This document discusses various anticoagulant and antiplatelet drugs. It begins by listing the coagulation factors and platelet adhesion proteins involved in thrombus formation. It then discusses the mechanisms and uses of several classes of anticoagulants including heparin, low molecular weight heparins, direct thrombin inhibitors, and vitamin K antagonists. The document also summarizes the mechanisms and applications of antiplatelet drugs such as aspirin, clopidogrel, and GP IIb/IIIa inhibitors for preventing thrombosis. In summary, the document provides an overview of the key drugs used to treat and prevent thrombosis through inhibition of coagulation factors and platelet activation.

1. Anti coagulants and
anti platelets
A discussion about the drugs

2. FACTOR NAME
I Fibrinogen
II Prothrombin
III Tissue factor or thromboplastin
IV Calcium
V Proaccelerin (Labile factor)
VII Proconvertin (Stable factor)
VIII
Antihaemophilic factor A,
Antihaemophilic globulin
IX
Antihaemophilic factor B,
Plasma thromboplastin component,
Christmas factor
X Stuart-Prower factor
XI
Plasma thromboplastin antecedent,
Haemophilia C,
Rosenthal syndrome
XII Hageman factor
XIII
Fibrin stabilising factor,
Laki-Lorand factor
.

3. Clotting Cascade

4. Vascular Injury
Exposure of collagen and vWF Tissue factor exposure
Platelet adhesion and release Activation of coagulation
Platelet recruitment and activation
Thrombin generation
Fibrin formationPlatelet aggregation
Platelet – fibrin thrombus

6. Consequences of thrombus
consequences
angina
Myocardial
infarction
stroke
Deep venous
thrombosis

7. Anticoagulant Therapy
Treatment of
thrombus
Prevent Thrombosis
Anticoagulants
Antiplatelets
Removing the
occlusion
Thrombolysis
Coronary angioplasty
Vasodilation
Nitrates
CCB

8. Antithrombotic drugs
Fibrinolytics

9. Antithrombotic drugs
Fibrinolytics

10. Antithrombotic drugs
Fibrinolytics

11. Antithrombotic drugs
Fibrinolytics

13. Anti coagulants

14. History of Anticoagulants
• Heparin was discovered in 1915 by McLean
• Warfarin has been the drug of choice for the
prevention and treatment of arterial and venous
thrombotic disorders for more than 60 years
• It was initially marketed as a
pesticide against rats and mice,
and is still popular for this purpose

15. Anti coagulants
• Direct thrombin inhibitors
• Indirect thrombin inhibitors

16. DIRECT THROMBIN INHIBITORS
 Hirudin – Lepirudin
 Bivalirudin
 Argatroban
 Melagatran
 Ximelagatran (oral)
 Dabigatran (oral)

17. INDIRECT THROMBIN INHIBITORS
• Heparin
• LMWH – Enoxaparin, dalteparin
• Fondaparinaux
• Rivaroxiban (1st oral factor Xa inhibitor)

18. Classification
Parenteral
• Heparin
• Heparinoids
• Agratroban
• Hirudins
• Epoprostenol
• Fondaparinux
Oral
• Warfarin
• Acenocoumarol
• Phenindione

19. Anti coagulants- uses
• Prevent thrombus formation
• Prevent extension of an existing thrombus
• Used in venous thrombus

20. Heparin-Plus and minus
Unfractionated heparin
• Short duration of action
• Bioavailability less (22-40%)
• Onset immediate(iv), s/c (2-4hr)
• ½ life 60-90 mins
• Continuous iv or intermittent s/c
infusion
• Can be withdrawn easily in case of any
complication
• Daily aPTT monitoring
LMWH
• Longer duration
• Bioavailability more (>90%)
• Onset (3-5hrs)
• ½ life 4.5 hrs
• Titrated dose
• Effect will remain even after withdrawal
• Weekly monitoring

21. Heparin
• Mechanism for low dose: Inactivates factor Xa
and inhibits conversion of prothrombin to
thrombin
• Mechanism for high dose: Inactivates factors
IX, X, XI, and XII and thrombin and inhibits
conversion of fibrinogen to fibrin
• Also inhibits activation of factor VIII
Mechanism of action

22. Prophylaxis
•5000 units SC q8-12hr, OR
•7500 units SC q12hr
Treatment
•80 units/kg IV bolus, THEN continuous infusion of 18 units/kg/hr,
OR
•5000 units IV bolus, THEN continuous infusion of 1300 units/hr, OR
•250 units/kg (alternatively, 17,500 units) SC, THEN 250 units/kg
q12hr
the heparin needs to be continued for at least 5 days and until the
INR is 2 for at least 24 hours
DVT / PE Uses

