Here are the answers to the questions: 1. C 2. B 3. A 4. B 5. C 6. B 7. I) D II) D III) E 8. I) B II) E 9. I) A II) E 10. C

1. Coagulants & anti-coagulants
Dr. Karun Kumar JR-II

2. • Haemostasis  Limiting blood loss
consequent to bleeding
• Homeostasis  Maintenance of body’s
internal environment within physiological
limits
• Thrombus  A clot that “adheres” to a vessel
wall (Bad  Blocks vessels)
• Embolus  Intravascular clot that “floats” in
blood
• “Detached” thrombus = Embolus
• Clot  Good (Stops bleeding)

3. Coagulation factors
Factor Common synonym
I Fibrinogen
II Prothrombin
III Tissue thromboplastin
IV Calcium
V Proaccelerin
VII Proconvertin
VIII AHF
IX Plasma thromboplastin component
X Stuart factor
XI Plasma thromboplastin antecedent
XII Hageman factor
XIII Fibrin stabilizing factor

4. 3 mechanisms of haemostasis
1. Vascular spasm (Damage to smooth muscle)
2. Platelet plug formation
3. Blood coagulation

5. Intrinsic pathway
• Activated by surface contact with foreign body
(Contact pathway)
• All factors and activators are contained within
(intrinsic to) the blood
• Responsible for clotting when blood is kept in
a glass tube (in vitro)

6. Extrinsic pathway
• Activated by thromboplastin
• As a consequence of trauma, a tissue protein
(tissue factor) leaks into the blood from cells
outside (extrinsic to) blood vessels
• Rate limiting step in coagulation cascade 
activation of factor X (converging pathway)

8. PT aPTT
Intrinsic
pathway
interfered
Normal (12-
14 secs)
Prolonged
Extrinsic
pathway
interfered
Prolonged
(WEPT)
Normal (26-
32 secs)
Common
pathway
interfered
Prolonged Prolonged

9. Pro & anti-aggregatory factors
• Pro-aggregatory factor  TXA2 (platelets)
↓ blood flow & ↑ platelet aggregation
• Anti-aggregatory factors
1. PGI2 Endothelial
2. NO cells
↑ blood flow & ↓ platelet aggregation

14. Coagulants
• Indication  Haemorrhagic states
• Best therapy  Fresh whole blood / plasma
1. Vitamin K (K1 , K2 & K3)  Cofactor in the
post-translational carboxylation of glutamate
residues on factors II, VII, IX, and X
2. Miscellaneous
• Fibrinogen
• Anti-haemophilic factor
• Desmopressin

15. Anticoagulants
• Drugs that impede blood
coagulation and prevent
the occurrence or
expansion of a thrombus

16. Classification
1. Vitamin K antagonist  Warfarin
2. Heparin & related drugs
a) Heparin
b) LMWH (Enoxaparin, Dalteparin,
Tinzaparin)
c) Synthetic heparin derivatives
(Fondaparinux – longer acting)

17. 3. Direct thrombin inhibitors
a) Parenteral  Hirudin, Lepirudin, Argatroban,
Bivalirudin)
b) Oral  Dabigatran
4. Active factor Xa inhibitor  Rivaroxaban,
Apixaban
RIVAR  Rivarsible (Reversible) ; O  Oral;
XA  X a ; BAN  Blocker

18. Warfarin (WEPT)
• Competitively inhibits vitamin K
epoxide reductase & inhibits the
posttranslational carboxylation of
glutamate residues on vitamin K
dependent coagulation factors II
(prothrombin), VII, IX, and X
• Causes WAR during pregnancy
• PT should be monitored

21. Heparin
• Antithrombin III  Irreversibly inactivates
thrombin & factor Xa
• Heparin potentiates anti-thrombin III activity
• Dosage determined by monitoring aPTT

24. Advantages of LMWH
1. Can be administered s.c.
2. Effects are consistent & dosing less frequent
(Long t1/2 & elimin. By 1st order kinetics)
3. Do not prolong aPTT & CT (Response is
predictable & monitoring not required)
4. Dose is given in mg (not in units) can be
easily calculated on body weight basis
5. Chance of haemorrhage chance is less
6. Risk of osteoporosis is decreased

