The document discusses drugs used in coagulation disorders and bleeding. It describes two major groups of drugs - those that decrease clotting like anticoagulants and thrombolytics, and those that increase clotting for deficiencies. Anticoagulants discussed include heparins, warfarin, and direct thrombin/factor Xa inhibitors. Antiplatelets to inhibit platelet aggregation are also covered. Drugs to arrest bleeding include local haemostatics applied topically and systemic agents like vitamin K and antifibrinolytics. Key points for dentists on managing patients taking these drugs emphasize safer options and monitoring coagulation levels before procedures.

1. Drugs Used in
Coagulation Disorders

2. Overview

3. 1 2 3

7. The drugs used in clotting and bleeding
disorders fall into 2 major groups:
(1) drugs used to decrease
clotting or dissolve clots
already present in patients
at risk for vascular occlusion
and
(2) drugs used to increase
clotting in patients with
clotting deficiencies.

8. Anti-clotting Drugs

9. 1. ANTICOAGULANTS
• Anticoagulants inhibit the formation of fibrin
clots.
• 3 major type are available:
1. Heparin and related compounds which
must be used parenterally;
2. the orally active coumarin derivatives
(warfarin)
3. direct thrombin inhibitors also used
parenterally; and

11. A. Heparin and related compounds
1. Unfractionated heparin (UFH)
– has a molecular weight range of 5000–30,000 (HMW)
– Heparin is given intravenously or subcutaneously
2. Low-molecular-weight (LMW)
– have molecular weights of 2000–6000.
– (eg, enoxaparin ,dalteparin)
– LMW heparins have greater bioavailability and
longer durations of action than unfractionated
heparin;
– thus, doses can be given less frequently (eg, once or
twice a day).
– They are given subcutaneously.
3. Fondaparinux - once-daily s.c

12. Mechanism and effects
• Unfractionated heparin binds to endogenous
antithrombin III (ATIII)
• The heparin–ATIII complex combines with and
irreversibly inactivates thrombin and factor Xa

13. Clinical use
—Because of its rapid effect, heparin is used when
anticoagulation is needed immediately (eg, when
starting therapy).
Common uses include:
• Treatment of Deep Vein Thrombosis,
• Pulmonary embolism,
• Acute myocardial infarction.
• In pregnancy heparin is the drug of choice . Because
it does not cross the placental barrier.
LMW heparins and fondaparinux have similar clinical
applications.

14. Adverse Effects
• The major adverse effect of heparin is
bleeding
• Allergy
• Long-term therapy has been associated with
osteoporosis
• Reversible alopecia has been reported
• Thrombocytopenia

15. Contraindications
• Heparin is contraindicated in patients with
– Thrombocytopenia,
– allergy to the drug,
– active bleeding,
– advanced hepatic or renal disease
• Should be avoided in patients who had a
recent surgery .

16. Warfarin
Mechanism of action:
• Factors II, VII, IX, and X (1972) require vitamin K
as a cofactor for their synthesis by the liver.
• Inhibits vitamin K epoxide reductase and thereby
interferes with production of functional vitamin K-
dependent clotting and anticlotting factors
Clinical use:
• Warfarin is used for chronic anticoagulation in all
of the clinical situations described previously for
heparin.

17. Warfarin
• The action of warfarin can be reversed with
vitamin K, but recovery requires the synthesis
of new normal clotting factor and is,
therefore, slow (6-24hr) .

18. Toxicity
• Hemorrhage is the main hazard
• Warfarin crosses the placenta
– abnormal bone formation of fetus
• Cutaneous necrosis

19. Management of the Dental Patient
Taking Warfarin
• Avoid aspirin and aspirin-containing
compounds;
– Paracetamol and opioids analgesic (eg:
tramadol) can be used.
• Oral hygiene with sub-gingival calculus
removal can produce bleeding
– use local pressure.
• Check with patient to ensure healing.

