Coagulation 2006: A Modern View of Hemostasis

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The authors propose that hemostasis occurs in a stepwise process, regulated by cellular components in vivo. The effectiveness of hemostasis in vivo depends not only on the procoagulant reactions but also on the fibrinolytic process. Causes of coagulopathic bleeding include consumption of coagulation factors and platelets, excessive fibrinolysis, hypothermia, and acidosis. Generation of the right amount of thrombin during the coagulation process not only may be essential for effective hemostasis but also may set the stage for effective wound healing.

Section snippets

How well do We Really Understand Coagulation?

In the 1960s two groups proposed a waterfall or cascade model of coagulation composed of a sequential series of steps in which activation of one clotting factor led to the activation of another, finally leading to a burst of thrombin generation [1], [2]. Each clotting factor was believed to exist as a proenzyme that could be converted to an active enzyme.

The original cascade models were subsequently modified to include the observation that some procoagulants were cofactors and did not possess

Can an Emphasis on the Role of Cells Improve our Understanding of Coagulation?

It was recognized from the earliest studies of coagulation that cells were important participants in the coagulation process. Of course, it is clear that normal hemostasis is not possible in the absence of platelets. In addition, TF is an integral membrane protein and thus its activity is normally associated with cells. Because different cells express different levels of pro- and anticoagulant proteins and have different complements of receptors for components of hemostasis, it is logical that

Fibrinolysis

Even as the fibrin clot is being formed in the body, the fibrinolytic system is being initiated to disrupt it. The final effector of the fibrinolytic system is plasmin, which cleaves fibrin into soluble degradation products. Plasmin is produced from the inactive precursor plasminogen by the action of two plasminogen activators: urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). The PAs are in turn regulated by plasminogen activator inhibitors (PAIs).

What does all this Mean for Clinical Laboratory Testing?

It should be clear from the preceding discussion that our commonly used clinical coagulation tests do not really reflect the complexity of hemostasis in vivo. That does not mean that the PT and aPTT are useless. We just need to understand what they can and cannot tell us. These screening coagulation tests are abnormal when there is a deficiency of one or more of the soluble coagulation factors. They do not tell us what the risk for clinical bleeding will be. Two patients who have identical aPTT

What Causes Bleeding in Previously Normal Patients?

Many patients who experience significant hemorrhage do not have an underlying bleeding tendency that can be identified before a bleeding episode. Bleeding following surgical or accidental trauma or during a medical illness is often associated with the development of an acquired coagulopathy. The hallmark of coagulopathy is microvascular bleeding, which means oozing from cut surfaces and minor sites of trauma, such as needle sticks. Microvascular bleeding can lead to massive blood loss.

Causes of

What Happens after the Bleeding Stops?

Once hemostasis is completed the process of wound healing can begin. The hemostatic plug must be stable enough to maintain hemostasis, yet be removed as the tissue defect is permanently closed. Fibrinolysis is accomplished by the action of plasmin, probably in concert with other leukocyte proteases. The neutrophils that initially accumulate at a site of injury are replaced over the course of a few days with macrophages that engulf and degrade cellular debris and components of the fibrin clot.

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    This work was supported by grant RO1 HL48320 from the National Institutes of Health and by the United States Department of Veteran's Affairs (MH).

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