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Hematology Elevated Coagulation Factor IX and Risk of Thrombosis Development Salma AlDallal Hematology Laboratory Specialist, Amiri Hospital, Kuwait Abstract Coagulation involves the regulated sequence of proteolytic activation of a series of zymogens to achieve an appropriate and timely hemostasis in an injured vessel in an environment that favors an anticoagulant state. Alteration of hemostatic balance between the prothrombotic and antithrombotic factors can result in insufficient inhibition of coagulation ‘thrombosis’ or bleeding due to excessive antithrombotic treatment. Fibrin is the key component of thrombi and anticoagulant drugs that reduce thrombin formation are effective in both prevention and treatment of thrombosis. Therefore, an increased circulating level of coagulation factor is a must for treatment mechanisms of both venous and arterial thrombosis. The existing anticoagulants may have only limited effects due to their modest therapeutic benefits, increased bleeding risks, narrow clinical applications, and drug-induced thrombophilia. However, some new oral anticoagulants, when administered optimally, are associated with significant anti-ischemic benefits and lower bleeding risk when compared with heparin and vitamin K antagonists. Since factor IX (FIX) plays a key role in tissue factor-mediated thrombin production, it may represent a promising target for drug development. This review aims to summarize the current data for FIX and its role in the development of thrombosis (although thrombosis is a platelet-centric process and FIX may not have any direct and specific effect on platelets). Keywords Factor IX, thrombosis, coagulation factors, venous, arterial, factor IXa Disclosure: Salma AlDallal has nothing to disclose in relation to this article. No funding was received in relation to the publication of this article Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects. performed by any of the authors. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: February 5, 2016 Accepted: March 14, 2016 Citation: Oncology & Hematology Review, 2016;12(1):15–9 Correspondence: Salma AlDallal, Amiri Hospital, Sharq, Kuwait. E: The coagulation cascade The formation of a blood clot inside a blood vessel obstructs the blood flow through the circulatory system. Hemostasis is the process that prevents blood loss after any injury. The coagulation process that directs hemostasis constitutes a complex set of reactions. In a study conducted by Davie and Ratnoff (1964), 1 a simple waterfall sequence is proposed to explain the function of the various protein clotting factors during the formation of the fibrin clot. When clotting is initiated, fibrinogen is converted to a form that exhibits enzymatic activity, and this occurs in a stepwise sequence where each newly formed enzyme reacts with its specific substrate, thus converting it to an active enzyme. The concept of the coagulation cascade as a series of stepwise enzymatic conversations was first proposed by MacFarlane (1964). 2 According to MacFarlane, there exist two pathways: the extrinsic pathway, involving tissue factor and factor VII, and the intrinsic pathway, involving factors such as XII, XI, IX, VIII, and V. Both pathways converge to activate factor X and lead to the transformation of prothrombin into thrombin. Subsequently, the fibrinogen gets converted into fibrin by the action of thrombin. Within this cascade model, the role of platelets in coagulation was considered as an independent mechanism. 3 TOU CH MED ICA L MEDIA During the following three decades, many studies were undertaken, culminating in simultaneous publications from two groups located in Houston and North Carolina. 4,5 Both groups described a ‘new cascade’, and this has been internationally accepted and demonstrated by a recent publication. 6 This new perspective built on the classical cascade has been represented in the following ways. • The complex formed by tissue factor and factor VII contributes to the activation of factor IX (FIX), showing that the intrinsic and extrinsic coagulation pathways are linked almost from the beginning of the process. • The complete process does not occur continuously, but rather in three consecutive phases: an initial phase, an amplification phase, and a propagation phase. The platelets and thrombin are actively involved in the amplification and propagation phases. 3 Coagulation is a complex process in which circulating cells and coagulation factors interface with tissue-based proteins to form an insoluble clot at the sites of vascular injury. The coagulation process involves a complex set of reactions involving approximately 30 different proteins. 7 These reactions 15