Principles of Blood Coagulation Hemostasis Principles of Blood Coagulation Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Hemostasis The ability of the body’s systems to maintain the integrity of the blood and blood vessels Involves: A number of complex pathways Platelets Coagulation factors Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Stabilized Platelet Plug Lipemic Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Phases Mechanical phase Initiated when blood vessel is ruptured or torn Exposed subendothelium of vessel is charged Platelets attract to this charged surface Undergo morphologic and physiologic changes Causes platelets to adhere to each other and the endothelium Activated platelets expose phosphatidylserine on their outer membrane Requires von Willebrand factor Stabilizes the platelet plug The adhesion and aggregation of platelets trigger the chemical phase The initial mechanical phase is initiated by interactions of negatively charged phospholipid surfaces of cells and platelets or microparticles. Microparticles are membrane-bound cytoplasmic fragments released from platelets, leukocytes, and endothelial cells that serve to increase the surface area on which coagulation complexes can form. Tissue factor binds to Factor VIII in the plasma to initiate the coagulation reactions and Factors I-XI serves to amplify the cascade. Thrombin continues to recruit and activate more platelets, as well as trigger the conversion of fibrinogen to fibrin. Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Phases (cont.) Chemical phase Final phase Coagulation cascade Involves a number of factors Intrinsic and extrinsic pathways Results in a fibrin mesh or clot Final phase Degradation of the fibrin clot   Generation of fibrin proceeds through two phases, with a soluble form generated initially and then an insoluble form consisting of cross-linked fibrin strands. The coagulation process is also modulated and resulting clots broken down through a series of interrelated reactions. In the presence of tissue plasminogen activator (tPA) and plasmin, the soluble fibrin is also broken down into fibrin degradation products (FDPs). Plasmin and tPA also act on the insoluble fibrin, producing a cross-linked version of FDPs and D-dimers. While the brief description above seems complex, the actual processes are a great deal more complicated and involve numerous additional serum proteins. The reader should refer to the recommended readings for more in-depth discussions of hemostasis. Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Initial Reactions for the Chemical Phase Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Functions of Thrombin During the Later Stages of Chemical Hemostasis and the Breakdown of Fibrin Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Summary of the Chemical Phase of Hemostasis Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Blood Coagulation Factors Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.

Summary Hemostasis requires platelets, a number of coagulation factors, and complex reaction pathways Mechanical and chemical pathways Thrombin enhances recruitment and activation of platelets Copyright © 2015 by Mosby, an imprint of Elsevier Inc. All rights reserved.