Introduction
Platelets comprise of a very important component in the blood. They prevent blood loss in the body. This is enhanced by formation of an entangled mesh made of fibrinogen which is activated by calcium ions and the von Willbrand factor. A complex physiology ensues within the first few minutes of exposure of the tissue underlying the epithelial tissue in the skin (Hoffman 2009, p.123). Platelets also play a very important role in ensuring the pathogenic organisms are prevented from entering the body through the exposed tissue on the skin. This paper comprise of various components which are intended to illustrate the mechanisms that are involved in the blood clotting process.
Platelet glycoprotein Ib (GP Ib)-IX-V receptors
integrin IIb 3 (GP IIb IIIa) receptors
structure
Consists of a disulfide-linked 140 kD alpha chain and 22 kD beta chain
Comprise of IIb 3 receptors.
Molecular classification
Consists of 7 molecules non-covalently linked.
Comprise of IIb 3 as the major complex molecules.
CD nomenclature
Is a combination of subunits: CD42b, c, a, d, b, CD61 in order.
Comprise of CD15, CD30 and CD45 depending on the location of the platelet membrane.
function
Generates intracellular signals for binding of the ligands.
It acts as a receptor for fibrinogen and aids in platelet activation
location in the platelet
Located in the platelet membrane.
Located on the platelet cytoplasm
ligands
Generates the activating signals
Responds by generating binding ligands.
activation
Activation occurs from inside out.
Platelet activation by ADP (adenosine diphosphate).
types of signaling involved
Involves trans-membrane signaling
how the receptor is kept from inappropriate activation
Requires vWF for activation, this is only present upon exposure of the platelets.
Only activated when Gp Ib/IX/V binds vWF
relative density on the platelet surface before platelet activation
Exists in low density
Exists in the cytoplasm in high density
relative density on the platelet surface after platelet activation
Exists in the cytoplasm membrane in low density
Exists in the cytoplasm membrane in high density
how its function can be tested
Functionality can be tested by introduction of vWF.
Functionality is tested by identification of the platelet shape prior the Gp Ib/IX/V – vWF binding
Abnormalities associated with the functionality.
Mutations as a result of Bernard-Soulier syndrome,velocardiofacial syndrome and giant platelet disorder
Major defects are Glanzmann's thrombasthenia
2) Vascular smooth muscle cells contain tissue factor cells as their constitutive protein cells. Tissue factor, which is mainly expressed in vivo, is necessary in the enhancement of vascular thrombosis. Vascular thrombosis is basically a defect which is caused by clotting of the blood in the veins of a living organism (Broos et al. 2011, p. 234). This defect is normally caused by inflamed blood vessels, turbulent blood flow as well as very slow blood flow in the body.
Tissue factor is induced in the epithelium of the body. The induction process is done through ligation of CD40 or rather formation of ligaments. The major effects of the vice are experienced in inflammatory diseases such as atherosclerosis.
Coagulation is a complex process through which clotting process occurs. The process begins with the tissue factor inducing changes in the structure of the platelets. Once the platelets are activated by the vWF – von Willbrand factor, which is released from the endothelium and the exposed platelets, further platelets are activated (Deutsch and Tomer 2006, p. 204). This factor initiates the release of fibrinogen which develops a links for aggregation by the activated platelets. Platelets change their shape from spherical to stellate to aid the binding process. Technically, the platelets cannot be able to bind in their spherical states.
Inflammation initiates clotting by activating the platelets and impairing major forms of anticoagulant mechanisms. Inflammation also destroys the fibrinolytic system, leading to the release of fibrinogen which in turn facilitates clotting (Rodak, Fritsma and Keohane 2006, p234). Despite the fact that clotting is necessary, inflammation interferes with the normal operation of the coagulation mechanisms.
3) Unintended activation occurs at times due to certain defects of the body. Platelet activation is controlled in the platelet activation pathway. Integrin αIIbβ3, which is mainly a receptor for activating the platelets, exists in inactive form so as to avoid any likelihood of accidental activation (Geddis 2010, p.87). Accidental activation could cause internal clotting which in turn could lead to stroke. The shape of the platelets also prevents any likelihood of attaching with each other. Additionally, they cannot be easily activated unless the platelets are exposed.
