Hemophilia causes: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(29 intermediate revisions by 3 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Hemophilia}}
{{Hemophilia}}
{{CMG}}
{{CMG}} {{AE}} {{Sab}}
 
Please help WikiDoc by adding more content here.  It's easy!  Click  [[Help:How_to_Edit_a_Page|here]]  to learn about editing.
 
==Overview==
==Overview==
Hemophilia A, B, and C are caused by [[mutations]] in ''F8'', ''F9'', and ''F11'' [[genes]] respectively. It can also occur as a result of [[Autoantibody|autoantibodies]] directed against the clotting factors.
==Causes==
==Causes==
 
*Hemophilia A is caused by [[Mutation|mutations]] in the ''F8'' [[gene]].<ref name="LakichKazazian1993">{{cite journal|last1=Lakich|first1=Delia|last2=Kazazian|first2=Haig H.|last3=Antonarakis|first3=Stylianos E.|last4=Gitschier|first4=Jane|title=Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A|journal=Nature Genetics|volume=5|issue=3|year=1993|pages=236–241|issn=1061-4036|doi=10.1038/ng1193-236}}</ref><ref name="Bagnall2002">{{cite journal|last1=Bagnall|first1=R. D.|title=Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A|journal=Blood|volume=99|issue=1|year=2002|pages=168–174|issn=00064971|doi=10.1182/blood.V99.1.168}}</ref>
*Hemophilia is caused by a mutation or change, in one of the genes, that provides instructions for making the clotting factor proteins needed to form a blood clot. This change or mutation can prevent the clotting protein from working properly or to be missing altogether. These genes are located on the X Chromosome. Males have one X and one Y chromosome (XY) and females have two X chromosomes (XX). Males inherit the X chromosome from their mothers and the Y chromosome from their fathers. Females inherit one X chromosome from each parent.
*Hemophilia B is caused by [[Mutation|mutations]] in the ''F9'' [[gene]].<ref name="PeyvandiGaragiola2016">{{cite journal|last1=Peyvandi|first1=Flora|last2=Garagiola|first2=Isabella|last3=Young|first3=Guy|title=The past and future of haemophilia: diagnosis, treatments, and its complications|journal=The Lancet|volume=388|issue=10040|year=2016|pages=187–197|issn=01406736|doi=10.1016/S0140-6736(15)01123-X}}</ref><ref name="pmid237463">{{cite journal |vauthors=Davie EW, Fujikawa K |title=Basic mechanisms in blood coagulation |journal=Annu. Rev. Biochem. |volume=44 |issue= |pages=799–829 |date=1975 |pmid=237463 |doi=10.1146/annurev.bi.44.070175.004055 |url=}}</ref><ref name="pmid2994716">{{cite journal |vauthors=Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K |title=Nucleotide sequence of the gene for human factor IX (antihemophilic factor B) |journal=Biochemistry |volume=24 |issue=14 |pages=3736–50 |date=July 1985 |pmid=2994716 |doi= |url=}}</ref>
 
*Hemophilia C is caused by [[Mutation|mutations]] in the ''F11'' [[gene]].<ref name="pmid2813350">{{cite journal |vauthors=Asakai R, Chung DW, Ratnoff OD, Davie EW |title=Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue=20 |pages=7667–71 |date=October 1989 |pmid=2813350 |pmc=298131 |doi= |url=}}</ref>
*The X chromosome contains many genes that are not present on the Y chromosome. This means that males only have one copy of most of the genes on the X chromosome, whereas females have 2 copies. Thus, males can have a disease like hemophilia if they inherit an affected X chromosome that has a mutation in either the factor VIII or factor IX gene. Females can also have hemophilia, but this is much rarer. In such cases both X chromosomes are affected or one is affected and the other is missing or inactive. In these females, bleeding symptoms may be similar to males with hemophilia.
*Generation of [[Autoantibody|autoantibodies]] directed against clotting factors can also result in hemophilia.<ref name="pmid28960809">{{cite journal |vauthors=Napolitano M, Siragusa S, Mancuso S, Kessler CM |title=Acquired haemophilia in cancer: A systematic and critical literature review |journal=Haemophilia |volume=24 |issue=1 |pages=43–56 |date=January 2018 |pmid=28960809 |doi=10.1111/hae.13355 |url=}}</ref>
A female with one affected X chromosome is a "carrier" of hemophilia.   Sometimes a female who is a carrier can have symptoms of hemophilia. In addition, she can pass the affected X chromosome with the clotting factor gene mutation on to her children. Learn more about the inheritance pattern for hemophilia.
*Two-thirds of the hemophilia cases are usually due to [[Family history|familial history]].<ref>{{cite book | last = Goodman | first = Catherine | title = Pathology : implications for the physical therapist | publisher = Elsevier Saunders | location = St. Louis, Missouri | year = 2015 | isbn = 9781455745913 }}</ref><ref name="pmid22776238">{{cite journal |vauthors=Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A |title=Guidelines for the management of hemophilia |journal=Haemophilia |volume=19 |issue=1 |pages=e1–47 |date=January 2013 |pmid=22776238 |doi=10.1111/j.1365-2516.2012.02909.x |url=}}</ref>
 
*One-third of the hemophilia cases result from spontaneous [[Mutation|genetic mutation]].<ref>{{cite book | last = Goodman | first = Catherine | title = Pathology : implications for the physical therapist | publisher = Elsevier Saunders | location = St. Louis, Missouri | year = 2015 | isbn = 9781455745913 }}</ref><ref name="pmid22776238">{{cite journal |vauthors=Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A |title=Guidelines for the management of hemophilia |journal=Haemophilia |volume=19 |issue=1 |pages=e1–47 |date=January 2013 |pmid=22776238 |doi=10.1111/j.1365-2516.2012.02909.x |url=}}</ref>
*Even though hemophilia runs in families, some families have no prior history of family members with hemophilia. Sometimes, there are carrier females in the family, but no affected boys, just by chance. However, about one-third of the time, the baby with hemophilia is the first one in the family to be affected with a mutation in the gene for the clotting factor.
===Haemophilia A===
Hemophilia A is caused by an inherited X-linked recessive trait, with the defective gene located on the X chromosome. Females have two copies of the X chromosome. So if the factor VIII gene on one chromosome does not work, the gene on the other chromosome can do the job of making enough factor VIII.
 
