Antiplatelets and anticoagulants

1. Antiplatelet and
anticoagulants
Edson Mutandwa mbbs v

2. What are they
• Antiplatelet agents prevent platelets from clumping and also prevent
clots from forming and growing. (primary hemostasis)
• Anticoagulants slow down clotting, thereby reducing fibrin formation
and preventing clots from forming and growing. (secondary
hemostasis)

3. Clotting mechanism

4. Medical uses of antiplatelet
1.Transient cerebral ischemic attacks.
2.Following coronary artery bypass grafting.
3.Prevention of myocardial infarction.
4.Following coronary artery angioplasty.
5.Prosthetic heart valves.
6.Chronic disseminated intravascular coagulation

5. Antiplatelet classification
1. COX inhibitors
2. ADP antagonist
3. Phosphodiesterase inhibitors
4. GPIIb/IIIa inhibitors
5. Others

6. COX inhibitors
 Examples : Aspirin
 Mechanism of action
• Aspirin produces the irreversible inhibition of the enzyme cyclooxygenase
• This effect inhibits platelet generation of thromboxane A2, resulting in an antithrombotic effect.
• Low doses (typically 75 to 81 mg/day) are sufficient to irreversibly acetylate serine 530 of cyclooxygenase (COX)-1
 USES OF ASPIRIN
• Prevention of AMI in patients of unstable angina
• Acute coronary syndrome; 160-325mg PO within minutes of presentation
• Prevention of reinfarction in patients of AMI(secondary prevention); 75-81 mg PO QID indefinitely
• Prevention of stroke in patients of cerebrovascular accidents and h/o TIA; 50-325 mg/day PO within 48 hrs
then 75-100 mg/day PO
• For improving prognosis in patients with atherosclerotic peripheral vascular diseases
• Percutaneous angioplasty for coronary thrombosis;
• Primary prophylaxis of thromboembolism in patients with prosthetic heart valves

7. Unwanted effect of COX inhibitors
• Angioedema
• Bronchospasm dermatological problems
• GI pai, ulceration, bleeding
• Hepatotoxicity
• Hearing loss
• Nausea and vomiting
• Renal damage
• etc

8. ADP antagonist
 Examples; clopidogrel, ticlodipine
 Mechanism of action
• inhibit adenosine diphosphate (ADP)-dependent platelet function by irreversible
modification of the platelet P2Y12 receptor through short-lived active metabolites,
generated by liver cytochrome P-450 (CYP) isozymes,
 Clinical use
• Acute coronary syndrome 300 mg loading dose, then 75mg/day for up to 12 months,
indefinitely if used in combination with aspirin
• Recent MI, Stroke or established peripheral arterial disease; 75 mg/day
• Coronary artery disease; 75 mg PO QID
• Cardio embolic stroke; if not candidate for oral anticoagulant
• Carotid artery stenting

9. Unwanted effects include
• Upper respiratory tract infection
• Chest pains
• headache
• flulike syndrome
• Arthralgia
• Dizziness, rash,
• TTP, acute liver failure hypotension eczema <1%

10. Phosphodiesterase inhibitors
 Examples; Dipyridamole, Cilostazol
 Mechanism of action
• It has been suggested that it inhibits types 3 and 5 PDEs, leading to the
intraplatelet accumulation of cAMP
• reduces cellular adenosine uptake
 Clinical use
• Thromboembilic prophylaxis post cardiac valve replacement; 75-100
mg PO QID as adjunct to warfarin
• Prevention of MI recurrence in combination with aspirin

11. Unwanted effects
• Chest pains
• Angina exacerbation
• Abnormal ECG
• Headache
• Dizziness, abdominal discomfort
• Nausea
• Hypotension
• Peripheral oedema etc

12. GPIIb/IIIa inhibitors
 Examples; abciximab, eptifibatide and tirofiban
 Mechanism of action
• The platelet integrin receptor αIIbβ3 (GPIIb/IIIa) plays a critical role in
thrombosis and hemostasis by mediating interactions between platelets and
several ligands, primarily fibrinogen. Inhibition of these receptors prevents
the aggregation of platelets hence their antiplatelet function
 Clinical use
• Adjunct to PCI
• Unstable angina with planned PCI within 24 hours (abciximab)
• Acute coronary syndrome (eptifibatide and tirofiban)

13. Side effects
• Bleeding
• Pelvic pain
• Bradycardia
• Thrombocytopenia
• Edema
• Dizziness
• Injection site pain
• Anemia
• etc

14. Other groups include
• Reversible P2Y12 Antagonists (ticagrelor, cangrelor, elinogrel)
• Thrombin Receptor Antagonists (disappointing results in clinical trials)
• Thromboxane Receptor Antagonists (under clinical trials)

15. Recommended antiplatelet medications for
selected clinical indications

16. Anticoagulants
An anticoagulant is a substance that prevents coagulation; that is,
which stops blood from clotting
This in turn prevents
• Deep vein thrombosis,
• Pulmonary embolism,
• Myocardial infarction
• Stroke.

