FXII And FXI Case Study

In an article published in JACC: Cardiovascular Interventions, Doctors Madan, Halvorsen, Di Mario, Tan, Westerhout, Cantor, Le May, and Borgia explored whether patients experienced greater risk of undergoing angiography after the administration of fibrinolytic therapy. They concluded that there was not a serious risk of bleeding or death if they receive angiography within four hours of undergoing fibrinolytic therapy (Madan et al., 2015). They also suggest that the patient be moved a center that can perform PCI within 2 hours after fibrinolysis. This article suggests that although fibrinolysis can be success a patient should receive PCI treatment.

First of all is necessary to analyze the differences in effectiveness of the products in treatments. The use of heparin has associated some general disadvantages like: • Unpredictable effects: it is difficult to use properly since its effectiveness depends on achieving a certain level of anticoagulation of the blood, too much might lead to uncontrolled bleeding and too little might not prevent a blood clot • • High risk of

The dabigatran etexilate (DE) is a prodrug that directly competes for the active site of thrombin.1 This direct inhibition inactivates both fibrin-bound and free form of thrombin. Because of its rapid onset and offset of action, there is no need for the initial parenteral anticoagulant treatment in patients with acute thrombosis.1 On the other hand, the enoxaparin indirectly inhibits factor Xa.2 It has a shorter duration of action (12h vs 24h) and a shorter half-life (4.5-7h vs 12-14h) in comparison to DE. The DE and the enoxaparin have no interaction with diet and alcohol. There is no routine monitoring required

Venous thrombosis is a multifactorial disease. In the majority of thrombosis patients a risk factor is not detectable. Virchow's triad refers to three primary influences for thrombus formation, endothelial injury, stasis, turbulence or abnormal blood flow, and blood hypercoagulability (Kyrle, 2009). A shift in balance between procoagulant and anticoagulant of the endothelium is responsible for thrombotic state (Kyrle, 2009). Endothelial injury is the physical loss of endothelium leading to exposure of subendothelial extra-cellular matrix, adhesion of platelets, release of tissue factor, depletion of PGI2 and plasminogen activators (Kumar, 2010). Abnormal blood flow refers to turbulence that causes endothelial injury, which is a major influence

The pharmacological intervention includes the use of low molecular weight heparin (LMWH) and low-dose unfractionated heparin (LDUH). A finding of the study suggests that there is a significant reduction of VTE (13%) using thrombo-prophylaxis than without using any thrombo-prophylaxis (27%) and the single use of LDUH decreases the case with 15% (McNamara, 2014, pp.645). Furthermore, the study elaborates the use of aspirin could be an intervention to minimize the VTE but there is a chance of gastrointestinal bleeding. Thus, aspirin and other antiplatelet drugs are less effective methods to reduce VTE. Moreover, the pharmacological method is not effective in certain case that is associated with bleeding disorder. Therefore, there is a need of non-pharmacological preventive

This organ system has a number of functions namely, to keep a constant body temperature as well as to ensure coagulation occurs specifically at the site of injury, as well as to ensure no added blood loss occurs to cause life-threatening effects. This process of blood coagulation is explained in three interconnected phases. In the first phase, the enzyme thrombokinase is activated due to the damage of tissue and the breaking down of platelets. Prothrombin is converted into thrombin by the disintegration of the thrombocytes, electrically charged calcium ions and other coagulation factors, as well as the blood activator and tissue activator which become involved in the coagulation process. The second phase includes production of the thrombin that transforms fibrinogen in the blood plasma into fibrin. The thrombus (or blood clotting) is formed by a fibrilliform mesh that encloses the blood cells. Lastly, the third phase, which takes place as retraction occurs of the fibres of the fibrin mesh. Solidification of the fibrous mesh takes place which closes the defect in the vascular wall. Coagulation is then followed by fibrinolysis (re-dissolution of the clot).

Representatives from Thrombolysis in Myocardial Infarction (TIMI), Duke Clinical Research Institute (DCRI), and Merck & Co., Inc.

