Disorders of coagulation and anticoagulants

Dr.Somit jain Department of Periodontics

Contents
        

Introduction Hemostasis Clotting factors Cascade of clotting Disorders of bleeding and clotting Laboratory investigations Anticoagulants Periodontal considerations References

Introduction
 Vertebrates

have evolved complex mechanisms to stem hemorrhage after injury.  Failure of the hemostatic mechanisms may lead to fatal exsanguination.  Any surgical procedure presents a severe challenge to the body s hemostatic mechanism.

HEMOSTASIS
 Normal

hemostasis results from well regulated processes that maintain blood in a fluid,clot free state in normal vessels while inducing the rapid formation of hemostatic plug at the site of vascular injury.  Dependent on the vascular wall,platelets and the coagulation cascade.

NORMAL HEMOSTASIS
Hemostasis, a complex process, can be divided into Four important steps: 1. Vasoconstriction due to local myogenic spasm, local neural response, and release of endothelin from the endothelium 2.Primary hemostatic plug: due to platelet adhesion, 2.Primary activation, RELEASE REACTION or degranulation (ADP, TXA2) and recruitment of other platelets 3.Secondary hemostasis due to activation of coagulation 3.Secondary cascade by tissue factor and phospholipid via extrinsic pathwaypathway- the end result being fibrin which traps the cells in the blood forming a clot 4. Clot organization/ Clot retractions

Vascular phase
 Vasoconstriction

in area of injury  Begins immediately after injury

Primary hemostasis
Platelet adhesion Platelet aggregation Platelet plug formation

Secondary haemostasis (Coagulation of Blood)

Involves activation of clotting process in plasma, resulting in fibrin formation  Important to stop bleeding from large vessels.


It comprises three separate though related systems

  

Coagulation system The coagulation inhibitory system Fibrinolytic system Pathological disturbances may occur in any or more of these systems and lead to bleeding tendency or intravascular coagulation

MECHNISM OF BLOOD COAGULATION

 In

the blood stream anticoagulants normally predominate, so that the blood does not coagulate while it is circulating in the blood vessels  When the blood vessel is ruptured, procoagulants from the area of tissue damage become activated and override the anticoagulants and then clot does develop

GENERAL MECHANISM Clotting takes place in 3 essential steps1. Formation of prothrombin activator 2. Conversion of Prothrombin to thrombin 3. Conversion of Fibrinogen to fibrin

Formation of prothrombin activator

The mechanism sets in to play by 1. Trauma to the vascular wall & adjacent tissue
2.

Trauma to the blood Contact of the blood with the damaged endothelial cells or with collagen & other tissue elements outside the blood vessel Each instance leads to the formation of prothrombin activator

3.

Prothrombin Activator generally formed in two ways & interact constantly with each other. Both the pathways occur simultaneously
EXTRINSIC PATHWAY  Explosive  With severe trauma clotting occurs in 15 sec  Begins with trauma to the vascular wall and surrounding tissue INTRINSIC PATHWAY  Much slower  Clotting occurs in 1- 6min Begins in the blood itself or exposure of the blood to the collagen from the traumatised blood vessel wall

Extrinsic pathway
 The

release of Tissue Factor or Tissue Thromboplastin (Composed of Phospholipid from the membrane of the tissue plus lipoprotien complex)  Activation of factor X.  Effect of activated factor X to form Prothrombin activator

EXTRINSIC PATHWAY

INTRINSIC PATHWAY
Activation of factor XII 1.Trauma Release of platelet Phospholipid 2.Activation of factor XI 3.Activation factor IX - by activated factor XI 4.Activation factor X Role of factor VIII 5. Activation of activated X to form Prothrombin activator Role of factor V

INTRINSIC PATHWAY

COMMON PATHWAY

CLOT RETRACTION
 

Once the fibrin meshwork has appeared, RBCs & platelets stick to the fibrin strands. The platelets then contract and the clot undergoes clot retraction which:  Pulls the torn edges of the vessel closer together, reducing residual bleeding and stabilizing the injury site  Reduces the size of the injured area, making it easier for fibroblasts, smooth muscle cells, and endothelial cells to complete repairs

Fibrinolytic system

Principles underlying coagulation tests

Test Blood clotting time Principle Causes of abnormality Deficiency of intrinsic pathway Deficiency of factorsXII,IX,XI,X,V,VIII Deficiency of factorsVII,X,V, Deficiency of fibrinogen or high level of FDPs Defect in platelets

Contact activation by glass tube Partial thromboplastin Intrinsic pathway time activated by kaolin Prothrombin time Extrinsic pathway activated by brain tissue. Fibrinogen is converted to fibrin by added thrombin Duration of bleeding from skin puncture is timed

Thrombin time

Bleeding time

LABORATORY TEST FOR ASSESSING HEMOSTASIS

TEST
Platelet count  Bleeding time
       

Normal Range

150,000 to 450,000/mm3 < 7 min (by simplate); 1 6 min (modified Ivy s test) Prothrombin time/international Control 1 s (eg, PT: 11 13 normalized ratio s/INR 1.0 Activated partial thromboplastin time Comparable to control ( eg 15-35 s ) 15Thrombin time Control 3 s (eg, 9 13 s) Fibrin degradation products < 10 g/dL g/dL Fibrinogen assay 200 400 mg/dL mg/dL von Willebrand s antigen 60 150% vWF activity Coagulation factor assays 6060-100% F VIII (eg F VIII assay) activity

