About Haemophilia A

The reduction of the blood's capacity to clot is connected with hemophilia, a frequent type of inherited illness. When a person sustains an injury, clotting is a crucial mechanism for stopping bleeding in the body tissues. Therefore, haemophilia causes excessive and protracted bleeding in the person who has bruising (Gilbert, Paroskie, Gailani, Debaun, and Sidonio 2015, 764). Additionally, it makes internal bleeding in the brain and joints more likely. The condition comes in two different forms: hemophilia A and hemophilia B. Those who experience haemophilia A have low clotting factor VIII, which is an essential blood- clotting protein. Haemophilia B, on the other hand, occurs due to lack of adequate clotting factor IX, which is one of the serine proteases of coagulation belonging to the peptidase family S1. This paper concentrates on Haemophilia A, one of the disorders that cause severe problems to the humanity. It discusses the genetics, biochemistry, clinical manifestation, laboratory determination, and treatment of the disorder.

Genetics of Haemophilia A

The two sex chromosomes in human beings are the X-chromosome and Y-chromosome. Any male has both the X and Y chromosomes while females have two X chromosomes (MyrinWestesson, Sparud-Lundin, Wallengren, and Baghaei 2015, 801). Upon mating, they pass genes to the young ones. Depending on the gene combination, a boy or girl child may be born (Martinowitz et al. 2015, 787). Haemophilia A is carried on the X chromosomes only. The disorder occurs due to the deficiency of functional plasma clotting factor VIII (FVIII), and the mother is usually the carrier. The mutations that cause haemophilia A are X- linked recessive; therefore, any female who has the genes of the disorder on one of the X chromosomes never feels its effect (Davies and Kadir 2016, 35). This is because the free X chromosome would express itself to provide the factor for clotting in case she needs it. The Y chromosomes in males, on the other hand, do not have gene factors VIII. If the genes that produce factor VIII are present on the X chromosomes of the male and are deficient, then haemophilia A will develop because the Y chromosome has no equivalent genes to cancel it out. This disorder is, therefore, more prompt in males than in females.

By transmission, a woman who is a carrier has a fifty percent probability of passing a defective X chromosome to the daughter (Minuk et al. 2015, 738). A father who has the disorder will always pass the infected gene to his daughter because he must pass an X chromosome during fertilisation (Evangelista, Lima, Idalino, Lima, and Moura 2015, 781). All the sons would be safe if only the father has the defect because they only receive non-recessive Y chromosome from him. The diagrams below illustrate how the genes of haemophilia A can be transmitted to the children whose parents have different conditions.

Normal male Carrier female









XX

Normal Female



XY

Normal male

Xx

Carrier





xY

Hemophiliac son



Figure 1: Inheritance of haemophilia A from a healthy male and a carrier female (Ohira, Kakinuma, Seki, and Kuchii 2015, 632).





Haemophilic male Carrier female







xx

Hemophilic daughter





xY

Hemophiliac son

XY

Normal male

Xx

Carrier





Figure 2: Inheritance of haemophilia A from a haemophilic male and a carrier female. (Nolan et al. 2016, 73)

Biochemistry of Haemophilia A

Blood clotting is a complicated process that involves a series of steps known as cascade reactions and clotting factors, for instance, factor VIII and IX. Any disruption in the cascade, for example, having a non-functioning factor would prevent any blood clotting (Fischer et al. 2015, 617). Under normal circumstances, when an injury occurs, enzymes and platelets become activated in response to the loss of blood (Almeida et al. 2015, 786). The clotting cascade is then activated as well as propagation of clots. Activation of a series of inactive precursors and proenzymes is a very critical process in coagulation. It results in stepwise amplification of the response (generation of factor VIIa in small amount but has the significant implication of activating a large number of molecules of factor IX and VIII) (Cayir et al. 2014, 310). The outcome is that a large amount of thrombin is produced (Brand, Dunn &Kulkarni 2015, 32). Clotting is so much dependent on the availability of VIII to provide the amount of thrombin required in the process. The absence of factor VIII would inhibit clotting and lead to the condition of haemophilia A (Kessler and Knöbl 2015, 37). Factor VIII is activated by both thrombin and Xa that enables it to accomplish the task of forming a clot in case there is a cut. The progress of clotting is determined by the level of factor IX, and VIII produced, and therefore Xa and thrombin are formed which aid in clotting. With haemophilia A, it is hard to complete the cascade because of the missing factor VIII. (Sockalingam, Othman and Mahyuddin 2015, 610). The clotting process is not achieved leading to profuse bleeding that could result in death if not properly managed (Foppen, Schaafand Fischer 2016, 122). Haemophilia A is induced by the mutation in G8 genes (Ljung and GretenkortAndersson 2015, 779).

