can aggravate clotting difficulties. Also contraindicated are those drugs which have "blood thinning"

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instructs that a boy must not be circumcised if he had two brothers who died due to complications arising from their circumcisions, and

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says that this excluded paternal half-brothers. This may have been due to a concern about hemophilia. The tenth century Arab surgeon

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Peyvandi F, Garagiola I, Young G (9 July 2016). "The past and future of haemophilia: diagnosis, treatments, and its complications".

554: 6040: 2250: 1306: 644:(heavy periods) due to the bleeding tendency. The pattern of inheritance is criss-cross type. This type of pattern is also seen in 4991: 4943: 3502: 1243:, one of Queen Victoria's granddaughters. The haemophilia of Alexei would result in the rise to prominence of the Russian mystic 3595: 3361: 1219:

and, through two of her daughters, Alice and Beatrice, to various royals across the continent, including the royal families of

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to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective.

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Chowdary P, Shapiro S, Makris M, Evans G, Boyce S, Talks K, Dolan G, Reiss U, Phillips M, Riddell A, Peralta MR (2022-07-21).

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Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY, Pasi KJ (December 2017).

1265:, who later became Queen of Spain. Two of her sons were haemophiliacs and both died from minor car accidents. Her eldest son, 1169:

The term "haemophilia" is derived from the term "haemorrhaphilia" which was used in a description of the condition written by

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trauma. In cases of moderate haemophilia symptoms are variable which manifest along a spectrum between severe and mild forms.

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Roosendaal G, Lafeber F (2007). "Prophylactic treatment for prevention of joint disease in hemophilia—cost versus benefit".

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on her other chromosome should express itself to produce the necessary clotting factors, due to X inactivation. Therefore,

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may be used to reduce pain and swelling in an affected joint. In those with severe hemophilia A already receiving FVIII,

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Factor VIII is used in haemophilia A and factor IX in haemophilia B. Factor replacement can be either isolated from

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A pregnant woman with a history of haemophilia in her family can test for the haemophilia gene. Such tests include:

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once they arise. In 2007, a trial comparing on-demand treatment of boys (< 30 months) with haemophilia A with

619:, a female carrying the defect on one of her X-chromosomes may not be affected by it, as the equivalent dominant 197: 3386: 572:

is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation,

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Singer, Isidore; et al., eds. (1901–1906). "Morbidity". The Jewish Encyclopedia. New York: Funk & Wagnalls.

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Mild haemophilia may only be discovered later, usually after an injury or a dental or surgical procedure.

683: 364: 240: 2188:"Diagnosis and care of patients with mild haemophilia: practical recommendations for clinical management" 1432: 247: 5960: 5846: 5819: 5792: 5744: 5698: 5393: 5064: 5054: 4872: 3821: 2761:"First Case of Acquired Hemophilia B in a Patient with HIV Infection: Case Report and Literature Review" 1236: 1163: 1158:

In 1924, a Finnish doctor discovered a hereditary bleeding disorder similar to haemophilia localised in

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from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints,

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Up until late 1985 many people with haemophilia received clotting factor products that posed a risk of

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amniocentesis: a sample of amniotic fluid is taken for testing, usually during weeks 15–20 of pregnancy

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that high doses did better than low doses. It is not currently an accepted treatment for haemophilia.

1269:, died at the age of 31 from internal bleeding after his car hit a telephone booth. Her youngest son, 1070:

Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from

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The method for the production of an antihaemophilic factor was discovered by Judith Graham Pool from

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As with all genetic disorders, it is also possible for a human to acquire it spontaneously through

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Benson G, Auerswald G, Dolan G, Duffy A, Hermans C, Ljung R, Morfini M, Šalek SZ (November 2018).

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Thalji N, Camire RM (September 2013). "Parahemophilia: new insights into factor v deficiency".

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In both haemophilia A and B, there is spontaneous bleeding but a normal bleeding time, normal

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will also be able to identify whether a child has haemophilia A or B, and how severe it is.

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Reviewed by: Larissa Hirsch, MD 2007. kidshealth.org by Nemours. Retrieved 23 January 2010.

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in 1964, and approved for commercial use in 1971 in the United States under the name

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Franchini M, Mannucci PM (December 2013). "Acquired haemophilia A: a 2013 update".

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Franchini M, Mannucci PM (December 2013). "Acquired haemophilia A: a 2013 update".

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to occur during early development, or haemophilia may develop later in life due to

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with an average lifespan approximately 10 years shorter than an unaffected male.

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300,000 per year. The author of an editorial published in the same issue of the

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Nicholas and Alexandra: The Classic Account of the Fall of the Romanov Dynasty

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Also contraindicated are activities with a high likelihood of trauma, such as

960: 871: 749: 415: 352: 289: 278: 4308: 3998: 3933: 3677: 3253: 3179:"Data Collection - WFH Annual Global Survey - World Federation of Hemophilia" 2995: 2987: 2938: 2786: 2519: 1888: 1841: 536:, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb. 418:

to the clotting factors which makes treatment more difficult. The medication

5990: 5732: 5727: 5591: 5569: 5444: 5408: 5145: 5109: 4732: 4589: 4497: 4493: 3756: 3731: 2759:

Páramo L, Enciso Olivera LJ, Noreña I, Amaya MA, Santacruz JC (2019-03-05).

2740: 2495: 1818:"Bioengineered factor Xa as a potential new strategy for hemophilia therapy" 1370: 1083: 1079: 1031: 996: 793: 547: 514: 384: 360: 336: 4362: 4316: 4267: 4232: 4223: 4047: 3963: 3941: 3765: 3685: 3554: 3486: 3261: 3164: 3129: 3087: 3054:"Management of Haemophilia in Developing Countries: Challenges and Options" 3013: 2956: 2891: 2804: 2527: 2511: 2377: 2342: 2221: 2126: 2025: 1973: 1923: 1896: 1849: 1794: 1786: 1756: 4299: 4282: 4213: 4154: 4079:"Commemoration of the Tainted Blood Tragedy – Canadian Hemophilia Society" 4006: 17: 5496: 5273: 5160: 5114: 5099: 4958: 4789: 4647: 4259: 3186: 3120: 3103: 2930: 2883: 2203: 1965: 1313: 1159: 1071: 1043: 980: 808: 789: 676: 506: 391: 372: 348: 309: 297: 293: 158: 4339:"Novel gene therapy could reduce bleeding risk for haemophilia patients" 4133:

Lowe GD (August 1987). "Haemophilia, blood products and HIV infection".

3156: 2777: 945:

may be given along with clotting factors to prevent breakdown of clots.

