The anti-coagulant drugs and their uses.

Anticoagulants refer to the substances which delay or prevent the process of coagulation of blood.
Anticoagulants derive their effect by acting at different sites of the coagulation cascade. Some act directly by enzyme inhibition, while others indirectly, by binding to antithrombin or by preventing their synthesis from the liver (vitamin K dependent factors).

1. ANTI
COAGULANTS
Dr Akriti
I MDS
1

2. Content
●INTRODUCTION
●COAGULATION CASCADE
●TERMINOLOGIES
●CLASSIFICATION OF DRUGS
●PARENTERAL DRUGS
●ORAL DRUGS
●in vitro DRUGS
●USES OF ANTICOAGULANTS
●HEMOSTASIS IN DENTISTRY
●THROMBOLYTICS
2

3. Anticoagulants refer to the substances which delay or prevent the process of coagulation
of blood.
Anticoagulants derive their effect by acting at different sites of the coagulation cascade.
Some act directly by enzyme inhibition, while others indirectly, by binding to antithrombin
or by preventing their synthesis from the liver (vitamin K dependent factors).
Hirsh J, O'Donnell M, Weitz JI. New anticoagulants. Blood. 2005 Jan 15;105(2):453-63
3

4. CHARACTERISTICS OF AN IDEAL ANTI-COAGULANT:
●High efficacy-to-safety index
●Predictable dose response that allows dosing without the need for laboratory
monitoring
●Administration by parenteral and oral routes
●Rapid onset of action
●Availability of a safe antidote
●Freedom from non-anticoagulant side effects
●Minimal interaction with other drugs
Hirsh J, O'Donnell M, Weitz JI. New anticoagulants. Blood. 2005 Jan 15;105(2):453-63
4

5. TERMINOLOGIES
5

6. INTERNATIONAL NORMALISED RATIO
●The INR is derived from prothrombin time (PT) which is calculated as a ratio of the
patient’s PT to a control PT standardized for the potency of the thromboplastin reagent
developed by the World Health Organization (WHO) using the following formula:
INR = Patient PT ÷ Control PT
○For normal patients who are not on anticoagulation, the INR is usually 1.0.
○For patients who are on anticoagulant therapy, the therapeutic INR ranges between 2.0 to 3.0.
○INR levels above 4.9 are considered critical values and increase the risk of bleeding.
●The blood specimens should be collected from venous blood and it is directly obtained
into a tube with a light blue top with (anticoagulant sodium citrate 3.2%). The tubes must
be filled to within 90% of the full collection volume. The total time between sample
collection and testing should not exceed 24 hours.

Shikdar S, Vashisht R, Bhattacharya PT. International normalized ratio (INR).
6

7. INTERNATIONAL NORMALISED RATIO
●INR monitoring is most commonly required for the patients who are on warfarin, a vitamin
K antagonist.
○The dose of warfarin is adapted based on INR scores so that it remains in the therapeutic range
to prevent thrombosis from subtherapeutic INR or hemorrhagic complications from
supratherapeutic INR.
○The anticoagulant effect of warfarin indicated by an INR in the target range also guides us when
to discontinue heparin.
●Other indications for obtaining an INR value are:
○Bleeding diathesis in patients with coagulation factors deficiency (fibrinogen and factors II, V,
VII, or X, or a combined deficiency) in the extrinsic pathway
○Disseminated intravascular coagulation (DIC)
○Baseline sample collection before starting anticoagulation

Shikdar S, Vashisht R, Bhattacharya PT. International normalized ratio (INR).
7

8. INTERNATIONAL NORMALISED RATIO
●The INR can be prolonged in conditions like:
○Vitamin K antagonists
○Other anticoagulants
○Liver dysfunction
○Vitamin K deficiency
○DIC
●Following are the drugs that cause prolongation of INR:
○Antibiotics: especially cotrimoxazole, macrolides, metronidazole, and fluoroquinolones
○Antifungals: azoles (fluconazole)
○Chemotherapeutics: imatinib, Fluorouracil (5-FU)
○Amiodarone, Allopurinol
●Several medications may decrease INR value, for example:
○Antibiotics: Dicloxacillin, nafcillin
○Azathioprine
○Antiepileptics (Carbamazepine, phenytoin)
Shikdar S, Vashisht R, Bhattacharya PT. International normalized ratio (INR).
8

