Fenn Rirr is a person with severe Hemophilia A. Sometimes others mistake his disorder as thalassemia instead of hemophilia.
Is an inherited bleeding disorder, manifesting predominantly in worldwide male population. However, about 30% of hemophilia patients have no prior family history of bleeding disorder. In these cases, it is caused by mutation in their genes that lead to bleeding disorder. It is a lifelong disease.
Is a group of inherited blood disorders. It can affect people of any nationality, but it is particularly common in people with ancestry from the Mediterranean and across a broad region extending through India, the Middle East and Asia. It can occur in both male and female population. It is a lifelong disease.
People with hemophilia have either defective or lack of clotting factors. Clotting factors are protein in blood necessary to stop bleeding. The body produces 13 clotting factors. If any of them are defective or deficient, blood clotting is affected. People with hemophilia usually have longer bleeding time compared to unaffected people.
People with thalassemia have either abnormal or lack of hemoglobin in their red blood cells. The bone marrow is responsible for the production of hemoglobin, using iron from diet intake to produce hemoglobin. For people with thalassemia, their bone marrow have abnormal hemoglobin production. Hemoglobin plays an important role in transporting the oxygen that we breathe from the lungs to the rest of the cells and organs in the body. For people with thalassemia, they have fewer healthy red blood cells circulating in their bloodstream, which leads to poorer delivery of oxygen supply to their cells and organs.
- The most common type of hemophilia is Hemophilia A. Instead of complete levels of all 13 clotting factors inside the blood, a person with Hemophilia A has deficiency in clotting factor number 8, or simply Factor VIII.
- The next common type of hemophilia is Hemophilia B. A person with Hemophilia B have a lack of clotting factor number 9, or Factor IX.
Hemophilia A is more common than Hemophilia B, representing 80-85% of the total hemophilia population.
Two alpha globin and two beta globin protein chains make up hemoglobin. There are 2 types of thalassemia.
- The first one is called alpha-thalassemia. In alpha-thalassemia, at least one of the alpha globin genes has a mutation or abnormality.
- In beta-thalassemia, at least one of the beta globin genes has a mutation or abnormality.
How They Are Inherited
In the following illustrations, the pattern of inheritance for Hemophilia and Thalassemia are presented.
- Red figures symbolize persons who are affected by the disorder. They display symptoms associated with the disorder and are the ones who required treatment.
- The red-black figures symbolize persons who will become carriers of the disorder. The carriers will pass on the disorder to their children. An important note; Hemophilia is a sex-linked X-chromosome disorder. As such, its inheritance pattern dictates that only men can be affected with hemophilia and women can only be carriers of the Hemophilia gene. However, a rare case is presented in one of the Hemophilia inheritance illustration below. On the other hand, thalassemia is not tied to sex-linked chromosome. Under various situations, men and women can either be the affected or be the carrier of the thalassemia gene.
- Black figures symbolize unaffected persons.
Severity and Associated Symptoms
The seriousness of Hemophilia A and Hemophilia B can be categorized into 3 levels of severity, depending on the amount of clotting factors that are missing from a person’s blood. For unaffected persons, their clotting factor level in the blood must be at least 40%. A person who has lower than 40% clotting factor level can then be categorized as a person with Hemophilia.
Clotting Factor Level
5% - 40%
Severe bleeding with major trauma or surgery. Spontaneous bleeding is rare
1% - 5%
Occasional spontaneous bleeding; prolonged bleeding with minor trauma or surgery
Spontaneous bleeding into joints or muscles, predominantly in the absence of factor concentrate therapy
Symptoms of Hemophilia A and Hemophilia B are the same. Bleeding episodes can happen externally and internally. Furthermore, the bleeding will take place for a longer time than normal.
- Muscles, especially in deep compartments (iliopsoas, calf, and forearm)
- Joints, especially in the ankles, knees and elbows
- Mucous membranes, especially in the mouth, gums, nose, and genitourinary tract
The severity of thalassemia depends on how many alpha globin genes are mutated (for alpha thalassemia) and how many beta globin genes are mutated (for beta thalassemia).
