10 Aptamers for Thrombotic Diseases
281
Current antithrombotics can be divided into two types, one is antiplatelet therapeutics for prevention of platelet activation and aggregation, and the other is anticoagulants against fibrin clot formation. Therapeutics of antiplatelet and anticoagulants
are usually employed during surgical procedures, including cardiopulmonary bypass
(CPB) and percutaneous coronary artery intervention (PCI) [4].
Antiplatelet agents include three categories. 1. Cyclooxygenase (COX) antagonists like aspirin; 2. Antagonists of both purinergic receptor P2Y and G-proteincoupled 12 (P2Y12) platelet receptor, include clopidogrel, prasugrel, and ticagrelor
[5]; 3. Platelet membrane receptor inhibitors include glycoprotein (GP) IIb/IIIa
inhibitors. These drugs are mainly used to treat or prevent ACS and stroke. Increasing
bleeding potential is the major limitation of current antiplatelet drugs [6]. Under the
condition of myocardial infarction, in comparison with clopidogrel, prasugrel is
associated with fewer thrombotic events in patients with ACS but with more major
bleeding events and higher mortality [7]. Meanwhile, ticagrelor is reported to be
associated with dyspnea and bradyarrhythmia [8, 9].
Anticoagulants mainly include the following: (1) FXa inhibitors like unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, and
apixaban; (2) Thrombin inhibitors such as UFH, LMWH, recombinant hirudins
(bivalirudin, desirudin, lepirudin), and argatroban; (3)Vitamin K antagonists like
warfarin. These agents are effective for various thromboembolic disorders. Besides
bleeding potential heparin can cause heparin-induced thrombocytopenia (HIT) and
warfarin requires regular determination of activated partial thromboplastin time
(APTT) and international normalized ratio of prothrombin time (PT-INR), respectively [10]. In addition, it is a challenge for the administration of fondaparinux,
LMWH, and recombinant hirudins in patients with severe renal insufficiency [10].
Nowadays, bivalirudin, instead of heparin and GPIIb/IIIa antagonist, is used for
patients undergoing invasive treatment of ACS. The results demonstrated that
bivalirudin improved the efficacy of the procedure in the Randomized Evaluation in
PCI Linking Angiomax to reduced Clinical Events (REPLACE)-2 trials and decrease
both cardiovascular complications and bleedings events [11]. However, bleeding is
still the most frequent adverse effect associated with PCI, up to 10% of patients and
as many as 60% of coronary artery bypass graft (CABG)-elective patients. When
bleeding happens, blood transfusions are required, which may result in relevant side
effects including acute febrile reactions, lung injury, and viral transmission [12–14].
New anticoagulant agents, such as LMWH (enoxaparin, fondaparinux, and idraparinux) and direct thrombin inhibitors (bivalirudin, argatroban, and lepirudin), have
more favorable pharmacokinetics and pharmacodynamics profiles. However, these
agents can’t be reversed with drug antidotes in case of bleeding, which limits their
clinical application [9, 15].
The risk factors for antithrombotic drug-related bleeding are multifaceted,
including narrow therapeutic indices, drug variability, undefined threshold of anticoagulation, drug-hemostatic factors interactions, and unpredictable pharmacodynamics [16].
An optimal antithrombotic should be efficient against thrombosis while free from
bleeding complications [12]. To achieve these goals, it must meet the following
281
Current antithrombotics can be divided into two types, one is antiplatelet therapeutics for prevention of platelet activation and aggregation, and the other is anticoagulants against fibrin clot formation. Therapeutics of antiplatelet and anticoagulants
are usually employed during surgical procedures, including cardiopulmonary bypass
(CPB) and percutaneous coronary artery intervention (PCI) [4].
Antiplatelet agents include three categories. 1. Cyclooxygenase (COX) antagonists like aspirin; 2. Antagonists of both purinergic receptor P2Y and G-proteincoupled 12 (P2Y12) platelet receptor, include clopidogrel, prasugrel, and ticagrelor
[5]; 3. Platelet membrane receptor inhibitors include glycoprotein (GP) IIb/IIIa
inhibitors. These drugs are mainly used to treat or prevent ACS and stroke. Increasing
bleeding potential is the major limitation of current antiplatelet drugs [6]. Under the
condition of myocardial infarction, in comparison with clopidogrel, prasugrel is
associated with fewer thrombotic events in patients with ACS but with more major
bleeding events and higher mortality [7]. Meanwhile, ticagrelor is reported to be
associated with dyspnea and bradyarrhythmia [8, 9].
Anticoagulants mainly include the following: (1) FXa inhibitors like unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, and
apixaban; (2) Thrombin inhibitors such as UFH, LMWH, recombinant hirudins
(bivalirudin, desirudin, lepirudin), and argatroban; (3)Vitamin K antagonists like
warfarin. These agents are effective for various thromboembolic disorders. Besides
bleeding potential heparin can cause heparin-induced thrombocytopenia (HIT) and
warfarin requires regular determination of activated partial thromboplastin time
(APTT) and international normalized ratio of prothrombin time (PT-INR), respectively [10]. In addition, it is a challenge for the administration of fondaparinux,
LMWH, and recombinant hirudins in patients with severe renal insufficiency [10].
Nowadays, bivalirudin, instead of heparin and GPIIb/IIIa antagonist, is used for
patients undergoing invasive treatment of ACS. The results demonstrated that
bivalirudin improved the efficacy of the procedure in the Randomized Evaluation in
PCI Linking Angiomax to reduced Clinical Events (REPLACE)-2 trials and decrease
both cardiovascular complications and bleedings events [11]. However, bleeding is
still the most frequent adverse effect associated with PCI, up to 10% of patients and
as many as 60% of coronary artery bypass graft (CABG)-elective patients. When
bleeding happens, blood transfusions are required, which may result in relevant side
effects including acute febrile reactions, lung injury, and viral transmission [12–14].
New anticoagulant agents, such as LMWH (enoxaparin, fondaparinux, and idraparinux) and direct thrombin inhibitors (bivalirudin, argatroban, and lepirudin), have
more favorable pharmacokinetics and pharmacodynamics profiles. However, these
agents can’t be reversed with drug antidotes in case of bleeding, which limits their
clinical application [9, 15].
The risk factors for antithrombotic drug-related bleeding are multifaceted,
including narrow therapeutic indices, drug variability, undefined threshold of anticoagulation, drug-hemostatic factors interactions, and unpredictable pharmacodynamics [16].
An optimal antithrombotic should be efficient against thrombosis while free from
bleeding complications [12]. To achieve these goals, it must meet the following