9. PROTHROMBIN TIME
● The PT is a measure of the integrity of the extrinsic and common pathways of the
procoagulant cascade.
●The PT represents the time, in seconds, for patient plasma to clot after the addition of
calcium and an activator of the extrinsic pathway (thromboplastin).
●Thus, deficiencies or inhibitors of clotting factors within the extrinsic and final common
pathways result in prolongation of the PT.
●Monitoring warfarin anticoagulation is the most common indication for PT.
●In general, PT reagents are more sensitive to deficiencies of factor VII within the extrinsic
pathway and less sensitive to deficiencies within the final common pathway (factors V, X,
and II and fibrinogen)
Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and
bleeding time in adults. InMayo Clinic Proceedings 2007 Jul 1 (Vol. 82, No. 7, pp. 864-873). Elsevier.
9

10. ACTIVATED PARTIAL THROMBOPLASTIN TIME
●The aPTT is a measure of the integrity of the intrinsic and final common pathways of the
coagulation cascade.
●The aPTT represents the time, in seconds, for patient plasma to clot after the addition of
phospholipid, an intrinsic pathway activator, and calcium.
●The aPTT reagent is called partial thromboplastin because tissue factor is not present in
conjunction with the phospholipid as it is in the PT reagent.
●Deficiencies or inhibitors of clotting factors within the intrinsic and final common
pathways result in prolongation of the aPTT.
Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time
in adults. InMayo Clinic Proceedings 2007 Jul 1 (Vol. 82, No. 7, pp. 864-873). Elsevier.
10

11. CLASSIFICATION OF DRUGS
11

12. PARENTERAL DRUGS : INDIRECT
THROMBIN INHIBITORS
12

13. HEPARIN
●It is a non-uniform mixture of straight chain mucopolysaccharides with 10,000-20,000
units.
●Heparin was discovered by Mclean in 1916 in an attempt to isolate a thromboplastic
agent.
●Heparin carries strong electronegative charges and is the strongest organic acid present
in the body.
●It occurs in mast cells and is loosely bound to the granular protein. Basophils also
secrete heparin.
●Commercially, heparin is produced from ox lung and pig intestinal mucosa.
●It contains polymers of two sulfated disaccharide units:
○D-glucosamine-L-iduronic acid
○D-glucosamine-D-glucuronic acid
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. Thrombosis and haemostasis. 2008;99(11):807-18.
Mclean, J. The Discovery of Heparin. Circulation 1959, 19, 75–78.
Oduah EI, Linhardt RJ, Sharfstein ST. Heparin: past, present, and future. Pharmaceuticals. 2016 Sep;9(3):38.
13

14. HEPARIN - actions
●Anticoagulant action
○effective both in vivo and in vitro
○acts indirectly by activating plasma antithrombin III which further inactivates factors Xa, IIa, IXa,
XIa, XIIa, XIIIa
○suppresses thrombin action
○Low concentrations of heparin prolong activated partial thromboplastin time (aPTT) without
significantly prolonging prothrombin time (PT). High concentrations prolong both.
●Inhibits platelet aggregation and prolongs bleeding time
●Lipaemia clearing
Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. Thrombosis and haemostasis. 2008;99(11):807-18.
14

15. HEPARIN - dose
Heparin injected i.v. acts instantaneously, but after s.c. injection anticoagulant effect develops
after ~60 min.
●Conventionally given i.v. in a bolus dose of 5,000-10,000 U followed by continuous
infusion. The rate of infusion is regulated by aPTT measurement which is kept at 50-80
sec or 1.5-2.5 times the patient’s pretreatment value.
●Low dose regimen (s.c.) 5,000 U is injected s.c. every 8-12 hours; started before surgery
and continued for 7-10 days.
Heparin is metabolized in liver by heparinase and fragments are excreted in urine. It is not a
physiologically circulating anticoagulant.

Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. Thrombosis and haemostasis. 2008;99(11):807-18.
15

16. HEPARIN - adverse effects
●Bleeding due to overdose is the most serious complication of heparin therapy.
●Aspirin, other NSAIDs and antiplatelet drugs enhance heparin-induced bleeding.
●Thrombocytopenia is another common problem.
Alban S. Adverse effects of heparin. Heparin-a century of progress. 2012:211-63.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
16

17. LOW MOLECULAR WEIGHT HEPARIN
●Molecular weight : 3,000-7,000 U
●They selectively inhibit factor Xa with little effect on IIa. As a result, LMW heparins have
smaller effect on aPTT.
●They have lesser antiplatelet action - less interference with haemostasis.
●INDICATIONS:
○Prophylaxis of deep vein thrombosis and pulmonary embolism in high-risk patients undergoing
surgery, stroke or other immobilized patients.
○Treatment of established DVT.
○Unstable angina treatment.
○To maintain patency of cannulae and shunts in dialysis patients and in extracorporeal
circulation.
Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. Thrombosis and haemostasis. 2008;99(11):807-18.
17

18. HEPARIN ANTAGONIST

Protamine sulfate is a strongly basic, low molecular weight protein which is used when
heparin action needs to be terminated rapidly, e.g. after cardiac or vascular surgery and
for heparin-induced bleeding.
Given i.v. it neutralises heparin weight for weight, i.e. 1mg is needed for every 100 U of
heparin.

K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
Jaques LB. Protamine—antagonist to heparin. Canadian Medical Association Journal. 1973 May 19;108(10):1291-00.
18

19. OTHER DRUGS
●FONDAPARINUX
○synthetically produced pentasaccharide segment present in some heparin molecules which
binds to AT III with high affinity to selectively inactivate factor Xa without binding to thrombin

●DANAPAROID
○heparin-like substance obtained from pig gut mucosa which can be used in patients who
develop thrombocytopenia with heparin
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
19

20. PARENTERAL DRUGS : DIRECT THROMBIN
INHIBITORS
20

21. DRUGS
Unlike heparin, these anticoagulants bind directly to thrombin and inactivate it.
●LEPIRUDIN and BIVALIRUDIN
○These are recombinant synthetic peptides which bind firmly to the catalytic site of thrombin to
cause prolonged inactivation.
●ARGATROBAN
○This is a synthetic nonpeptide compound which reversibly binds to the catalytic site of thrombin
producing short lasting inhibition.
These anticoagulants are administered i.v. only in patients at risk of developing
thrombocytopenia with heparin.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
21

22. ORAL DRUGS : COUMARIN
DERIVATIVES
22

23. MECHANISM OF ACTION
23

24. DRUGS
●WARFARIN SODIUM
○It is the most commonly used oral anticoagulant, action develops over 2-3 days and lasts for 3-6
days.
○Alopecia and dermatitis are infrequent side effects.
●ACENOCOUMAROL
○It is relatively faster and shorter acting, used occasionally.
○Oral ulceration, bowel upset and dermatitis are the side effects.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
24

25. ADVERSE EFFECTS
●Bleeding as a result of extension of the desired pharmacological action is the most
important adverse effect, which can further result in :
○ecchymosis,
○epistaxis,
○hematuria,
○bleeding in the g.i.t.,
○Intracranial hemorrhages, etc., which may be fatal.
●Treatment includes :
○withholding of the anticoagulant
○fresh blood transfusion/fresh frozen plasma
○Vitamin K is the specific antidote, but it takes 6-24 hrs for the clotting factors to be
resynthesized and released in blood after vit K administration.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
25

26. DOSE REGULATION
The dose of oral anticoagulants must be individualized by repeated measurement of
prothrombin time.
●A standardized system called the International Normalized Ratio (INR) has been
developed by WHO to quantify the effect of oral anticoagulants.
○Currently, most guidelines indicate that patients with an INR less than 3.5 can undergo minor
oral surgery (e.g., simple single extraction) without any adjustment in anticoagulation.
Withdrawal or temporary interruption of anticoagulant medication, could lead to
thromboembolic events.
○In case of emergency dental bleed, the effect of oral anticoagulant is reversed by i.v. infusion of
fresh frozen plasma. Vit K may be injected in addition. Adequate packing and local measures
must be applied.
Dinkova A, Kirova D, Delev D. Management of patients on anti-coagulant therapy undergoing dental surgical procedures. Review Article. World
Health. 2013;12(13):14. 26

