Prothrombin Functions in Physiological Processes - Paper Example

The body produces a lot of protein elements designed to assist in many physiological processes. The synthesis occurs in the liver and then is hematogenously transported to the target organs or tissues. Prothrombin is one of these proteins designed to participate in the normal hemostatic reflex. It is also called factor II and is an essential component in the final steps of the coagulation cascade (Palta, Saroa, & Palta, 2014). The body continuously engages the liver to synthesize the prothrombin, which is simultaneously utilized throughout the body. Because of its generation within the body, its levels depend on the individuals well-being. Some peoples congenital or acquired anomalies hinder the average production of the protein or the one produced may be dysfunctional, resulting in the pathogenesis of coagulopathies. Furthermore, any damage to the liver decreases its production activity, resulting in additional disorders. In as much as prothrombin is an essential factor in the clotting pathway, the complications arising from its abnormality may facilitate the need for screening.

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Overview of prothrombins involvement in Clotting

The alteration of blood vessels integrity results in release of different agents that mediate the healing of the blood vessel wall. The damage triggers the release of prothrombin activator as one of the components of the process hemostatic cascade. According to Palta et al. (2014), the disrupted endothelial walls of the vessel stimulates this activator through the help of calcium ions in the plasma, causing the conversion of prothrombin to thrombin, in concerted efforts with the activated factors X and V. The thrombin formed mediates the polymerization of fibrinogen to form fibrin. In a rhythmic cascade of events, the fibrin is aids in the formation of a plug, thereby slowing or completely stopping the bleeding. Palta et al. (2010) note that this sequence requires vitamin K for the coagulation process to be realized. The essence of the vitamin resides in its requirement by the liver to synthesize prothrombin and other clotting factors. As a result, any form of deficiency of vitamin K or injury to the liver has the potential of altering the amounts of clotting factors in the plasma, therefore, exacerbating coagulopathies.

Prothrombin Disorders

Conditions arising from prothrombin disorders are often rare. In as much as many of them result from deficiency states, that observation does not rule out the likelihood of excess synthesis of the protein by the liver. Decreased synthesis or the production of dysfunctional prothrombin often leads to deficits, which account for the largest proportion of the disorders. Although cases of defective or lower quantities of prothrombin are prevalent, states in which the individual has too much prothrombin also occur. The former often leads to massive bleeding while the latter leads to incidences of thrombosis. According to Schwartz (2016), the conditions can either be acquired, or inherited, and usually, affects one in every 2 million people.

Inadequate production of the clotting factor is mainly a consequence of the inherited Factor II deficiency. The heredity pattern is often autosomal recessive, with the ability to cause insufficient production of prothrombin (hypoprothrombinemia) or dysfunctional proteins (Dysprothrombinemia) (Schwartz, 2016). As a result of the reduced amounts, individuals from these disorders express prothrombin levels of 2-25%. The limited quantities of the clotting factor, as shown by the deficiency state implies, that the patient is at a risk of hemorrhage, epistaxis, easy bruising, and other possible symptoms like muscle hematomas, mucosal and intracranial bleeding, as well as significant postoperative blood losses (Schwartz, 2016). The problem is exacerbated when the individuals suffer from limited vitamin K levels or liver injuries. Schwartz (2016) acknowledges that the gene coding for prothrombin is expressed in the liver, and any damage to this organ predisposes the victim to insufficient amounts of factor II. Another grim reality is that prothrombin is a vitamin k-dependent proenzyme, meaning that if one has liver disease or any form of damage, and also experiencing inadequate intake or limited secretion of the nutrient, the person will not only suffer from the deficiency states, but also the lower amounts of secreted factor will be dysfunctional. In the case of such an occurrence, the possibility of fatality is unquestionable, hence, the need to urgently address any suspected lower levels of the factor.

Notwithstanding the reduced levels mentioned above, a mutation in factor II results in an inherited disorder. Unlike the deficiency state, which predisposes the patient to massive bleeding, this type of condition exposes the person to abnormal clotting in their blood vessels. According to Schwartz (2016), the abnormality leads to heightened incidences of thromboembolism, which, in turn, increases the possibility of deep venous thrombosis and pulmonary embolism. Since these disorders appear to affect women more than men, having the condition and becoming pregnant has an almost sure probability of placental abruption (a causative factor in miscarriages) and preeclampsia (high blood pressure induced by pregnancy). However, despite the high thrombotic incidences, these patients can benefit from anticoagulant therapy, whether orally-administered or delivered parenterally.