25. Heparin Warfarin
Route of
admin.
I.v., S.c. Oral
Onset of action Immediate Delayed
Mechanism Activ. Of AT-III ↓ activ. Of c.f.
2,7,9,10
Antagonist Protamine
sulphate
Vitamin K
Lab control aPTT PT
Drug interact. Few Many
Use To initiate
therapy
For maintenance

26. Uses of anti-coagulants
1. Prevention & t/t of DVT & PE
2. Myocardial infarction
3. Unstable angina
4. Rheumatic heart disease
5. Cerebrovascular disease
6. Haemodialysis
7. Defibrination syndrome (DIC)

27. Antiplatelet drugs (ATD)
1. Aspirin
2. Cilostazol, Dipyridamole (PDE III inhib.)
3. P2Y12 receptor blocker
a) Reversible antag.  Ticagrelor, Cangrelor
b) Irrev. Antag.  Ticlopidine, Clopidogrel,
Prasugrel
4. GP IIb/IIIa antag.
Abciximab, Tirofiban, Eptifibatide

28. Aspirin
• It irreversibly
inhibits
1. COX-1
2. TX-synthase
• It does NOT inhibit
TXA2 directly

29. Why low dose Aspirin ?
• 75-150 mg  TXA2 formation suppressed
• > 900 mg  ↓ PGI2 & TXA2
• TXA2  Platelets (Life span  5-7 days)
• PGI2  Endothelial cells
• Low dose (80-160 mg)  Antiplatelet effect
• Moderate dose (650-975 mg)  Analgesic &
antipyretic effects
• High dose (3-6 g)  Anti inflammatory effect

32. • GP IIb/IIIa  Protein
complex on the
surface of platelets.
• When activated, it
aggregates platelets
by binding to fibrin

33. Summary

34. Uses of anti-platelet drugs
1. MI  Low dose Aspirin
2. Unstable angina  Aspirin / Clopidogrel
3. Coronary bypass implants
4. Prosthetic heart valves
5. Arteriovenous shunts
6. Venous thromboembolism
7. Peripheral vascular disease
8. Cerebrovascular transient ischemic attacks

35. Fibrinolytic drugs (USA)
• Lyse (dissolve) the thrombi (clots) in blood
vessels by activating firbrinolytic system
1. Urokinase
2. Streptokinase
3. Anistreplase
4. Alteplase
5. Reteplase
6. Tenecteplase

36. Mechanism of action

37. Uses of fibrinolytics
1. Acute myocardial infarction
2. Deep vein thrombosis
3. Pulmonary embolism
4. Peripheral arterial occlusion
5. Stroke

39. Anti fibrinolytic drugs
1. Epsilon Aminocaproic acid
Blocks plasminogen activation (stops
bleeding)
2. Tranexamic acid
Cyclic heavy menstrual bleeding
A/E  Thrombosis

40. Q.1. For each drug description, select the
correct answer from the following choices:
(A)Eptifiatide (B) prasugrel (C) dabigatran
(D) Rivaroxaban (E) enoxaparin
1. This orally administered drug directly and
selectively inhibits thrombin.
2. This drug produces irreversible blockade of
platelet adenosine diphosphate P2Y receptors.
3. This orally administered inhibitor of active
factor X (Stuart factor) is used to prevent DVT in
persons undergoing hip-replacement surgery
4. This drug is a reversible fibrinogen antagonist
at GP IIb/ IIIa receptors.

41. Q.2. Which of the P2Y12 ADP receptor
antagonists reversibly binds the receptor?
A. Clopidogrel
B. Prasugrel
C. Ticagrelor
D. Ticlopidine

42. Q.3. A 70-year-old female is diagnosed with
nonvalvular atrial firillation. Her past medical
history is significant for chronic kidney disease,
and her renal function is moderately diminished.
All of the following anticoagulants would be
expected to require a reduced dosage in this
patient except:
A. Apixaban.
B. Dabigatran.
C. Rivaroxaban.
D. Warfarin.

43. Q.4. An 80-year-old male is taking warfarin
indefinitely for the prevention of deep venous
thrombosis. He is a compliant patient with a stable
INR and has no issues with bleeding or bruising. He
is diagnosed with a urinary tract infection and is
prescribed sulfamethoxazole/ trimethoprim. What
effect will this have on his warfarin therapy?
A. Sulfamethoxazole/trimethoprim will decrease
the anticoagulant effect of warfarin.
B. Sulfamethoxazole/trimethoprim will increase the
anticoagulant effect of warfarin.
C. Sulfamethoxazole/trimethoprim will activate
platelet activity.
D. Sulfamethoxazole/trimethoprim will not change
anticoagulation status.