27. ORAL DRUGS : DIRECT FACTOR Xa
INHIBITOR
27

28. RIVAROXABAN
● It is a highly selective direct Factor Xa inhibitor with oral bioavailability and rapid onset
of action (3-4 hrs).
●It also has a shorter duration of action (~24 hrs).
●Rivaroxaban interrupts the intrinsic and extrinsic pathway of the blood coagulation
cascade, inhibiting both thrombin formation and development of thrombi.
●It also provides stable anticoagulation at a fixed dose without the need for routine INR
monitoring.
●It is effective for prophylaxis of post surgical DVT and of stroke following atrial fibrillation.
Dinkova A, Kirova D, Delev D. Management of patients on anti-coagulant therapy undergoing dental surgical procedures. Review Article. World
Health. 2013;12(13):14.
28

29. ORAL DRUGS : ORAL DIRECT THROMBIN
INHIBITOR
29

30. DABIGATRAN ETEXILATE
●It binds reversibly to the catalytic site of thrombin and inhibits it directly (within 2 hrs).
●It is able to provide stable anticoagulation at a fixed dose without the need for routine
laboratory monitoring of INR and associated dosage adjustments.
●No specific antidote or reversal agent exists to counter the anticoagulant effect of
dabigatran. However, owing to dabigatran’s short half-life (12-14 hours, 14-17 hours in the
elderly), merely discontinuing the administration of the drug is thought to be sufficient to
resolve minor bleeding in most circumstances.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
Dinkova A, Kirova D, Delev D. Management of patients on anti-coagulant therapy undergoing dental surgical procedures. Review Article. World
Health. 2013;12(13):14.
30

31. DRUG INTERACTIONS
●ENHANCED ANTICOAGULANT ACTION
○BROAD-SPECTRUM ANTIBIOTICS inhibit gut flora and reduce vit K production.
○NEWER CEPHALOSPORINS (CEFTRIAXONE, CEFOPERAZONE) cause hypoprothrombinaemia
by the same action as warfarin - additive action.
○ASPIRIN inhibits platelet aggregation and causes g.i. bleeding.
○SULFONAMIDES, INDOMETHACIN, PHENYTOIN displace warfarin from plasma protein binding.
○METRONIDAZOLE, CHLORAMPHENICOL, ERYTHROMYCIN, CIMETIDINE, ALLOPURINOL,
AMIODARONE inhibit warfarin metabolism.
●REDUCED ANTICOAGULANT ACTION
○BARBITURATES, CARBAMAZEPINE, RIFAMPIN, GRISEOFULVIN induce the metabolism of oral
anticoagulants.
○ORAL CONTRACEPTIVES increase blood levels of clotting factors.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003. 31

32. HEPARIN vs WARFARIN
32

33. in vitro COAGULANTS
33

34. SODIUM EDETATE (EDTA)
●Available in two forms:
○Disodium salt (Na2 EDTA)
○Tripotassium salt (K3 EDTA).
●These substances prevent blood clotting by removing calcium from blood.
●Applications of EDTA:
○EDTA is used as an anticoagulant both in vivo and in vitro.
○When used as an anticoagulant in the laboratory (in vitro), 0.5 to 2.0 mg of EDTA per mL of
blood is sufficient to preserve the blood for at least 6 hours.
○On refrigeration, it can preserve the blood up to 24 hours.
Banfi G, Salvagno GL, Lippi G. The role of ethylenediamine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes.
34

35. SODIUM CITRATE
●Available in two concentrations:
○3.2% (109 mmol/L)
○3.8% (129 mmol/L)
●Citrate combines with the calcium in blood to form insoluble calcium citrate.
●Applications of citrate:
○It is used to store blood in the blood bank as:
■ Acid citrate dextrose (ACD): 1 part of ACD with 4 parts of blood
■Citrate phosphate dextrose (CPD): 1 part of CPD with 4 parts of blood
○Citrate is also used in laboratory in the form of formol-citrate solution (Dacie’s solution) for RBC
and platelet counts.
Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. American journal of clinical
pathology. 1997 Jan 1;107(1):105-10.
35

