Haemophilia A

What is Haemophilia A?

Haemophilia A (also spelled hemophilia A or hæmophilia A) is the most common form of haemophilia which is the most common genetic disorder associated with serious bleeding. It is caused by a reduction in the amount or activity of factor VIII. This protein serves as a cofactor for factor IX in the activation of factor X in the coagulation cascade. The lack of this section of the coagulation cascade results in the formation of fibrin deficient clots which makes coagulation much more prolonged, and the the clot more unstable.

Haemophilia A is inherited as an X-linked recessive trait, and thus occurs in males and in homozygous females. However, mild haemophilia A has been described in heterozygous females, presumably due to extremely unfavourable lyonization (inactivation of the normal X chromosome in most of the cells). Approximately 30% of patients have no family history; their disease is presumably caused by new mutations . Approximately, 1 in 5,000 males are affected.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Haemophilia A" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Haemophilia A Diagnosis

The diagnosis may be suspected as coagulation testing reveals an increased PTT in the context of a normal PT and bleeding time. PTT test are the first blood test done when hemophilia is indicated. However, the diagnosis is made in the presence of very low (<10 IU) levels of Factor VIII.

A family history is frequently present, although not essential. Recently, genetic testing has been made available to determine an individual's risk of attaining or passing on haemophilia.

Diagnosis of haemophilia A also includes a severity level which can range from mild to severe based the the amount of active and functioning factor VIII detected in the blood. Factor VIII levels do not typically change throughout an individual's life. Severe haemophilia a is the most common form occurring in 60% of patients. Severe haemophilia A is indicated by active Factor VIII levels less than 1 or 2%. Severe haemophiliacs have frequent serious bleeds (20+ times per year), these bleeds often occur spontaneously without trauma or injury. Moderate haemophilia is indicated by active Factor VIII levels between 1-5% and a lower, but variable frequency of bleeding episodes, particularly of spontaneous bleeds. Mild haemophilia is indicated by active Factor VIII levels between 5-25%. Patients with mild haemophilia often experience few or no bleeding episodes except in the case of serious trauma (i.e. compound fracture of a bone), tooth extraction, or surgery.

Differential diagnosis

The two most common differential diagnoses are haemophilia B (also known as Christmas disease) which is a deficiency in Factor IX, are von Willebrand Disease which is a deficiency in von Willebrand factor, which is needed for the proper functioning of Factor VIII. Haemophilia C is also a possible, but rare, differential diagnosis.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Haemophilia A" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Haemophilia A Complications

A particular therapeutic conundrum is the development of "inhibitor" antibodies against factor VIII due to frequent infusions. These develop as the body recognises the "normal form" factor VIII as foreign, as the body does not have its own "copy".

The problem is that in these patients, factor VIII infusions are ineffective. activated factor VII (NovoSeven) has become available as a treatment for haemorrhage in patients with haemophilia and factor inhibitors.

Prior to the use of modern blood screening methods and the advent of recombinant Factor VIII, blood born diseases such as hepatitis and HIV were very common in patients with haemophilia as a result of treatment.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Haemophilia A" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Haemophilia A Symptoms

If forceps or vacuum extraction are used in vaginal births, the first signs of haemophilia may be severe head bruising or haematomas or even intercranial haemorrhage. Prolonged bleeding from a circumcision wound is another common early sign of haemophilia. These signs may lead to blood tests which indicates haemophilia, in other patients, especially those with moderate or mild haemophilia a later trauma will lead to the first serious bleed.

Haemophilia leads to a severely increased risk of prolonged bleeding from common injuries, or in severe cases bleeds may be spontaneous and without obvious cause. Bleeding may occur anywhere in the body. Superficial bleeding such as those cause by abrasions, or shallow lacerations may be prolonged and the scab may easily be broken up due to the lack of fibrin, which may cause re-bleeding. While superficial bleeding may be troublesome, by far the most serious sites of bleeding are:

  • joints
  • muscles
  • digestive tract
  • brain

The muscle and joint haemorrhages are indicative of haemophilia, while digestive tract and cerebral haemorrhages are also germane to other coagulation disorders.

Though typically not life threatening, joint bleeds are one of the most serious symptoms of haemophilia. Repeated bleeds into the a joint capsule can cause permanent joint damage and disfigurement resulting in chronic arthritis and disability. Joint damage is not a result of blood in the capsule but rather the healing process. When blood in the joint is broken down by enzymes in the body, the bone in that area is also degraded.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Haemophilia A" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Haemophilia A Treatment

Most severe haemophilia patients require regular supplementation with intravenous recombinant or plasma concentrate Factor VIII. The prophylactic treatment regime is highly variable and individually determined.

Apart from "routine" supplementation, extra factor concentrate is given around surgical procedures and after trauma. In children, an easily accessible intravenous port (e.g. Port-a-Cath) may have to be inserted to minimise frequent traumatic intravenous cannulation.

These devices have made prophylaxis in haemophilia much easier for families because the problems of "finding a vein" for infusion two to three times a week are eliminated. However, there are risks involved with their use, the most worrisome being that of infection. Studies differ but some show an infection rate as high as 50 per cent. These infections can usually be treated with intravenous antibiotics but sometimes the device must be removed. Also, there are other studies that show a risk of clots forming at the tip of the catheter. Still, many families choose to use the device because of the benefits.

Some patients with severe haemophilia and most with moderate and mild haemophilia treat only as needed without a regular prophylactic schedule. Due to risk of permanent disability, prophylactic treatment is always indicated if a "target joint" (a joint which has repeated bleeding episodes) is identified.

Mild haemophiliacs often manage their condition with desmopressin, which releases stored factor VIII from blood vessel walls.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Haemophilia A" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.