1. Anticoagulants, Thrombolytic Agents and Antiplatelet Drugs
Management and Prevention of
Vascular Thrombosis
Benedict R. Lucchesi, M.D., Ph.D.
Department of Pharmacology
University of Michigan Medical School
Revised 10/03

2. Anticoagulant Therapy
Areas of Concentration and Drugs to Know
Required Reading Goodman and Gilman 10 ed pages
Mechanisms for hemostasis
Thrombus Formation
Role of platelets
Venous thrombosis
Arterial thrombosis
Biochemistry of coagulation
Role of vitamin K
Platelet Biology
Thrombolysis

3. Drugs to Know Anticoagulants and Adjuncts Heparin Protamine Sulfate
Low-molecular weight heparins -
Enoxaparin (Lovenox™)
Dalteparin (Fragmin™)
Danaparoid (Orgaran™)
Lepirudin [rDNA] (Refludan™)
Bivalirudin (Hirulog, Angiomax™)
Argatroban

4. Coumarin Derivatives Antiplatelet Drugs Warfarin Dicumarol Aspirin
Dipyridamole
Ticlopidine (Ticlid™)
Clopidogrel (Plavix™)
Abciximab (ReoPro™; Antibody to platelet GPIIb/IIIa receptor)
Tirofiban (Aggrastat™) Reversible, nonpeptide GPIIb/IIIa receptor antagonist
Eptifibatide (Integrilin™) cyclic peptide GPIIb/IIIa receptor blocker
Anagrelide (Agrylin™)

5. Thrombolytic Agents Streptokinase Tissue plasminogen activator (rt-PA)
Alteplase (Activase™)
Reteplase (Retavase™)
Tenecteplase, TNK-tPA (TNKase™)
Urokinase
Anisoylated plasminogen streptokinase activator complex (APSAC)

6. Development of Atherosclerotic Plaques

7. Anticoagulant Therapy - Coagulation Mechanism
Intrinsic System
XII XIIa
XI XIa
IX IXa
X Xa
II Thrombin
XIII XIIIa
HMW kininogen
Kallikrein
HMW kininogen
Extrinsic System
TPL
VIIa VII PL
Ca++
VIII PL
Ca++
VIII
Fibrinogen Fibrin PL
Ca++
VIII
Stabilization

8. X-Linked Fibrin XIII XIIIa
Surface
XII, HK,
Prekallikrein
VIIa VII
Tissue Factor
XI XIa
VIIa X
IX IXa
X-Linked
Fibrin
VIII
X Xa V
Prothrombin Thrombin
XIII
XIIIa
Fibrinogen Fibrin

9. Thrombin

10. Fibrinogen Prothrombin Thrombin Fibrin
INTRINSIC PATHWAY EXTRINSIC PATHWAY
IXa VIIa / Tissue Factor
VIIIa
TFPI
Platelet
Aggregation
aPC
FACTOR Xa
Fibrinogen
Prothrombin Thrombin Va
aPC
XIIIa
PC / Thrombomodulin
Fibrin
Protein S aPC Inactivation Va & VIIIa

11. Thrombin Direct & Indirect Thrombin Inhibitors
Direct Inhibitors Indirect Inhibitors
Hirudin ATIII
Hirulog Heparin
Argatroban LMWHs
Lepirudin [rDNA] -dalteparin
-enoxaparin
Other Agents
Danaparoid
Dermatan Sulfate

12. Anticoagulant Therapy
Reduce the formation of fibrin clots
Consist of two major types
Heparin and other Factor Xa, IIa inhibitors
LMWHs
Danaparoid
Lepirudin (Refludin™)
Bivalirudin (Angiomax™)
Argatroban
Warfarin