20. Mechanism of Action :
• Binds to thrombin’s active site and inhibits its
enzymatic action in the circulation and within
clots.
Clinical use :
• Anticoagulation in patients with heparin-
induced thrombocytopenia (HIT)
• Lepirudin: IV administration
• Dabigatran: oral administration
B. Direct Thrombin Inhibitors
Lepirudin, & Dabigatran

21. C. Direct factor X inhibitors
Rivaroxaban and Apixaban
Mechanism of Action :
• Binds to the active site of factor Xa and inhibits its
enzymatic action thereby preventing its ability to
convert prothrombin to thrombin.
Clinical use :
• Venous thrombosis,
• pulmonary embolism,
• prevention of stroke
• in patients with atrial fibrillation
Adverse effects:
• Bleeding is the most serious adverse effect.

22. Concerns in a Patient Taking Factor Xa
or a Direct Thrombin Inhibitor
• Anticoagulant effects, which can last up to 24
hours, cannot be reversed.
– No antidote is available
• Patient should avoid aspirin and non-steroidal
anti-inflammatory drugs (NSAIDs).
– Risk of bleeding is increased.

23. Anti-platelets
• Drugs that inhibit platelet aggregation
Classification :
1. Thromboxane (TXA2) synthesis inhibitor:
Low-dose aspirin.
2. Phosphodiesterase inhibitor: Dipyridamole.
3. ADP receptor antagonists : clopidogrel.
4. Glycoprotein (GP)-IIb/IIIa-receptor
antagonists: Abciximab.

24. Uses
• Acute MI: Low-dose aspirin is most commonly
used in high-risk individuals to reduce the
incidence of MI and in post-MI patients to
prevent recurrent attacks.
• Clopidogrel - prevention of re-stenosis after PCI
• Dipyridamole
– Adjuvent with warfarin to Prevention of
thromboembolic complications of cardiac valve
replacement .
– combined with aspirin for secondary prevention of
ischemic stroke

25. Adverse Effects
• All cause bleeding.
• Aspirin - GI ulcer

26. 3. THROMBOLYTIC AGENTS
• Plasmin is an endogenous fibrinolytic enzyme that
degrades clots by splitting fibrin into fragments.
• promote the conversion of plasminogen to plasmin.
• Plasmin degrades fibrin into fibrin degradation
products and thus rapidly dissolves the blood clot
• Reteplase, alteplase, Streptokinase, Urokinase.

27. 3. THROMBOLYTIC AGENTS
Clinical use :
• Coronary artery thrombosis,
• Ischemic stroke,
• pulmonary embolism
Adverse effects :
• Bleeding, especially cerebral hemorrhage
• Contraindications
• These include recent trauma, recent surgery,
recent stroke, severe hypertension, severe liver
damage, peptic ulcer and bleeding disorders.

28. DRUGS USED IN
BLEEDING

29. Haemostatic Agents
• They arrest bleeding either by vasoconstriction
or by promoting coagulation of blood.

30. Local Haemostatics
• These drugs are commonly used to control
bleeding from capillaries
– e.g. bleeding following tooth extraction,abrasions,
epistaxis, etc.
1. Astringents: They precipitate proteins locally
in the bleeding site and control capillary
oozing
– e.g. tannic acid, ferric chloride, ferric sulfate,
aluminum chloride, aluminum sulfate, etc.

31. Local Haemostatics
2. Adrenaline: It causes vasoconstriction (α1) and
arrests bleeding.
– A cotton pad soaked in 0.1% adrenaline solution is
applied on the bleeding site to control capillary oozing
– e.g., epistaxis, bleeding after tooth extraction etc.
– Adrenaline should be avoided in patients with
cardiovascular disease and uncontrolled
hyperthyroidism as it may precipitate myocardial
infarction (MI) or aggravate the existing condition.

32. Local Haemostatics
3. Thrombin: It converts fibrinogen to fibrin, thus
facilitating the last step in the coagulation
cascade and promoting haemostasis.
– Bovine plasma-derived thrombin, human plasma-
derived thrombin.
– Hypersensitivity reactions can occur to bovine
thrombin.
– Human plasma-derived thrombin carries the risk of
virus transmission.
– Thrombin is placed in the tooth socket to arrest
bleeding.