5975: 5435: 5403: 5296: 5119: 4246:

van den Berg HM (December 2017). "A Cure for Hemophilia within Reach".

2972:"Factor VIII inhibitors in hemophilia A: rationale and latest evidence" 2016: 1999: 1305: 1251: 1228: 1038:

should be avoided by people with haemophilia. Other active sports like

992: 976: 952: 875: 672:, is available to pregnant women who may be carriers of the condition. 518: 458: 313: 4457: 1833: 5104: 4488: 4469: 4414:"FDA Approves First Gene Therapy for Adults with Severe Hemophilia A" 4283:"Phase 1–2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B" 3924: 3899: 3383: 1121: 1086:

and obstruction of air or blood flow due to soft tissue haemorrhage.

1027: 1023: 620: 573: 502: 490: 441:. The difference between haemophilia A and B was determined in 1952. 403: 399: 376: 270: 253: 3621:

Chapter 38 Coagulation Factors V and VIII by GC White and GE Gilbert

3520: 1817: 1239:, famously had haemophilia, which he had inherited from his mother, 4603: 926:

limited or no access to commercial blood clotting factor products.

218:

1 in 7,500 males (haemophilia A), 1 in 40,000 males (haemophilia B)

1304: 1198: 841: 596: 581: 486: 448: 4116:"Iraqis Infected by H.I.V.-Tainted Blood Try New Tool: A Lawsuit" 3634:. 2003. Eds. Robert I. Handin, Samuel E. Lux, Thomas P. Stossel. 3447:

Hemostasis and Thrombosis: Basic Principles and Clinical Practice

2000:"Acquired hemophilia: a case report and review of the literature" 4537: 4534: 4531: 344: 5246: 4619: 3732:"Genotype Analysis Identifies the Cause of the 'Royal Disease'" 3500:

DIGITISED EARLY PAPERS AND BOOKS ON HUMAN AND MEDICAL GENETICS

1325: 910: 100: 3509:

Genetics and Medicine Historical Network, Cardiff University.

339:. They are typically inherited from one's parents through an 1003:

should not be taken because they are well known to have the

5242: 1873:"Traumatic Hyphema and Factor XI Deficiency (Hemophilia C)" 124: 121: 106: 901:

any sort are difficult to obtain in developing countries.

3632:

Blood: principles and practice of hematology: 2nd edition

2551:"How Hemophilia is Inherited | Hemophilia | NCBDDD | CDC" 1162:, southwest of Finland. This bleeding disorder is called 792:

genetic disorder involving a lack of functional clotting

422:

may be used in those with mild haemophilia A. Studies of

115: 3403:"Otto JC. The Medical Repository. 1803; Vol VI (1): 1–4" 3300:

Playing it Safe: Bleeding Disorders, Sports and Exercise

1120:

The excessive bleeding was known to ancient people. The

4197:"AAV5-Factor VIII Gene Transfer in Severe Hemophilia A" 2496:"Historical review on genetic analysis in hemophilia A" 2494:

Oldenburg J, Pezeshkpoor B, Pavlova A (November 2014).

1595:

The Encyclopedia of Genetic Disorders and Birth Defects

913:. Preventative treatment, however, resulted in average 355:

forming against a clotting factor. Other types include

2850:

2017;9(12):344–345. doi:10.1213/XAA.0000000000000611.

1312:

was an American haemophiliac who became infected with

937:(DDAVP) may be used in those with mild haemophilia A. 896:(CHO) tissue culture cells and involve little, if any 807:

is a mild and rare form and is due to a deficiency in

3701:"Case Closed: Famous Royals Suffered From Hemophilia" 1361:

In July 2022 results of a gene therapy candidate for

112: 4447: 1998:

Mulliez SM, Vantilborgh A, Devreese KM (June 2014).

1211:

and thus is sometimes known as 'the royal disease'.

558:

from blood transfusions that are given as treatment.

501:. Their first symptoms are often frequent and large 118: 5933: 5871: 5632: 5560: 5515: 5424: 5295: 5280: 5135: 5092: 5013: 4957: 4899: 4892: 4885: 4813: 4775: 4688: 4681: 4569: 4451: 4442: 3898:Pool JG, Hershgold EJ, Pappenhagen AR (July 1964). 3058:

