BLEEDING & CLOTTING DISORDERS

PRESENTED BY JASMINE . PP Vth 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. Fibrinol ytic phase.(r ate limiting step)

VASCULAR PHASE:
After tissue injury immediate vasoconstriction occurs. Serotonin, histamine, PGs 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,FSINTRINSIC PATHWAY V,VII,IX,X,XI,XII & XIII.--------- Vitamin K EXTRINSIC PATHWAY dependant-FS-II,VII, IX & X. COMMON PATHWAY .

Involves 3 separate pathways

FIBRINpolymerizes to a gel

 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 aliquid 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

tPA Factor XIIa + high Mol.wt kininogen

parakallikren

kallikren F V plasminogen plasmin F VIII

fibrin

FDPs

CLINICAL & LABORATARY FINDINGS

CLINICAL FEATURES
Ble edin g from su perf ici al cut s & sc rat che s . Del ayed b leed ing . Spo ntan eo us g ing ival bl eed ing . Pet echi ae . Ecc hymo se s . Epi stax is . Dee p di ss ecti ng hema tom as . Hem arth ro ses .

CLINICAL LABORATARY TESTS

Help to Identify deficiency of required elements Dysfunction of the phases of coagulation

PLATELET

COUNT:

Normal-150,000 to 450,000/mm3 If < 50,000/mm3 Hemorrhagic stroke Surgical/traumatic hemorrhage etc. may occur. In such cases platelet transfusion may be necessary.

TESTS OF PLATELET FUNCTION:

Bleeding time{ 1-6 mins}modified Ivys test. PFA-100 CT-Platelet Function Analyzer 100 closure time. ADV Used in vWD. Dis ADV Simple to use. Neither specific nor predictive. Use restricted to research studies &

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.

f PT that adjusts for the sensitivity of the thromboplastin reagants,such that nor

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. Itzaltered 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.

ates the presence of a D-dimer of fibrinogen / fibrin

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

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 VitC level falls below 10mg/d. VitC is essential for synthesis of collagen. Hemorrhage in muscles , joints , nail beds & gingival tissues. GINGIVA- swelling, friability,

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

CUSHINGS SYNDROME,EHLERS DANLOS SYNDROME,RENDUOSLER- WEBER SYNDROME(HHT)

CUSHINGS 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:
ACQUIRED CONGENITAL Thrombocytopaenia-Quantity of - platelets when reduced by * edproduction in the bone marrow * edsequestration in

the spleen.

destruction.

Accelerated

CONGENITAL
THROMBOCYTOPENIC May-hegglin anomaly Wiskott-Aldrich syndrome Neonatal alloimmune thrombocytopenia .

NONTHROMBOCYTOP ENIC Glanzmans thrombasthenia Platelet type vonwillebrands disease Bernard soulier syndrome

ACQUIRED
THROMBOCYTOPE NIC

NONTHROMBOCYTO PENIC

TTP(Thrombotic thrombocytopenic purpura) Cytotoxic chemotherapy Drug induced Leukemia Aplastic anemia Systemic lupus erythematosus DIC Asso with :

Drug induced Uremia Alcohol dependancy Liver disease Myeloma Macroglobulinaemi a Acquired platelet tpe von-

ITP
Caused by accelerated antibody mediated platelet consumption. Oral hematomas & hemorrhagic bullae may occur. Intracerebral hemorrhage is the most common cause of death. Corticosteroids TREATMENT: Splenectomy
Rituximab Anti-D Thrombopoietin like agents.

TTP:
CAUSES:metastaticmalignancy,pregnancy,mit omycin & high dose chemotherapy. SYMPTOMS:

 Platelet count may also decreased by medications. ASPIRIN

 ASPIRIN : USES--- ANTIPLATELET THERAPY FOR THROMBOEMBOLIC PROTECTION. INEXPENSIVE & EFFECTIVE

COAGULATION DISORDERS
HEMOPHILIA A CONGENITAL-- HEMOPHILIA B F XI DEFICIENCY F XII ,, F X ,, F V ,, F XIII & I ,, VON - WILLEBRAND S DISEASE . ACQUIRED- .Secondary to drugs (Heparin , Coumarin) or disease process(Liver disease, Vit K deficiency ,DIC).

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(0.00.9% 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

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

HEMATOLOGICAL FINDINGS:

MANAGEMENT:

AIM-Raise the F VIII level. Replacement therapy- Plasma DISADV , Viral transmission Cryoprecipitate . Large volume needed F VIII concentrates.

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

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:

Complications of factor replacement therapy

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.

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

 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 THEREFOR 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 WILLEBRANDS 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.

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.

TREATMENT:
Type I- DDAVP, F VIII concentrates,FFP,Cryoprecipita te-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 .VitK dependent factors are

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

 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