44. Q.5 Which must heparin bind to in order to
exert its anticoagulant effect?
A. GP IIb/IIIa receptor.
B. Thrombin.
C. Antithrombin III.
D. von Willebrand factor.

45. Q.6. Which is most appropriate for reversing the
anticoagulant effects of heparin?
A. Aminocaproic acid
B. Protamine sulfate
C. Vitamin K
D. Tranexamic acid

46. Q.7. A 58-year-old business executive is brought
to the emergency department 2 h after the
onset of severe chest pain during a vigorous
tennis game. She has a history of poorly
controlled mild hypertension and elevated blood
cholesterol but does not smoke. ECG changes
confirm the diagnosis of myocardial infarction.
The decision is made to attempt to open her
occluded artery.

47. I) Which of the following drugs accelerates the
conversion of plasminogen to plasmin?
(A) Aminocaproic acid
(B) Heparin
(C) Lepirudin
(D) Reteplase
(E) Warfarin

48. II) If a fibrinolytic drug is used for treatment of
this woman’s acute myocardial infarction, which
of the following adverse drug effects is most
likely to occur?
(A) Acute renal failure
(B) Development of antiplatelet antibodies
(C) Encephalitis secondary to liver dysfunction
(D) Hemorrhagic stroke
(E) Neutropenia

49. III) If this patient undergoes a percutaneous
coronary angiography procedure and placement
of a stent in a coronary blood vessel, she may be
given eptifibatide. Which of the following most
accurately describes the mechanism of
eptifibatide anticlotting action?
(A) Activation of antithrombin III
(B) Blockade of post-translational modification
of clotting factors
(C) Inhibition of thromboxane production
(D) Irreversible inhibition of platelet ADP rec.
(E) Reversible inhibition of GP IIb/IIIa receptors

50. Q. 8. A 65-year-old man is brought to the
emergency department 30 min after the onset
of right-sided weakness and aphasia (difficulty
speaking). Imaging studies ruled out cerebral
hemorrhage as the cause of his acute symptoms
of stroke.

51. I) Prompt administration of which of the
following drugs is most likely to improve this
patient’s clinical outcome?
(A) Abciximab
(B) Alteplase
(C) Factor VIII
(D) Streptokinase
(E) Vitamin K

52. II) Over the next 2 d, the patient’s symptoms
resolved completely. To prevent a recurrence of
this disease, the patient is most likely to be
treated indefinitely with which of the following?
(A) Aminocaproic acid
(B) Aspirin
(C) Enoxaparin
(D) Lepirudin
(E) Warfarin

53. Q.9. A 67-year-old woman presents with pain in
her left thigh muscle. Duplex ultrasonography
indicates the presence of deep vein thrombosis
(DVT) in the affected limb.

54. I) The decision was made to treat this woman
with enoxaparin. Relative to unfractionated
heparin, enoxaparin
(A) Can be used without monitoring the
patient’s aPTT
(B) Has a shorter duration of action
(C) Is less likely to have a teratogenic effect
(D) Is more likely to be given intravenously
(E) Is more likely to cause thrombosis and
thrombocytopenia

55. II) During the next week, the patient was started on
warfarin and her heparin was discontinued. Two
months later, she returned after a severe
nosebleed. Laboratory analysis revealed an INR
(international normalized ratio) of 7.0 (INR value in
such a warfarin-treated patient should be 2.0–3.0).
To prevent severe hemorrhage, the warfarin should
be discontinued and this patient should be treated
immediately with which of the following?
(A) Aminocaproic acid
(B) Desmopressin
(C) Factor VIII
(D) Protamine
(E) Vitamin K

56. Q. 10. A patient develops severe
thrombocytopenia in response to treatment
with unfractionated heparin and still requires
parenteral anticoagulation. The patient is most
likely to be treated with which of the following?
(A) Abciximab
(B) Cilostazol
(C) Lepirudin
(D) Plasminogen
(E) Vitamin K1