Indian Journal of Hematology and Blood Transfusions

2471:"Information for Women | Hemophilia | NCBDDD | CDC" 870:, or a combination of the two. Some people develop 214: 203: 193: 183: 172: 164: 151: 139: 109: 103: 97: 85: 58: 53: 3475:Sydsvenska Medicinhistoriska Sallskapets Arsskrift 3232:Boggio LN, Green D (2001). "Acquired Hemophilia". 2425:"Hemophilia and Pregnancy – Hemophilia News Today" 1365:called FLT180 were announced, it works using an 1215:passed the mutation for haemophilia B to her son 1181:, discovered anti-haemophilic globulin. In 1947, 4067:. Japan Center for International Exchange. 2004. 3730:Evgeny I. Rogaev, et al. (8 October 2009). 3032:GEN – Genetic Engineering and Biotechnology News 2819:"Hemophilia B: MedlinePlus Medical Encyclopedia" 2709:"Hemophilia A: MedlinePlus Medical Encyclopedia" 1433:"What Are the Signs and Symptoms of Hemophilia?" 796:. Haemophilia C is not completely recessive, as 32:"Hemophiliac" redirects here. For the band, see 3473:Nilsson IM (1994). "Haemophilia—then and now". 3234:Reviews in Clinical and Experimental Hematology 1918:, Treasure Island (FL): StatPearls Publishing, 1871:Al-Fadhil N, Pathare A, Ganesh A (2001-10-01). 1638:. U.S. Centers for Disease Control. 12 May 2020 1103: 818:A non-genetic form of haemophilia is caused by 4363:"Transformational therapy cures haemophilia B" 3818:Aspirin: The Remarkable Story of a Wonder Drug 2703: 2701: 2004:International Journal of Laboratory Hematology 1257:In Spain, Queen Victoria's youngest daughter, 1177:. In 1937, Patek and Taylor, two doctors from 664:is recommended for families with haemophilia. 615:. Since the mutations causing the disease are 439:was common within the royal families of Europe 327:, which occurs due to low amounts of clotting 5258: 4631: 3654:"The history of haemophilia – a short review" 2309:"Musculoskeletal Complications of Hemophilia" 2063: 1468: 1466: 1464: 1462: 1460: 1458: 632:is not masked and the disorder will develop. 335:, which occurs due to low levels of clotting 8: 4062:"Japan's Response to the Spread of HIV/AIDS" 2735: 2733: 2061: 2059: 2057: 2055: 2053: 2051: 2049: 2047: 2045: 2043: 1548: 1546: 1544: 1542: 1427: 1425: 1423: 1421: 1074:to HIV/AIDS acquired through treatment with 4178:"RCMP lay 32 charges in tainted-blood case" 3339:Frequently Asked Questions About Hemophilia 3309:". Booklet. National Hemophilia Foundation. 1768: 1766: 1686: 1684: 1682: 1680: 1267:Prince Alfonso of Spain, Prince of Asturias 5547:Reproductive endocrinology and infertility 5292: 5265: 5251: 5243: 4896: 4889: 4685: 4638: 4624: 4616: 4448: 3468: 3466: 2555:Centers for Disease Control and Prevention 2475:Centers for Disease Control and Prevention 2100: 2098: 2096: 2094: 1993: 1991: 800:individuals also show increased bleeding. 453:An illustration of a woman with hemophilia 69: 50: 5888:Bachelor of Medicine, Bachelor of Surgery 4298: 4222: 4212: 4037: 3923: 3755: 3544: 3119: 3102:K, Soucie JM, Austin H, Evatt BL (2007). 3077: 3003: 2946: 2873: 2794: 2776: 2332: 2211: 2015: 1955: 1910:Chaudhry R, Usama SM, Babiker HM (2022), 1746: 1721:Franchini M, Mannucci PM (October 2011). 1592:Wynbrandt J, Ludman MD (1 January 2009). 1587: 1585: 1583: 1581: 1579: 1511: 1509: 1507: 1505: 1503: 1501: 1499: 323:There are two main types of haemophilia: 1727:British Journal of Clinical Pharmacology 991:. For instance, medicines which contain 760:There are several types of haemophilia: 296:for a longer time after an injury, easy 27:Genetic disease involving blood clotting 3275: 3273: 3271: 2585:"Haemophilia – Diagnosis – NHS Choices" 2243: 2241: 2239: 2237: 2235: 2233: 2231: 1417: 1396:Purpura secondary to clotting disorders 1301:Contaminated haemophilia blood products 1173:in 1828, while he was a student at the 822:against factor VIII and so is known as 2079:from the original on 17 September 2016 1564:from the original on 15 September 2016 1443:from the original on 17 September 2016 2578: 2576: 2574: 2572: 2570: 2500:Seminars in Thrombosis and Hemostasis 2446:Kumar & Clark's Clinical Medicine 1775:Seminars in Thrombosis and Hemostasis 1702:from the original on 8 September 2016 1207:Haemophilia has featured prominently 7: 6026: 5787:Physical medicine and rehabilitation 3364:from the original on 12 October 2007 1598:. Infobase Publishing. p. 194. 390:Prevention may occur by removing an 371:, which occurs due to low levels of 359:, which occurs due to low levels of 6036: 3846:"Tragic Drama Under the Miami Moon" 3358:"U.S. National Library of Medicine" 2448:(7th ed.). Saunders Elsevier. 1612:from the original on 8 January 2014 1527:from the original on 27 August 2016 1484:from the original on 4 October 2016 1152:The New England Journal of Medicine 1058:Like most aspects of the disorder, 284:that impairs the body's ability to 5923:Medical Scientist Training Program 2976:Therapeutic Advances in Hematology 2676:"What Is Hemophilia? – NHLBI, NIH" 1912:"Physiology, Coagulation Pathways" 1353:In those with severe haemophilia, 25: 4418:U.S. Food and Drug Administration 4392:U.S. Food and Drug Administration 4114:Zielbauer Pv (4 September 2006). 