BLEEDING & CLOTTING DISORDERS

PRESENTED BYJASMINE.PPVth BATCH

• Dental procedures resulting in bleeding can have serious consequences in a pt. having bleeding disorder……… severe hemorrhage or even death.

BASIC MECHANISM OF HAEMOSTASIS

• Vascular phase.• Platelet phase.• Coagulation phase.• Fibrinolytic phase.(rate limiting

step)

VASCULAR PHASE:

• After tissue injury immediate vasoconstriction occurs.

• Serotonin,histamine,PG’s etc causes vasoconstriction of the micro vascular bed.

PLATELET PHASE:

Circulating blood platelets are activated Aggregates Primary

vascular plug( es blood loss from small blood vessels & capillaries)

Adheres to exposed basement membrane.

COAGULATION PHASE:

• Generation of THROMBIN and FIBRIN.• INVOLVES VARIOUS PROTEINS: Fibrinogen,prothrombin,FS-

V,VII,IX,X,XI,XII & XIII.--------- Vitamin K dependant-FS-II,VII, IX & X.

• Involves 3 separate pathways • FIBRIN polymerizes to a gel stabilizes

the platelet plug.

INTRINSIC PATHWAYEXTRINSIC PATHWAYCOMMON PATHWAY.

• 2 theories:::• Prothrombin to thrombin & fibrinogen to

fibrin conversion system ( MARKOWITZ----1903)

• CASCADE / WATERFALL theory(1964)-the coagulation mechanism results in a final explosive change of a liquid to a gel.

COAGULATION FACTORS:

FIBRINOLYTIC PHASE:

• Propagation of the clot is limited by fibrinolysis.

• Tissue plasminogen activator(tPA) released from the endothelial cells converts PLASMINOGEN to PLASMIN.

• Plasmin degrades fibrinogen & fibrin to fibrin degradation products [FDPs] .

FIBRINOLYTIC SYSTEM:

Factor XII Factor XIIa

+ high Mol.wt kininogen

kallikrenparakallikren

tPA

plasminogen plasmin

fibrinFDPs

F V F VIII

tPA:Used in thromboembolic

disoders asso with Myocardial infarction.(effective within 1st 6

hrs postinfarction.Fibrinolytic system

activation turned off

by……α2antiplasmin/ by plasminogen

activator inhibitors( PAI-1,PAI-2)

CLINICAL &

LABORATARY FINDINGS

CLINICAL FEATURES

Bleeding from superficial cuts & scratches.Delayed bleeding.Spontaneous gingival bleeding.Petechiae.Ecchymoses.Epistaxis.Deep dissecting hematomas.Hemarthroses.

CLINICAL LABORATARY TESTS

• Help to Identify deficiency of required elementsDysfunction of the phases of coagulation

Platelet countBleeding time

PFA-100 CTPT/INRaPTTTT

FDPsFactor assays

Tests of capillary fragility

PLATELET COUNT:

• Normal-150,000 to 450,000/mm3 • If < 50,000/mm3

• In such cases platelet transfusion may be necessary.

Hemorrhagic strokeSurgical/traumatic

hemorrhageetc. may occur.

TESTS OF PLATELET FUNCTION:

• Bleeding time{ 1-6 mins}-modified Ivy’s test.• PFA-100 CT-Platelet Function Analyzer – 100

closure time. Used in vWD. Simple to use.Neither specific nor predictive.Use restricted to research studies & clinical trials.

ADV

Dis ADV

PT & INR• Normal-11 to 30 secs• Bcoz of Individual lab.reagant variability &

inorder to compare the PT from one lab. To the other its now commonly reported with its INR.

INR Intro.by WHO(1983):itz the ratio of PT that adjusts for

the sensitivity of the thromboplastin reagants,such

that normal coagulation profile is reported as an INR

of 1.0

USES of PT/INR:

• Evaluates extrinsic coagulation system.• Measures the presence/absence of Fs-

I,II,V,VII & X.• Measures the effects of coumarin anti

coagulants.• Reduction of vit K dependant Fs-I,II,VII &

X.• Measures the metabolic aspects of protein

synthesis in liver.• Does not measure the reduction of Fs-

VIII / IX.

Activated partial thromboplastin time:

• Activator – rare earth.• Considered normal if the control aPTT & test

aPTT are within 10 secs of each other.• Control aPTT = 15-35secs.• Itz altered in hemophilias A & B. and with

the use of heparin.

