The drugs used in clotting and bleeding disorders fall into 2 major groups: (1) drugs used to decrease clotting or dissolve clots already present in patients at risk for vascular occlusion and (2) drugs used to increase clotting in patients with clotting deficiencies. The first group, the anticlotting drugs, includes some of the most commonly used drugs in the United States. Anticlotting drugs are used in the treatment and prevention of myocardial infarction and other acute coronary syndromes, atrial fibrillation, ischemic stroke, and deep vein thrombosis (DVT). Within the anticlotting group, the anticoagulant and thrombolytic drugs are effective in treatment of both venous and arterial thrombosis, whereas antiplatelet drugs are used primarily for treatment of arterial disease.
|Activated partial thromboplastin time (aPTT) test||Laboratory test used to monitor the anticoagulant effect of unfractionated heparin and direct thrombin inhibitors; prolonged when drug effect is adequate|
|Antithrombin III||An endogenous anticlotting protein that irreversibly inactivates thrombin and factor Xa. Its enzymatic action is markedly accelerated by the heparins|
|Clotting cascade||System of serine proteases and substrates in the blood that provides rapid generation of clotting factors in response to blood vessel damage|
|Glycoprotein IIb/IIIa (GPIIb/IIIa)||A protein complex on the surface of platelets. When activated, it aggregates platelets primarily by binding to fibrin. Endogenous factors including thromboxane A2, ADP, and serotonin initiate a signaling cascade that activates GPIIb/IIIa|
|Heparin-induced thrombocytopenia (HIT)||A hypercoagulable state plus thrombocytopenia that occurs in a small number of individuals treated with unfractionated heparin|
|LMW heparins||Fractionated preparations of heparin of molecular weight 2000—6000. Unfractionated heparin has a molecular weight range of 5000—30,000|
|Prothrombin time (PT) test||Laboratory test used to monitor the anticoagulant effect of warfarin; prolonged when drug effect is adequate|
Anticoagulants inhibit the formation of fibrin clots. Three major types of anticoagulants are available: heparin and related products, which must be used parenterally; direct thrombin and factor X inhibitors, which are used parenterally or orally; and the orally active coumarin derivatives (eg, warfarin). Comparative properties of the heparins and warfarin are shown in Table 34–1.
Table 34–1 Properties of Heparins and Warfarin. ||Download (.pdf)
Table 34–1 Properties of Heparins and Warfarin.
|Structure||Large acidic polysaccharide polymers||Small lipid-soluble molecule|
|Route of administration||Parenteral||Oral|
|Site of action||Blood||Liver|
|Onset of action||Rapid (minutes)||Slow (days); limited by half-lives of preexisting normal factors|
|Mechanism of action||Activates antithrombin III, which proteolyzes coagulation factors including thrombin and factor Xa||Impairs post-translational modification of factors II, VII, IX and X|
|Monitoring||aPTT for unfractionated heparin but not LMW heparins||Prothrombin time|
|Antidote||Protamine for unfractionated heparin; protamine reversal of LMW heparins is incomplete||Vitamin K1, plasma, prothrombin complex concentrates|
|Use||Mostly acute, over days||Chronic, over weeks to months|
|Use in pregnancy||Yes...|