23. Acute Coronary Syndromes
PCI
•Without GPIIb/IIIa inhibitor: Initial IV bolus of 70-100 units/kg (target ACT 250-
300 sec)
•With GPIIb/IIIa inhibitor: Initial IV bolus of 50-70 units/kg (target ACT >200 sec)
STEMI
•Patient on fibrinolytics: IV bolus of 60 units/kg (max: 4000 units), THEN 12
units/kg/hr (max 1000 units/hr) as continuous IV infusion
•Dose should be adjusted to maintain aPTT of 50-70 sec
Unstable Angina/NSTEMI
•Initial IV bolus of 60-70 units/kg (max: 5000 units), THEN initial IV infusion of
12-15 units/kg/hr (max: 1000 units/hr)
•Dose should be adjusted to maintain aPTT of 50-70 sec

24. Anticoagulation
Intermittent IV injection
•8000-10,000 units IV initially, THEN 50-70 units/kg (5000-
10,000 units) q4-6hr
Continuous IV infusion
•5000 units IV injection, followed by continuous IV infusion of
20,000-40,000 units/24 hr
Catheter Patency
Prevention of clot formation within venous and arterial
catheters
Use 100 units/mL; instill enough volume to fill lumen of
catheter

25. Contraindications
Severe thrombocytopenia
Uncontrolled, active bleeding (except DIC)
Conditions in which coagulation tests cannot be performed at appropriate
intervals
Cautions
Any risk factor for hemorrhage (eg, subacute bacterial endocarditis, blood
dyscrasias, menorrhagia, dissecting aneurysm, major surgery, spinal
anesthesia, hemophilia, GI ulcerative lesions, liver disease, impaired
hemostasis)
Adverse effect
Heparin-induced thrombocytopenia may occur (with or without thrombosis)

26. Mechanism of Action
LMWH; antithrombotic that inhibits factor Xa by increasing inhibition rate of
clotting proteases that are activated by antithrombin III
Generally does not increase PT or PTT
LMWH

27. Deep Vein Thrombosis (Prophylaxis)
Abdominal surgery
•40 mg SC qDay; initiate 2 hr preoperatively
Knee or hip replacement surgery
•30 mg SC q12hr; initiate therapy 12-24 hr postoperatively and continued for 10 days or up to 35 days
postoperatively or until risk of DVT has been significantly reduced or patient is on anticoagulant therapy
•For hip replacement surgery, may consider administering 40 mg SC qDay, initiated 9-15 hr preoperatively
and continued for 10 days or up to 35 days postoperatively or until risk of DVT has been significantly reduced
or patient is on anticoagulant therapy
Medical patients with restricted mobility
•40 mg SC qDay; continue until risk of DVT has been significantly (6-11 days) reduced or patient is on
anticoagulant therapy

28. Deep Vein Thrombosis (Treatment)
Inpatient treatment
•Acute DVT with or without PE, when administered in conjunction with warfarin
sodium
•1 mg/kg SC q12hr, OR 1.5 mg/kg SC qDay (administer at same time each day)
Outpatient treatment
•Acute DVT without PE, when administered in conjunction with warfarin sodium
•1 mg/kg SC q12hr
Unstable Angina & Non-Q-Wave MI
Prophylaxis of ischemic complications of unstable angina and non-Q-wave
myocardial infarction, when concurrently administered with aspirin
1 mg/kg SC q12hr
Regimen includes aspirin (100-325 mg/day PO)

29. Acute STEMI
<75 years
•Loading dose: 30 mg IV bolus once plus 1 mg/kg SC once; not to exceed 100 mg cumulative loading
dose
•Maintenance: 1 mg/kg SC q12hr
>75 years
•No IV bolus
•0.75 mg/kg SC q12hr
•Not to exceed 75 mg/dose for first 2 doses only, followed by 0.75 mg/kg for remaining doses
With PCI
•If last enoxaparin was given <8 hr before balloon inflation, no additional dosing is needed
•If last enoxaparin was given 8-12 hr before balloon inflation, an IV bolus of 0.3 mg/kg should be
administered
•If PCI occurs >12 hr after last SC dose; use established anticoagulation therapy (full-dose
unfractionated heparin or LMWH
•Patient that has not received prior anticoagulant therapy: 0.5-0.75 mg/kg bolus dose

