| HEPARIN TREATMENT IS INEFFECTIVE IN ANTITHROMBIN DEFICIENCY |
| A 40-year-old man was admitted from the Emergency Room of his local hospital because of acute pain and swelling of his left leg 10 days after recent major surgery. Ultrasound imaging of the leg confirmed occlusion of the left femoral vein by thrombus. He was prescribed anticoagulant therapy with low molecular weight heparin at standard doses. The patient volunteered a strong family history of 'clots in the legs' at a young age. A thrombophilia screening test was performed, and showed a low plasma antithrombin level. |
| Comment. The patient was treated with intravenous antithrombin concentrate, which increased his plasma antithrombin levels to within the normal range. This allows heparin to be effective. The clinical response was satisfactory, and the patient's medication was subsequently changed from heparin to oral warfarin. |
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The term 'extrinsic' refers to the effect of tissue factor, which (after combining with coagulation factor VII) greatly accelerates coagulation, by activating both factor IX and factor X (Fig. 6.4). Tissue factor is a polypeptide that is expressed in all cells other than endothelial cells. The clinical test of this pathway is the prothrombin time (PT), in which tissue factor is added to plasma. The normal range is about 10-15 seconds; prolongations are observed in deficiencies of factors VII, X, V, II, or I. In clinical practice, the test is used to diagnose both the rare congenital defects of these factors and,
much more commonly, to diagnose acquired bleeding disorders, resulting from:
- vitamin K deficiency (e.g. malabsorption, obstructive jaundice; see Chapters 10 and 28), which reduces hepatic synthesis of factors II, VII, IX, and X. Treatment is by injections of vitamin K;
- oral anticoagulants (e.g. warfarin) which are vitamin K antagonists, reducing hepatic synthesis of these factors. Excessive bleeding in patients taking warfarin can be treated by stopping the drug, giving vitamin K, or replacing factors II, VII, IX, and X with fresh frozen plasma or concentrates;
- liver disease, which reduces hepatic synthesis of these factors. For example, the prothrombin time is a prognostic marker of liver failure after acetaminophen
 (paracetamol) overdose (see Chapter 28). Treatment is by replacing factors II, VII, IX, and X with fresh frozen plasma or concentrates.
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