bleeding & clotting disorders
TRANSCRIPT
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