Haemophilia A

Hemophilia A 1

HAEMOPHILIA A

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Hemophilia A 2

Haemophilia A

Introduction

Haemophilia is a common form of disorders that people inherit, and it is associated

with the impairment of the clotting ability of the blood. Clotting is an essential process in

stopping bleeding in the body tissues when an injury occurs on an individual. Haemophilia,

therefore, results in excess and prolonged bleeding in the victim of bruises (Gilbert, Paroskie,

Gailani, Debaun, and Sidonio 2015, 764). It also increases the risk of internal bleeding in the

joints and the brain. There are two distinct forms of the disorder, that is, Haemophilia A and

Haemophilia 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

Hemophilia A 3

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

Figure 1: Inheritance of haemophilia A from a healthy male and a carrier female (Ohira,

Kakinuma, Seki, and Kuchii 2015, 632).

Normal male

Normal Female

Carrier

Hemophiliac son

Hemophilia A 4

Haemophilic male Carrier female

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 pro-enzymes 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

Normal male

Carrier

Hemophilic

daughter

Hemophiliac son

Hemophilia A 5

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

Hemophilia A 6

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)

Hemophilia A 7

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.

Hemophilia A 8

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.

Hemophilia A 9

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Hemophilia A 12

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Hemophilia A 13

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