THROMBIN TIME:

• Normal-9 to 13 secs.• Measure the activity of heparin,FDPs,other

para proteins that inhibit conversion of fibrinogen to fibrin.

FACTOR ASSAYS:

• IDENTIFY FACTOR DEFICIENCIES.

FIBRIN DEGRADATION PRODUCTS:

• Measured using a specific latex agglutination system.

Evaluates the presence of a D-dimer of

fibrinogen / fibrin above normal levels.

CLASSIFICATION OF BLEEDING DISORDERS:

Vessel wall disorders.Platelet disorders.Coagulation disorders.CONGENITAL COAGULOPATHIES: HEMOPHILIA A HEMOPHILIA B FACTOR XI DEFICIENCY FACTOR XII ,, FACTOR X ,, FACTOR V ,, FACTOR XIII & I DEFICIENCIES. VON WILLEBRAND’S DISEASE.

ANTI COAGULANT RELATED COAGULOPATHIES: Heparin Coumarin.DISEASE RELATED COAGULOPATHIES: Liver disease Vitamin K deficiency DIC Fibrinolytic disorders.

VESSEL WALL DISORDERS:

• SCURVY( vitamin C deficiency)• When Vit C level falls below 10mg/d.• Vit C is essential for synthesis of collagen.• Hemorrhage in muscles , joints , nail beds &

gingival tissues.• GINGIVA-

swelling,friability,bleeding,secondary infection & loosening of teeth.

• Treatment:Diet rich in Vit C , Admn of 1g/d of Vit C supplements.

• CUSHING’S SYNDROME,EHLER’S DANLOS SYNDROME,RENDU-OSLER- WEBER SYNDROME(HHT)

CUSHING’S syndrome:

Resulting from excessive corticosteroid Intake / production.Patient shows skin bleeding & easy

bruising.

EHLERS-DANLOS syndrome:

• Autosomal dominant disorder:• Fragile skin vessels & easy bruising.

RENDU-OSLER-WEBER syndrome:

• HHT• Abnormal telangiectatic capillaries.• Frequent episodes of nasal & GI

bleeding.• Telangiectases common on lips,

tongue & palate.

TREATMENT:

• Cryotherapy.• Laser ablation.• Electrocoagulation.• Blood replacement & iron therapy.

PLATELET DISORDERS:• CONGENITALThrombocytopaenia-Quantity of platelets when

reduced by * ed production in the bone marrow * ed sequestration in the spleen. * Accelerated destruction.TREATMENT: Platelet Transfusion.Thrombocytopathies Qualitative defects in platelet

ADHESION, AGGREGATION, GRANULE RELEASE.

• ACQUIRED

CONGENITAL

THROMBOCYTOPENIC• May-hegglin anomaly• Wiskott-Aldrich syndrome• Neonatal alloimmune

thrombocytopenia.

NONTHROMBOCYTOPENIC• Glanzman’s

thrombasthenia• Platelet type

von-willebrands disease• Bernard soulier syndrome

ACQUIRED

T H R O M B O C Y TO P E N I C• TTP(Thrombotic

thrombocytopenic purpura)• Cytotoxic chemotherapy• Drug induced• Leukemia• Aplastic anemia• Systemic lupus

erythematosus• DIC• Asso with :

HIV,mononucleosis,malaria.

N O N T H R O M B O C Y T O P E N I C

• Drug induced• Uremia• Alcohol dependancy• Liver disease• Myeloma• Macroglobulinaemia• Acquired platelet tpe von-

willebrand’s disease.

ITP• Caused by accelerated antibody mediated

platelet consumption.• Oral hematomas & hemorrhagic bullae may

occur.• Intracerebral hemorrhage is the most

common cause of death.• TREATMENT:

CorticosteroidsSplenectomy

RituximabAnti-D

Thrombopoietin like agents.

TTP:

• CAUSES:metastaticmalignancy,pregnancy,mitomycin & high dose chemotherapy.

• SYMPTOMS:Thrombocytopaenia

Microangiopathic hemolytic anemia

Renal dysfunctionOccasional fever

Fluctuating neurologic abnormalities.

• Platelet count may also decreased by medications.

• ASPIRIN

• ASPIRIN :• USES----

• INEXPENSIVE & EFFECTIVE

ANTIPLATELET THERAPY FOR THROMBOEMBOLIC

PROTECTION.

