Haemophilia A
Encyclopedia
Haemophilia A is a deficiency in clotting factor VIII.

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
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...

 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.

Severity

There are numerous different mutations which cause haemophilia A. Due to differences in changes to the gene involved (and the subsequent resulting protein), patients with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those with 1–5% active factor have moderate haemophilia, and those with mild haemophilia have between 5–40% of normal levels of active clotting factor.

Signs and symptoms

Characteristic symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s vary with severity. In general symptoms are internal or external bleeding episodes, which are called "bleeds". Patients with more severe haemophilia suffer more severe and more frequent bleeds. While patients with mild haemophilia typically suffer more minor symptoms except after surgery or serious trauma. Moderate haemophiliacs have variable symptoms which manifest along a spectrum between severe and mild forms.

If forceps or vacuum extraction are used in vaginal births, the first signs of haemophilia may be severe head bruising
Bruise
A bruise, also called a contusion, is a type of relatively minor hematoma of tissue in which capillaries and sometimes venules are damaged by trauma, allowing blood to seep into the surrounding interstitial tissues. Bruises can involve capillaries at the level of skin, subcutaneous tissue, muscle,...

 or haematoma
Hematoma
A hematoma, or haematoma, is a localized collection of blood outside the blood vessels, usually in liquid form within the tissue. This distinguishes it from an ecchymosis, which is the spread of blood under the skin in a thin layer, commonly called a bruise...

s or even intracranial haemorrhage. Prolonged bleeding from a circumcision
Circumcision
Male circumcision is the surgical removal of some or all of the foreskin from the penis. The word "circumcision" comes from Latin and ....

 wound or a venepuncture or heelprick 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
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....

, which may cause re-bleeding. While superficial bleeding may be troublesome, by far the most serious sites of bleeding are:
  • joint
    Joint
    A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...

    s
  • muscle
    Muscle
    Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

    s
  • digestive tract
  • brain
    Brain
    The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...



The muscle and joint haemorrhages
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

 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 a joint capsule
Joint capsule
An articular capsule is an envelope surrounding a synovial joint.-Layers:Each capsule consists of two layers:* an outer layer composed of avascular white fibrous tissue...

 can cause permanent joint damage and disfigurement resulting in chronic arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

 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. Therefore, this exerts massive amounts of pain the person afflicted with the disease.

Diagnosis

The diagnosis may be suspected as coagulation testing reveals an increased PTT
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...

 in the context of a normal PT
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...

 and bleeding time
Bleeding time
Bleeding time is a medical test done on someone to assess their platelet functionThe term "template bleeding time" is used when the test is performed to standardized parameters. This makes it easier to compare data collected at different facilities....

. PTT test are the first blood test done when haemophilia is indicated. However, the diagnosis is made in the presence of very low (<10 IU) levels of Factor VIII.

A family history
Family history (medicine)
In medicine, a family history consists of information about disorders from which the direct blood relatives of the patient have suffered. Genealogy typically includes very little of the medical history of the family, but the medical history could be considered a specific subset of the total history...

 is frequently present, although not essential. Recently, genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...

 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 on 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
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

 (i.e. compound fracture of a bone), tooth extraction, or surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

.

Differential diagnosis

The two most common differential diagnoses
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 are haemophilia B
Haemophilia B
Haemophilia B is a blood clotting disorder caused by a mutation of the Factor IX gene, leading to a deficiency of Factor IX. It is the second most common form of haemophilia, rarer than haemophilia A. It is sometimes called Christmas disease after Stephen Christmas, the first patient described...

 (also known as Christmas disease) which is a deficiency in Factor IX
Factor IX
Factor IX is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes hemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to...

 and von Willebrand Disease
Von Willebrand disease
von Willebrand disease is the most common hereditary coagulation abnormality described in humans, although it can also be acquired as a result of other medical conditions. It arises from a qualitative or quantitative deficiency of von Willebrand factor , a multimeric protein that is required for...

 which is a deficiency in von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...

 needed for the proper functioning of Factor VIII. Haemophilia C
Haemophilia C
Haemophilia C is a mild form of haemophilia affecting both sexes. However, it predominantly occurs in Jews of Ashkenazi descent. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B...

 is also a possible, but rare, differential diagnosis.

Therapy

Most severe haemophilia patients require regular supplementation with intravenous recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...

 or plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 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
Infusion
An infusion is the outcome of steeping plants with desired chemical compounds or flavors in water or oil.-History:The first recorded use of essential oils was in the 10th or 11th century by the Persian polymath Avicenna, possibly in The Canon of Medicine.-Preparation techniques:An infusion is very...

 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%. 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 that has repeated bleeding episodes) is identified.

Mild haemophiliacs often manage their condition with desmopressin
Desmopressin
Desmopressin is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet...

, which releases stored factor VIII from blood vessel walls.

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
Factor VII
Factor VII is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients...

 (NovoSeven) has become available as a treatment for haemorrhage in patients with haemophilia and factor inhibitors

See also

  • Haemophilia
    Haemophilia
    Haemophilia is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken. Haemophilia A is the most common form of the disorder, present in about 1 in 5,000–10,000 male births...

  • List of haemophilia organizations
  • Contaminated haemophilia blood products
    Contaminated haemophilia blood products
    Contaminated hemophilia blood products were a serious public health problem in the late 1970s through 1985. These products caused large numbers of haemophiliacs to become infected with HIV and hepatitis C...

  • Haemophilia B
    Haemophilia B
    Haemophilia B is a blood clotting disorder caused by a mutation of the Factor IX gene, leading to a deficiency of Factor IX. It is the second most common form of haemophilia, rarer than haemophilia A. It is sometimes called Christmas disease after Stephen Christmas, the first patient described...

  • Haemophilia C
    Haemophilia C
    Haemophilia C is a mild form of haemophilia affecting both sexes. However, it predominantly occurs in Jews of Ashkenazi descent. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B...

  • Ryan White
    Ryan White
    Ryan Wayne White was an American teenager from Kokomo, Indiana, who became a national poster child for HIV/AIDS in the United States, after being expelled from middle school because of his infection. A hemophiliac, he became infected with HIV from a contaminated blood treatment and, when diagnosed...


External links

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