Hemophilia 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.
Hemophilia A is the most common type of this condition, affecting 1 in 5,000 to 10,000 males worldwide. Hemophilia B is less common; it affects 1 in 20,000 to 34,500 males worldwide.
http://www.youtube.com/watch?v=RDaCtJp0ta8&feature=player_embedded This is a video showing that the Royal Family of Britain also had this disease from Queen Victoria. This video also shows how this disease is passed down from 1 generation to another.
Hemophilia has featured prominently in European royalty and thus is sometimes known as "the royal disease".
Queen Victoria passed the mutation for Hemophilia B to her son Leopold and, through some of her daughters, to various royals across the continent, including the royal families of Spain, Germany, and Russia. In Russia, Tsarevich Alexei Nikolaevich, son of Nicholas II, was a descendant of Queen Victoria through his mother Empress Alexandra and suffered from hemophilia.
It was claimed that Rasputin was successful at treating the Tsarevich's hemophilia. At the time, a common treatment administered by professional doctors was to use aspirin, 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 Alexei.
In Spain, Queen Victoria's youngest daughter, Princess Beatrice, had a daughter Victoria Eugenie of Battenberg, who later became Queen of Spain. Two of her sons were hemophiliacs and both died from minor car accidents: Her eldest son, Prince Alfonso of Spain, Prince of Asturias, died at the age of 31 from internal bleeding after his car hit a telephone booth. Her youngest son, Infante Gonzalo, died at age 19 from abdominal bleeding following a minor car accident where 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.
A diagram depicting the possible outcomes of offsprings with haemophilic father & carrier of haemophilic gene in mother.
Females have 2 X-chromosomes while males have 1 X-chromosome & 1 Y-chromosome
Mutations causing the disease are X-linked - A woman carrying the defect on one of her X-chromosomes may not be affected by it, as her other X-chromosome can express itself to produce the necessary clotting factors.
However, the Y-chromosome in men 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, the Y-chromosome is unable to produce the necessary clotting factors. So, the deficient gene is not masked and he will develop the illness.
Severity
Numerous different mutations which cause each type of hemophilia.Due to differences in changes to the genes involved, patients with hemophilia often have some level of active clotting factor.
< 1% active factor are classified as having severe hemophilia
1-5% active factor have moderate hemophilia
5-40% of normal levels of active clotting factor have mild hemophilia
External Bleeding: 1) Bleeding in the mouth from biting a lip, having a tooth pulled, etc... 2) Nosebleeds for no obvious reasons 3) Heavy bleeding from a minor cut 4) Bleeding from a cut that resumes after stopping for awhile
Internal Bleeding: 1) Blood in the urine (Bleeding in the kidneys or bladder) 2) Blood in stool (Bleeding in the intestines or stomach) 3) Large bruises that are unusual in location or number (Bleeding into the larger muscles of body)
Bleeding in the Joints: 1) Causes tightness in the joint with no real pain or any visible signs of bleeding. 2) Swollen, hot to touch, and painful to bend.
Bleeding in the Brain:
1) Long-lasting, painful headaches or neck pain or stiffness 2) Repeated vomiting 3) Sleepiness or changes in behavior 4) Sudden weakness or clumsiness of the arms or legs or problems walking 5) Double vision 6) Convulsions or seizures
Reid was diagnosed with hemophilia at birth and has been relying on Puget Sound Blood Center for medical care and education his entire life. It takes thousands of donations to allow a baby with hemophilia to grow up to be a man, he says.
The current possible cure for hemophilia is gene therapy. As hemophilia is caused by the lack of blood clotting proteins (usually factor 8 or factor 9), gene therapy is to aim to produce enough of these protein to reverse the effect of hemophilia.
Gene therapy works by removing cells with hemophilia and alter the cells genetically which do not cause hemophilia. They usually use liver cells but other kinds of cells are also proven successful. Cells are then reprogrammed by inserting new genetic materials. The new materials allow the cell to produce factor 8 and 9 blood clotting proteins now which is then reinserted back into the patient. The cells multiply and take over the others which allow the patient to be hemophilia-free now. The processes are still being perfected and are still under researches.
Hemophiliacs have to inject themselves with artifically produced clotting factors every few days. The regular infusion of clotting factors into their body allow the clotting levels to be fairly high to prevent extreme spontaneous bleeding episodes. Recombinant clotting factors are preferred over extracted clotting factors due to it's high purity and safety. However, it is very expensive which usually only allow developed countries to be available with it.
As hemophilia originates from genetic inheritance, prevention can only be done by gene testing which can only allow early detection of it and counseling before having a baby for people with hemophilia.
such as skating, biking and sports with possible high risk contact and injuries. This is to prevent any possible injuries that may cause huge blood loss and risk the life of the hemophiliac.
Hemophiliacs should constantly do exercise at joints (knees, elbows etc) to strengthen the areas muscles to prevent from constant bleeding. This should be done on a daily basis. A physiotherapist should also guide the hemophilic patient on the routines of exercises and to aid on doing the exercises.
Multiple mutations such as frameshift mutations, missense mutations, nonsense mutations, gene inversions, large deletions and splicing errors have been linked to the cause of hemophilia.
Blood Clotting Cascade:
When there is tissue damage, enzymes get activated. Those enzymes (commonly known as factors) cleave other enzymes, and those enzymes cleave other enzymes. A cascade starts, sort of like a domino-effect and eventually they work together to make a blood clot.
However, in the case of Hemophilia, either Factor VIII or IX is missing. Think of it this way, if one domino is missing, it is harder to make the next one fall and to continue the cascade to make the best clot possible.
For hemophilia A, it is a complex of a large inert carrier protein and a noncovalently bound small fragment which contains the procoagulant active site. The factor VIII complex, with a molecular weight in excess of 1 million, has 2 components:
(1) factor VIII (molecular weight of 293,000 ) called factor VIII C, when measured by procoagulant activity and factor VIII Ag, when measured immunologically
(2) factor VIII R (the von Willebrand factor or vWF) has a molecular weight of 220,000. Polymerization leads to the high molecular weight of the factor VIII complex (Levin, 1979). Factor VIII is encoded by the factor VIII gene on Xq28.
Although there are many various ways to allow hemophiliacs to cope with the illness now, complications can still occur. Almost one third of hemophiliacs will develop an antibody,also known as an inhibitor, to the products that is used to treat or prevent bleeding episodes. Developing an inhibitor is one of the most serious and costly complications of hemophilia.
About Inhibitors
Treatment products called factor clotting concentrate are used for hemophiliacs which improves blood clotting and is used to stop or prevent a bleeding episode. Inhibitors develop when the body’s immune system stops accepting the factor (factor VIII for hemophilia A and factor IX for hemophilia B) as a normal part of blood. The body thinks the factor is a foreign substance and tries to destroy it using inhibitors. The inhibitors stop the factor from working. This makes it more difficult to stop a bleeding episode. People with hemophilia who develop an inhibitor do not respond as well to treatment. Inhibitors most often appear during the first year of treatment but they can appear at any time. This disallow the treatment to work thus the symptoms of hemophilia will not alleviate. This causes inconvenience and pain to the hemophiliacs.
