Appropriate preoperative assessment of the dental patient should always include an analysis of the patient's medications. This article reviews the actions and indications for the various categories of antithrombotic medications and considers actual risks for postoperative bleeding and potential interactions with drugs the dental provider might administer or prescribe.Abstract
Thrombogenesis. A thrombus consists of 2 principal components: an aggregate of platelets and a fibrin mesh. Platelet activity consists of adherence to vessel walls (adhesion) and to one another (aggregation). The fibrin mesh is synthesized during a complex cascade of enzymatic reactions leading to the formation fibrin strands (coagulation). The body also has a natural thrombolytic system, essentially comprised of plasmin, an enzyme that cleaves fibrin strands. Antithrombotic drugs are classified according to action on each of these processes: antiplatelet drugs, anticoagulants, and thrombolytics (fibrinolytics).
Platelet aggregation and actions of antiplatelet drugs. 1,3 Resting platelets have specific receptors for ligands that trigger activation: epinephrine, thrombin, serotonin, collagen, adenosine diphosphate (ADP), and thromboxane A2 (TXA2). When activated, intracellular calcium levels elevate and the platelet expresses glycoprotein (GP) IIb/IIIa receptors that bind to strands of fibrinogen. This results in platelet aggregation. The various antiplatelet drugs inhibit aggregation by targeting specific aspects of this process.
The coagulation pathway and target sites for anticoagulant drugs. 3,18 The coagulation pathway is a cascade of enzymatic conversions, each activating the next enzyme (factor) in the sequence. The final enzyme in this pathway is thrombin (factor IIa), which catalyzes the conversion of fibrinogen to fibrin strands. Warfarin acts by inhibiting synthesis of factors in the liver. In contrast, heparin acts to inhibit factors that have become activated within the bloodstream. Thrombin can be activated by either of 2 pathways. The intrinsic pathway is initiated within the bloodstream by platelet thromboplastin. Heparin influences this pathway by inhibiting factors XIIa, XIa, and IXa, which requires its activity to be monitored using the activated partial thromboplastin time. The extrinsic pathway functions outside the bloodstream, initiated by tissue thromboplastin. This pathway is influenced most by warfarin because it inhibits hepatic synthesis of factor VII, the most essential factor in the extrinsic pathway. Therefore the anticoagulant activity of warfarin must be monitored using the prothrombin time (PT), which is now standardized as the international normalized ratio (INR). Newer agents, commencing with the low-molecular-weight heparins, have greater specificity for inhibiting only factors Xa or IIa (thrombin) within the common pathway and therapeutic monitoring is not required.
Actions of heparin and derivatives. 3 Heparin and its derivatives impart their anticoagulant effect indirectly by facilitating the interaction of antithrombin with activated factors, primarily Xa and thrombin (IIa). (A) Heparin is a large polysaccharide capable of surrounding and potentiating antithrombin against both factors Xa and thrombin (IIa). (B) The low-molecular-weight heparins (LMWH) are smaller in size and are more active in potentiating antithrombin against factor Xa than thrombin (IIa). (C) Fondaparinux is a synthetic pentasaccharide that only potentiates antithrombin activity against factor Xa.
Contributor Notes
eISSN: 1878-7177
ISSN: 0003-3006