30. Contraindications
Active major bleeding, thrombocytopenia with antiplatelet antibody in presence
of enoxaparin or heparin
Hypersensitivity to enoxaparin, heparin, pork products, or other ingredients
Cautions
Epidural or spinal hemorrhage and subsequent hematomas reported with the
use of enoxaparin
epidural or spinal anesthesia/analgesia or spinal puncture procedures,
resulting in long-term or permanent paralysis

32. Mechanism of Action
Protamine that is strongly basic combines with acidic heparin forming a stable
complex and neutralizes the anticoagulant activity of both drugs
Pharmacokinetics
Half-life elimination: 7 min
Onset: 5 min
Time Elapsed Since Heparin Dose
Dose of protamine (mg) to neutralize 100 units of heparin
•<1/2 hr: 1-1.5 mg/100 units of heparin
•30-120 min: 0.5-0.75 mg/100 units of heparin
•>2 hr: 0.25-0.375 mg/100 units of heparin
Protamine sulphate

33. Mechanism of Action
Antithrombotic agent; inhibits factor Xa,
which interrupts blood coagulation cascade
and inhibits thrombin formaiton and
thrombus development; generally does not
increase prothrombin time (PT) or partial
thromboplastin time (PTT)
Absorption
Bioavailability: 100%
Peak plasma time: 2-3 hr
Fondaparinux

34. Deep Vein Thrombosis/Acute Pulmonary Embolism
Treatment
<50 kg: 5 mg SC once daily
50-100 kg: 7.5 mg SC once daily
>100 kg: 10 mg SC once daily
Administer for 5-9 days; up to 26 days administered in clinical trials
Prophylaxis
>50 kg: 2.5 mg SC once daily for 5-9 days or up to 10 days following abdomonal surgery; for hip replacement, 11
days recommended and a minimum 10-14 days recommended for patients undergoing total hip or knee
arthroplasty, or hip fracture surgery; administered for up to 35 days in some instances
Heparin-Induced Thrombocytopenia (Off-label)
Prophylaxis of deep vein thrombosis (DVT) in patient with history of heparin-induced thrombocytopenia (HIT)
until patient can switch to warfarin
2.5 mg SC once daily
American College of Chest Physicians (ACCP) guidelines assign low evidence rating to treatment of HIT with
fondaparinux and conclude that further studies evaluating its role in HIT treatment are needed

35. Mechanism of Action
Interferes with hepatic synthesis of vitamin K-dependent clotting factors II, VII,
IX, and X, as well as proteins C and S; S-warfarin is 4 times more potent than
R-warfarin
Warfarin 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 1 (VKOR1)
Absorption
Onset: 36-48 hr
Duration: 2-5 days
Peak plasma time: 1.5-3 days
Distribution
Protein bound: 99% (albumin)
Warfarin

36. Venous Thrombosis
Prophylaxis and treatment of venous thrombosis and its extension, pulmonary
embolism (PE)
Initial dose: 2-5 mg PO/IV qDay for 2 days, OR 10 mg PO for 2 days in healthy
individuals
Initiate warfarin on day 1 or 2 of LMWH or unfractionated heparin therapy and
overlap until desired INR, THEN discontinue heparin
Check INR after 2 days and adjust dose according to results
Typical maintenance dose ranges between 2 and 10 mg/day
DVT and PE treatment
•Initiate warfarin on day 1 or 2 of parenteral anticoagulation therapy (eg, LMWH or
unfractionated heparin)
•Overlap warfarin and parenteral anticoagulant for at least 5 days until desired INR
(>2.0) maintained for 24 hours, then discontinue parenteral therapy

37. Stroke & Thromboembolism
Prophylaxis and treatment of systemic embolic complications (eg, stroke) associated
with atrial fibrillation (AF)
Initial dose: 2-5 mg PO/IV qDay × 2 days, OR 10 mg PO × 2 days in healthy
individuals
Typical maintenance dose ranges between 2-10 mg/day
Cardiac Valve Replacement
Prophylaxis and treatment of thromboembolic complications associated with cardiac
valve replacement
Initial dose: 2-5 mg PO/IV qDay × 2 days, OR 10 mg PO × 2 days in healthy
individuals
Post-Myocardial Infarction
Reduction in the risk of death, recurrent MI, and thromboembolic events (eg, stroke,
systemic embolization) after MI
Initial dose: 2-5 mg PO/IV qDay × 2 days, OR 10 mg PO × 2 days in healthy
individuals

