HAEMOSTATIC AGENT USED IN DENTISTRY TO

CONTROL BLEEDING

AVISHEK PANDAINTERNEE

UNDER NORMAL CONDITION BLOOD CIRCULATE THROUGH INTACT VASCULATURE WITHOUT THROMBUS FORMATION.

HEMOSTASISSTATE OF FLUID EQUILIBRIUM IN THE VESSEL

VESSELS

COAGULATIONPROTEIN

FIBRINOLYSIS INHIBITOR

PLATELET

HEMOSTASISA PROCESS WHICH CAUSES BLEEDING TO STOP

PHASES OF HEMOSTASIS

PRIMARY HEMOSTASIS

ARTERIOLES CONSTRICTION

FORMATION OF PLATELET PLUG

SECONDARY HEMOSTASISACTIVATION OF COAGULATION CASCADE

FORMATION OF PERMANENT PLUG

VESSEL CONSTRICTIONTHERE ARE TWO MECHANISMS

LOCAL SMOOTH MUSCLE CONTRACTILE RESPONSE

THROMBOXANE A2 RELEASE FROM EPITHELIUM

FORMATION OF PLATELET PLUGEXPOSURE OF SUBEPITHELUAL LAYER CAUSE PLATELET TO ADHERE

THEY RELEASE ADP &TxA2 WHICH FURTHER CAUSES PLATELET AGGREGATION &ACTIVATION

ADHESION REQUIRE VON WILLBRAND FACTOR FROM SUB ENDOTHELIAL LAYER

COAGULATION FACTOR

Factor I FibrinogenFactor II ProthrombinFactor III Tissue ThromboplastinFactor IV Calcium IonsFactor V Labile Factor, ProaccelerinFactor VII Stable Factor, ProconvertinFactor VIII Antihemophilic FactorFactor IX Christmas FactorFactor X Stuart-Prower FactorFactor XI Plasma Thromboplastin

AntecedentFactor XII Hageman FactorFactor XIII Fibrin Stabilizing Factor

All coagulation factors are made in the liver, except for vWF

COAGULATION CASCADE

NATURAL INHIBITOR OF COAGULATION CASCADE

THOMBOMODULIN

ANTITHROMBIN III

TISSUE FACTOR PATHWAY INHIBITOR

PROTEIN C

PROTEIN S

• Visual obstruction of the surgical field • Need for blood transfusions • Reduction in core temperature • Thrombocytopenia • Hypovolemic shock • Economic consequences

Adverse effects of Surgical bleeding

• Type of procedure • Patient position • Surgical incisions • Exposed bone • Large surfaces of exposed

capillaries • Unseen sources of bleeding • Tissues that cannot be sutured or

low-pressure suture lines • Adhesions stripped during surgery

Procedural factors

• Specific anatomical considerations

• Medications (eg. Anticoagulants) • Coagulopathies • Platelet dysfunction or deficiency • Fibrinolytic activity • Coagulation factor deficiencies

• Medical conditions • Nutritional status

Patient factors

Factors influencing Surgical bleeding

Why Use Hemostatic Agents• Minimize blood loss• Improve visualization• Save operative time• Reduce or avoid transfusion• Manage anticoagulated patient• Avoid conversion of lap procedures• Prevent leakage of non-bloody fluids• Decrease post-op drainage and infection• Decrease hospital length of stay

Characteristics of an Ideal hemostatic agents for clinical use:

(1) capability to stop large vessel arterial and venous bleeding within minutes of application when applied to an actively bleeding wound through a pool of blood;

(2) no requirement for mixing or pre-application preparation;

(3) simplicity of application(4) light weight and durable; (5) long shelf life in extreme environments;(6) safe to use with no risk of injury to tissues or

transmission of infection;(7) cost-effective

Methods of Hemostasis

Direct pressure • Simplest & fastest • Surgeon’s first choice • Arterial bleeding better controlled than venous

Fabric pads/gauzes/sponges• Application of direct pressure • Packaging of body cavity • No. of sponges used during surgery needs to be counted • Temporary measures

Sutures/staples/ligating clips • Sutures and ties used as ligatures to tie off blood vessels • Chances of tissue reaction, injury & allergic reactions • For staples, stapling device required • Efficient method when diving tissue • Ligating clips – quick & easy to apply • Applicator required • Site of application should be clearly visible

Mechanical methods

Electro-surgery • Use of high frequency alternating current for cutting, coagulating and vaporizing

tissues • Potential risks – patient injuries, user injuries, fires & electromagnetic interference • Monopolar – most frequently used • Bipolar – better on delicate tissues/small anatomical structures • Bipolar vessel sealing device – applies heat with high compression. Capable of

simultaneously sealing and transecting vessels upto 7 mm diameter, large tissue pedicles, vascular bundles

• Argon enhanced coagulation technology

Ultrasonic devices • Converts electrical energy to mechanical energy• Simultaneously cuts & coagulates • Less thermal damage to tissues

Lasers • Laser energy delivered to target site can be reflected, scattered, transmitted or

absorbed

Thermal/energy based method

Epinephrine

• Causes direct vasoconstriction & increases heart rate • Can be applied topically or injected with local anesthesia

Vitamin K • Administered pre-operatively to reverse effects of warfarin

& to avoid need of transfusion of FFP • Reversal of raised INR takes app. 24 hours

Protamine • Only agent with ability to reverse heparin anticoagulation • Can cause anaphylaxis, acute pulmonary

vasoconstriction, right ventricular failure

Chemical methods – pharmacological agents

Topical Agents – Passive Provides a physical, lattice like matrix that adheres to bleeding site

Matrix activates the extrinsic clotting pathway

Platelets aggregate and form a clot

Passive agents rely on fibrin production and hence can be used only in a patient with intact coagulation cascade

Passive agents can absorb several times its weight in fluid. However, this expansion of the agent can cause complications like compression of surrounding tissues.

