Conversion of Fibrinogen to Fibrin- Formation of the Clot

Conversion of Fibrinogen to Fibrin- Formation of the Clot

Fibrinogen. Fibrinogen is a high-molecular-weightprotein (MW = 340,000) that occurs in the plasma in quantities of 100 to 700 mg/dl. Fibrinogen is formed in the liver, and liver disease can decrease the concen-tration of circulating fibrinogen, as it does the concen-tration of prothrombin, pointed out above.

Because of its large molecular size, little fibrinogen normally leaks from the blood vessels into the inter-stitial fluids, and because fibrinogen is one of the essen-tial factors in the coagulation process, interstitial fluids ordinarily do not coagulate. Yet, when the permeabil-ity of the capillaries becomes pathologically increased, fibrinogen does then leak into the tissue fluids in suf-ficient quantities to allow clotting of these fluids in much the same way that plasma and whole blood can clot.

Action of Thrombin on Fibrinogen to Form Fibrin. Thrombinis a protein enzyme with weak proteolytic capabilities. It acts on fibrinogen to remove four low-molecular-weight peptides from each molecule of fibrinogen, forming one molecule of fibrin monomer that has the automatic capability to polymerize with other fibrin monomer molecules to form fibrin fibers. Therefore, many fibrin monomer molecules polymerize within seconds into long fibrin fibers that constitute the retic-ulum of the blood clot.

In the early stages of polymerization, the fibrin monomer molecules are held together by weak non-covalent hydrogen bonding, and the newly forming fibers are not cross-linked with one another; therefore, the resultant clot is weak and can be broken apart with ease. But another process occurs during the next few minutes that greatly strengthens the fibrin reticulum.

This involves a substance called fibrin-stabilizingfactor that is present in small amounts in normalplasma globulins but is also released from platelets entrapped in the clot. Before fibrin-stabilizing factor can have an effect on the fibrin fibers, it must itself be activated. The same thrombin that causes fibrin for-mation also activates the fibrin-stabilizing factor. Then this activated substance operates as an enzyme to cause covalent bonds between more and more of the fibrin monomer molecules, as well as multiple cross-linkages between adjacent fibrin fibers, thus adding tremendously to the three-dimensional strength of the fibrin meshwork.

Blood Clot. The clot is composed of a meshwork offibrin fibers running in all directions and entrapping blood cells, platelets, and plasma. The fibrin fibers also adhere to damaged surfaces of blood vessels; there-fore, the blood clot becomes adherent to any vascular opening and thereby prevents further blood loss.

Clot Retraction—Serum. Within a few minutes after aclot is formed, it begins to contract and usually expresses most of the fluid from the clot within 20 to 60 minutes.The fluid expressed is called serum because all its fibrinogen and most of the other clotting factors have been removed; in this way, serum differs from plasma. Serum cannot clot because it lacks these factors.

Platelets are necessary for clot retraction to occur. Therefore, failure of clot retraction is an indication that the number of platelets in the circulating blood might be low. Electron micrographs of platelets in blood clots show that they become attached to the fibrin fibers in such a way that they actually bond different fibers together. Furthermore, platelets entrapped in the clot continue to release procoagulant substances, one of the most important of which is fibrin-stabilizing factor, which causes more and more cross-linking bonds between adjacent fibrin fibers. In addition, the platelets themselves contribute directly to clot contraction by activating platelet throm-bosthenin, actin, and myosin molecules, which are all contractile proteins in the platelets and cause strong contraction of the platelet spicules attached to the fibrin. This also helps compress the fibrin meshwork into a smaller mass. The contraction is activated and accelerated by thrombin as well as by calcium ions released from calcium stores in the mitochondria, endoplasmic reticulum, and Golgi apparatus of the platelets.

As the clot retracts, the edges of the broken blood vessel are pulled together, thus contributing still further to the ultimate state of hemostasis.