38. Contraindications
Pregnancy, except in women with mechanical heart valves
Hemorrhagic tendencies or blood dyscrasias
Recent or contemplated CNS or eye surgery or traumatic surgery resulting in large open surfaces
Bleeding tendencies associated with CNS hemorrhage, cerebral aneurysms, dissecting aorta,
pericarditis and pericardial effusions, bacterial endocarditis, and active ulceration or overt bleeding of
the GI, GU, or respiratory tract
Threatened abortion, eclampsia, and preeclampsia
Unsupervised patients with conditions associated with potential high level of noncompliance (eg,
dementia, alcoholism, psychosis)
Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding
Major regional or lumbar block anesthesia
Known hypersensitivity
Malignant hypertension
Cautions
Lower doses may be warranted in the elderly, debilitated patients, malnutrition, CHF, or liver disease

39. The future for anticoagulants
• Factor Xa is an attractive
target for the design of
new oral anticoagulants
because of the unique
role factor Xa plays in the
coagulation cascade as a
connection between the
extrinsic and intrinsic
pathways

40. ANTIPLATELETS
• Aspirin
• ADP receptor antagonists – clopidogrel, ticlopidine
• GP IIB/IIIA inhibitors – Abciximab, Eptifibatide,
Tirofiban
• Dipyridamole
• Cilostazol

41. Uses
1.Prophylaxis of venous thrombosis.
2.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.

43. The role of platelets

44. The role of platelets

45. The role of platelets

46. The role of platelets

47. Aspirin ( Acetylsalicylic Acid )
Mechanism of Action
1. Irreversible inhibition of cyclooxygenase enzyme via
acetylation.
2. Small dose inhibits thromboxane synthesis in platelets
(TXA2) But not prostacyclin (PGI2) synthesis in
endothelium (larger dose).
Bioavailability: 80-100%
Onset: PO, 5-30 min; PR, 1-2 hr
Duration: PO, 4-6 hr; PR, >7 hr
Metabolized by liver via microsomal enzyme system
Excretion: Urine (80-100%), sweat, saliva, feces

48. Acetylsalicylic acid –
mechanism of action

49. Acetylsalicylic acid –
mechanism of action

50. Acetylsalicylic acid –
mechanism of action

51. Acute Coronary Syndrome
For use as adjunctive antithrombotic effects for ACS (ST-segment elevation myocardial infarction
[STEMI], unstable angina [UA]/non-ST-segment elevation myocardial infarction [NSTEMI])
Acute symptoms
•160-325 mg PO; chew nonenteric-coated tablet upon presentation (within minutes of symptoms)
•If unable to take PO, may give 300-600 mg suppository PR
Maintenance (secondary prevention)
•75-81 mg PO qDay indefinitely (preferred dose); may give 81-325 mg/day
•Regimen may depend on coadministered drugs or comorbid conditions
Percutaneous transluminal coronary angioplasty
•Adjunctive aspirin therapy to support reperfusion with primary PCI (with or without fibrinolytic
therapy)
•Preoperative dose: 162-325 mg PO before procedure
•Maintenance: 81 mg PO qDay indefinitely (preferred dose) may give 81-325 mg/day

52. Pain & Fever
325-650 mg PO/PR q4-6hr PRN
Ischemic Stroke & Transient Ischemic Attack
50-325 mg/day PO within 48 hours of stroke or TIA, then 75-100 mg/day PO
Osteoarthritis/Rheumatoid Arthritis
/Spondyloarthropathy Up to 3 g/day PO in divided doses
Colorectal Cancer (Off-label)
Prophylaxis
600 mg/day PO
Decreases risk of developing hereditary colorectal cancer (ie, Lynch syndrome) by 60% if taken
daily for at least 2 years

53. Contraindications
Hypersensitivity to aspirin or NSAIDs; aspirin-associated hypersensitivity reactions include aspirin-
induced urticaria (HLA-DRB1*1302-DQB1*0609 haplotype), aspirin-intolerant asthma (HLA-DPB1*0301)
Allergy to tartrazine dye
Absolute
•Bleeding GI ulcers, hemolytic anemia from pyruvate kinase (PK) and glucose-6-phosphate
dehydrogenase (G6PD) deficiency, hemophilia, hemorrhagic diathesis, hemorrhoids, lactating mother,
nasal polyps associated with asthma, sarcoidosis, thrombocytopenia, ulcerative colitis
Relative
•Appendicitis, asthma (bronchial), chronic diarrhea, bowel outlet obstruction (for enteric-coated
formulations), dehydration, erosive gastritis, hypoparathyroidism
Cautions
Anemia, GI malabsorption, history of peptic ulcers, gout, hepatic disease, hypochlorhydria,
hypoprothrombinemia, renal impairment, thyrotoxicosis, vitamin K deficiency, renal calculi, ethanol use
(may increase bleeding)
Discontinue therapy if tinnitus develops
Should be taken with food or 8-12 oz of water to avoid GI effects
Not indicated for children with viral illness; use of salicylates in pediatric patients with varicella or
influenza like illness is associated with increased incidence of Reye syndrome

