QuestionSBA
QuestionChoice
This patient has haemophilia. The clinical presentation of nosebleeds and excessive bleeding alongside family history suggests an inherited bleeding disorder. His maternal grandfather would have been treated with clotting factors. Males only carry one X chromosome which contains the mutation in the gene. This means that they pass on their X chromosome to their daughters who become carriers, but do not present with the disease (or may have very mild manifestations) due to the inheritance being x-linked recessive. Carrier females can pass the affected X chromosome to their sons, which has happened in this case.
53257
a
X-linked recessive
QuestionChoice
This is incorrect because haemophilia is not an autosomal recessive condition. In an autosomal recessive condition, disease occurs when a child inherits one mutated copy of a gene from both parents. There is no suggestion to state that this patient's father is a carrier. His sister is unaffected which suggests that it is related to the inheritance of the X chromosome from his mother.
53259
c
Autosomal recessive
QuestionChoice
This is incorrect because haemophilia is not an autosomal dominant condition. In an autosomal dominant condition, a single copy of the mutated gene is enough to cause disease. This patient's mother is a carrier but she is unaffected which suggests that this is not autosomal dominant. You would expect any family member who inherits the mutated gene to have the disease.
53260
d
Autosomal dominant
QuestionChoice
This is incorrect because haemophilia is not inherited through an X-linked dominant pattern. In an X-linked dominant condition, one copy of the mutated gene is enough to cause disease in males and females. As the patient's mother is a carrier and unaffected, this suggests that the condition is inherited through an X-linked recessive pattern instead.
53258
b
X-linked dominant
QuestionChoice
This is incorrect because haemophilia is not inherited via mitochondrial inheritance. This is a rare pattern of maternal inheritance due to mutated genes within the mitochondrial DNA within oocytes, which is subsequently passed on to the developing embryo (and child, therefore.) Spermatozoa have mitochondria but their mitochondria are degraded shortly after fertilisation, so genetic defects within the spermatozoa's mitochondrial DNA cannot be transmitted to the foetus.
53261
e
Mitochondrial
QuestionComment
Bleeding from the gums I thought VWD would be more likely, as well as nose bleeds.  They of course could happen in both, however could some kind person tell us other reasons why haemophilia was more likely?
19828
QuestionComment
VWD is autosomal dominant which means the mother or father will need to be affected for the boy to have the disease. Haemophilia A is x-linked recessive and so for a boy to be affected, the pathology will come from the mother's side and usually skips a generation. 
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Monoclonal Polyps
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Jargon Defibrillator
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# Summary

Haemophilia A and B are inherited bleeding disorders caused by deficiencies in clotting factors VIII and IX respectively, both of which are integral components of the instrinsic pathway of the coagulation cascade. They typically present early in life with deep and severe bleeding into soft tissues, joints, and muscles. Diagnosis is established with a factor assay (VIII for Haemophilia A and IX for Haemophilia B). Minor bleeds can be managed with Desmopressin (for Haemophilia A), and major bleeds with recombinant factor VIII (for Haemophilia A) or recombinant factor IX (for Haemophilia B).

# Definition

Haemophilia A and B are both X-linked recessive inherited bleeding disorders, caused by deficiencies in clotting factors VIII and IX respectively, both of which are integral components of the instrinsic pathway of the coagulation cascade.

# Aetiology 


| Haemophilia A        | Haemophilia B           | 
| :-------------: |:-------------:| 
| X-linked recessive inherited bleeding disorder that causes a deficiency in clotting factor VIII |  X-linked recessive inherited bleeding disorder that causes deficiency in clotting factor IX 
|Occurs in 1 in 5,000 men worldwide      | Affects 1 in 25,000 men | 
| Caused by a range of mutations within the factor VIII gene – 70% of these mutations are inherited and 30% are spontaneous

# Signs and Symptoms

- They typically presents early in life with spontaneous deep and severe bleeding into soft tissues, joints and muscles – historically, joint damage resulted in a deforming arthropathy
- Boys often present with excessive bleeding following trauma or surgical intervention (e.g. tonsillectomy)
- Cerebral haemorrhage was a major cause of mortality in severe haemophilia before the widespread use of blood products

