unit four


A scanning electron micrograph of fibrin threads (2,800x).


A scanning electron micrograph of fibrin threads (2,800x).

In disseminated intravascular clotting, coagulation is abnormally activated in several regions of the cardiovascular system. This condition is usually associated with bacterial infection or bacterial toxins in the blood, or with a disorder causing widespread tissue damage. Many small clots form and obstruct blood flow into various tissues and organs, particularly the kidneys. As plasma clotting factors and platelets are depleted, severe bleeding occurs.

Intrinsic Clotting Mechanism

Unlike extrinsic clotting, all of the components necessary for intrinsic clotting are in the blood. Activation of a substance called the Hageman factor (factor XII) initiates intrinsic clotting. This happens when blood is exposed to a foreign surface such as collagen in connective tissue instead of the smooth endothelial lining of intact blood vessels or when blood is stored in a glass container. Activated factor XII activates factor XI, which activates factor IX. Factor IX then joins with factor VIII and platelet phospholipids to activate factor X. These reactions, which also depend on the presence of calcium ions, lead to the production of pro-thrombin activator. The subsequent steps of blood clot formation are the same as those described for the extrinsic mechanism (fig. 14.19). Table 14.10 compares extrinsic and intrinsic clotting mechanisms. Table 14.11 lists the clotting factors, their sources, and clotting mechanisms.

Laboratory tests commonly used to evaluate blood coagulation mechanisms include prothrombin time (PT) and partial thromboplastin time (PTT). These tests measure the time it takes for fibrin threads to form in a sample of blood plasma. The prothrombin time test checks the extrinsic clotting mechanism, whereas the partial thromboplastin test evaluates intrinsic clotting.

Fate of Blood Clots

After a blood clot forms, it soon begins to retract as the tiny processes extending from the platelet membranes adhere to strands of fibrin within the clot and contract. The blood clot shrinks, pulling the edges of the broken vessel closer together and squeezing a fluid called serum from the clot. Serum is essentially plasma minus all of its fibrinogen and most of the other clotting factors. Platelets associated with a blood clot also release platelet-derived growth factor (PDGF), which stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls.

Fibroblasts invade blood clots that form in ruptured vessels, producing connective tissue with numerous fibers throughout the clots, which helps strengthen and seal vascular breaks. Many clots, including those that form in tissues as a result of blood leakage (hematomas), disappear in time. In clot dissolution, fibrin threads absorb a plasma protein called plasminogen (profibrinolysin). Then a substance called plasminogen activator released from the lyso-somes of damaged tissue cells converts plasminogen to plasmin. Plasmin is a protein-splitting enzyme that can digest fibrin threads and other proteins associated with blood clots. Plasmin formation may dissolve a whole clot; however, clots that fill large blood vessels are seldom removed naturally.

A blood clot abnormally forming in a vessel is a thrombus (throm'bus). If the clot dislodges or if a fragment of it breaks loose and is carried away by the blood flow, it is called an embolus (em'-bo-lus). Generally, em-boli continue to move until they reach narrow places in vessels where they may lodge and block blood flow, causing an embolism.

A blood clot forming in a vessel that supplies a vital organ, such as the heart (coronary thrombosis) or the brain (cerebral thrombosis), blocks blood flow and kills tissues the vessel serves (infarction) and may be fatal. A blood clot that travels and then blocks a vessel that supplies a vital organ, such as the lungs (pulmonary embolism), affects the portion of the organ that the blocked blood vessel supplies.

Drugs based on "clot-busting" biochemicals can be lifesavers. Tissue plasminogen activator (tPA) may restore blocked coronary or cerebral circulation if given within four hours of a heart attack or stroke. A drug derived from bacteria called streptokinase may also be successful, for a fraction of the cost. Another plasminogen activator used as a drug is urokinase, an enzyme produced in certain kidney cells. Heparin and coumadin are drugs that interfere with clot formation.

Extrinsic Clotting Mechanism

Tissue damage


Intrinsic Clotting Mechanism

Blood contacts foreign surface


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