Clinical Manifestation of Haemophilia A

The frequency and severity of bleeding in haemophilia A patient is inversely related to the level of residual factor VIII protein that is circulating in the blood (Harrington et al. 2016, 105). The disorder majorly affects the weight-bearing joints such as the hips, knees, shoulders, and ankles. When the patient does not go for early treatment of this gene disorder, it can lead to a severe swelling and pain at the joints (Khair, Meerabeau, and Gibson 2015, 1109). The highly irritating blood in the synovial fluid would cause synovial overgrowth that may lead to excessive bleeding from the vascular tissues of the joints. The bleeding at the joints results in the deposition of iron in the chondrocytes that may result in the development of arthritis (Berntorp, Mauser-Bunschoten, Jiménez-Yuste, and Spears 2015, 12). During the treatment of haemophilia A, a patient feels fatigue, especially in the joints. This is because internal bleeding may have occurred in the parts of the body. Under normal conditions, joints have spaces left to allow movements of bones and tissues (Dargaud et al. 2016, 13). When one has haemophilia A, blood occupies the spaces in the joints. Individuals who are haemophiliac with type A also produce stool and urine that have traces of blood. Although this may be one condition for detecting some diseases, it would be wise not to overlook the possibility of one having the defect (Goodeve 2015, 1188).

Laboratory Determination of Haemophilia A

Screen Tests are the most common ways of determining whether individuals have the defect because of its ability to show whether the blood can clot properly (Fischer et al. 2015, 613).There are various types of screen tests for diagnosing Haemophilia A. The first one is Complete Blood Count (CBC). It is a common test used in determining the amount of haemoglobin, the quantity of red and white blood cells, and platelets in the blood (Moerloose et al. 2015, 4). People with haemophilia A always have low haemoglobin and red blood cells count. The second test is the Activated Partial Thromboplastin Time (APTT) test, which technicians use to determine the length of time it takes before blood clots (Rocino et al. 2016, 98). It also helps in assessing the ability of the factors involved in clotting including VIII. When this factor is lower than normal, it takes longer for clots to be formed in people with haemophilia A. Another test is Fibrinogen Test that helps the doctors to assess the ability of the patient to form a blood clot (Carcao et al. 2015, 17). The test is carried out along with other blood clotting tests or when the results from APPT test are abnormal. Haemophilia A can be severe, moderate or mild.

Classification

Factor VIII levels

Severe

< 1% of the normal

Moderate

About 1-5% of the normal level

Mild

5-30% of the normal level

Table 1: Classification of Haemophilia A (Chai-Adisaksopha, Hillis, Thabane, and Iorio 2015, 733)

Forms of Screening

Screening

Role

Complete Blood Count (CBC

Measuring the amount of haemoglobin, size and the number of RBC and the number of white blood cells

Activated Partial Thromboplastin Time (APTT) Test

Determine the clotting ability of the factor VIII

Fibrinogen Test

Tests the ability of the patient to form clots when tissues are cut or bruised and is done parallel to PT and APTT.

Table 2: Types of tests for Haemophilia A (Nijdam et al. 2016, 146)

Treatment of Haemophilia A

The process of treating haemophilia A is regarded as replacement therapy. The treatment process involves introducing clotting factor VIII for haemophilia A into the veins slowly (Henrard, Speybroeck, and Hermans 2015, 717). Factor VIII (FVIII) is administered three times in a week to make the process effective. This factor is concentrated after being acquired from human blood. However, the blood has to be treated for other communicable diseases. Although treatment is done on the blood, the risk of getting infections from the clot factors is minimal (Olsson et al. 2015, 743). Also, the risk can further be reduced by taking the clotting factors that are not made from the blood of humans, that is, the recombinant clotting factors.



Conclusion

Haemophilia A as a bleeding disorder makes the process of clotting challenging and is associated with lack of essential elements of clotting such as factors VIII. Profuse bleeding is the primary outcome of developing this inherited coagulation disorder that affects more males than females especially due to a mutation that occurs in the genes. Females only serve as carriers while males, especially those with the recessive chromosome form of X, suffer from it. This genetic disorder can end if people put strategies in place and work towards meeting the set target of realising zero haemophilia A patients.



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