2913:Mannucci PM, Franchini M (2017). 1665:from the original on 6 March 2008 1381:contains a gene for Factor VIII. 803:The type of haemophilia known as 555:Transfusion transmitted infection 6055: 6045: 6035: 6025: 6016: 6015: 4992:platelet storage pool deficiency 4944:Heparin-induced thrombocytopenia 4026:Trans. Am. Clin. Climatol. Assoc 3699:Michael Price (8 October 2009). 3328:Frequently Asked Questions. 2005 3246:10.1046/j.1468-0734.2001.00049.x 2686:from the original on 2 July 2016 2370:10.1111/j.1365-2516.2007.01534.x 1739:10.1111/j.1365-2125.2010.03899.x 811:. This type can be inherited or 93: 6056: 4287:New England Journal of Medicine 3979:New England Journal of Medicine 3409:from the original on 2014-09-04 3337:World Federation of Hemophilia 2829:from the original on 2016-07-05 2719:from the original on 2016-07-05 2595:from the original on 2017-01-01 2198:(6). Blood Transfus.: 535–544. 2167:Key facts: what is haemophilia? 2157:National Hemophilia Foundation. 1203:Haemophilia in European royalty 1195:Haemophilia in European royalty 611:, and males have one X and one 607:Typically, females possess two 5913:Doctor of Osteopathic Medicine 5347:Oral and maxillofacial surgery 4711:Activated protein C resistance 4443:World Federation of Hemophilia 3670:10.1016/j.thromres.2013.10.020 3319:World Federation of Hemophilia 2297:Mayo Clinic Staff. 16 May 2009 1554:"How Is Hemophilia Diagnosed?" 1406:World Federation of Hemophilia 1369:(AAV) to restore the clotting 1263:Victoria Eugenie of Battenberg 602:X-linked recessive inheritance 414:. Up to 20% of people develop 402:before transferring it to the 318:altered level of consciousness 277: 'love of'), is a mostly 1: 2307:Rodriguez-Merchan EC (2010). 2119:10.1016/s0140-6736(15)01123-x 1659:"Online Etymology Dictionary" 437:. In the 1800s haemophilia B 6087:X-linked recessive disorders 5893:Bachelor of Medical Sciences 5660:Neurosurgical anesthesiology 4805:Trousseau sign of malignancy 3582:10.1111/hae.2012.18.issue-s6 3382:Canadian Hemophilia Society 2069:"How Is Hemophilia Treated?" 890:Food and Drug Administration 485:where blood enters into the 431:X-linked recessive disorders 5125:Nonthrombocytopenic purpura 4701:Antithrombin III deficiency 3991:10.1056/NEJM196512302732701 3596:"The History of hemophilia" 3537:10.1056/NEJM181307010020302 3280:How to Deal with Hemophilia 2624:"Chorionic villus sampling" 1822:Expert Review of Hematology 1318:contaminated blood products 1076:contaminated blood products 475:partial thromboplastin time 426:are in early human trials. 300:, and an increased risk of 6108: 5080:Congenital afibrinogenemia 4984:Glanzmann's thrombasthenia 4748:Essential thrombocythaemia 4147:10.1177/003693308703200404 4032:: 61–73, discussion 74–5. 2970:Witmer C, Young G (2013). 2862:Thrombosis and Haemostasis 2739:Prasad Mathew, MBBS, DCH, 1944:Thrombosis and Haemostasis 1298: 1192: 263: 260: 'blood' and 246: 38: 31: 6011: 5196:Gastrointestinal bleeding 4998:Hermansky–Pudlak syndrome 4767:Antiphospholipid syndrome 4658: 3449:. Wolters Kluwer Health. 3070:10.1007/s12288-015-0562-x 3052:Ghosh K, Ghosh K (2016). 2444:Kumar P, Clark M (2009). 2325:10.1007/s11420-009-9140-9 1877:Archives of Ophthalmology 1692:"What Causes Hemophilia?" 1247:, at the imperial court. 943:epsilon aminocaproic acid 708:bleeds or easy bruising. 576:, loss of consciousness, 343:carrying a nonfunctional 292:. This results in people 198:Preimplantation screening 77: 68: 5847:Transplantation medicine 5738:Clinical neurophysiology 5655:Obstetric anesthesiology 5575:Interventional radiology 5335:Digestive system surgery 5166:Subconjunctival bleeding 5156:Intracranial haemorrhage 4972:Bernard–Soulier syndrome 4935:Upshaw–Schulman syndrome 4909:Thrombocytopenic purpura 4738:Sticky platelet syndrome 2988:10.1177/2040620712464509 2741:eMedicine – Hemophilia C 2288:Hemophilia Complications 2176:The Haemophilia Society. 1816:Camire RM (2012-01-01). 1164:"Von Willebrand Disease" 569:Intracranial haemorrhage 39:Not to be confused with 5718:Intensive care medicine 5692:Mass gathering medicine 5537:Maternal–fetal medicine 3757:10.1126/science.1180660 2654:National Health Service 2628:National Health Service 1007:of prolonged bleeding. 5310:Cardiothoracic surgery 5070:Factor XIII deficiency 5050:Hypoprothrombinemia/II 5045:von Willebrand disease 5003:Gray platelet syndrome 3707:. AAAS. Archived from 2512:10.1055/s-0034-1395161 1787:10.1055/s-0033-1349224 1401:Von Willebrand disease 1367:adeno-associated virus 1321: 1235:, the son and heir of 1204: 1107: 907:prophylactic treatment 888:In early 2008, the US 851: 824:acquired haemophilia A 782:acquired haemophilia B 778:acquired haemophilia A 604: 534:Deep internal bleeding 454: 365:Von Willebrand disease 302:bleeding inside joints 288:, a process needed to 207:Replace missing blood 78:A drawing of clotting 5961:Personalized medicine 5820:Reproductive medicine 5745:Occupational medicine 5699:Evolutionary medicine 5065:Factor XII deficiency 5055:Factor VII deficiency 4873:Renal vein thrombosis 4300:10.1056/NEJMoa2119913 4214:10.1056/NEJMoa1708483 3850:www.biscaynetimes.com 3822:Bloomsbury Publishing 3705:ScienceNOW Daily News 2848:A&A Case Reports. 