SBCC Home  Biological Sciences Home  BioMed 108:  Human Physiology
 Physiology Chapters

The HeartBlood VesselsCardiac Output and Blood PressureBlood Cells   Hemostasis



  1. Vasoconstriction
  2. Platelet plug formation
  3. Clotting of blood


  • Local controls. Vasoconstrictors such as thromboxane are released at the site of the injury.
  • Systemic control. Epinephrine released by the adrenal glands stimulates general vasoconstriction.


2. Formation of a Platelet Plug.
Platelets, also called thrombocytes, are small cellular fragments that lack a nucleus and are derived from megakaryocytes. When a blood vessel is damaged, the blood is exposed to collagen fibers in the basement membrane of the vessel (shown in green below). Platelets stick to collagen and become activated. Activated platelets release chemicals such as ADP, and thromboxane, that cause the aggregation of more platelets to the site of injury. Platelet aggregation results in the formation of a platelet plug which acts to stem the flow of blood from the broken vessel. It is essential that platelets become activated only at the site of a broken vessel. Otherwise activated platelets would form plugs and induce clots in inapropriate places. Healthy vessels secrete an enzyme called prostacyclin that functions to inhibit platelet activation and aggregation.



Aspirin inhibits platelet activation by inhibiting the action of thromboxane. By inhibiting platelet activation, aspirin limits blood clotting in general. Aspirin is used clinically as a "blood thinner" in individuals that are at risk for developing life-threatning clots. Patients with advanced atherosclerosis take one baby aspirin per day to reduce the probability of heart attack and stroke.

Thrombocytopenia. Small tears of the capillaries and arterioles are happening all the time. Platelets are responsible for quickly sealing these tears before the slower process of clotting completes the job. In the absence of adequate numbers of platelets these micro-tears allow blood to seep into the tissues. This is evidenced by purple blotches (thrombocytopenia purpura) visible on the skin. Thrombocytopenia can be acute or chronic and has many causes. Severe, untreated cases result in death.


3. Clotting of Blood




Control of the Clotting Cascade

From the diagram above we can see that thrombin is the key to the clotting mechanism. If thrombin is present then clotting will procede, but if thrombin is absent then clotting will not occur. How then is thrombin controlled? Thrombin is derived from an inactive precursor called prothrombin. There are two pathways that lead to the conversion of prothrombin to thrombin; (1) the intrinsic pathway and (2) the extrinsic pathway.

Intrinsic Pathway

The intrinsic pathway, which is triggered by elements that lie within the blood inself (intrinsic to the blood), occurs in the following way. Damage to the vessel wall stimulates the activation of a cascade of clotting factors (for the sake of simplicity we will not consider the individual factors). This cascade results in the activation of factor X. Activated factor X is an enzyme that converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin monomers, which then polymerize in fibrin fibers. Fibrin fibers form a loose meshwork that is stabilized by crosslinks created by factor XIII. The stabilzed meshwork of fibrin fibers is now a clot that traps red blood cells and platelets and thus stops the flow of blood.

Extrinsic Pathway

The extrinsic pathway is triggered by tissue damage outside of the blood vessel. This pathway acts to clot blood that has escaped from the vessel into the tissues. Damage to tissue stimulates the activation of tissue thromboplastin, an enzyme that catalyzes the activation of factor X. At this point the intrinsic and extrinsic pathways converge and the subsequent steps are the same as those described above.


Inhibition of Excessive Clotting




Clot Removal




Clot Busting Drugs

Blood clots can be life-threatening if they form inappropriately in critical locations. Clots that block coronary arteries cause heart attacks, while clots that block arteries in the brain cause stroke. Drugs that can mediate the removal of clots, "clot busters", are used in cases of heart attack and stroke to decrease the damage caused by the clot. Drugs used clinically to remov clots include:

  1. Tissue plasminogen activator (TPA) was recently cloned and is now produced in mass quantities by the biotech firm, Amgen. It is used clinically to dissolve clots in coronary arteries following a heart attack. It is also used to dissolve clots in the brain following stroke.
  2. Streptokinase is an enzyme that directly dissolves blood clots. It is produced by streptococcus bacteria. The bacteria use streptokinase to dissolve clots that negatively effects their growth in the human host. This clot dissolving enzyme is apparently as effective as recombinant TPA.

Streptokinase cost $2 dollars per dose while TPA costs $2000 dollars per dose. Based on economic concerns, streptokinase is the drug of choice. However, streptokinase is not a human enzyme, therefore the immune system sees it as a foreign molecule that should be destroyed. The immune response increases with repeated use of the drug. This limits the effectiveness of the drug over time. TPA, on-the-other-hand is a human molecule which the immune system does not destroy.


Anticoagulants are substances that inhibit the process of clotting.

  1. Heparin
    • acts as an anticoagulant by inhibiting the activity of thrombin
  2. Coumadin (dicoumarol, warfarin)
  3. Citrates
    • Calcium is required for polymerization of fibrin.
    • Citrates are used in long term blood storage.


Blood Clotting Disorders

Individuals with this inherited disorder bleed excessively due to an inability to rapidly form blood clots. This defect could be caused by a deficiency of any of the clotting factors, however 80% of all hemophilics are deficient in factor VIII.


Vitamin K deficiency
Vitamin K is essential to the maturation of several clotting factors including factor X and prothrombin. In the absence of vitamin K these clotting factors are defective and thus inhibit the clotting mechanism. People with a Vitamin K deficiency experience excessive bleeding.


 Copyright and Credits
(Revised October 11 1999)
Table of contents
 Go Back  Top
©The art on this page is reproduced by permission from McGraw-Hill Companies, Inc.