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<p>These genetic deficiencies may lower blood plasma <a title="Clotting factor" href="http://en.wikipedia.org/wiki/Clotting_factor">clotting factor</a> levels of coagulation factors needed for a normal clotting process. When a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent fibrin formation which is necessary to maintain the blood clot. Thus a haemophiliac does not bleed more intensely than a normal person, but for a much longer amount of time. In severe haemophiliacs even a minor injury could result in blood loss lasting days, weeks, or not ever healing completely. The critical risk here is with normally small bleeds which due to missing factor VIII take long times to heal. In areas such as the brain or inside joints this can be fatal or life debilitating.</p>

<p>The bleeding with <a title="Hemorrhage" href="http://en.wikipedia.org/wiki/Hemorrhage">external</a> injury is normal, but incidence of late re-bleeding and <a title="Internal bleeding" href="http://en.wikipedia.org/wiki/Internal_bleeding">internal bleeding</a> is increased, especially into muscles, joints, or bleeding into closed spaces. Major complications include <a title="Hemarthrosis" href="http://en.wikipedia.org/wiki/Hemarthrosis">hemarthrosis</a>, <a title="Hemorrhage" href="http://en.wikipedia.org/wiki/Hemorrhage">hemorrhage</a>, <a title="Gastrointestinal bleeding" href="http://en.wikipedia.org/wiki/Gastrointestinal_bleeding">gastrointestinal bleeding</a>, and <a title="Menorrhagia" href="http://en.wikipedia.org/wiki/Menorrhagia">menorrhagia</a>.</p>

<p><a id="Causes" name="Causes"></a></p>

<p>It is caused by a lack of clotting factors:</p>

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</ul>

<p><a id="History" name="History"></a></p>

<div class="thumb tright">

<div class="thumbinner" style="WIDTH: 182px"><a class="image" title="A young Queen Victoria passed haemophilia on to many of her descendants." href="http://en.wikipedia.org/wiki/Image:The_Young_Queen_Victoria.jpg"><img class="thumbimage" height="243" alt="A young Queen Victoria passed haemophilia on to many of her descendants." width="180" border="0" src="http://upload.wikimedia.org/wikipedia/commons/thumb/7/77/The_Young_Queen_Victoria.jpg/180px-The_Young_Queen_Victoria.jpg" /></a>

<p>In the UK one of every four baby boys with Haemophilia will be born to a family with no previous history of the condition. <sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since October 2007" style="WHITE-SPACE: nowrap">[<em><a title="Wikipedia:Citation needed" href="http://en.wikipedia.org/wiki/Wikipedia:Citation_needed">citation needed</a></em>]</span></sup>)</p>

<p><a id="Genetics" name="Genetics"></a></p>

<div class="floatright"><span><a class="image" title="X-linked recessive inheritance" href="http://en.wikipedia.org/wiki/Image:XlinkRecessive.jpg"><img height="396" alt="X-linked recessive inheritance" width="307" border="0" src="http://upload.wikimedia.org/wikipedia/commons/a/a3/XlinkRecessive.jpg" /></a></span></div>

<p>Females possess two X-chromosomes, whereas males have one X and one <a title="Y chromosome" href="http://en.wikipedia.org/wiki/Y_chromosome">Y chromosome</a>. Since the mutations causing the disease are <a title="Recessive gene" href="http://en.wikipedia.org/wiki/Recessive_gene">recessive</a>, a woman carrying the defect on one of her X-chromosomes may not be affected by it, as the equivalent <a title="Allele" href="http://en.wikipedia.org/wiki/Allele">allele</a> on her other chromosome should express itself to produce the necessary clotting factors. However the Y-chromosome in men has no <a title="Gene" href="http://en.wikipedia.org/wiki/Gene">gene</a> for factors VIII or IX. If the genes responsible for production of <a title="Factor VIII" href="http://en.wikipedia.org/wiki/Factor_VIII">factor VIII</a> or <a title="Factor IX" href="http://en.wikipedia.org/wiki/Factor_IX">factor IX</a> present on a male's X-chromosome is deficient there is no equivalent on the Y-chromosome, so the deficient gene is not masked by the <a title="Autosomal" href="http://en.wikipedia.org/wiki/Autosomal">dominant</a> allele and he will develop the illness.</p>

