Dissolution of Clots

As the damaged blood vessel wall is repaired, activated factor XII promotes the conversion of an inactive molecule in plasma into the active form called kallikrein. Kallikrein, in turn, catalyzes the conversion of inactive plasminogen into the active molecule plasmin. Plasmin is an enzyme that digests fibrin into "split products," thus promoting dissolution of the clot.

Table 13.4

Factor

The Plasma Clotting Factors

Name

Function

Pathway

I

Fibrinogen

Converted to fibrin

Common

II

Prothrombin

Converted to thrombin (enzyme)

Common

III

Tissue thromboplastin

Cofactor

Extrinsic

IV

Calcium ions (Ca2+)

Cofactor

Intrinsic, extrinsic, and common

V

Proaccelerin

Cofactor

Common

VII*

Proconvertin

Enzyme

Extrinsic

VIII

Antihemophilic factor

Cofactor

Intrinsic

IX

Plasma thromboplastin component; Christmas factor

Enzyme

Intrinsic

X

Stuart-Prower factor

Enzyme

Common

XI

Plasma thromboplastin antecedent

Enzyme

Intrinsic

XII

Hageman factor

Enzyme

Intrinsic

XIII

Fibrin stabilizing factor

Enzyme

Common

*Factor VI is no longer referenced; it is now believed to be the same substance as activated factor V.

*Factor VI is no longer referenced; it is now believed to be the same substance as activated factor V.

■ Figure 13.8 The extrinsic and intrinsic clotting pathways. Both pathways lead to the formation of insoluble threads of fibrin polymers.

Table 13.5

Some Acquired and Inherited Clotting Disorders and a Listing of Anticoagulant Drugs

Category

Cause of Disorder Comments

Acquired clotting disorders

Vitamin K deficiency Inadequate formation of prothrombin and other clotting factors in the liver

Inherited clotting disorders

Hemophilia A (defective factor VIIIahf) Recessive trait carried on X chromosome; results in delayed formation of fibrin

von Willebrand's disease (defective factor VIIIvwf) Dominant trait carried on autosomal chromosome; impaired ability of platelets to adhere to collagen in subendothelial connective tissue

Hemophilia B (defective factor IX); also called Christmas disease Recessive trait carried on X chromosome; results in delayed formation of fibrin

Anticoagulants

Aspirin

Inhibits prostaglandin production, resulting in a defective platelet release reaction

Coumarin

Inhibits activation of vitamin K

Heparin

Inhibits activity of thrombin

Citrate

Combines with Ca2+, and thus inhibits the activity of many clotting factors

In addition to kallikrein, a number of other plasminogen activators are used clinically to promote dissolution of (J clots. An exciting development in genetic engineering technology is the commercial availability of an endogenous compound, tissue plasminogen activator (TPA), which is the product of human genes introduced into bacteria. Streptoki-nase, a natural bacterial product, is a potent and more widely used activator of plasminogen. Streptokinase and TPA may be injected into the general circulation or injected specifically into a coronary vessel that has become occluded by a thrombus (blood clot).

Anticoagulants

Clotting of blood in test tubes can be prevented by the addition of sodium citrate or ethylenediaminetetraacetic acid (EDTA), both of which chelate (bind to) calcium. By this means, Ca2+ levels in the blood that can participate in the clotting sequence are lowered, and clotting is inhibited. A mucoprotein called heparin can also be added to the tube to prevent clotting. Heparin activates antithrom-bin III, a plasma protein that combines with and inactivates thrombin. Heparin is also given intravenously during certain medical procedures to prevent clotting. The coumarin drugs, whose mechanism of action is different from that of heparin, are also used as anticoagulants. These drugs (dicumarol and warfarin) prevent blood

Heart and Circulation

Table 1 3.6 Terms Used to Describe Acid-Base Balance

Term

Definition

Acidosis, respiratory Increased CO2 retention (due to hypoventilation), which can result in the accumulation of carbonic acid and thus a fall in blood pH to below normal

Acidosis, metabolic Increased production of "nonvolatile" acids, such as lactic acid, fatty acids, and ketone bodies, or loss of blood bicarbonate (such as by diarrhea), resulting in a fall in blood pH to below normal Alkalosis, respiratory A rise in blood pH due to loss of CO2 and carbonic acid (through hyperventilation)

Alkalosis, metabolic A rise in blood pH produced by loss of nonvolatile acids (such as excessive vomiting) or by excessive accumulation of bicarbonate base Compensated acidosis Metabolic acidosis or alkalosis are partially compensated for by opposite changes in blood carbonic acid levels (through changes in ventilation). or alkalosis Respiratory acidosis or alkalosis are partially compensated for by increased retention or excretion of bicarbonate in the urine.

clotting by inhibiting the cellular activation of vitamin K, thereby causing a vitamin K deficiency at the cellular level.

Vitamin K is needed for the conversion of glutamate, an amino acid found in many of the clotting factor proteins, into a derivative called gamma-carboxyglutamate. This derivative is more effective than glutamate at bonding to Ca2+ and such bonding is needed for proper function of clotting factors II, VII, IX, and X. Because of the indirect action of vitamin K on blood clotting, coumarin must be given to a patient for several days before it becomes effective as an anticoagulant.

Test Yourself Before You Continue

1. Distinguish between the different types of formed elements of the blood in terms of their origin, appearance, and function.

2. Describe how the rate of erythropoiesis is regulated.

3. Explain what is meant by "type A positive" and describe what can happen in a blood transfusion if donor and recipient are not properly matched.

4. Explain the meaning "intrinsic" and "extrinsic" as applied to the clotting pathways. How do the two pathways differ from each other? Which steps are common to both?

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