MAHARANA PRATAP COLLEGE OF DENTISTRY

COAGULANTS AND ANTI COAGULANTS

DRUGS

SUBMITTED BY- PRIYANSHI GUPTA SUBMITTED TO- Dr.BUSHRA MALIK

BDS II Yr.
ANTICOAGULANT
• Anticoagulants(blood thinners) are the drugs used to prevent clot formation by
reducing the ability of the blood to form clot,also prevents a clot that has already
formed from getting bigger. These drugs do not dissolve already formed clots.
• Thrombolytic drugs or fibrinolytics dissolves already formed clot.
• Thrombosis- process of formation of a clot(thrombus).this is often triggered by
atherosclerotic plaque that narrows and damages the blood vessels. Thrombus causes
MI, DVT.
• Embolus- is a clot that travels through the blood stream until it lodges in a blood
vessel and block it. Can cause stroke, PE.
 Haemostasis or clot formation
• Haemostasis- stopping bleeding or haemorrhage from the body is haemostasis and blood clotting is a
normal homeostatic function of the body. It occurs in a series of overlapping processes called clotting
cascade in which platelets and other proteins (clotting factors) play a vital role.
1) Vasoconstriction(primary haemostasis)- following injury to blood vessel, the blood vessel constricts
this allows reduced bleeding and platelets and plasma to contact the damaged area of blood vessel.
2) Platelet plug formation-damage to the blood vessel exposes collagen and elastin fibres that causes
platelets to adhere to the site of injury and to themselves called platelet plug. The platelets release
serotonin(vasoconstriction), ADP(platelet adhesion) and thromboxane(TXA)(adhesion and
vasoconstriction). This process is activated by a glycoprotein called von Willebrand factor which is
present in plasma.
3) Formation of fibrin/blood clot(secondary haemostasis)- this phase involves dozen plasma clotting
factors. That travel along the plasma in an inactive state. They are activated in a sequence of events
known as clotting cascade to form a stable clot.
4) Dissolving of fibrin clot-dissolving of clot is slow process than building of clot. Fibrin is dissolved by
plasmin which is derived from an inactive protein called plasminogen(triggered by plasma clotting factor
VII, red, white and certain renal cells)
CLOTTING CASCADE
This clotting cascade of events is triggered by two distinctive ways.
Extrinsic pathway-can be triggered by physical injury to the blood vessels., first damaged cells
release a substance called thromboplastin or tissue factor comes in contact with blood and combines
with factor VII that results in active production of factor, X. As thromboplastin is not a part of blood,
its called extrinsic pathway.
Intrinsic pathway- the second trigger involves contact of blood with exposed collagen fibres, which
are not usually exposed since they lie under the inner surface(endothelium) of blood vessel.
• Surface contact activates factor XII
• Factor XIIa activates factor XI
• Factor XIa activates factor IX
• Factor XIa combines with VIIIa and Ca2+ ions to activate factor Xfactor
• Factor Xa activates the final common pathway eventually resulting in the formation of prothrombin
activator which further activates the enzyme thrombin, which converts inactive fibrinogen to
insoluble threads of fibrin which stabilises the platelet plug
CLOTTING FACTORS
• Factor I Fibrinogen
• Factor II Prothrombin
• Factor III Tissue Thromboplastin
• Factor IV Calcium lons
• Factor V Labile Factor
• Factor VII Stable Factor