Prothrombin Complex Concentrates (PCC)

The decreased levels of factor II in inherited deficiency states predisposes the individual to a host of bleeding disorders. According to Schwartz (2016), patients with prothrombin coagulopathies express a 2-25% factor II quantity. From these statistics, it is evident that the prothrombin time in such persons will be highly elongated. The outcome of this reality means that the individuals will have an international normalized ratio (INR) of four or more. Ferreira and DeLosSantos (2013, p. 1201) report that an INR greater than four is associated with fatal or life-threatening bleeding such as intracranial hemorrhage and hematoma expansion, whose rates of fatalities are overly high. The insufficient levels of prothrombin from deficiency disorders have the likelihood of transforming to such outcomes, although it is arrested by the prothrombin complex concentrates. Blatt (1978, p. 827) notes that the PCCs are mainly used in an emergency to reverse vitamin K antagonist therapy. However, its evolution into the current therapeutic intervention for massive bleeding disorders makes it an ideal option for prothrombin coagulopathies induced by deficiency states. This way, the fatalities arising from bleeding can be arrested and controlled.

The PCC were originally developed to supplement factor IX deficiency as expressed in hemophilia B (Blatt, 1978). A lot of scientific research went into this product to draw up an intervention that could minimize bleeding, from a multifactorial scientific problem. Ferreira and DeLosSantos (2013) note that some bleeding disorders are caused by perioperative or trauma-related incidents, oral vitamin K antagonist therapy, or hemophilia B. The reality around the elevated INR values implies that their prothrombin times were significantly elongated. Since vitamin K-dependent clotting factors are involved in the coagulation cascade, the persistence in hemorrhage was likely an outcome or consequence of antagonism. The researchers participating in the development of a formulation that could counter this blockade used the rationale that supplementing the factors was a possible way of combating the bleeding. As a result, current PCCs contain a mix of three or four of the vitamin K-dependent factors. According to Ferreira and DeLosSantos (2013, p. 1202), the preparations contain factors II, VII, IX, and X, although not all have factor VII. This delineation means that some PCC products have three-factor components while others have four.

The way these formulations work facilitates an understanding of their therapeutic applications. Hemorrhage caused by vitamin K blockers like warfarin implies that the following coagulation factors, which rely on the nutrient for activity, have reduced levels. They include factors II, VII, IX, and X. For coagulopathies, such as those induced by insufficient amounts of prothrombin, arresting hemorrhage requires increased thrombin generation. And since prothrombin is the precursor to this intermediate protein, supplying Factor II, in the form of a PCC formulation. Grottke and Levy (2015) note that supplying prothrombin, whose conversion to thrombin is made possible by the active forms of factors X and V will initiate the clotting cascade and prevent additional bleeding. From this analogy, the PCC formulations are essential in the treatment of prothrombin-related coagulopathies.

Conclusion

Prothrombin is an essential clotting protein that is produced by the liver in the presence of vitamin K. It acts as a trigger to coagulation cascade in the common pathway by forming thrombin. A deficiency state or overproduction of the protein can cause coagulopathies, which have potential fatalities. Hypoprothrombinemia, dysprothrombinemia and prothrombin thrombophilia are the commonest disorders of factor II abnormalities. The symptoms of the first two can be minimized or eliminated by prothrombin complex concentrates while those of thrombophilia can be reduced by anticoagulant therapy. Nonetheless, the individuals INR values will indicate their levels of prothrombin.

References

Blatt, P. M. (1978). Prothrombin complex concentrates. Archives of Internal Medicine, 138(5),

827-827.

Ferreira, J., & DeLossantos, M. (2013). The clinical use of prothrombin complex concentrate.

Journal of Emergency in Medicine, 44(6), 1201-1210.

Grottke, O., & Levy, J.H. (2015). Prothrombin complex concentrates in trauma and perioperative

bleeding. Anesthesiology, 122, 923-931.

Palta, S., Saroa, R., & Palta, A. (2014). Overview of the coagulation system. Indian Journal of

Anaesthesia, 58(5), 515-523.

Schwartz, R.A. (2016). Factor II deficiency. Medscape. Accessed on January 19, 2017, from

http://emedicine.medscape.com/article/209742-overview