COAGULATION DISORDERS

• CONGENITAL--

ACQUIRED-.Secondary to drugs (Heparin , Coumarin) or disease process(Liver disease, Vit K deficiency ,DIC).

HEMOPHILIA AHEMOPHILIA BF XI DEFICIENCYF XII ,,F X ,,F V ,,F XIII & I ,,VON-WILLEBRAND’S DISEASE.

HEMOPHILIA

HEMOPHILIA -A

• Def of F VIII (Antihaemophilic factor)• Inheritted as an X – linked trait.• 10 times more commonly than hemophilia –

B.• TYPES- Mild(< 4% of AHF) Moderate(1 – 3 % of AHF) Moderate to severe(0.0-0.9% of AHF) Severe( 0 % of AHF)

CLINICAL FEATURES:

• No racial predilection• AGE-Bleeding manifestations begin after 6

months of age.• SIGNS: Hematomas,

Hemarthroses,Hematuria,GI bleeding, Bleeding from laceration , head trauma,spontaneous intra cranial bleeding. Hemorrhage into joints that causes muscle spasm.

ORAL MANIFESTATIONS• Persistant bleeding sites-Frenum of lip & the

Tongue.• There is prolonged bleeding after tooth

extraction.• Physiological processes of tooth eruption &

exfoliation are associated with severe & prolonged hemorrhage.

• Gingival hemorrhage occurs due to gingival injury.

HEMATOLOGICAL FINDINGS:• CT is prolonged• BT , platelet count ,PT are all normal.• Prothrombin consumbtion time & pTT are

prolonged.

MANAGEMENT:

• AIM-Raise the F VIII level.• Replacement therapy- Plasma ,

Cryoprecipitate .• F VIII concentrates.

DISADVViral transmission

Large volume needed.

F VIII CONCENTRATES:

• 1U= Amount present in 1ml fresh normal plasma.

• High purity F VIII products mfg. by recombinant & monoclonal antibody purification tech. VIRAL SAFETY

• To reduce complications of above treatments before dental extraction a synthetic analogue of 1-deamino 8-D-arginine vasopressin(DDAVP) in combination with tranexamic acid and Epsilon- aminocaproic acid(EACA) can be given.

• 0.3µg/kg body wt. by IV/SC route. Prior to extractions / surgery.

• Intra nasal spray.

CHRISTMAS DISEASE:

• Heriditary def of F IX.• Inheritted as X – linked recesive trait.• Very rare compared to Hemophilia-A.• C/F same as Hemophilia A.• TREATMENT:

Highly purified recombinant & monoclonal FIX conc.(mononine)F IX complex conc.(prothrombin

complex conc.---PCC) proplex-T,

Autoplex-T

Complications of factor replacement therapy

Allergic reactionsViral disease

transmission(hepatitis B & C, CMV,HIV)thromboembolic

disorder,DIC,

Devpt.of antibodies against factor concs.

DENTAL MANAGEMENT OF HEMOPHILIA:

• ANESTHESIA-LA is contra indicated B4 replacement therapy.If to be given-intrapulpal anesthesia,PDL ligament & papillary injection.sedation with dizepam or NO2/O2 analgesia can be given.

• ENDODONTIC therapy– provided care is taken,not to exceed beyond the apex of tooth.

• RESTORATIVE:RUBBERDAM must be used to prevent trauma to gingiva & soft tissues.

PROSTHODONTIC THERAPY:Maintenance of oral hygiene is necessary.If food entrapped in the clasp------ Gingivitis-------- Hemorrhage.

PERIODONTIC THERAPY:Conservative periodontic treatment is desirable.

• ORAL SURGICAL PROCEDURE:Local hemostatic agents & techniques are used.

• Aspirin & other NSAIDs are avoided.

• Preoperative factor level should be 30 – 40 % of normal activity.

• Electro surgery is contra indicated.

F XI DEFICIENCY:

• Plasma thromboplastin antecedent deficiency.• Mild• Autosomal dominant trait.• Controlled with infusions of FFP.

• FXII DEFICIENCY: • HAGEMAN FACTOR DEFICIENCY.• PROLONGED PT & PTT.• CLINICAL SYMPTOMS ARE NON EXISTENT HENCE RX IS

THERFORE CONTRA INDICATED.

F X DEFICIENCY(STUART FACTOR DEF)

• Rare.• Autosomal recessive trait.• If < 1% then symptoms r similar to

hemophilia A & hemophilia B.

