HAEMOPHILIA: The Bleeder's Disease

HAEMOPHILIA: The Bleeder's Disease

Hemophiliacs within our population need advanced diagnostic facilities, sound treatment facilities

J&K lacks policy to care for hemophilia patients, 3000 cases in state (Greater Kashmir: 14, January, 2015).As per the news report, haemophilia care unit located in Government Medical College (GMC)-Srinagar is short of anti-haemophilia factor, a life-saving treatment, for past more than six months.

In the absence of diagnosis facility and shortage of anti-haemophilia treatment, haemophilia patients are compelled to seek treatment outside the state.  

Each year on an average haemophilia kills three to four patients in Kashmir but neither government nor civil society wakes up to the threat posed by the disease. Earlier, a news item related to the disease appeared in GK which read: “Fresh Frozen Plasma risks lives of haemophilia patients” (GK: 5 Jan, 2015). As per the news report, despite experts warning of high risk of contracting Hepatitis C and HIV, the haemophilia patients in the Valley continue to receive Fresh Frozen Plasma (FFP) instead of the recommended Factor-VIII. 

WHAT IS HAEMOPHILIA? 

Haemophilia is a genetic disorder that impairs the body’s ability to control blood clotting.  Haemophilia is a sex-linked trait caused by a recessive gene (say h) located in the X-chromosome (Xh). Haemophilia patients have lower blood plasma clotting factor level or impaired activity of the coagulation factors needed for a normal clotting process. Thus 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. A haemophiliac does not bleed more intensely than a person without it, but can bleed for a much longer time. In severe haemophiliacs even a minor injury can result in blood loss lasting days or weeks, or even never healing completely. In areas such as the brain or inside joints, this can be fatal or permanently debilitating.

CAUSES

Haemophilia A:  is a recessive X-linked genetic disorder involving a lack of functional clotting Factor-VIII and represents 80% of haemophilia cases (present in about 1 in 5,000–10,000 male births).

Haemophilia B:  is a recessive X-linked genetic disorder involving a lack of functional clotting Factor-IX. It comprises approximately 20% of haemophilia cases (occurs in about 1 in 20,000–34,000 male births).

Haemophilia C:  is an autosomal genetic disorder (i.e. not X-linked) involving a lack of functional clotting Factor-XI. Haemophilia C is not completely recessive, as heterozygous individuals also show increased bleeding.

SYMPTOMS

Characteristic symptoms vary with severity. In general symptoms are internal or external bleeding episodes, which are called "bleeds". In both haemophilia A and B, there is spontaneous bleeding but internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces. This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement. 

COMPLICATIONS

Complications are much more common in severe and moderate haemophiliacs. Complications may be either both directly from the disease or from its treatment.

Deep internal bleeding: e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb.

Joint damage: from haemarthrosis (haemophilic arthropathy), potentially with severe pain, disfigurement, and even destruction of the joint and development of debilitating arthritis.

Transfusion transmitted infections: from blood transfusions that are given as treatment. Patients who received untested and unscreened clotting factor are at an extreme risk for contracting HIV and Hepatitis-C via these blood products. 

Adverse reactions:  to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective.

Intracranial hemorrhage: it is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation, nausea, loss of consciousness, brain damage, and death

GENETICS

Primarily males are affected

Being a sex-linked recessive trait, haemophilia is more likely to occur in males than females. Man has one X and one Y chromosome (XY genotype). The gene for haemophilia (h), being located in the X chromosome, is able to produce the defect because there is no homologue of this gene in the Y chromosome to check its expression in males (XhY). Females have 2 X chromosomes (XX genotype) and in them haemophilia appears when both the sex chromosomes carry recessive genes and such females die before birth (XhXh). A woman having a single allele of the trait appears normal, but is carrier of the disease Xh X. 

Criss-cross inheritance

It is a type of sex-linked inheritance where the genes of one parent are transferred to the grand children through the children of opposite sex. It is called Dygynic when transfer of trait occurs from male parent to grandson through daughter (Male→Female→Male). In Dyandric there is transfer from mother to granddaughter through her son (Female→Male→Female). Hemophilia shows dygynic type of criss-cross inheritance in which males show the traits whereas carrier-females only transmit them.

Marriages

Marriage between Haemophilic-male (XhY) and Carrier-female (XhX) produces Haemophilic-sons (50%), Normal-sons (50%), Carrrier-daughters (50%) and Hemophilic-daughters [(50%) (Die before birth)].  

Marriage between Hmophilic-male (XhY) and Normal-female (XX) produces Normal-sons and Carrier-daughters.

Marriage between Normal-male (XY) and Carrier-female (XhX) produces Normal-sons (50%), Normal-daughters (50%), Carrier-daughters (50%) and Hemophilic-sons (50%).

LIFE EXPECTANCY

Like most aspects of the disorder, life expectancy varies with severity and adequate treatment. People with severe haemophilia who don’t receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years. By the 1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years. Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.

EUROPEAN ROYALTY

Haemophilia has featured prominently in European royalty and thus is sometimes known as ‘the royal disease’. Queen Victoria passed the mutation for Haemophilia 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, the son of Nicholas II, was a descendant of Queen Victoria through his mother Empress Alexandra and suffered from haemophilia. In Spain, Queen Victoria’s youngest daughter, Princess Beatrice, had a daughter who later became Queen of Spain. Two of her sons were haemophiliacs and both died from minor car accidents. 

MANAGEMENT

Diagnosis

Characteristic symptoms and ancestral background are suggestive of the disease. Disease needs to be differentiated from Vitamin K deficiency, Disseminated Intravascular Coagulation (DIC), Von-Willebrand Disease, Thrombocytopenia etc which show similar symptoms. Hemophilia is characterized by hematological parameters like normal bleeding time, normal prothrombin time, normal thrombin time, unaffected platelet count, but prolonged partial thromboplastin time.

Treatment

Though there is no cure for haemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in Haemophilia A or factor IX in Haemophilia B. Factor replacement can be either from human blood, recombinant, or a combination of the two. Some haemophiliacs develop antibodies (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.

Preventive exercises

 It is recommended that people affected with haemophilia do specific exercises to strengthen the joints, particularly the elbows, knees, and ankles. Exercises include elements which increase flexibility, tone, and strength of muscles, increasing their ability to protect joints from damaging bleeds. 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.

Genetic counseling

Most of the genetic diseases require counseling between prospective partners to check the transmission of disease to their children. Similarly, genetic testing and genetic counseling is recommended for prospective couples with familial history of haemophilia. Prenatal testing such as amniocentesis is available to pregnant women who may be carriers of the condition. 

zubi744@rediffmail.com