• Factor VIII Antihemophilic Factor
• Factor IX Christmas Factor, orPlasma ThromboplastinComponent (PTC)Factor
• Factor X Stuart-Prower
• Factor XI Plasma Thromboplastin Antecedent (PTA)
• Factor XII Hageman Factor
• Factor XIII Fibrin Stabilizing Factor
INTRINSIC & EXTRINIC PATHWAY
Uses of anticoagulants
• anticoagulants prevents the formation of new clots or the extension of existing clots Heparin is utilized for rapid and short-lived
action, while oral anticoagulants are suitable for maintenance therapy. Generally, the two are started together; heparin is
discontinued after 4-7 days when warfarin has taken effect.
• 1)Preventing or treating venous thromboembolism (VTE)- DVT and pulmonary embolism(PE), prevents clot formation in patient
who are at bed rest for a long periods.
• 2) Treat arterial clotting and preventing embolus formation in patients with atrial fibrillation, and arrhythmia in which
ineffective atrial contractions causes pooling of blood in atria, increasing the risk of clot formation, reduce the risk of strokeIn
arterial clot(contains more platelet) we mostly use antiplatelet drugs and in venous clot(more fibrin) we mostly use
anticoagulants.
• 3) Preventing thrombus formation and promoting circulation in an acute myocardial infarction (MI) by preventing further clot
formation at the site of already formed clot. Unstable angina Short-term use of heparin has reduced the occurrence of MI in
unstable angina patients; aspirin is equally effective. Current recommendation is to use aspirin + heparin followed by warfarin
• 4) Prevents clot formation after a heart valve replacement, during open heart surgery, during intra-abdominal surgery and
orthopaedic surgeryIntended responses of all anticoagulant drugs are
 Clotting time is increased
 Clot formation is decreased
 Existing clots do not become larger
 Blood flow and oxygenation are maintained
 Anticoagulants classification
• Used in vivo-
• ➤ Thrombin inhibitors
• A)Indirect thrombin inhibitor
• Parenteral 1) Heparin- Unfractionated Heparin
• 2) Low molecular weight heparin (LMWH) - Dalteparin, enoxaparin, tinzaparin, fondaparinux
• B) Direct thrombin inhibitors-
• oral- Apixaban, rivaroxaban, Argatroban, bivalirudin, dabigatran, lepirudin
• > Clotting factor synthesis inhibitor
• oral-Warfarin sod
• Used in vitro
• A) heparin- 150 U to prevent clotting of 100 ml blood.
• B) Citrates- Sodium citrate,1.65 g for 350ml of blood; used to keep blood in the fluid state for transfusion
• Anticoagulant Acid Citrate Dextrose Solution 2.2g/100ml(75 ml is used for 1 unit of blood)
• Anticoagulants used in blood taken for investigation- Sodium oxalate-10mg for 1 ml of blood
• Sodium edetate- 2mg for 1 ml of blood
• Ethylenediaminetetraacetic acid (EDTA)- strongly and irreversibly binds calcium ions, preventing blood from clotting,
 How do they work
• Action of thrombin inhibitors- thrombin inhibitors indirectly or directly interfere
with blood clotting by blocking the action of thrombin, which convert fibrinogen into
fibrin to form clots.
• Indirect thrombin inhibitors- works by increasing the activity of a
substance(antithrombin III) in the blood, which then inhibits thrombin.
• Direct thrombin inhibitors- block thrombin directly without affecting the action of
antithrombin III.
• Antithrombin III is a protein in the blood produced by liver that blocks abnormal
blood clots from forming.
Adverse effects of anticoagulants