1632:"What Is Hemophilia?" 1474:"What Is Hemophilia?" 1308: 1202: 894:Chinese hamster ovary 845: 600: 452: 5981:Traditional medicine 5941:Alternative medicine 5808:Addiction psychiatry 5622:Transfusion medicine 5617:Medical microbiology 5532:Gynecologic oncology 5384:Reproductive surgery 4821:Deep vein thrombosis 4716:Protein S deficiency 4706:Protein C deficiency 4260:10.1056/NEJMe1713888 4103:. 30 September 2002. 3121:10.1056/NEJMoa067659 2931:10.2450/2016.0030-16 2884:10.1160/TH13-05-0363 2204:10.2450/2017.0150-17 1966:10.1160/TH13-05-0363 1288:Cryoprecipitated AHF 1175:University of Zurich 1116:Scientific discovery 495:subcutaneous tissues 398:it, and testing the 381:autoimmune disorders 6003:History of medicine 5986:Veterinary medicine 5793:Preventive medicine 5645:Adolescent medicine 5487:Infectious diseases 5186:Pulmonary haematoma 5060:Factor X deficiency 4949:May–Hegglin anomaly 4726:Prothrombin G20210A 3916:1964Natur.203..312P 3816:Jeffreys D (2008). 3748:2009Sci...326..817R 3658:Thrombosis Research 3519:Hay J (July 1813). 3405:. Genmedhist.info. 3157:10.1056/NEJMe078098 2778:10.7759/cureus.4179 2248:Hemophilia Overview 1523:. August 26, 2014. 1295:Blood contamination 1283:Stanford University 1209:in European royalty 1082:infections causing 662:genetic counselling 412:recombinant methods 157:Easy and prolonged 5951:Molecular oncology 5908:Doctor of Medicine 5898:Master of Medicine 5815:Radiation oncology 5687:Emergency medicine 5640:Addiction medicine 5607:Clinical chemistry 5602:Clinical pathology 5394:Transplant surgery 5352:Orthopedic surgery 5330:Colorectal surgery 5093:Signs and symptoms 4868:Pulmonary embolism 4673:Bleeding diathesis 4570:External resources 4182:The Globe and Mail 4120:The New York Times 4085:. 17 October 2017. 3879:The New York Times 3787:Massie RK (2011). 3711:on 12 October 2009 3652:Schramm W (2014). 3626:2017-09-11 at the 3505:2011-07-21 at the 3389:2008-02-13 at the 3344:2008-06-12 at the 3324:2014-02-01 at the 3305:2010-09-14 at the 3285:2007-02-14 at the 2746:2008-12-02 at the 2549:CDC (2022-08-01). 2469:CDC (2019-04-19). 2293:2010-01-21 at the 2267:Medical News Today 2253:2009-09-27 at the 2172:2009-05-23 at the 2153:2010-02-13 at the 2017:10.1111/ijlh.12210 1517:"Hemophilia Facts" 1322: 1205: 1179:Harvard University 1110:John C. Otto, 1803 852: 651:A mother who is a 617:X-linked recessive 605: 517:, an accident, or 455: 445:Signs and symptoms 34:Hemophiliac (band) 6069: 6068: 5903:Master of Surgery 5867: 5866: 5852:Tropical medicine 5798:Prison healthcare 5713:Hospital medicine 5677:Disaster medicine 5667:Aviation medicine 5482:Hospital medicine 5389:Surgical oncology 5374:Pediatric surgery 5368: 5315:Endocrine surgery 5240: 5239: 5236: 5235: 5088: 5087: 5075:Dysfibrinogenemia 4959:Platelet function 4881: 4880: 4760:Purpura fulminans 4613: 4612: 4254:(26): 2592–2593. 4207:(26): 2519–2530. 4083:www.hemophilia.ca 4020:White GC (2010). 3985:(27): 1443–1447. 3831:978-1-59691-816-0 3802:978-0-307-78847-4 3664:(Suppl 1): S4–9. 3640:978-0-7817-1993-3 3525:N Engl J Med Surg 2919:Blood Transfusion 2680:www.nhlbi.nih.gov 2455:978-0-7020-2993-6 2364:(Suppl 3): 10–3. 2192:Blood Transfusion 2113:(10040): 187–97. 2075:. July 13, 2013. 1883:(10): 1546–1547. 1834:10.1586/ehm.12.13 1698:. July 13, 2013. 1605:978-1-4381-2095-9 1560:. July 13, 2013. 1480:. July 13, 2013. 1439:. July 13, 2013. 1261:, had a daughter 1259:Princess Beatrice 1241:Empress Alexandra 1183:Alfredo Pavlovsky 1020:American football 968:Contraindications 627:females are just 562:Adverse reactions 479:Internal bleeding 222: 221: 185:Diagnostic method 48:Medical condition 16:(Redirected from 6099: 6059: 6058: 6049: 6039: 6038: 6029: 6028: 6019: 6018: 5723:Medical genetics 5708:General practice 5585:Nuclear medicine 5460:Gastroenterology 5416:Vascular surgery 5366: 5293: 5267: 5260: 5253: 5244: 5181:Haemopericardium 4901:Thrombocytopenia 4897: 4890: 4846:Lowenberg's sign 4696:Clotting factors 4686: 4640: 4633: 4626: 4617: 4449: 4430: 4429: 4427: 4425: 4410: 4404: 4403: 4401: 4399: 4394:. 