17. Indications for anticoagulants
oDeep Vein Thrombosis
oPulmonary Embolism
oMyocardial Infarction
oUnstable Angina
oRheumatic Heart Diseases; Atrial Fibrillation
oCerebrovascular Diseases
oDefibrination Syndrome
oVascular Surgery, Prosthetic Heart Valves, Retinal Vessel Thrombosis,
oExtracorporeal Circulation, Haemodialysis

18. Anticoagulants
• Heparin and derivative substances
• Coumarins (vitamin K antagonists)
• Synthetic pentasaccharide inhibitors of factor Xa
• Direct thrombin inhibitors
• Antithrombin protein therapeutics

19. Heparin and derivative substances
• Examples; UH, LMWH
• Mechanism of action
• low dose inactivates Factor Xa and inhibit nof prothrombin to thrombin
• High dose inactivates Factor iX, X, XI and XII and thrombin and inhibits
conversion of fibrinogen to fibrin
 Medical use
• Acute coronary syndrome
• Catheter patency
• DVT and PE both prophylaxis and treatment

20. Side effects
• Heparin induced thrombocytopenia
• Hematoma
• Hemorrhage
• Erythema
• Injection site ulcer
• Anaphylaxis
• Osteoporosis
• etc

21. Coumarins (vitamin K antagonists)
 Examples; warfarin
 mechanism of action
• Depletes functional vitamin K reserves, which in turn reduces synthesis of active clotting
factors, by competitively inhibiting subunit 1 of the multi-unit vitamin k epoxide
reductase complex
 Clinical use
• Venous thrombosis; both prophylaxis and treatment; initial dose 2-5 mg PO/iv QID for 2
days.. Initiate on day 1 or 2 of LMWH or UH and overlap until desired INR (2-3), then
discontinue heparin
• Stroke and thromboembolism
• Cardiac valve replacement
• Post myocardial infaction

22. Undesirable effects
• Cholesterol embolus syndrome
• Intraocular hemorrhage
• Abdominal pain
• Flatulence
• Alopecia
• Pruritus
• Hematuria
• Respiratory track bleeding
• Hypersensitivity reaction
• etc

23. Synthetic pentasaccharide inhibitors of factor
Xa
 Examples; Fondaparinux, Idraparinux
 Mecahnism of action
• Inhibits factor Xa which interrupts blood coagulation cascade and
inhibits thrombin formation and thrombus development. It generally
does not increase PT or PTT
 Clinical use
• Deep vein thrombosis
• Acute pulmonary embolism

24. Unwanted effects
• Anemia
• Fever
• Nausea
• Rash
• Constipation
• hypokalemia
• Insomnia
• Urinary retention/ UTI
• etc

25. Direct factor Xa inhibitors
 Examples; rivaroxaban, apixaban and edoxaban
 Mechanism of action
• factor Xa inhibitor that inhibits platelet activation by selectively blocking
the site of factor Xa without requiring a cofactor (eg antithrombim) for
activity
 clinical use
• DVT prophylaxis (orthopedic surgery) eg, rivaroxaban 10 mg PO
• Nonvalvular atrial fibrillation; eg rivaroxaban 20 mg/day PO
• DVT or PE treatment eg rivaroxaban 15 mg PO BD for 21 days then 20mg
PO QID for 6 months

26. Side effects
• Bleeding; GI, intracranial, intraocular
• Hypersensitivity reaction
• syncope

27. Antithrombin protein therapeutics
 Examples; Atryn
 Mechanism of action
• Serine protease inhibitor; important natural inhibitor of blood
coagulation; inhibits thrombin and factor VIIa/tissue factor complex
 Clinical use
• Prophylaxis of venous thromboembolism in surgery of patients with
congenital antithrombim deficiency

28. Side effects
• Application site pruritus
• Chest pain; non cardiac
• Dizziness
• dyspnea
• Headache
• Hemorrhage
• Postprocedural hemorrhage
• Hepatic enzyme changes

29. Contraindications to anticoagulants and
antiplatelets
Absolute Contraindications
• Known large esophageal varices.
• Significant thrombocytopenia (platelet count < 50
• Within 72 hours of major surgery with risk of severe bleeding
• Previously documented hypersensitivity to either the drug
• Acute clinically significant bleed
• Decompensated liver disease or deranged baseline clotting screen (INR>1.5) (Contraindication
applies to oral anticoagulants only)
• Severe renal impairment GFR < 30 mL/min/1.73 m2 or on dialysis).Contraindication applies to
dabigatran only.

30. Contraindications cont……
Relative Contraindications
• Previous history intracranial haemorrhage
• Recent major extracranial bleed within the last 6 months where the
cause has not been identified or treated
• Recent documented peptic ulcer (PU) within last 3 months
• Recent history recurrent iatrogenic falls in patient at higher bleeding
risk
• Pregnancy or within 48 hours post-partum (Contraindication applies
to oral anticoagulants only.

31. References
American heart association; cardiovascular drugs
http://circ.ahajournals.org/content/101/10/1206.full
Antiplatelet Agents for the Treatment and Prevention of
Atherothrombosis
http://www.medscape.com/viewarticle/755091_3
Uptodate
accessmedicine