• Minor to severe bleeding/ haemorrhage

• Bruising, haematoma formation, necrosis of skin or other tissue,
and thrombocytopenia.
 Indirect thrombin inhibitors - Heparin
Unfractionated Heparin(UFH) -
• Heparin is a complex protein found in the liver and mast cells.it is comprised of many chains of varying molecular weight.it is broken down by
digestive enzymes and thus given by IV/SC. Heparin results in anticoagulation both inside and outside the blood vessels. Heparin is utilized for
rapid and short-lived action, while oral anticoagulants are suitable for maintenance therapy.
• Heparin is not given IM because of the risk of localised bleeding.
Action- works by activating antithrombin III (naturally occurring anticoagulant in the body) which then stops fibrinogen- to-fibrin stage of blood
clotting from taking place. The end result is prevention of a stable fibrin clot.it affects the intrinsic pathway of coagulation.
Half life- heparin acts immediately following IV administration and its elimination half life is approx. 40-90 min. In emergencies, it is usually
given in bolus dose, followed by a constant rate of infusion. heparin is metabolized by liver and metabolites excreted in urine.
Dose- weight based usual range 5000-10,000 units
Side effects/ adverse effects
• main concern when administering heparin is haemorrhage. Monitor for signs of bleeding.
• Heparin-induced thrombocytopenia(HIT)- platelet count should be monitored in patient receiving heparin therapy. Patient who develops HIT
should be switched to direct thrombin inhibitors.
• Hyperkalaemia, osteoporosis, dizziness, decreased aldosterone, and hair loss with prolonged use.
• Monitoring PTT in unfractionated Heparin therapy- partial thromboplastin time (PTT) is a blood test that looks at how long it takes for blood to
clot with unfractionated heparin. Close monitoring PTT is necessary to ensure therapeutic effectiveness without increased risk of bleeding.
• Normal levels- 30s to 40s
• The therapeutic PTT range for heparin is 60-80saPTT(activated partial thromboplastin time)- an activator is added that speeds up the clotting
time and results in a narrower reference range.
 Low molecular weight heparin(LMWH)-
• Dalteparin, enoxaparin, tinzaparin, fondaparinux
• These are a form of heparin 60% of their chains are of a low molecular weight. LMWH
can be given SC.
• Dose-100-200 units/kg per day
• Side effects -
• Less likely to cause thrombocytopenia compared to unfractionated heparin
• Mild irritation, pain, bruising, haematoma formation, necrosis of skin or other tissue,
mild bleeding, redness or swelling at the injection site.
• Monitor for signs of haemorrhage.
Dose reduction is required in patients with hepatic and renal impairment
OLMWH doesn't require PTT monitoring. Currently, no laboratory test exists to assess the
effectiveness of LMWH therapy.
Antidote of heparin

• Protamine sulphate reverse the action of heparin. 1mg of

protamine sulphate neutralizes approximately 100 units of heparin.

Important alert- teach patients to read labels of all over the counter
and prescription drugs to determine whether they contain aspirin
 Oral Anticoagulants
Cattle that were fed on spoiled sweet clover hay, developed a hemorrhagic disease in
North America in 1924. This turned out to be due to bishydroxycoumarin, an anticoagulant
in the spoiled sweet clover. Many related compounds were then developed and are also
being used as rat poison.
- Mechanism of action: Warfarin and its congeners act as anticoagulants only in vivo
because they act by interfering with the synthesis of vitamin K dependent clotting factors
in the liver. They block the y carboxylation of glutamate residues in prothrombin, factors
VII, IX and X. y carboxylation is necessary for these factors to participate in coagulation.
The onset of action is slow; anticoagulant effect develops over 1-3 days because oral =
anticoagulants do not destroy the already circulating clotting factors. Prothrombin time
(PT) is measured to monitor the treatment. It takes 5-7 days for PT to return to normal
after stopping oral anticoagulants.
Pharmacokinetics: Warfarin is completely absorbed orally and is 99% bound to plasma
proteins.
Adverse effects

• Hemorrhage is the main side effect. Bleeding in the intestines or brain can be
troublesome. Minor episodes of epistaxis and bleeding gums are common
• Treatment depends on the severity: Stop the anticoagulant Fresh blood
transfusion is given
• supply clotting factors
Antidote: The specific antidote is vitamin K, oxide. It allows the synthesis of
clotting factors. However, even on IV administration, the response to vitamin K,
oxide needs several hours. Hence in emergency, fresh whole blood is necessary
to counter the effects of oral anticoagulants.
• Other adverse effects include allergic reactions, gastrointestinal disturbances
and teratogenicity.
Drug Interactions

• Many drugs potentiate warfarin action

• Drugs that inhibit platelet function-NSAIDS like aspirin increase the risk of bleeding
Drugs that inhibit hepatic drug metabolism like cimetidine, chloramphenicol and
metronidazole, allopurinol, erythromycin enhance plasma levels of warfarin.
• Some drugs reduce the effect of oral Drugs that enhance the metabolism of
anticoagulants.
• oral anticoagulants-microsomal enzyme embolism. inducers like barbiturates,
rifampicin, griseofulvin enhance the metabolism of oral anticoagulants. When
these drugs are suddenly withdrawn, excess anticoagulantactivity may result in
hemorrhages Drugs that increase the synthesis of clotting factors counter the
effect of oral contraceptives.
Factor Xa inhibitor:

• Rivaroxaban directly binds to factor Xa and inactivates it. Since

the binding is direct, its onset of action is faster (3-4 h). Constant
laboratory monitoring is not required and is orally effective. It is
useful in the prophylaxis of postoperative deep vein thrombosis
and following stroke.
 Oral direct thrombin inhibitor
•Dabigatran binds directly to thrombin andto inactivates it.
•Advantage are
•Orally effective (given as dabigatranetexilate)
• Fast onset of action (<2 hr)
•No need for constant lab monitoring
•Long-acting; given once daily
•An antidote idarucizumab is recentlyits effectsmade available which can quickly
reverse
Through currently, dabigatran is being used for the prevention of deep vein thrombosis
postoperatively, it could soon be one of thepopular anticoagulants.
 COAGULANTS
Coagulants are drugs that promote coagulation (procoagulants) and control bleeding. They are also called
hemostatics. They may be used locally or systemically. Local hemostatics are called styptics. Physical methods
like local application of pressure, tourniquet or ice can control bleeding.
Styptics are used on bleeding sites like tooth socket and wounds.
They are:
1. Adrenaline: Sterile cotton soaked in 1:10,000 solution of adrenaline is com- monly used in tooth sockets and
as nasal packs for epistaxis. Adrenaline arrests bleeding by vasoconstriction.
2. Thrombin powder: It is dusted over the bleeding surface following skin grafting. It is obtained from bovine
plasma.
3. obtained from human plasma is available as sheets. It is used for covering or packing bleeding surfaces.
4. Gelatin foam is porous spongy gelatin used with thrombin to control bleeding from wounds. It gets
completely absorbed in 4 to 6 weeks and can be left in place after suturing of the wound.
5.Thromboplastin powder: Is used in surgery as a styptic.
6. Astringents: Like tannic acid are used onbleeding gums.(alum)
Coagulants Used Systemically are
 Vitamin K
Vitamin K
FibrinogenSpecific deficient factor-factors, II, VII, VIII, IX, X
Ethamsylate
Vitamin K: Vitamin K is a fat-soluble vitamin essential for the biosynthesis of clotting factors.
There are three compounds:
Vitamin K1-present in food from plant source
Vitamin K2-produced in the gut bybacteria
Vitamin K3 a synthetic compound used therapeutically.
Actions: Vitamin K is essential for thebiosynthesis of clotting factors-prothrombinand factors VII, IX
and X by the liver.
Human requirement: Not clearly known- recommended intake in adults is 50-70 mg/day.
Deficiency: Vitamin K deficiency results from liver diseases, malabsorption, long-term antibiotic
therapy and rarely by dietary deficiency. It is manifested as bleeding tendencies.
 Vitamin K
• Adverse reactions are seen on parenteral administration of vitamin K-allergic
reactions and jaundice can occur.
• Uses
• Vitamin K deficiency
• Newborn babies lack intestinal flora and have low levels of prothrombin and other
clotting factors. Routine administration of vitamin K-1 mg IM prevents hemorrhagic
disease of the newborn
• Oral anticoagulant toxicity.
 Other Coagulants
• Fresh plasma or whole blood is useful in most coagulation disorders as it contains all the clotting
factors
• Concentrated plasma fractions likefibrinogen, factors VIII, II, VII, IX and Xare available for the
treatment of specific deficiencies
• Snake venom: Some venoms like Russelsviper venom stimulate thrombokinase andpromote coagulation
• Ethamsylate is used orally to arrest bleeding.
• The exact mode of action is not known but it is thought that it acts by inhibiting the synthesis of
prostacycline (PGI,) and correct the abnormal platelet function.
• It may also stabilize the wall of the capillaries and reduce capillary bleeding. Ethamsylate is given
orally to control bleeding in:
• Dental extraction and other proceduresin patients with coagulation disorders
• Menorrhagia
• Postpartum hemorrhage
• Hematemesis and malena.
Dentistry and Drugs Affecting Coagulation

• Most dental procedures including minor ones like scaling and tooth
extraction involve some bleeding stops by itself. However, even
minor dental procedures may result in continuous bleeding from the
site in the following patients:
• Patients receiving drugs that inhibitcoagulation
• Thrombocytopenic purpura
• Vitamin C deficiency
• Hemophiliacs
• Long-term glucocorticoid therapy. For management of bleeding.
THANK YOU