36. SODIUM OXALATE
●Sodium oxalate, like citrates, can be used to remove calcium from the blood plasma. It
thus prevents blood from clotting.
●Other oxalates are also used now a days, like potassium oxalate. Potassium oxalates
increase the osmotic pressure of plasma which draws water from the red blood cells,
thus diluting the plasma and further causing shrinkage of the red blood cells.
Honorato R, Rojas C, Ivanovic N. Sodium Oxalate as Anticoagulant. Proceedings of the Society for Experimental Biology and Medicine. 1948
Jun;68(2):300-1.
Boyd EM, Murray RB. The effect of anticoagulants on blood lipids. Journal of Biological Chemistry. 1937 Feb 1;117(2):629-38.
36

37. USES OF ANTICOAGULANTS
37

38. ●The aim of using anticoagulants is to prevent thrombus extension and
embolic complications by reducing the rate of fibrin formation.

●They do not dissolve already formed clot, but prevent recurrences.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
38

39. DVT AND PULMONARY EMBOLISM
●Venous thrombi are mainly fibrin thrombi, thus anticoagulants are highly effective.
●When deep vein thrombosis/pulmonary embolism has occurred, 3 months or longer
anticoagulant therapy has been recommended.
●Prophylaxis is needed by bedridden, elderly, postoperative, postpartum, poststroke and
leg fracture patients.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. The
Lancet. 1992 Oct 10;340(8824):873-6.
39

40. MYOCARDIAL INFARCTION
●Arterial thrombi are mainly platelet thrombi, thus anticoagulants are of questionable
value. Their use in acute MI has declined.
●Heparin (followed by oral anticoagulant) is generally given after recanalization of
coronary artery by fibrinolytic therapy.
●Heparin cover is generally provided during coronary angioplasty and stent placement.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
40

41. UNSTABLE ANGINA
●Short-term use of heparin has reduced the occurrence of angina.
●Current recommendation is to give aspirin+heparin followed by warfarin.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
41

42. RHEUMATIC HEART DISEASE, ATRIAL FIBRILLATION
●Warfarin is particularly effective in preventing stroke (due to embolism from fibrillating
atria).
●Low dose heparin and aspirin can be used as alternatives.
●Anticoagulants are given for 3-4 weeks before and after attempting conversion of atrial
fibrillation to sinus rhythm.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
42

43. PREVENTION OF THROMBOEMBOLISM
●Anticoagulants are indicated along with antiplatelet drugs in conditions like:
○vascular surgery,
○prosthetic heart valves,
○retinal vessel thrombosis,
○extracorporeal circulation and
○haemodialysis for prevention of thromboembolism.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
43

44. HAEMOSTASIS IN DENTISTRY
44

45. Almost all dental procedures cause at least some bleeding: the dentist has to routinely
deal with haemostasis (arrest of blood loss).

After tooth extraction or similar procedures, bleeding occurs due to disruption of
arterioles and smaller blood vessels that cannot be sutured. Many diseases and drugs can
affect the vascular response to injury, platelet function or coagulation to create
haemostatic problems. Even minor dental procedures like scaling can put certain patients
(haemophilia cases) at great risk of bleeding.

When dental surgery is contemplated in patients with such defects, careful planning and
consultation with their physician are needed. In patients treated with anticoagulants, due
consultation and monitoring of their INR prior to dental surgery is essential.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
45

46. LOCAL HAEMOSTATICS (styptics) are substances used to stop bleeding from a local and
approachable site.
They are particularly effective on oozing surfaces, e.g. tooth socket, abrasions, etc.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
46

47. LOCAL HAEMOSTATICS
●Certain materials provide a meshwork which activates the clotting mechanism and
checks bleeding. Left in situ, these materials are absorbed in 1-4 weeks and generally
cause no foreign body reactions.
○Absorbable materials like FIBRIN, prepared from human plasma and dried as sheet or foam.
○GELATIN FOAM, OXIDIZED CELLULOSE (as strips which can be cut and placed in the socket.)
●THROMBIN obtained from bovine plasma may be applied as dry powder or freshly
prepared solution to the bleeding surface in haemophiliacs.
●VASOCONSTRICTORS like 1% Adr solution may be soaked in sterile cotton-gauze and
packed in bleeding socket.
●Astringents such as TANNIC ACID OR METALLIC SALTS (e.g. alum, ferric chloride) are
occasionally applied for bleeding gums.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
47

