Platelets Reversion of Thrombocytopenia Using Bovi

CHAPTER 2 REVIEW OF RELATED ARTICLES

A. Platelets

A.1 Description of Platelets Platelets are the smallest of the blood cells. Platelets, along with red blood cells and plasma, form a major proportion of both human and animal blood. Microscopically, they look like little spiky ovals, as the average size is about four hundred thousandths of an inch or 1.0-3.5 µm Wisegeek [updated 2010]. Like the red blood cells, they lack a nucleus and are incapable of cell division, or mitosis, but they have a more complex metabolism and internal structure than the red blood cells ―blood‖ Encyclopaedia Britannica 2011. Platelets are only about 20 of the diameter of red blood cells. The normal number of platelets in humans is 150,000- 350,000 platelets per microliter µL of blood. Since platelets are so small, they make up just a tiny fraction of the blood volume. Although much more numerous than the white blood cells, platelets occupy a smaller fraction of the volume of the blood because of their relatively small size. Platelets are actually not true cells but merely circulating fragments of megakaryocyte cytoplasm. But even though platelets are merely cell fragments, they contain many structures that are critical to stop bleeding. Their principal function is to prevent bleeding www.ouhsc.edu [updated 2009]. They contain proteins on their surface that allow them to stick and to break in the blood vessel wall, and also to stick to one another. They contain granules that secrete other proteins required for creating a firm plug, called platelet plug, to seal blood vessel breaks. Also, platelets contain proteins similar to muscle proteins that allow them to change shape when they become sticky www.ouhsc.edu [updated 2009]. Mouse platelets appear discoid when viewed by light or electron microscopy. On a blood smear, mouse platelets appear round to oval to elongated, and have a diameter of 1-4 µm. Platelet clumps are frequently observed on mouse blood smears. The presence of these platelet clumps invalidates the platelet count that is why the blood collected must be stored in an EDTA tube. The EDTA tube is a blood collection tube that protects the blood sample and its platelet and cells at its original condition for a longer time. Mouse platelets are known to differ from human platelets in a number of fundamental ways, including, platelet size and platelet number. Nonetheless, studies of fundamental aspects of platelet function are quite reassuring about the similarities between human and mouse platelets, and so there is reason to extrapolate the observations made in mice to humans . A.2 Production of Platelets Platelets arise from large megakaryocytes found in the bone marrow, which are derived from hematopoietic stem cells HSC. HSCs generate the multiple hematopoietic lineages through a successive series of intermediate progenitors. These include common lymphoid progenitors CLPs, which can generate only B cells, T cells, and natural killer cells, and common myeloid progenitors CMPs, which can generate only red cells, platelets, granulocytes, and monocytes. Platelets are released from megakaryocytes as small subcellular discs with high fidelity into blood where they function to preserve the integrity of the vascular system. A megakaryocyte‘s brief lifetime follows a maturation process involving the destruction and removal of the residual cell body and the nuclear material and culminates in the release of 100-1000 platelets. Megakaryocytes are rare myeloid cells that reside primarily in the bone marrow but are also found in the lung and peripheral blood. They arise from pluripotent hematopoietic stem cells that develop into precursors. Development of these precursors continues along an increasingly restricted lineage culminating in the formation of megakaryocyte precursors that develop into megakaryocytes. Megakaryocytes tailor their cytoplasm and membrane systems for platelet biogenesis. They experience significant maturation as internal membrane systems, granules, and organelles are assembled in bulk during their development. As terminally differentiated megakaryocytes complete maturation, they are fully equipped with the elements and machinery required for the major task of platelet biogenesis Patel and others 2005. A.3 Role of Platelets in the Human Body Platelets normally move freely through the lumen of blood vessels as components of the circulatory system. Maintenance of normal vascular integrity involves nourishment of the endothelium by some platelet constituents or the actual incorporation of platelets into the vessel wall. When the vessel wall is damaged, subendothelial structures, including basement membrane collagen and microfibrils, are exposed. Circulating platelets react with these exposed collagen fibers, and their adherence to the damaged surface is mediated by high molecular weight multimers of the factor VIII von Willebrand Factor vWF and probably fibronectin. When activated, platelets immediately change shape, losing their discoid shape, and form tiny spheres with numerous projecting pseudopods. After adhesion of a single layer of platelets to the damaged vascular endothelium, they stick to one another and form aggregates. Certain substances react with specific platelet membrane surface receptors and initiate platelet aggregation and further activation Turgeon 1988. Platelets are responsible for several distinct activities in response to vascular damage, including: 1 maintenance of vascular integrity by sealing minor deficiencies of the endothelium, 2 formation of a ―platelet plug‖ to initially stop bleeding, 3 stabilization of the platelet plug by the action of phospholipid procoagulant, and 4 promotion of vascular healing Turgeon 1988. A study done by Poole and others 1997 stated the mouse platelets responded in a similar manner to human platelets when stimulated with collagen, but are less sensitive to thrombin. A.4 Categories of Thrombocytopenia The normal numbers of circulating platelets in the human body ranges from 1.50 x 10 11 to 4.50 x 10 11 per L of blood while the normal range of platelets in a mouse is 1.60 x 10 5 to 4.10 x 10 5 per mm 3 of blood. When the number of platelets falls below this range, a condition called thrombocytopenia exists. On the other hand, thrombocytosis occurs when the number of platelets rises above the range Turgeon 1988. Thrombocytopenia is any disorder in which there is an abnormally low amount of platelets in the blood. This condition may arise as a result of a wide variety of conditions such as severe bleeding or liver disease. Thrombocytopenic conditions are classified into three major categories: 1 decreased production of platelets, 2 increased destruction or utilization of platelets, and 3 disorders in platelet distribution Turgeon 1988. Decreased production of platelets can result from damage to hematopoietic stem cells of the bone marrow. This may be due to irradiation, drugs, chemicals, infiltration of the bone marrow by malignant cells, and non-malignant conditions. Thrombocytopenia of this type is a manifestation of a nutritional disorder Turgeon 1988. Increased destruction or utilization of platelets may result from a number of mechanisms. This may be due to antigens, antibodies, complement activities, snake bite, autoimmune and isoimmune disorders, and vascular injury Turgeon 1988. Platelet distribution disorders can result from pooling of platelets in the spleen which is frequent if splenomegaly, or enlargement of the spleen beyond the normal size, is present. This kind or thrombocytopenia occurs when more than double or triple increase in platelet production is needed to maintain a normal platelet count Turgeon 1988.

B. Albumin