What is the role of cell surface–directed hemostasis in the pathophysiology of factor IX (FIX) deficiency (hemophilia B)?

Updated: Mar 09, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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The concept of coagulation as a waterfall or cascade, with a series of reactions each impacting the subsequent reaction, has been prevalent for a long time. The fact that fluid-phase reactions are inefficient and that platelets and other cell surfaces provide the anionic phospholipids needed for complex formation so that reactions can proceed efficiently also has been recognized. This model allowed the reader to conceptually visualize activated partial thromboplastin time (aPTT) and prothrombin time (PT) tests as the intrinsic and extrinsic pathways. One review proposed that coagulation is essentially a cell surface–based event in overlapping phases, suggesting the need for a paradigm shift from the old concept in which coagulation reactions were controlled by coagulation proteins to a new concept in which the "process is controlled by cellular elements."

In this model, diagrammed below, 3 phases are proposed including (1) initiation of coagulation on the surface of a TF-bearing cell, with formation of FXa, FIXa, and thrombin, (2) amplification of this reaction next on the platelet surface as platelets are activated, adhere, and accumulate factors/cofactors on their surfaces, and (3) the propagation phase in which the large second burst of thrombin occurs on the platelet surface resulting from the interaction of proteases with their cofactors, resulting in fibrin polymerization. Platelets are an early and essential feature of hemostasis, making them an ideal cell to regulate this process, and these authors provide a series of cogent reasons for switching to this new concept of hemostasis. [9, 10]

Cell surfaced-directed hemostasis. Initially, a sm Cell surfaced-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor–bearing (TF-bearing) cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. (Adapted from Hoffman and Monroe, Thromb Haemost 2001, 85(6): 958-65.)

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