48. ABSORBENT GAUGE
HAEMOSTATIC PACKING
MATERIAL
TRANEXAMIC ACID
MOUTHWASH
48

49. Mingarro-de-León A, Chaveli-López B, Gavaldá-Esteve C. Dental management of patients receiving anticoagulant and/or antiplatelet treatment. J
Clin Exp Dent. 2014 Apr 1;6(2):e155-61. doi: 10.4317/jced.51215.
49

50. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surgery, Oral Medicine,
Oral Pathology, Oral Radiology, and Endodontology. 2007 Mar 1;103:S45-e1. 50

51. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surgery, Oral
Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2007 Mar 1;103:S45-e1.
51

52. THROMBOLYTICS
52

53. These are drugs which dissolve thrombi/clot to recanalize occluded blood vessels (mainly
coronary artery). They work by activating the natural fibrinolytic system.

Fibrinolytics like Streptokinase, Urokinase, Alteplase, Reteplase and Tenecteplase have
been produced. Tenecteplase, a genetically engineered mutant of tissue plasminogen
activator (t-PA), is the latest and most favoured.

All fibrinolytics are administered i.v.
Hemorrhage is their major complication.
K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
53

54. MECHANISM OF ACTION:

54

55. USES of FIBRINOLYTICS
●ACUTE MYOCARDIAL INFARCTION is the prime indication.
○They are an alternative to emergency percutaneous coronary intervention (PCI) with stent
placement.
○They help by recanalizing the occluded vessel.
○Best results are obtained if thrombolysis is achieved within 1-2 hrs of symptom onset.
●DEEP VEIN THROMBOSIS in leg, pelvis, shoulder, etc.
●Fibrinolytic therapy is indicated in large, life threatening PULMONARY EMBOLISM.

K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) LTD, New Delhi, 2003.
55

56. REFERENCES
●Hirsh J, O'Donnell M, Weitz JI. New anticoagulants. Blood. 2005 Jan 15;105(2):453-63.
●Shikdar S, Vashisht R, Bhattacharya PT. International normalized ratio (INR).
●Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin
time, activated partial thromboplastin time, and bleeding time in adults. InMayo Clinic
Proceedings 2007 Jul 1 (Vol. 82, No. 7, pp. 864-873). Elsevier.
●K. D. Tripathi, “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers
Medical Publishers (P) LTD, New Delhi, 2003.
●Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin.
Thrombosis and haemostasis. 2008;99(11):807-18.
●Mclean, J. The Discovery of Heparin. Circulation 1959, 19, 75–78.
●Oduah EI, Linhardt RJ, Sharfstein ST. Heparin: past, present, and future.
Pharmaceuticals. 2016 Sep;9(3):38.
●Alban S. Adverse effects of heparin. Heparin-a century of progress. 2012:211-63.
56

57. REFERENCES
●Jaques LB. Protamine—antagonist to heparin. Canadian Medical Association Journal. 1973
May 19;108(10):1291-00.
●Dinkova A, Kirova D, Delev D. Management of patients on anti-coagulant therapy undergoing
dental surgical procedures. Review Article. World Health. 2013;12(13):14.
●Banfi G, Salvagno GL, Lippi G. The role of ethylenediamine tetraacetic acid (EDTA) as in vitro
anticoagulant for diagnostic purposes.
●Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on
routine coagulation testing. American journal of clinical pathology. 1997 Jan 1;107(1):105-10.
●Honorato R, Rojas C, Ivanovic N. Sodium Oxalate as Anticoagulant. Proceedings of the
Society for Experimental Biology and Medicine. 1948 Jun;68(2):300-1.
●Boyd EM, Murray RB. The effect of anticoagulants on blood lipids. Journal of Biological
Chemistry. 1937 Feb 1;117(2):629-38.
●Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for
deep-vein thrombosis and pulmonary embolism. The Lancet. 1992 Oct
10;340(8824):873-6.00.
57

58. REFERENCES
●Mingarro-de-León A, Chaveli-López B, Gavaldá-Esteve C. Dental management of patients
receiving anticoagulant and/or antiplatelet treatment. J Clin Exp Dent. 2014 Apr
1;6(2):e155-61. doi: 10.4317/jced.51215.
●Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common
hemostasis-altering medications. Oral Surgery, Oral Medicine, Oral Pathology, Oral
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