NOACs are considered to be ideal for prevention of stroke associated with AF and other thromboembolic conditions. Some of the prominent advantages include their predicatable pharmacodyanmic and pharmacokinetic profils, relatively wider therapeutic window that do not require routine monitoring, limited drug interaction and have no dietary restrictions(17). Results from clinical trials showed that NOACs such as thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban, apixaban) were found to be at least as effective as warfarin in preventing AF related stroke. Most importantly, intracranial bleeding, the most severe side effect of warfarin was found to be less prevalent in patients treated with NOACs (18-21). In view of such findings, NOACs seem to have an important share in the management of patients with AF. However, use of warfarin for thromboprophylaxis is still considered to be vital as there are certain issues related with the use of NOACs in AF. Warfarin has been used for a couple of decades resulting in extensive experience for prevention of thromboembolism. Some pharmacokinetic controversies regarding NOACs include; shorter acting than warfarin, hence missed doses could increase the risk of thrombosis. Moreover, NOACs have no specific antidotes to reverse their therapeutic effect. One study

Tranexamic acid is anti-fibrinolytic agent which prevents breakdown of fibrin clots. The mechanism of action of the drug is a complex one. The acid initially acts by hindering the binding of plasminogen and plasmin. Tranexamic acid has more potency and efficacy than aminocaproic acid. Tranexamic acid is used in multiple emergency medical conditions. The drug is used in prevention of postoperative bleeding disorders such as hemophilia. The drug proves to very useful in treating conditions such as menorrhagia, epistaxis, angioedema, and surface bleeding from tumors. In conditions such as DIC, tranexamic acid should not be used. The acid should not be used because it works against clots and hence activates

Hemostasis is the process whereby blood coagulates at the site of an injury to a blood vessel. Cellular components involved in hemostasis include platelets, endothelial cells of blood vessels, tissue factor-bearing cells, and coagulation factors (Davoren & Wang, 2014). Coagulation factors are specialized plasma proteins that circulate in the bloodstream in inactive forms. Most coagulation factors are activated by enzymes that catalyze their conversion to active forms. The active forms then contribute to hemostasis. Factors VIII (FVIII) and IX (FIX) are the factors involved in the most common forms of hemophilia. The coagulation cascade has many steps and reciprocal interactions; however, FVIII and FIX are most involved with the following steps:

After injury Platelets adhere to the site of injury, then platelet gets activated and aggregated followed by activation of coagulation cascade and formation of clot.28,29

Hemophilia is a rare blood condition in which an individual’s blood cannot clot appropriately to stop bleeding. There are two types of Hemophilia, Hemophilia A and Hemophilia B. This paper will be focusing on Hemophilia A, also known as classic hemophilia. “Hemophilia A is a genetic disorder caused by a missing or defective factor VIII, a clotting protein” (National Hemophilia Foundation, n.d., para. 1). Clotting proteins work with cell fragments called platelets to stop bleeding. “When blood vessels are injured, clotting factors help platelets stick together to plug cuts and breaks on the vessels and stop bleeding (National Heart, Lung, and Blood Institute, 2013, para.

Tissue plasminogen activator is a fibrinolytic drug which is used to treat thromboembolic disorders, such as ischaemic strokes. These agents initiate secondary fibrinolysis to occur; altering the haemostatic capability. The primary purpose of this agent is to clear occluded blood vessels within the systemic circulation (Bryant & Knights 2011, pp.534-536).

The production of ClotX is built upon recombinant protein technology, which involves the isolation of human protein genes that are then cloned into expression vectors. These expression vectors are used to transform human protein genes into a target cell, which has conventionally been bacterial and mammalian cells. Currently, competing technology that exists involves the production of recombinant fibrinogen, which is a coagulation factor, utilizing a mammalian cell culture system that has the production capacity of 5 μg protein product/ml culture every month. Current production of recombinant fibrinogen utilizes mammalian cells, specifically CHO DG44, however, high-level expression of

Thromboembolic diseases are increasing all over the globe and always require anti-coagulant therapy. Heparin is one of the most available drugs for anti-coagulant activity and is the second-most used naturally occurring drug after insulin (REF). It is a highly sulfated glycosaminoglycan made up of disaccharide units containing a hexuronic acid (α-L-iduronic acid or β-D-glucuronic acid) linked 1, 4 to α-D-glucosamine. The heparin molecules consist of a heterogeneous mixture of polymers with a similar backbone, which results from variations of sulfation on the uronic acid residue (O-sulfated at C2) and on the D-glucosamine (N-acethylated, N-sulfated, O-sulfated at C6 and/or C3). Heparin is one of the potent anti-coagulant because of its unique