4 January 2023 4384: 4378: 4377: 4375: 4374: 4359: 4353: 4352: 4350: 4349: 4335: 4329: 4328: 4302: 4278: 4272: 4271: 4243: 4237: 4236: 4226: 4216: 4192: 4186: 4185: 4173: 4167: 4166: 4130: 4124: 4123: 4111: 4105: 4104: 4093: 4087: 4086: 4075: 4069: 4068: 4066: 4058: 4052: 4051: 4041: 4017: 4011: 4010: 3974: 3968: 3967: 3960: 3954: 3953: 3927: 3925:10.1038/203312a0 3895: 3889: 3888: 3886: 3885: 3871: 3865: 3864: 3862: 3861: 3852:. Archived from 3842: 3836: 3835: 3813: 3807: 3806: 3784: 3778: 3777: 3759: 3727: 3721: 3720: 3718: 3716: 3696: 3690: 3689: 3649: 3643: 3618: 3612: 3611: 3609: 3607: 3602:on 31 March 2009 3598:. Archived from 3592: 3586: 3585: 3565: 3559: 3558: 3548: 3516: 3510: 3497: 3491: 3490: 3470: 3461: 3460: 3442: 3436: 3433: 3427: 3424: 3418: 3417: 3415: 3414: 3399: 3393: 3380: 3374: 3373: 3371: 3369: 3354: 3348: 3335: 3329: 3316: 3310: 3296: 3290: 3277: 3266: 3265: 3229: 3223: 3222: 3220: 3219: 3204: 3198: 3197: 3195: 3194: 3185:. Archived from 3175: 3169: 3168: 3140: 3134: 3133: 3123: 3098: 3092: 3091: 3081: 3049: 3043: 3042: 3040: 3039: 3024: 3018: 3017: 3007: 2967: 2961: 2960: 2950: 2910: 2904: 2903: 2877: 2857: 2851: 2844: 2838: 2837: 2835: 2834: 2815: 2809: 2808: 2798: 2780: 2756: 2750: 2737: 2728: 2727: 2725: 2724: 2705: 2696: 2695: 2693: 2691: 2672: 2666: 2665: 2663: 2661: 2646: 2640: 2639: 2637: 2635: 2620: 2614: 2610: 2604: 2603: 2601: 2600: 2580: 2565: 2564: 2562: 2561: 2546: 2540: 2539: 2491: 2485: 2484: 2482: 2481: 2466: 2460: 2459: 2441: 2435: 2434: 2432: 2431: 2420: 2414: 2413: 2411: 2410: 2396: 2390: 2389: 2353: 2347: 2346: 2336: 2304: 2298: 2285: 2279: 2275: 2269: 2264: 2258: 2245: 2226: 2225: 2215: 2183: 2177: 2164: 2158: 2145: 2139: 2138: 2102: 2089: 2088: 2086: 2084: 2065: 2038: 2037: 2019: 1995: 1986: 1985: 1959: 1939: 1933: 1932: 1931: 1930: 1907: 1901: 1900: 1868: 1862: 1861: 1813: 1807: 1806: 1770: 1761: 1760: 1750: 1718: 1712: 1711: 1709: 1707: 1688: 1675: 1674: 1672: 1670: 1657:Douglas Harper. 1654: 1648: 1647: 1645: 1643: 1628: 1622: 1621: 1619: 1617: 1589: 1574: 1573: 1571: 1569: 1550: 1537: 1536: 1534: 1532: 1513: 1494: 1493: 1491: 1489: 1470: 1453: 1452: 1450: 1448: 1429: 1245:Grigori Rasputin 1237:Tsar Nicholas II 1233:Tsarevich Alexei 1189:European royalty 1142:colour blindness 1138:John Conrad Otto 1111: 957:physical therapy 838:Clotting factors 724:During pregnancy 715:Before pregnancy 666:Prenatal testing 646:colour blindness 515:dental procedure 473:, but prolonged 467:prothrombin time 286:make blood clots 282:genetic disorder 274: 267: 257: 250: 237:American English 209:clotting factors 131: 130: 127: 126: 123: 120: 117: 114: 111: 108: 105: 102: 99: 73: 51: 21: 6107: 6106: 6102: 6101: 6100: 6098: 6097: 6096: 6072: 6071: 6070: 6065: 6007: 5996:Chief physician 5929: 5874: 5863: 5857:Travel medicine 5842:Sports medicine 5825:Sexual medicine 5765:Palliative care 5760:Pain management 5704:Family medicine 5682:Diving medicine 5628: 5556: 5518: 5511: 5427: 5420: 5379:Plastic surgery 5325:General surgery 5305:Cardiac surgery 5286: 5284: 5276: 5271: 5241: 5232: 5206:Haemoperitoneum 5131: 5084: 5015:Clotting factor 5009: 4953: 4877: 4826:Bancroft's sign 4809: 4800:Virchow's triad 4771: 4721:Factor V Leiden 4677: 4654: 4644: 4614: 4609: 4608: 4565: 4564: 4460: 4439: 4434: 4433: 4423: 4421: 4412: 4411: 4407: 4397: 4395: 4386: 4385: 4381: 4372: 4370: 4361: 4360: 4356: 4347: 4345: 4337: 4336: 4332: 4280: 4279: 4275: 4248:N. Engl. J. Med 4245: 4244: 4240: 4201:N. Engl. J. Med 4194: 4193: 4189: 4175: 4174: 4170: 4132: 4131: 4127: 4113: 4112: 4108: 4095: 4094: 4090: 4077: 4076: 4072: 4064: 4060: 4059: 4055: 4019: 4018: 4014: 3976: 3975: 3971: 3962: 3961: 3957: 3897: 3896: 3892: 3883: 3881: 3873: 3872: 3868: 3859: 3857: 3844: 3843: 3839: 3832: 3824:. p. 121. 3815: 3814: 3810: 3803: 3795:. p. 532. 3786: 3785: 3781: 3729: 3728: 3724: 3714: 3712: 3698: 3697: 3693: 3651: 3650: 3646: 3628:Wayback Machine 3619: 3615: 3605: 3603: 3594: 3593: 3589: 3567: 3566: 3562: 3518: 3517: 3513: 3507:Wayback Machine 3498: 3494: 3472: 3471: 3464: 3457: 3444: 3443: 3439: 3434: 3430: 3425: 3421: 3412: 3410: 3401: 3400: 3396: 3391:Wayback Machine 3381: 3377: 3367: 3365: 3356: 3355: 3351: 3346:Wayback Machine 3336: 3332: 3326:Wayback Machine 3317: 3313: 3307:Wayback Machine 3297: 3293: 3287:Wayback Machine 3278: 3269: 3231: 3230: 3226: 3217: 3215: 3206: 3205: 3201: 3192: 3190: 3177: 3176: 3172: 3145:N. Engl. J. Med 3142: 3141: 3137: 3108:N. Engl. J. Med 3100: 3099: 3095: 3051: 3050: 3046: 3037: 3035: 3026: 3025: 3021: 2969: 2968: 2964: 2912: 2911: 2907: 2875:10.1.1.684.7962 2859: 2858: 2854: 2845: 2841: 2832: 2830: 2823:www.nlm.nih.gov 2817: 2816: 2812: 2758: 2757: 2753: 2748:Wayback Machine 2738: 2731: 2722: 2720: 2713:www.nlm.nih.gov 2707: 2706: 2699: 2689: 2687: 2674: 2673: 2669: 2659: 2657: 2656:. 