<p>As with all genetic disorders, it is of course also possible for a human to acquire it spontaneously through <a title="Mutation" href="http://en.wikipedia.org/wiki/Mutation">mutation</a>, rather than inheriting it, because of a new mutation in one of their parents' gametes. Spontaneous mutations account for about ⅓ of all <a title="Haemophilia A" href="http://en.wikipedia.org/wiki/Haemophilia_A">haemophilia A</a> and 20% of all <a title="Hemophilia B" href="http://en.wikipedia.org/wiki/Hemophilia_B">hemophilia B</a> cases. <a title="Genetic testing" href="http://en.wikipedia.org/wiki/Genetic_testing">Genetic testing</a> and <a title="Genetic counseling" href="http://en.wikipedia.org/wiki/Genetic_counseling">genetic counseling</a> is recommended for families with haemophilia. <a title="Prenatal testing" href="http://en.wikipedia.org/wiki/Prenatal_testing">Prenatal testing</a>, such as <a title="Amniocentesis" href="http://en.wikipedia.org/wiki/Amniocentesis">amniocentesis</a>, is available to pregnant women who may be carriers of the condition.</p>

<p><a id="Probability" name="Probability"></a></p>

<p>If a female gives birth to a haemophiliac child, either the female is a carrier for the disease or the haemophilia was the result of a <a title="Mutation" href="http://en.wikipedia.org/wiki/Mutation">spontaneous mutation</a>. Until modern direct <a title="Genetic fingerprinting" href="http://en.wikipedia.org/wiki/Genetic_fingerprinting">DNA testing</a>, however, it was impossible to determine if a female with only healthy children was a carrier or not. Generally, the more healthy sons she born, the higher the probability that she was not a carrier. If the <a title="Rhesus blood group system" href="http://en.wikipedia.org/wiki/Rhesus_blood_group_system">RH factor</a> of the born male is different from the mother, the child will not be affected.</p>

<p>If a male is afflicted with the disease and has children, his daughters will be carriers of haemophilia. His sons, however, will not be affected with the disease. This is because the disease is X-linked and the father can not pass haemophilia through the Y chromosome. Males with the disorder are then no more likely to pass it on to their children than carrier females, although the outcome for each sex is a certainty for males.</p>

<p><a id="Differential_diagnosis" name="Differential_diagnosis"></a></p>

<p>Haemophilia A can be mimicked by <a title="Von Willebrand Disease" href="http://en.wikipedia.org/wiki/Von_Willebrand_Disease">von Willebrand Disease</a></p>

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</ul>

<p><a id="Treatment" name="Treatment"></a></p>

<p>Though there is no cure for haemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. <a title="Factor VIII" href="http://en.wikipedia.org/wiki/Factor_VIII">factor VIII</a> in haemophilia A or <a title="Factor IX" href="http://en.wikipedia.org/wiki/Factor_IX">factor IX</a> in haemophilia B. Some haemophiliacs develop <a title="Antibodies" href="http://en.wikipedia.org/wiki/Antibodies">antibodies</a> (inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as <a title="Porcine" href="http://en.wikipedia.org/wiki/Porcine">porcine</a> factor VIII.</p>

<p>If a patient becomes refractory to replacement coagulation factor as a result of circulating inhibitors, this may be overcome with recombinant human <a title="Factor VII" href="http://en.wikipedia.org/wiki/Factor_VII">factor VII</a> (NovoSeven&reg;), which is registered for this indication in many countries.</p>

<p>People affected with Hemophilia are recommended to do some specific exercises for elbow, knee, and ankles like stretching of calves, ankle circles, elbow flexion, and Quadriceps set etc. These exercises are recommended after an internal bleed occurs and on a daily basis to strengthen the muscles and joints to prevent new bleeding problems.</p>

<p><a id="Quality_of_Life" name="Quality_of_Life"></a></p>

<p>Thanks to scientific advances, haemophiliacs can lead lives that are almost normal. Their life expectancy does not differ greatly from that of an ordinary person, provided that proper treatment is available.</p>

<p><a id="References" name="References"></a></p>

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<p><a id="External_links" name="External_links"></a></p>

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<li><a class="external text" title="http://jul.2003.med-bib.com/12828679.htm" rel="nofollow" href="http://jul.2003.med-bib.com/12828679.htm">Immune tolerance induction in patients with haemophilia A with inhibitors</a> </li>