In vivo assessment of anticoagulation.

All methods of assessing anticoagulation rely on in vitro techniques. Although these may reflect the clotting tendency in a specimen of blood accurately, they do not necessarily indicate the effectiveness of the anticoagulant in the body where stasis, acidosis, catecholamines, endotoxin, and exposed collagen may alter the coagulability of blood locally. We have utilized autologous 125I-labelled fibrinogen to assess fibrinogen half-life in normal subjects and in patients with clotting complications before and after the administration of anticoagulants. Fibrinogen half-life has varied from normal (104 hours) to markedly abbreviated (13 hours) in patients apparently fully anticoagulated, utilizing standard laboratory parameters. Although there are many potential causes of the shortening of fibrinogen half-life, including fibrinogenolysis and extravascular losses into the interstitial space and wounds, we have been able to establish whether the disappearance of the radioactive-labelled fibrinogen is due to these causes or to clotting by increasing the levels of anticoagulation. Plateauing of fibrinogen half-life values despite increased doses of heparin, or return of the half-life to normal, indicates full anticoagulation. This has permitted determination and administration of the theoretically optimal dose of heparin. In situations involving life-threatening clotting complications, such as massive pulmonary embolism, the use of 125I-labelled fibrinogen provides a means for controlling anticoagulant therapy in a rational fashion by this technique of assessing clotting.