Activated on contact with bleeding. Provide stable matrix for clot formation, enhance platelet aggregation, degranulation and release of clotting factors

Collagen Based Products

Microfibrillar collagen hemostat (Avitene)• Derived from purified bovine dermal collagen • Effective agents when there is capillary, venous or small arterial bleeding• MCH attract platelet & promote plug formation • It inactivates thrombin as a result of ph factor.• Potential adverse events: allergic reaction, adhesion formation, inflammation,potentiation

of infection and abscess formation

Absorbable collagen hemostat sponge (Instat)• Derived from purified and lyophilized bovine dermal tendon• Adhere to surface when wet,does not stick into the instrument. • Collagen sponge gets absorbed into 8 to 10 weeks • Control bleeding 2-5 mins.

Oxidized regenerated cellulose (Surgicel)• ORC reacts with blood, increases in size and forms a gelatinous

mass(after 24-48 hrs )and promotes clot formation • Potential AEs: encapsulation of fluid and FB reaction, stenosis of

vascular structures, burning or stinging sensations, headaches , etc

Gelatins (Gelfoam) • Derived from purified bovine gelatin solutions • Can be used in dry or wet form • Conforms easily to wounds and therefore can be used for irregular

wounds

Polysacchride hemospheres • Derived from vegetable starch • Contains no human or animal component

Topical agents – active Have biological activity

Participate directly at the end of coagulation cascade

Stimulate fibrinogen at the bleeding site to produce a clot

Thrombin acts at the end of the clotting cascade, action of agent is not affected by clotting factor deficiencies or platelets malfunction. Can also be given to patients receiving anti-platelets/anti-coagulation

Active topical agents provide hemostasis within 10 minutes and they are more effective in controlling bleeding than passive agents

Bovine thrombin • Applied using a pump or spray kit, or in a saturated, absorbable

gelatin sponge • AEs: antibody formation to bovine thrombin can lead to

coagulopathy, allergic reactions, death

Pooled human plasma thrombin • Delivered via saturated, absorbable gelatin sponge • Has potential risk of viral or prion disease transmission

Recombinant thrombin • Reduced risk of antibody formation and eliminates risk of viral

or prion disease transmission

Thrombin products

• Combine passive and active hemostatic agents into a single application product

• Work by blocking blood flow & actively converting fibrinogen into fibrin

• Two types of products: – Absorbable bovine gelatin + pooled human thrombin – Absorbable porcine gelatin + either of the 3 thrombin types

• Both the products do not contain fibrinogen. Hence direct contact with blood is necessary

• Both products are indicated for all types of surgeries except ophthalmic surgeries

• AEs: anemia, arrhythmia, arterial thrombosis, atelectasis, atrial fibrillation, hemorrhage, infection, pleural effusion, right heart failure

Flowable hemostatic agents

Fibrin sealants • Consists of conc. fibrinogen and thrombin which upon mixing with blood

create a fibrin clot.• Increases rate of clot formation by providing higher conc of both fibrinogen

& thrombin at bleeding site .• 3 types: pooled human plasma, individual human plasma with bovine

collagen and bovine thrombin, pooled human plasma and equine collagen • Fibrin sealants control local as well as diffuse bleeding • Do not control vigorous bleeding.• Fibrin sealants can be used in patients with coagulopathies. • Also in patients receiving heparin.• Clinical concerns: difficulty of reconstitution, time taken for surgeon to learn

application. • AEs: viral or prion disease transmission, antibody formation with bovine

thrombin, swelling associated with collagen use.

Sealants Sealants work by forming a barrier that is impervious to the flow of most liquids

Polyethylene glycol polymers

CoSeal • Combination of 2 PEG polymers to form synthetic, hydrogel matrix • Polymers cross-link to each other & to contact tissue - forms barrier

DuraSeal • Combination of PEG, trilysine amine, blue dye • On combination form a hydrogel - water tight seal

ProGel • PEG polymer combined with human serum albumin • Only product approved by FDA for lung sealing • Safety concern: swelling, allergic reaction to blue dye, infection.

Delayed wound healing

• Contains 10% glutaraldehyde sol and 45% bovine serum albumin

• Glutaraldehyde cross-links the residual proteins in albumin to cell proteins at wound site and forms a tough scaffold to which clot can adhere

• Commonly used for sealing holes around suture or staple lines in complex CV procedures and in peripheral vascular procedures

• AEs: tissue injury, muscle necrosis, emboli, delayed pseudoaneurysm formation, sensitivity to glutaraldehyde

Albumin-Glutaraldehyde

• Consists of 2 cyanoacrylate monomers – 2-octyl cyanoacrylate– Butyl lactoyl cyanoacrylate

• Product to be used as a sealant and not as a substitute for sutures, staples, or other methods of mechanical closure

Cyano-acrylates

• Rapidly and effectively control bleeding • Effectively contact the bleeding surface • Work reliably • Be handled easily • Be prepared easily • Be available in multiple delivery options • Be compatible with patient’s physiology • Be safely used • Be cost effective

Key considerations in the selection of topical agent

Reference:TEXTBOOK OF PATHOLOGY 6TH ED.-HARSH MOHAN

TEXTBOOK OF PATHOLOGY -ROBBINS

DENTAL MANAGEMENT OF MEDICALLY COMPROMISED PATIENT -FALACE

TEXTBOOK OF PHARMACOLOGY –K.D.TRIPATHY

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