Biology of Disease

They are a popular item in the diet in the Mediterranean, an area where

G6PD is endemic. Favism is frequently fatal unless a large volume of blood is

transfused promptly.

13.8 Clinical Aspects of Clotting

Clinical problems occur if the blood fails to clot as, for example, in hemophilia

(Box 13.5), or if it clots too easily or inappropriately, as in a coronary

thrombosis (Chapter 14). Thus analytical methods to clinically investigate

the clotting abilities of blood samples are necessary. These blood samples

require the addition of Ca2+ chelating agents, such as oxalate, citrate, EDTA

or heparin to prevent them clotting and centrifugation to remove blood cells.

The addition of excess Ca2+ or the removal of the chelating agents to the

remaining plasma allows it to clot. Thus, the clotting of blood from patients

can be studied in the pathology laboratory and any defects identified to

help with the diagnosis and monitoring of treatment. For example, the

prothrombin time, a measure of the activity of the extrinsic pathway, can be

estimated. Thromboplastin is added to blood from the patient into a tube

containing citrate to chelate the Ca2+ and the time taken for a fibrin clot to

form noted. The thrombin time is a measure of the activity of thrombin. It is

determined by adding thrombin to plasma and waiting for the clot to form. It

is also possible to measure the activity of the intrinsic pathway by estimating

the partial thromboplastin time. Calcium ions and phospholipids are added

to plasma which is then exposed to a surface to activate Factor XII and the

time taken for a clot to form is noted.

Vitamin K and Anticoagulants

Like most of the other blood clotting proteins, prothrombin is synthesized in

the liver in a process that requires vitamin K, one of the fat-soluble vitamins

(Chapter 10). A lack of vitamin K leads to the production of abnormal

prothrombin that is activated by Factor X at only about 1% of the normal

rate. Normal prothrombin contains 10 G-carboxyglutamate residues. Vitamin

K (Figure 13.26 (A)) is a cofactor required for the enzymic conversion of the

relevant glutamates in the protein to the G-carboxyglutamate residues (Figure

13.26 (B)). Dicoumarol and warfarin (Figure 13.27 (A)and(B)) are competitive

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C

O

O

CH CH

CH 3

CH 3 CH 3

CH 2 CH 2 (CH 2 CH 2 CH 2 CH

CH 3

) 2 CH 2 CH 2 CH 3

A)

Figure 13.26 Structures of (A) vitamin K 1 and (B) G-carboxyglutamate.

COO-

COO-

COO-

H

C

C

CH 2

H

H 3 +N

B)

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