For Alpha Thalassemia;
Number of Mutated Genes
Alpha Thalassemia Minima
No symptoms, Sometimes very mild symptoms
Alpha Thalassemia Minor
Hemoglobin H Disease
Chronic anemia, Enlarged spleen
Alpha Thalassemia Major
For Beta Thalassemia, 2 mutated genes can either result in Beta Thalassemia Major (BTM)/Colley's anemia (severe form) or Beta Thalassemia Intermedia (BTI) (milder form);
Number of Mutated Genes
Beta Thalassemia Minor
Severe anemia, Generally appears before a child's second birthday
Milder form of BTM/Colley's Anemia
Symptoms of thalassemia can be divided into 2. These symptoms are associated with Hemoglobin H Disease and BTM. Infants born with Alpha Thalassemia Major are usually stillborn or die shortly after being born.
1. Symptoms of Hemoglobin H Disease
Symptoms will range from mild to moderate anemia.
- Shortness of breath
- Overgrow of cheeks, jaw, forehead
2. Symptoms of BTM
The symptoms of BTM mirror severe anemia and can be life threatening.
- Delayed growth
- Frequent infections
- Poor apetite
- Delayed puberty
- Enlarged organs
- Shortness of breath
Types of screening tests:
Blood sample is taken and the activity of clotting factor in the blood is measured. Hemophilia A is diagnosed by testing the level of factor VIII activity. Hemophilia B is diagnosed by measuring the level of factor IX activity.
Bleeding Time (BT)
The bleeding time is the time taken for a standardized skin cut of fixed depth and length to stop bleeding.
Prothrombin Time (PT)
This test also measures the time it takes for blood to clot.
Activated Partial Thromboplastin Time (APTT)
Taken in conjunction with a normal prothrombin time, it is the most useful screening test for detecting deficiencies of factors VIII, IX, XI, and XII.
Types of screening tests:
Complete Blood Count (CBC)
Measurement of hemoglobin levels, quantities of red blood cells and their size.
Evaluation of the number and type of white blood cells, red blood cells and platelets to see if they are normal and mature.
Measurement of different aspects of the body's iron storage and usage. Can be used to help determine whether an iron deficiency is the cause of a person's anemia.
Assessment of the type and relative amounts of hemoglobin present in red blood cells.
When there is a bleeding, the missing clotting factors are administered by intravenous infusion. The missing clotting factors are called factor concentrates. A person with Hemophilia A should be treated with infusion of Factor VIII concentrates, while Factor IX concentrates should be given to a person with Hemophilia B.
Both Factor VIII and Factor IX concentrates are in the form of white powder. They are mixed with sterile water that comes with the factor concentrates. The factor concentrates should be administered according to the doctor's/specialist's prescribed dose.
Factor concentrates can be manufactured from blood plasma. The final products from the blood plasma are called plasma derived factor concentrates. Alternatively, they can be manufactured through a recombinant cell line. These are known as recombinant factor concentrates, or 'synthetic' factor concentrates.
Bleeding episode should be treated as early as possible to minimize pain and damage to the bleeding site. Delayed treatment may cause irreversible damage to the affected joint and muscle. Consequently, higher doses of factor concentrates are necessary whenever treatment is delayed. This will lead to an increase in the cost of treatment and prolonged recovery time.
It is recommended that the infusion of factor concentrates is followed up with R.I.C.E practice to further alleviate the pain and speed up recovery. The components of R.I.C.E are:
- Rest - refrain the affected muscle and joint from moving around and load-bearing routine.
- Ice - apply ice pack to the the bleeding site to reduce pain and swelling.
- Compression - wrap the affected muscle and joint with an elastic bandage to help limit the swelling and provide additional support to the affected joint and muscle.
- Elevation - elevate the affected muscle and joint at or above heart level. If this is not possible, at least align it parallel to the ground.
- Blood transfusion
This is the main treatment option for people suffering from moderate to severe thalassemia. Blood transfusion will replenish the body with fresh red blood cells containing normal hemoglobin.
- Iron chelation therapy
The drawback from regular blood transfusion is iron overload in the bloodstream which can cause damage to the liver, heart and other parts of the body. Thus, iron chelation therapy can be carried out to remove excess iron from the body. The therapy can be administered orally or through subcutaneous infusion.
- Folic acid supplements
Folic acid is a B vitamin that helps build healthy red blood cells.
- Bone marrow transplant
Bone marrow transplant from a compatible donor is considered the best option for treatment. However, the procedure is quite risky and is only reserved for severe cases. The most compatible donor for bone marrow usually comes from the siblings of thalassemia sufferer.