54. Clopidogrel (ADP pathway inhibitor)
Mechanism of Action
Inhibits the binding of ADP to its platelet receptor by irreversibly modifying the platelet ADP receptor.
Absorption
Bioavailability: >50%
Onset: 2 hr
Peak serum time: 0.75 hr
Peak plasma concentration: 3 mg/L
Metabolism
Metabolized in liver by hepatic CYP450 enzymes
Elimination
Half-life: 6 hr (parent drug); 30 min (active metabolite)
Excretion: Urine (50%), feces (46%)

55. ADP-receptor antagonists –
mechanism of action

56. ADP-receptor antagonists –
mechanism of action

57. ADP-receptor antagonists –
mechanism of action

58. ADP-receptor antagonists –
mechanism of action

59. Acute Coronary Syndrome
Unstable angina, non-ST-segment elevation MI (NSTEMI): 300 mg loading dose,
then 75 mg/day PO for up to 12 months; administer indefinitely if used in
combination with aspirin 75-100 mg/day
ST-segment elevation MI (STEMI): 75 mg/day PO in combination with aspirin 162-
325 mg/day and then 81-162 mg/day
<75 years
•300 mg loading dose followed by 75 mg for 14 days up to 12 months (if no
bleeding)
•Concomitant therapy with aspirin: Administer in combination with aspirin 75-325
mg qDay with or without thrombolytics
>75 years
•No loading dose
•75 mg for 14 days up to 12 months (if no bleeding)

60. Recent MI, Stroke, or Established Peripheral Arterial Disease
75 mg PO qDay; recommended as alternative to aspirin or concomitantly with aspirin
if patient not at increased risk for bleeding but at high risk for cardiovascular disease
Coronary Artery Disease
75 mg PO qDay
Cardioembolic Stroke
Prophylaxis if patient not candidate for oral anticoagulation
75 mg/day PO
Carotid Artery Stenting (Off-label)
300 mg PO plus aspirin 81-325 mg for 1 dose on day before carotid artery stenting
(CAS), then 75 mg/day PO plus aspirin 81-325 mg/day for at least 30 days after CAS
Alternative: 300-600 mg PO once, then 75 mg/day for 4 days before CAS in
combination with aspirin 81-325 mg/day

61. Contraindications
Hypersensitivity
Active pathologic bleeding (eg, peptic ulcer, intracranial hemorrhage)
Cautions
Use with caution in patients with bleeding or platelet disorders
May increase risk of major hemorrhage in patients with recent lacunar
stroke
CYP2C19 inhibition & poor metabolizers

62. Dipyridamole
Mechanism of Action
Phosphodiestrase inhibitor   cAMP in the blood platelets 
inhibition of platelet aggregation.
AMP  cAMP  degradation of cAMP
Non-nitrate coronary vasodilator
Inhibition of RBC uptake of adenosine thereby inhibiting platelet
reactivity
Phosphodiesterase inhibition increasing cAMP in platelet, OR
Inhibition of Thromboxane A2 formation (vasoconstrictor and a
stimulator of platelet activation)

63. Dipyridamole –
mechanism of action

64. Dipyridamole –
mechanism of action

65. Dipyridamole –
mechanism of action

66. Thromboembolism Prophylaxis Post-Cardiac Valve
Replacement
75-100 mg PO q6hr as adjunct to warfarin
Adjunct to Thallium Myocardial Perfusion Imaging (Off-label)
Adjusted according to body weight; recommended 0.142
mg/kg/min IV infusion over 4 minutes; not to exceed 60 mg
Contraindications
Hypersensitivity
Thrombocytopenia
Cautions
FDA approval for chronic angina withdrawn
uses

67. GPIIb/IIIa-receptor antagonists –
mechanism of action

68. GPIIb/IIIa-receptor antagonists –
mechanism of action

69. GPIIb/IIIa-receptor antagonists –
mechanism of action

70. GPIIb/IIIa-receptor antagonists –
mechanism of action

71. GPIIb/IIIa-receptor antagonists –
mechanism of action

73. fibrinolytics

74. Thrombolytic drugs –
mechanism of action

75. Thrombolytic drugs –
mechanism of action

76. Thrombolytic drugs –
mechanism of action

77. Thrombolytic drugs –
mechanism of action

78. The end