17 April 2019 2650:"Amniocentesis" 2648: 2647: 2643: 2633: 2631: 2622: 2621: 2617: 2611: 2607: 2598: 2596: 2582: 2581: 2568: 2559: 2557: 2548: 2547: 2543: 2493: 2492: 2488: 2479: 2477: 2468: 2467: 2463: 2456: 2443: 2442: 2438: 2429: 2427: 2422: 2421: 2417: 2408: 2406: 2398: 2397: 2393: 2355: 2354: 2350: 2306: 2305: 2301: 2295:Wayback Machine 2286: 2282: 2276: 2272: 2265: 2261: 2255:Wayback Machine 2246: 2229: 2185: 2184: 2180: 2174:Wayback Machine 2165: 2161: 2155:Wayback Machine 2148:Types of Bleeds 2146: 2142: 2104: 2103: 2092: 2082: 2080: 2067: 2066: 2041: 1997: 1996: 1989: 1957:10.1.1.684.7962 1941: 1940: 1936: 1928: 1926: 1909: 1908: 1904: 1870: 1869: 1865: 1815: 1814: 1810: 1772: 1771: 1764: 1720: 1719: 1715: 1705: 1703: 1690: 1689: 1678: 1668: 1666: 1656: 1655: 1651: 1641: 1639: 1630: 1629: 1625: 1615: 1613: 1606: 1591: 1590: 1577: 1567: 1565: 1552: 1551: 1540: 1530: 1528: 1515: 1514: 1497: 1487: 1485: 1472: 1471: 1456: 1446: 1444: 1431: 1430: 1419: 1414: 1387: 1351: 1346: 1303: 1297: 1279: 1271:Infante Gonzalo 1197: 1191: 1171:Friedrich Hopff 1118: 1113: 1109: 1101: 1092: 1065:quality of life 1060:life expectancy 1056: 1001:naproxen sodium 985:contraindicated 970: 939:Tranexamic acid 932: 840: 832: 805:parahaemophilia 774:parahaemophilia 758: 745: 726: 717: 705: 696: 658:Genetic testing 595: 527: 457:Characteristic 447: 369:parahaemophilia 229:British English 135: 96: 92: 49: 44: 37: 28: 23: 22: 15: 12: 11: 5: 6105: 6103: 6095: 6094: 6089: 6084: 6074: 6073: 6067: 6066: 6064: 6063: 6053: 6043: 6033: 6023: 6012: 6009: 6008: 6006: 6005: 6000: 5999: 5998: 5988: 5983: 5978: 5973: 5968: 5963: 5958: 5953: 5948: 5943: 5937: 5935: 5934:Related topics 5931: 5930: 5928: 5927: 5926: 5925: 5915: 5910: 5905: 5900: 5895: 5890: 5885: 5883:Medical school 5879: 5877: 5869: 5868: 5865: 5864: 5862: 5861: 5860: 5859: 5849: 5844: 5839: 5837:Sleep medicine 5834: 5833: 5832: 5822: 5817: 5812: 5811: 5810: 5800: 5795: 5790: 5784: 5779: 5778: 5777: 5767: 5762: 5757: 5752: 5747: 5742: 5741: 5740: 5730: 5725: 5720: 5715: 5710: 5701: 5696: 5695: 5694: 5684: 5679: 5674: 5669: 5664: 5663: 5662: 5657: 5650:Anesthesiology 5647: 5642: 5636: 5634: 5630: 5629: 5627: 5626: 5625: 5624: 5619: 5614: 5609: 5604: 5599: 5589: 5588: 5587: 5582: 5580:Neuroradiology 5577: 5566: 5564: 5558: 5557: 5555: 5554: 5549: 5544: 5539: 5534: 5529: 5523: 5521: 5517:Obstetrics and 5513: 5512: 5510: 5509: 5504: 5499: 5494: 5489: 5484: 5479: 5474: 5469: 5468: 5467: 5457: 5452: 5447: 5442: 5432: 5430: 5422: 5421: 5419: 5418: 5413: 5412: 5411: 5401: 5399:Trauma surgery 5396: 5391: 5386: 5381: 5376: 5371: 5370: 5369: 5362:Otolaryngology 5359: 5354: 5349: 5344: 5339: 5338: 5337: 5332: 5322: 5317: 5312: 5307: 5301: 5299: 5290: 5288:subspecialties 5278: 5277: 5272: 5270: 5269: 5262: 5255: 5247: 5238: 5237: 5234: 5233: 5231: 5230: 5229: 5228: 5220: 5219: 5218: 5216:Haematosalpinx 5213: 5208: 5203: 5198: 5190: 5189: 5188: 5183: 5178: 5170: 5169: 5168: 5163: 5158: 5153: 5148: 5139: 5137: 5133: 5132: 5130: 5129: 5128: 5127: 5117: 5112: 5107: 5102: 5096: 5094: 5090: 5089: 5086: 5085: 5083: 5082: 5077: 5072: 5067: 5062: 5057: 5052: 5047: 5042: 5041: 5040: 5035: 5030: 5019: 5017: 5011: 5010: 5008: 5007: 5006: 5005: 5000: 4988: 4987: 4986: 4976: 4975: 4974: 4963: 4961: 4955: 4954: 4952: 4951: 4946: 4940: 4939: 4938: 4937: 4932: 4922: 4921: 4920: 4918:Evans syndrome 4905: 4903: 4894: 4887: 4883: 4882: 4879: 4878: 4876: 4875: 4870: 4865: 4864: 4863: 4858: 4853: 4851:Peabody's sign 4848: 4843: 4838: 4833: 4828: 4817: 4815: 4811: 4810: 4808: 4807: 4802: 4797: 4792: 4787: 4781: 4779: 4773: 4772: 4770: 4769: 4764: 4763: 4762: 4752: 4751: 4750: 4745: 4743:Thrombocytosis 4740: 4730: 4729: 4728: 4723: 4718: 4713: 4708: 4703: 4692: 4690: 4683: 4679: 4678: 4676: 4675: 4670: 4665: 4659: 4656: 4655: 4645: 4643: 4642: 4635: 4628: 4620: 4611: 4610: 4607: 4606: 4597: 4586: 4574: 4573: 4571: 4567: 4566: 4563: 4562: 4551: 4540: 4523: 4515: 4500: 4481: 4461: 4456: 4455: 4453: 4452:Classification 4446: 4445: 4438: 4437:External links 4435: 4432: 4431: 4420:. 30 June 2023 4405: 4379: 4354: 4330: 4293:(3): 237–247. 4273: 4238: 4187: 4168: 4125: 4106: 4088: 4070: 4053: 4012: 3969: 3955: 3890: 3866: 3837: 3830: 3808: 3801: 3779: 3722: 3691: 3644: 3613: 3587: 3560: 3511: 3492: 3462: 3455: 3437: 3428: 3419: 3394: 3375: 3349: 3330: 3311: 3291: 3267: 3240:(4): 389–404. 3224: 3199: 3170: 3151:(6): 603–605. 3135: 3114:(6): 535–544. 3093: 3064:(3): 347–355. 3044: 3019: 2962: 2925:(4): 365–368. 2905: 2868:(6): 1114–20. 2852: 2839: 2810: 2751: 2729: 2697: 2667: 2641: 2630:. 20 July 2018 2615: 2605: 2566: 2541: 2506:(8): 895–902. 2486: 2461: 2454: 2436: 2415: 2391: 2348: 2299: 2280: 2270: 2259: 2227: 2178: 2159: 2140: 2090: 2039: 2010:(3): 398–407. 1987: 1950:(6): 1114–20. 1934: 1902: 1863: 1828:(2): 121–123. 1808: 1762: 1713: 1676: 1649: 1623: 1604: 1575: 1538: 1495: 1454: 1416: 1415: 1413: 1410: 1409: 1408: 1403: 1398: 1393: 1386: 1383: 1350: 1347: 1345: 1342: 1299:Main article: 1296: 1293: 1278: 1275: 1213:Queen Victoria 1193:Main article: 1190: 1187: 1117: 1114: 1102: 1100: 1097: 1091: 1088: 1055: 1052: 973:Anticoagulants 969: 966: 949:Pain medicines 931: 928: 857:preventive use 839: 836: 831: 828: 820:autoantibodies 757: 756:Classification 754: 744: 741: 737: 736: 733: 725: 722: 716: 713: 704: 701: 695: 692: 594: 591: 586: 585: 565: 559: 551: 537: 526: 523: 446: 443: 435:Ashkenazi Jews 220: 219: 216: 212: 211: 205: 201: 200: 195: 191: 190: 187: 181: 180: 174: 170: 169: 166: 162: 161: 155: 149: 148: 143: 137: 136: 134: 133: 89: 87: 83: 82: 75: 74: 66: 65: 60: 56: 55: 47: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 6104: 6093: 6092:Rare diseases 6090: 6088: 6085: 6083: 6080: 6079: 6077: 6062: 6054: 