There exist three major mechanisms that control blood clotting. During the injury of a blood vessel, the vessel constricts to limit the amount of flood to the damaged part. Additionally, increase in the amount of blood oozing to the damaged part decreases with increase on the pressure mounted by the oozed blood at the site of damage (Fritsma 2012, p. 321).
Another major role is played by regulators of G-protein signaling (RGS), which ensures a dependent and controlled signaling mechanism. This protein allele also prevents any unnecessary haemostatic responses which mainly induce increased activation of platelets. Similarly, the RGS prevents secretion by the α-granule, which is induced by the vWF factor. This is a directed and dependent response which ensures that the major factors do not operate in isolation but enhance looped response mechanisms which prohibit unnecessary activation of platelets.
The anti-thrombin plays another significant role in prevention of unintended activation of platelets. A complex control mechanism is integrated in the entire system so as to ensure that platelets keep in an inactive provided there is the presence of the endothelial tissue. In the coagulation cascade, the clotting process exists in phases to prevent undirected responses. The clotting process is controlled by factors in the platelets as well as the endothelial tissue. For instance, the receptors in the platelets must receive the von Willebrand Factor for activation to occur. The platelets shape prevents even the likelihood of interlocking during the process of blood flow.
4) Pathophysiology :
Von Willebrand disease is caused by deficiency of von Willebrand Factor in the blood. VWF is mainly a multimeric protein factor which is necessary for coagulation via platelet adhesion. The initial stages of diagnostic response involve identification of qualitative and quantitative deficiencies that exist in the blood. Qualitative identification involve identification of the various factors that exist in protein, a good example is factor VIII; this mainly protects the factor from breakdown within the blood.
Major symptoms in the body include excessive nose bleeding which is in many instances regular. Many of these tests are done in vivo as well as in vitro especially when there is need to verify the platelet response in cases where the vitro tests tend to give unreliable identification of the problem. This is where aspects such as determining the response of the platelets in the clotting process.
The disorders associated with this form of disease are classified depending on the factors deficient. The first classification is the type 1disorder, which is a quantitative complication. Quantities of von Willbrand factor are detected to be less than half of the normal blood vWF (Brass 2009, p. 122). It is a defect characterized with impaired clotting which is mainly regarded as a bleeding disorder.
The second vWF disease is the type 2 disorder. This is basically qualitative and the defect’s impacts vary depending on the infected individuals. It is characterized with the abnormality of the structure of the multimer, which is a very essential component in the blood. However, the levels of the vWF in the blood are normal (Abrams and Plow 2009, p. 129).
Other defects are regarded as the subgroups of the two classifications discussed above. The first classification is type 2A. This form of defect is characterized by small multimer units in the blood which results from abnormal synthesis of the vWF multimers.
Type 2B is caused by absence of large multimers in the blood. A vitro experiment indicates that a lower than normal amount of ristocetin is found to take part in the clotting process. Use of platelet rich plasma implies that the number of vMF is sufficient in the test sample. Desmopressin, which is a treatment used bleeding cannot be used on this defect because it causes abnormal aggregation of platelets.
Type 2M is another qualitative deficit in which there is a decreased functionality in the von Willbrand factor due to reduced RICOF (ristocetin cofactor activity), which is essential in an effective clotting process. Therefore molecular weight of the multimers is reduced.
Type 2N is also referred to as Normandy which is a deficiency of the binding of the vWF to factor VIII. Basically, protein level is normal but factor 7 is low. This defect is confused with hemophilia A, normally in the research findings.
Finally, the major defect is type 3, which is the most severe form of von Willbrand diseases. It is sometimes characterized with extensive mucosal bleeding. There is normally a negative vWF antigen and a low factor 7. Its symptoms are mostly related to hemarthrones, disorder of bleeding of joints. A similar case is hemophilia.
These defects are diagnosed using, PFA, platelet function assay, is mainly used to give an abnormal collagen closure time and in basic cases, it gives adenosine diphosphate closure time. RIPA ( ristocetin induced platelet agglutination) is used to prevent the breakdown of factor VIII during the normal blood flow. Another viable alternative is the RICOF (ristocetin cofactor activity assay which prevents platelets aggregation in the flood. RICOF measures the ability of the plasma vWF to agglutinate the platelets.
These two factors measure the ability of the response of the major factors involved in clotting process. These ensure an effective control during the induced action of antibiotics. RIPA and RICOF assays have been extensively used in controlled binding of GpIb factor with the platelets in vitro as well as in vivo.