# Differential Diagnosis

* **Von Willebrand Disease**: This inherited bleeding disorder is often confused with hemophilia due to similar symptoms but is caused by a deficiency or dysfunction of von Willebrand factor.
* **Factor Deficiencies**: Rare factor deficiencies, such as deficiencies in factors I, V, VII, X, XI, and XIII, can lead to bleeding tendencies and mimic haemophilia.
* **Platelet Disorders**: Conditions like idiopathic thrombocytopenic purpura (ITP) and thrombocytopathy can result in bleeding symptoms and should be considered.
* **Liver Disease**: Liver dysfunction can lead to impaired synthesis of clotting factors, resembling a bleeding disorder.
* **Haematological Malignancies**: Leukemias, lymphomas, and myelodysplastic syndromes can lead to coagulation abnormalities and bleeding.
* **Trauma**: Traumatic injuries can lead to bleeding and may be mistaken for hemophilia in cases where the family history is unknown.
* **Infectious Diseases**: Certain infections, such as dengue fever or viral hepatitis, can lead to bleeding tendencies.
* **Vasculitis**: Conditions like Henoch-Schönlein purpura can result in skin and joint bleeding.
* **Drug-Induced Thrombocytopenia**: Some medications, such as heparin or quinine, can lead to low platelet counts and bleeding.


# Investigations

- Diagnosis is with a factor VIII/IX assay 
	- For boys with severe haemophilia A or B (factor VIII or factor IX <1%, respectively):
	  - Two-thirds are diagnosed at birth when the boy is born to a known or suspected carrier 
	  - The rest are picked up later on in childhood when the baby begins to crawl or fall, or there is an eruption of dentition
	- Some patients have a milder clinical severity – this is directly related to higher factor levels  
	  - Mild haemophilia >5% 
	  - Moderate haemophilia 1–5% 
- Blood tests show:
  - Clotting profile - APTT is elevated
  - vWF antigen is normal in haemophilia A
  - Defective platelet function 

# Management 

- Minor bleeds in patients with Haemophilia A can be managed with **desmopressin** (DDAVP) – increases factor VIII sufficiently to deal with the minor bleeding 
- Major bleeds require **recombinant factor VIII or IX**
- In patients with severe haemophilia, the use of regular prophylactic recombinant clotting factor treatment, physiotherapy and education in learning how to avoid bleeds have all contributed to the prevention of joint arthropathy 
  - Gene therapy has also been shown to be successful
- Mild and moderate haemophilia require 'on demand' treatment in response to bleeding or in preparation for surgery
- Supportive management includes:
  - **Antifibrinolytics** (eg. tranexamic acid) – useful for bleeding wounds but should be avoided in muscle haematomas, haemarthrosis and urinary bleeding as they can lead to fibrosis
  - Vaccination against hepatitis B, hydrotherapy, orthopaedic and dental advice are also beneficial 

- One-third of boys with severe haemophilia A will develop an **inhibitor to factor VIII** following factor VIII treatment
  - This can worsen bleeding and complicate therapy
  - Treatment of haemophilia with inhibitors should be directed from a specialist centre
- Life expectancy for patients with haemophilia A and B is well into middle age in this era of blood product-free concentrates


Historical context of haemophilia treatment:

-  Before viral screening for HIV and hepatitis C was introduced, the use of blood products however lead to high levels of viral transmission resulting in AIDS, hepatocellular carcinoma and death 
- Many of these patients have also been exposed to the prion that causes Creutzfeldt–Jakob disease, with the effects of this still presently unknown 
- Viral transmission is no longer an issue following the change to the use of recombinant factor VIII

# References

[The Haemophilia Society - Haemophilia](https://haemophilia.org.uk/bleeding-disorders/haemophilia-a-and-b/)

[NHS UK - Haemophilia](https://www.nhs.uk/conditions/haemophilia/)
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Haemophilia
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Haematology
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Haemophilia
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Clinical haematology
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Haemophilia is an X-linked recessive disorder, primarily affecting males, leading to prolonged bleeding due to deficient clotting factors.
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Epistaxis
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Clinical haematology
An 11-year-old boy presents to the GP with his mother with several nosebleeds and excessive bleeding from his gums after visiting the dentist. He says his 8-year-old sister does not have any of these symptoms, but his maternal grandfather used to have regular hospital appointments for an injection. His blood tests show a prolonged APTT.

Given the most likely diagnosis, which of the following is the most likely pattern of inheritance?
a