6052: 6048: 6044: 6042: 6034: 6032: 6024: 6022: 6014: 6013: 6010: 6004: 6001: 5997: 5994: 5993: 5992: 5989: 5987: 5984: 5982: 5979: 5977: 5974: 5972: 5969: 5967: 5966:Public health 5964: 5962: 5959: 5957: 5954: 5952: 5949: 5947: 5946:Allied health 5944: 5942: 5939: 5938: 5936: 5932: 5924: 5921: 5920: 5919: 5916: 5914: 5911: 5909: 5906: 5904: 5901: 5899: 5896: 5894: 5891: 5889: 5886: 5884: 5881: 5880: 5878: 5876: 5870: 5858: 5855: 5854: 5853: 5850: 5848: 5845: 5843: 5840: 5838: 5835: 5831: 5828: 5827: 5826: 5823: 5821: 5818: 5816: 5813: 5809: 5806: 5805: 5804: 5801: 5799: 5796: 5794: 5791: 5788: 5785: 5783: 5780: 5776: 5773: 5772: 5771: 5768: 5766: 5763: 5761: 5758: 5756: 5755:Oral medicine 5753: 5751: 5750:Ophthalmology 5748: 5746: 5743: 5739: 5736: 5735: 5734: 5731: 5729: 5726: 5724: 5721: 5719: 5716: 5714: 5711: 5709: 5705: 5702: 5700: 5697: 5693: 5690: 5689: 5688: 5685: 5683: 5680: 5678: 5675: 5673: 5670: 5668: 5665: 5661: 5658: 5656: 5653: 5652: 5651: 5648: 5646: 5643: 5641: 5638: 5637: 5635: 5631: 5623: 5620: 5618: 5615: 5613: 5612:Cytopathology 5610: 5608: 5605: 5603: 5600: 5598: 5595: 5594: 5593: 5590: 5586: 5583: 5581: 5578: 5576: 5573: 5572: 5571: 5568: 5567: 5565: 5563: 5559: 5553: 5552:Urogynecology 5550: 5548: 5545: 5543: 5540: 5538: 5535: 5533: 5530: 5528: 5525: 5524: 5522: 5520: 5514: 5508: 5505: 5503: 5500: 5498: 5495: 5493: 5490: 5488: 5485: 5483: 5480: 5478: 5475: 5473: 5470: 5466: 5463: 5462: 5461: 5458: 5456: 5455:Endocrinology 5453: 5451: 5448: 5446: 5443: 5441: 5437: 5434: 5433: 5431: 5429: 5423: 5417: 5414: 5410: 5407: 5406: 5405: 5402: 5400: 5397: 5395: 5392: 5390: 5387: 5385: 5382: 5380: 5377: 5375: 5372: 5365: 5364: 5363: 5360: 5358: 5355: 5353: 5350: 5348: 5345: 5343: 5340: 5336: 5333: 5331: 5328: 5327: 5326: 5323: 5321: 5318: 5316: 5313: 5311: 5308: 5306: 5303: 5302: 5300: 5298: 5294: 5291: 5289: 5283: 5279: 5275: 5268: 5263: 5261: 5256: 5254: 5249: 5248: 5245: 5227: 5226:Haemarthrosis 5224: 5223: 5221: 5217: 5214: 5212: 5209: 5207: 5204: 5202: 5199: 5197: 5194: 5193: 5191: 5187: 5184: 5182: 5179: 5177: 5174: 5173: 5171: 5167: 5164: 5162: 5159: 5157: 5154: 5152: 5149: 5147: 5144: 5143: 5141: 5140: 5138: 5134: 5126: 5123: 5122: 5121: 5118: 5116: 5113: 5111: 5108: 5106: 5103: 5101: 5098: 5097: 5095: 5091: 5081: 5078: 5076: 5073: 5071: 5068: 5066: 5063: 5061: 5058: 5056: 5053: 5051: 5048: 5046: 5043: 5039: 5036: 5034: 5031: 5029: 5026: 5025: 5024: 5021: 5020: 5018: 5016: 5012: 5004: 5001: 4999: 4996: 4995: 4994: 4993: 4989: 4985: 4982: 4981: 4980: 4977: 4973: 4970: 4969: 4968: 4965: 4964: 4962: 4960: 4956: 4950: 4947: 4945: 4942: 4941: 4936: 4933: 4931: 4928: 4927: 4926: 4923: 4919: 4916: 4915: 4914: 4910: 4907: 4906: 4904: 4902: 4898: 4895: 4891: 4888: 4884: 4874: 4871: 4869: 4866: 4862: 4859: 4857: 4854: 4852: 4849: 4847: 4844: 4842: 4841:Louvel's sign 4839: 4837: 4836:Lisker's sign 4834: 4832: 4829: 4827: 4824: 4823: 4822: 4819: 4818: 4816: 4812: 4806: 4803: 4801: 4798: 4796: 4793: 4791: 4788: 4786: 4785:Thrombophilia 4783: 4782: 4780: 4778: 4774: 4768: 4765: 4761: 4758: 4757: 4756: 4753: 4749: 4746: 4744: 4741: 4739: 4736: 4735: 4734: 4731: 4727: 4724: 4722: 4719: 4717: 4714: 4712: 4709: 4707: 4704: 4702: 4699: 4698: 4697: 4694: 4693: 4691: 4687: 4684: 4680: 4674: 4671: 4669: 4666: 4664: 4661: 4660: 4657: 4653: 4649: 4646:Disorders of 4641: 4636: 4634: 4629: 4627: 4622: 4621: 4618: 4605: 4601: 4598: 4596: 4592: 4591: 4587: 4585: 4581: 4580: 4576: 4575: 4572: 4568: 4561: 4557: 4556: 4552: 4550: 4546: 4545: 4541: 4539: 4536: 4533: 4529: 4528: 4524: 4521: 4520: 4516: 4514: 4510: 4509: 4505: 4501: 4499: 4495: 4491: 4490: 4486: 4482: 4480: 4476: 4472: 4471: 4467: 4463: 4462: 4459: 4454: 4450: 4444: 4441: 4440: 4436: 4419: 4415: 4409: 4406: 4393: 4389: 4383: 4380: 4368: 4364: 4358: 4355: 4344: 4340: 4334: 4331: 4326: 4322: 4318: 4314: 4310: 4306: 4301: 4296: 4292: 4288: 4284: 4277: 4274: 4269: 4265: 4261: 4257: 4253: 4249: 4242: 4239: 4234: 4230: 4225: 4224:10044/1/57163 4220: 4215: 4210: 4206: 4202: 4198: 4191: 4188: 4183: 4179: 4172: 4169: 4164: 4160: 4156: 4152: 4148: 4144: 4141:(4): 109–11. 4140: 4136: 4129: 4126: 4121: 4117: 4110: 4107: 4102: 4101:health.gov.ie 4098: 4092: 4089: 4084: 4080: 4074: 4071: 4063: 4057: 4054: 4049: 4045: 4040: 4035: 4031: 4027: 4023: 4016: 4013: 4008: 4004: 4000: 3996: 3992: 3988: 3984: 3980: 3973: 3970: 3965: 3959: 3956: 3951: 3947: 3943: 3939: 3935: 3931: 3926: 3921: 3917: 3913: 3910:(4942): 312. 3909: 3905: 3901: 3894: 3891: 3880: 3876: 3870: 3867: 3856:on 2020-06-25 3855: 3851: 3847: 3841: 3838: 3833: 3827: 3823: 3819: 3812: 3809: 3804: 3798: 3794: 3790: 3783: 3780: 3775: 3771: 3767: 3763: 3758: 3753: 3749: 3745: 3742:(5954): 817. 3741: 3737: 3733: 3726: 3723: 3710: 3706: 3702: 3695: 3692: 3687: 3683: 3679: 3675: 3671: 3667: 3663: 3659: 3655: 3648: 3645: 3641: 3637: 3633: 3629: 3625: 3622: 3617: 3614: 3601: 3597: 3591: 3588: 3583: 3579: 3575: 3571: 3564: 3561: 3556: 3552: 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