33. Local Haemostatics
4. Fibrin glue: It consists of fibrinogen, factor
XIII, thrombin, Ca2+ and other clotting
components.
– It is used to control bleeding during surgical
procedures or as a spray on the bleeding surface.
– Fibrin sealant in combination with tranexamic
acid mouthwash helps to reduce bleeding during
dental extraction in haemophilic patients.
– Fibrin sealants made from human plasma carry
the risk of transmitting viral infections.

35. Local Haemostatics
5. Collagen: It controls bleeding by promoting
aggregation of platelets and accelerating
coagulation.
– Collagen sponges are placed in tooth socket
following extraction to arrest bleeding.

36. Local Haemostatics (Styptics)
6. Gelatin: It is a protein. It produces haemostasis
by providing a physical meshwork on which
clotting can occur.
– It is an absorbable haemostatic and is available as a
sponge or a film.
– Adverse effects are infection, granuloma formation
and fibrosis.

37. Local Haemostatics
7.Oxidized Cellulose: It is an absorbable
haemostatic. It should be applied dry so that
it swells up and form a clot.
• It is used to control bleeding from capillaries
and arterioles where ligation is not possible.
• It may cause tissue necrosis, nerve damage or
vascular stenosis.

38. Local Haemostatics
9. Calcium alginate: It is obtained from sea
weeds.
• It is an absorbable haemostatic and
• is used to promote wound healing.

39. Local Haemostatics
10. Haemocoagulase: Haemocoagulase enzyme
complex is isolated from the venom of Bothrops
atrox (viper).
Mechanism of action
It has a powerful haemostatic effect. It promotes
coagulation by two enzymes:
– one that has thrombin- like action
– another that has thromboplastin-like action.
– It can also shorten the bleeding and clotting time;
– thereby it controls capillary bleeding.

40. Local Haemostatics
10. Haemocoagulase:
Pharmacokinetics
• It is available for topical, intravenous, intramuscular
and subcutaneous administration.
• It has a rapid onset of action—within 5–10 min of i.v.;
20–30 min after i.m. administration and within a
minute of topical application (spray/soaked swab).
Indications
– To control bleeding following tooth extraction or any other
dental procedure.
Adverse effects are rare; they may cause anaphylactic
reaction on intravenous administration.

41. Systemic Agents
• Vitamin K
– Vitamin K, a fat-soluble vitamin, is required for the
synthesis of clotting factors.
– In vitamin K deficiency, there is an increased tendency to
bleed—epistaxis, haematuria, gastrointestinal bleeding
and post-operative bleeding.
• Uses
– For prevention and treatment of bleeding associated with
vitamin K deficiency.
– To control bleeding due to oral anticoagulant therapy
– in salicylate poisoning with haemorrhagic complications.

42. Systemic Agents
• Adverse effects:
– Oral vitamin K is safe.
– Intravenous injection may cause flushing,
sweating, dyspnea, hypotension, cyanosis, and
anaphylactic reaction.
– intramuscular and s.c. routes may cause severe
pain and bleeding at the site of injection

43. Systemic Agents
Antiplasmin drugs (Aminocaproic acid & Tranexamic acid)
• Competitively inhibits plasminogen activation in
Excessive fibrinolysis used.
• Tranexamic acid-It is available for oral, i.v. and
topical administration. It is more potent.
– In dentistry, tranexamic acid soaked gauze or
mouthwash can be used to reduce bleeding
postoperatively in haemophiliacs and in patients on
anticoagulant therapy.
• Adverse effcts : Thrombosis, hypotension,
nausea, vomiting, diarrhoea, headache.

45. Antidotes

46. Key Points for Dentists
• Low molecular-weight heparins are safer than
unfractionated heparin.
• Patient on anticoagulants should be instructed to
report signs of bleeding.
• NSAIDs should be avoided in patients on
anticoagulants and antiplatelet agents. Paracetamol
and selective COX-2 inhibitors are safer as they have
no antiplatelet action.
• Avoid intramuscular injections in patients on
anticoagulants.
• Oral anticoagulants are contraindicated in pregnancy.
• INR and aPTT should be monitored in patients on
warfarin and heparin, respectively, before a dental
procedure.

47. Study Well !