Males have only one X chromosome. If the factor VIII gene is missing on a boy's X chromosome, he will have hemophilia A. For this reason, most people with hemophilia A are male.
 
If a woman has a defective factor VIII gene, she is considered a carrier. This means the defective gene can be passed down to her children. Boys born to such women have a 50% chance of having hemophilia A. Their daughters have a 50% chance of being a carrier. All female children of men with hemophilia carry the defective gene.
===Haemophilia B===
Hemophilia B is caused by an inherited X-linked recessive trait, with the defective gene located on the X chromosome.
 
Females have two copies of the X chromosome. If the factor IX gene on one chromosome does not work, the gene on the other chromosome can do the job of making enough factor IX.
 
Males have only one X chromosome. If the factor IX gene is missing on a boy's X chromosome, he will have Hemophilia B. For this reason, most people with hemophilia B are male.
 
If a woman has a defective factor IX gene, she is considered a carrier. This means the defective gene can be passed down to her children. Boys born to such women have a 50% chance of having hemophilia B. Their daughters have a 50% chance of being a carrier.
 
All female children of men with hemophilia carry the defective gene.
In 1990, George Brownlee and Merlin Crossley showed that two sets of genetic mutations were preventing two key proteins from attaching to the DNA of people with a rare and unusual form of haemophilia B – haemophilia B Leyden – where sufferers experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty. This lack of protein attachment to the DNA was thereby turning off the gene that produces clotting factor IX, which prevents excessive bleeding.
===Haemophilia C===
It is caused by a deficiency of coagulation factor XI and is distinguished from haemophilia A and B by the fact it does not lead to bleeding into the joints. Furthermore, it has autosomal inheritance, since the gene for factor XI is located on chromosome 4 (close to the prekallikrein gene); and it is not completely recessive, individuals who are heterozygous also show increased bleeding. Many mutations exist, and the bleeding risk is not always influenced by the severity of the deficiency.


==References==
==References==
{{reflist|2}}
{{reflist|1}}


{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Needs content]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Pediatrics]]
[[Category:Pediatrics]]

Latest revision as of 14:08, 2 August 2019

Hemophilia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hemophilia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Hemophilia causes On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Hemophilia causes

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Hemophilia causes

CDC on Hemophilia causes

Hemophilia causes in the news

Blogs on Hemophilia causes

Directions to Hospitals Treating Hemophilia

Risk calculators and risk factors for Hemophilia causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

Overview

Hemophilia A, B, and C are caused by mutations in F8, F9, and F11 genes respectively. It can also occur as a result of autoantibodies directed against the clotting factors.

Causes

References

  1. ↑ Lakich, Delia; Kazazian, Haig H.; Antonarakis, Stylianos E.; Gitschier, Jane (1993). "Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A". Nature Genetics. 5 (3): 236–241. doi:10.1038/ng1193-236. ISSN 1061-4036.
  2. ↑ Bagnall, R. D. (2002). "Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A". Blood. 99 (1): 168–174. doi:10.1182/blood.V99.1.168. ISSN 0006-4971.
  3. ↑ Peyvandi, Flora; Garagiola, Isabella; Young, Guy (2016). "The past and future of haemophilia: diagnosis, treatments, and its complications". The Lancet. 388 (10040): 187–197. doi:10.1016/S0140-6736(15)01123-X. ISSN 0140-6736.
  4. ↑ Davie EW, Fujikawa K (1975). "Basic mechanisms in blood coagulation". Annu. Rev. Biochem. 44: 799–829. doi:10.1146/annurev.bi.44.070175.004055. PMID 237463.
  5. ↑ Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K (July 1985). "Nucleotide sequence of the gene for human factor IX (antihemophilic factor B)". Biochemistry. 24 (14): 3736–50. PMID 2994716.
  6. ↑ Asakai R, Chung DW, Ratnoff OD, Davie EW (October 1989). "Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations". Proc. Natl. Acad. Sci. U.S.A. 86 (20): 7667–71. PMC 298131. PMID 2813350.
  7. ↑ Napolitano M, Siragusa S, Mancuso S, Kessler CM (January 2018). "Acquired haemophilia in cancer: A systematic and critical literature review". Haemophilia. 24 (1): 43–56. doi:10.1111/hae.13355. PMID 28960809.
  8. ↑ Goodman, Catherine (2015). Pathology : implications for the physical therapist. St. Louis, Missouri: Elsevier Saunders. ISBN 9781455745913.
  9. ↑ 9.0 9.1 Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A (January 2013). "Guidelines for the management of hemophilia". Haemophilia. 19 (1): e1–47. doi:10.1111/j.1365-2516.2012.02909.x. PMID 22776238.
  10. ↑ Goodman, Catherine (2015). Pathology : implications for the physical therapist. St. Louis, Missouri: Elsevier Saunders. ISBN 9781455745913.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Hemophilia_causes&oldid=1578151"