Haematology: Thrombotic Thrombocytopenic Purpura (TTP) - Essay Example

Haematology: Thrombotic Thrombocytopenic Purpura (TTP) Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder that is found in a meagre percentage of the population. To understand and address the question which asks us to determine whether TTP can be classified as both clotting and bleeding disorders, it is necessary to first look at the way the disorder is manifested in an organism (human), and the criteria that can be used to classify it as a bleeding and clotting disorder. Thrombotic thrombocytopenic purpura involves the formation of small blood clots in entirely all the vessels of the body (William, Timothy, and Dirk, 2006). This blockage consequently hinders the delivery of oxygen rich blood to the body organs and parts involved. This may include blockage to serious organs such as the heart and the brain. As the disease further manifests itself in the body, the clots increase, and this causes the using-up of the platelets that are found in the blood. Since the platelets are the blood fragments that are responsible for blood clotting, the disease therefore lowers the body’s blood clotting ability. The failure of blood to clot is associated with a number of further complications which make the blood continue getting lost, for example in case of a skin fracture. Blood has its own mechanism that is responsible for preventing it from clotting unless the skin is broken at a point eliciting a bleeding spree. This is mainly done by heparin, which is the anticlotting factor in the blood. In case heparin is lacking in the blood, clotting can occur at any point, and it can be a predisposing factor in TTP. However, in normal cases heparin is neutralised when the skin is injured, and the series of processes that will be discussed in this work causes blood to clot. This essay will therefore establish whether thrombotic thrombocytopenic purpura can be described as both bleeding and clotting disorders. Thrombotic Thrombocytopenic Purpura Pathogenesis TTP involves the coagulation of blood in the blood vessels, which consequently leads to the formation of many small clots in them. The blood clots are microscopic and distributed throughout the body. The clots are known as thrombi. These clots are known to have the potentiality to destroy major body organs including the kidney, heart and the brain. Thrombotic thrombocytopenic purpura arises from the inhibition of an enzyme that is responsible for ensuring that blood does not clot in the blood vessels, or when the circulation is still going on. The enzyme is known as a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, shortly ADAMTS13 enzyme (Chun-Yet Lian, 2005). This is a zinc containing metalloprotease enzyme, and it works by cleaving the von Willebrand Factor (vWF), which is a large protein responsible for blood clotting. The degradation of vWF multimers is important in decreasing their effect, and hence blood clotting is discouraged in the flowing blood. In TTP, however, the enzyme is not produced, which means that there will be the formation of clots due to the rising levels of vWF multimers. As discussed earlier in the introduction, the formation of clots hinders the delivery of oxygen rich blood to the target organs where it is needed. The cleaving of vWF done by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), is supposed to maintain low levels of the multimer so that clotting should not take place. However, its deficiency, which can be genetically acquired in rare conditions, explains why the disorder is described as a clotting disorder. The next part of the essay will look at the way the disease is described as a bleeding disorder. Idiopathic and Secondary TTP TTP is caused by spontaneous aggregation of platelets and coagulation in the blood vessels. During the aggregation process (clotting), the platelets present in the blood are consumed in a major way and then bind to vWF multimer (Sadler, 1998). The formation of these complexes (platelet-vWF) produces microthrombi, which circulate in the blood vessels and further cause serious shearing of the erythrocytes. This results in hemolysis. In idiopathic TTP, inhibition of the enzyme ADAMTS13 occurs due to the presence of antibodies. ADAMTS13 is the enzyme responsible for the breakdown of von Willebrand Factor (vWF). This protein is responsible for linking platelets, the blood vessels, and the clots formed during the process of coagulation in this disorder (George, 2006). Secondary TTP is not found in many of the TTP cases. It is brought about by a number of predisposing factors which include cancer and HIV-1 infection. In this type, the activity of ADAMTS13 is not totally depressed, and this makes the understanding of the disorder really tough. Medical research, however, relates it to the damage of the endothelial tissues. Symptoms and Signs The signs and symptoms of this disorder further help describe it as a bleeding and clotting disorder. The symptoms include thrombocytopenia, which is characterized by extremely low levels of platelets in the body. This consequently leads to purpura. Another significant symptom is microangiopathic haemolytic anemia (Hatton, 2008). This is evident as a result of the mechanical fragmentation, and shearing of erythrocytes as a result of aggregation of the platelets. This leads to low levels of erythrocytes and platelets in the body (Furlan and Lammie, 2001). The lowering platelet levels mean that in case of an injury the blood may take more time to clot or fail to clot at all. Other symptoms associated with TTP include neurologic disorders, which are seen with abnormalities such as having hallucinations and regular headaches. Kidney failure is also common in many patients having the disease. Why TTP Can Be Described as a Bleeding and Clotting Disorder From the discussion above, we have been able to establish the aetiology of TTP. The disease can be described as a clotting disorder since the depletion or the absence of the enzyme ADAMTS13 leads to increased levels of multimer vWF, which makes the platelets coagulate and form thrombi in the blood vessels (Handin, 2005). These clots have a negative effect as they block the delivery of oxygen rich blood to the target organs (Furie, 2008). The organs include the brain, liver and the kidneys. The increased destruction of the platelets is used to describe why the disease is also a bleeding disorder. Since platelets are responsible for the process of blood clotting, their destruction and lowering count in cases of TTP means that where the patient is injured, the blood will continue to be lost without clotting to form the mesh around the wound. This describes the disease as a bleeding one on top of it being categorised as a clotting disease. References Chun-Yet Lian, E., 2005. Pathogenesis of thrombotic thrombocytopenic purpura: ADAMTS13 deficiency and beyond. Seminars in Thrombosis and Hemostasis, 6(31), p. 625. Furie, B., 2008. Mechanisms of thrombus formation. New England Journal of Medicine, 359(9), pp. 944–951. Furlan, M. and Lammie, B., 2001. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Heamatol, 14(2), pp. 437–454. George, J. N., 2006. Clinical practice: thrombotic thrombocytopenic purpura. English Journal of Medicine, 354(18), p. 1927. Handin, R. I., 2005. Chapter 53: bleeding and thrombosis. In Kasper, D. L. et al. (eds.), Harrison's principles of internal medicine (16th ed.). New York, NY: McGraw-Hill. Hatton, C., 2008. Haematology. Cambridge: Blackwell Publishers. Sadler, J. E., 1998. Biochemistry and genetics of von Willebrand Factor. Annu. Rev. Biochem., 67, pp. 395–425. William, J. D., Timothy, G. B. and Dirk, M. E., 2005. Andrews of the Skin. New Delhi: W B Saunders Co. Read More