• F V DEFICIENCY:• Proaccelerin def .• Rare.• Autosomal recessive trait.

F XIII & F I DEFICIENCY:

• Fibrin stabilizing factor def & Fibrinogen def.

• Very rare.• Autosomal recessive traits.• Rx -Factor replacement

therapy & FFP.

VON WILLEBRAND’S DISEASE:

• Defect in the structure , conc. / function of vWF.(multimeric high Mwt glycoprotein.)

Functions of vWF--* Supports adhesion of platelets to vessel wall. *Carrier of F VIII in plasma.• Autosomal dominant trait.• Normal plasma level = 10mg/L.

CLINICAL FEATURES:

• Mucosal bleeding.• Soft tissue hemorrhage.• Menorrhagia in women.• Rare hemarthrosis.• Both females & males

affected.

TYPES:

• TYPE I : (85% of vWD)- partial quantitative deficiency.• TYPE II : (10-15%)- Qualitative defects. TYPE 2A-Decreased platelet adhesion

TYPE 2B –Increased affinity for platelet glycoprotein Ib TYPE 2M- Defective platelet adhesion. TYPE 2N- Decreased affinity for F VIII.• TYPE III: Rare , complete deficiency.• TYPE IV: Pseudo / platelet type vWD(platelet disorder that

mimics vWD)

TREATMENT:

• Type I- DDAVP,• F VIII concentrates,FFP,Cryoprecipitate-for

nonresponders to DDAVP.• Type II & III-F VIII conc.(Humate P,Koate

HS),cryoprecipitate,FFP.• DENTAL PROCEDURES: Local hemostatic

agents & Antifibrinolytic agents.

ANTI-COAGULANT RELATED COAGULOPATHIES:

• HEPARIN:• Used for prophylaxis / Rx for

thromboembolism.• ACTION- Reduces thrombin generation &

fibrin formation.• COMPLICATIONS: Bleeding into surgical sites

& into the retroperitoneum.• PROTAMINE SULFATE – Antidote for heparin.

COUMARIN• Include Warfarin & dicumarol.• USES:Prevent pulmonary thromboembolism,

venous thrombosis,stroke, MI,to treat AF & in conjunction with prosthetic valves.

• ACTION: Slow thrombin production & clot formation by blocking the action of Vit K .Vit K dependent factors are reduced.

• Anticoagulant effect is reversed by infusion of FFP.

DISEASE RELATED COAGULOPATHY:

• LIVER DISEASE:• Impaired protein synthesis--Fs II,VII,IX & X

(Vit K dependant) are reduced.• Thrombocytopenia & thrombocytopathy also

may result.

• VITAMIN K DEF:• Fs II, VII, IX,X are reduced & decreased

coagulation. TREATMENT: Supplemental Vit K injection restores the

clotting mechanism. FFP infusion,DDAVP THERAPY,Antifibrinolytic

agents.

RENAL DISEASE:

• In uremic patients Dialysis is the primary & therapeutic modality for bleeding control.

• DDAVP & CRYOPRECIPITATE.• Conjugated estrogen preparations &

Recombinant Erythropoietin also are beneficial.

• DIC (Disseminated Intravascular Coagulation):

• Here thrombosis results in rapid consumption of both coagulation factors & platelets.

• Bleeding at skin & mucosal sites.• Sometimes massive hemorrhage occurs &

can be life threatening.

• TREATMENT:• IV-unfractionated heparin , LMWH to

prevent from thrombin acting on fibrinogen & prevent clot formation.

• Infusion of activated protein C , Antithrombin III.

FIBRINOLYTIC DISORDERS:

• Lead to hemorrhage when clot breakdown mechanism is impaired.

Plasminogen activator inhibitor deficiency-- Hemorrhage.

TREATED with FFP THERAPY & Antifibrinolytics.

PROGNOSIS

• Depends on the APPROPRIATE DIAGNOSIS & the ability to prevent and manage acute bleeding episodes.

IDENTIFICATION OF THE DENTAL PATIENT WITH A BLEEDING DISORDER:

• Family history of bleeding problems.(inheritted disorders)

• Past history of bleeding following surgical procedures.(dental extractions)

• Surveying the patient for current medication use.

• History of heavy alcohol intake.• Medical conditions – hepatitis/cirrhosis,renal

disease,hematologic malignancy&thrombocytopenia predispose patients to bleeding problems.

THANK U