Thalassemia Linked To Increased Risk Of Stroke Biology Essay

Published: Last Edited:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

This paper reviews the contributions of stroke and its correlation with the increased occurrences among persons positive for thalassemia. It also examines the relationship between the person's type of thalassemia, hemostatic changes, coagulation factors, thromboembolic manifestations such as deep venous thrombosis and pulmonary embolism; including plasma markers and abnormal red blood cell phenotype.


thalassemia is a genetic blood disorder where red blood cells (RBC) cannot manufacture normal forms of hemoglobin therefore resulting in the reduction of the total amount of oxygen-carrying capabilities of the cell. Normal RBC's are visually large, round and numerous in size and association. Microscopy of a person with thalassemia will exhibit a RBC with a phenotype resembling a smaller version of a normal RBC (Figure 1.) There are two forms of thalassemia; α-thalassemia and thalassemia. The Greek letters represent the proteins affected in the hemoglobin residing in the RBC of a person with thalassemia. Alpha thalassemia's occur when the genes correlating to the alpha globin protein are changed or mutated. Beta thalassemia's occur when there are changes or mutations to the beta globin protein. thalassemia will be the key focal point of this collaboration. Both of the thalassemia's can be sub-typed into two additional forms; thalassemia major and thalassemia minor (also referred to as intermedia.) Thalassemia major occurs when progeny inherit 2 defective genes from both parents, and is often fatal; and thalassemia minor occurs when progeny inherit only one defective gene from a parent. The defective gene in thalassemia has been isolated and referred as the hemoglobin, beta (HBB) gene. Beta globin is a smaller caliber protein that makes up 2 of the four subunits of hemoglobin where the final two subunits are alpha globins. Beta globin carries along with it an iron rich molecule better known as heme. Heme is necessary for the proper uptake of oxygen by the RBC's and transportation of that compound into the pleural cavity for disbursal throughout the entire human body. A normal RBC carries four oxygen molecules that are attached directly to the heme molecule donated by both alpha and beta globin. This process is what gives blood its indicative red pigment. Alterations in this process result in over 250 known mutation of the HBB gene giving rise to thalassemia. Most mutations are directly linked to mutations of a single nucleotide in the HBB gene, and even include the deletion of a several nucleotides in the same HBB gene region. The HBB gene is located on the short arm of chromosome 11 at cytogenic location 11p15.5 (Figure 2.) Mutations and deletions occurring in or around the HBB gene include several other diseases such as sickle cell and methemoglobinemia.

The current status of thalassemia is giving insight into the correlation between the increased risks of stroke in persons carrying the defective gene. Plasma markers have given the ability to foresee hypercoagulability in persons with the blood disorder. These plasma markers illuminated the existence of thalassemia by isolating thrombin-ATIII (TAT) complexes found in those carrying the genetic defect on chromosome 11. Research conducted in 1978 included insight into higher than normal platelet counts in patients with thalassemia that had undergone splenectomy. This was thought to be the result of the bleeding disorder and not given much attention. However in 1981 doctors has noticed 71% of splenectomized patients vs. 35% of non-splenectomized patients both with thalassemia exhibited existence of a hypercoagulable state. Researchers investigated 10 patients who received a splenectomy where individuals with thalassemia has a mean platelet lifespan of 107 +/- 36 hours compared to the mean of healthy patients who did not have thalassemia and underwent a splenectomy due to trauma and exhibited a platelet lifespan of 248 +/- 51 hours. Coagulation factors and inhibitors have also become a useful tool in deciphering the correlation between elevated risks of stroke and persons with thalassemia. The study of coagulation proteins marks great emphasis on the existence of a hypercoagulable state (also referred to as thrombophilia) regarding those with a genetic predisposition for thalassemia. Thrombophilia refers to the ability of the blood platelets to aggregate at higher than normal instances when clotting is not necessary creating an environment within the body that may become vulnerable when a clot is thrown. A thrown clot in the venous system can cause deep vein thrombosis (DVT) which is located in the upper and lower limbs, the pelvis, kidneys, and liver; or even a pulmonary embolus where a clot is located in the lungs and is often fatal. Blood clots thrown in the arterial pathways can increase risks for stroke, severe leg pain, and even the loss of a limb. Thrombophilia is the epicenter of concern for persons with thalassemia since it has been shown that these persons are susceptible to reduced amounts of coagulation inhibitors. Coagulation inhibitors include proteins C and S which are both found in clinically reduced levels in people with thalassemia. These proteins, including antithrombin, are important for the proper anticoagulation of the blood which steadily adjusts clotting ability to ensure the thickness is not so much as to create a clot, or not enough that it can create a bleeding event. Without this measure of homeostasis for blood coagulation chances of having complications from blood clots and/or hemophilic events are greater and more likely to occur than in a healthy non-thrombophilia individual.

Future direction in research and development to aid individuals with thalassemia is unfortunately not a field where funds are being directed into. thalassemia is one of the largest blood disorders in the world and also the most common hereditary disease spanning the globe, yet, is lacking comprehensive reviews. Treatment modalities are still very palliative, and little is being done in aid of better therapies. Gene therapy, bone marrow transplants, transfusions and chelation therapies are all options in effort to pioneer better treatments for the disease. These "options" are smoke and mirror modalities available to individuals with a financial foundation to embrace them, and are not useful to the average human being. Downtime is not considered, rejection to transplant marrow is not addressed, adverse reactions to chelation in excess is undetermined, and time and financial burdens can only dictate whether gene therapy is even an option. Even considering if an individual was able to utilize the treatments listed the therapies are so invasive that it would weigh the benefit to burden ratio. In individuals with thalassemia Major who have survived past adolescence transfusion and chelation have been some of the only methods available to aid in a lengthy lifespan.