ASSESSMENT OF A PATIENT WITH POSSIBLE BLEEDING DISORDER

Clinical history Physical examination Lab investigations

PREPRE-OPERATIVE EVALUATION
HISTORY  Prolonged bleeding after trauma/dental extraction  Medications  Bruises without apparent injury  Excessive menstrual bleeding  Relatives with bleeding problems  Bleeding problems associated with major/minor surgery

CLASSIFICATION OF BLEEDING DISORDERS

1. VASCULAR DISORDERS Congenital
Heriditary hemorrhagic telangiectasia Ehler Danlos syndrome

Acquired
Henoch schonein purpura Easy bruishing purpura Senile purpura Factitial purpura Scurvy Severe infection Drugs

QUALITATIVE DISORDERS OF PLATELETS

1) Disorders of adhesion Congenital - Bernard soulier syndrome Acquired - Uremia 2) Disorders of aggregation Congenital - Thrombasthenia Acquired - Drugs - Para proteinemia 3) Disorders of platelet secretion Congenital - Storage pool disease Acquired - Myeloproliferative disorder

Quantitative Disorders Of Platelets

THROMBOCYTOPENIAS
1) Production of platelets Hypoplasia - Idiopathic - Drugs Infiltration - Carcinoma - Leukemia - Myeloma - Myelofibrosis Nutritional deficiency - Iron - B12 / Folate

2) Consumption of platelets Immune - ITP - Sec.immune thrombocytopenia - Post transfusion purpura Coagulation - DIC - Gram

ve septicemia

3) Sequestration of platelets - Hypersplenism 4) Loss of platelets - Hemorrhage - Massive transfusion of stored blood - Hemodialysis

COAGULATION DISORDERS
Classification of Coagulation Disorders:  Acquired Usually multiple factors are involved  Hereditary Usually single factor is involved

Acquired Coagulation Disorders: The followings disorders are associated with acquired coagulation disorders: 1. Vitamin K deficiency a. Obstructive jaundice b. Coeliac disease c. Liver disease i. Defective synthesis of coagulation factors (I, II, V, VII, IV and X) ii. Increased fibrinolytic activity iii. Intravascular coagulation 2. Anticoagulant drugs 3. Disseminated intravascular coagulation 4. Active fibrinolysis 5. Massive transfusion of stored blood 6. Circulating inhibitors of coagulation

Common Hereditary Coagulation Disorders: 1. Hemophilia a. Hemophilia A b. Hemophilia B 2. Von-Willebrand disease 3. Other congenital deficiency disorders a. Fibrinogen deficiency b. Factor V deficiency c. Factor XIII

Factor VIII deficiency factor IX deficiency

HEMOPHLIA A
 

      

X-linked recessive disorder resulting from deficiency of factor VIII Body fails to synthesize this essential globulin due to the absence of the specific enzyme which is controlled by the mutant gene Affects males. Sons of carriers have 50:50 chance developing hemophilia. Daughters of carriers have 50:50 chance of being carriers All daughters of an affected males are carriers but sons are normal Carriers rarely have bleeding tendency Prevalence of 5 per 100000 of population 10 times more common than hemophilia B

The hemophilia gene is carried on the X chromosome in males who lack a normal allele, the defect is manifested by clinical haemophilia. Women may be carriers

Hemophilia
Clinical manifestations (hemophilia A & B are indistinguishable) Hemarthrosis (most common) Fixed joints Soft tissue hematomas (e.g., muscle) Muscle atrophy Shortened tendons Other sites of bleeding Urinary tract CNS, neck (may be life-threatening) Prolonged bleeding after surgery or dental extractions

ORAL MANIFESTATIONS
   

Hemorrhage from many sites in oral cavity. Gingival bleeding massive and prolonged. Tooth eruption and exfoliation with severe prolonged hemorrhage Subperiosteal bleeding with reactive new bone formation causing tumor like expansion of bone (MANDIBULAR PSEUDOTUMOR) Uncontrolled or delayed hemorrhage may result from SURGICAL EXCISION,DENTAL EXTRACTION, PERIODONTAL CURETTAGE. Slight trauma may lead to HEMATOMA formation in

tongue, lip and palate.  Oropharyngeal bleeding(severe complication)

Haemarthrosis in elderly hemophiliac has caused crippling arthritis

Haemophilia

(Christmas Disease)
Christmas disease is a congenital sex-linked hemorrhagic disorder due to absence, reduction or functional abnormality of factor IX Incidence 1 per 50,000 male Clinical features are same as Hemophilia Pathophysiology Factor IX coagulation activities is reduced or absent. A

Level of factor VIIIc activity Normal activity: 50-200% 50(0.5(0.5-2 g/ml) Mild activity : 5-25% 5(0.05(0.05-0.25 g/ml) Moderate activity : 1-5% 1(0.01(0.01-0.05 g/ml) Severe activity : <1% (0.01 g/ml)

Severity of clinical Symptoms

Hemorrhage secondary to trauma, surgery and dental extraction. Occasional spontaneous bleeding, hemarthrosis, musculoskeletal bleeding. Severe spontaneous bleeding since childhood. Intracranial bleeding, bleeding into tongue and frenum, Bleeding in facial spaces of the neck.

Replacement therapy
 Infusion

of plasma products enriched with factor VIII cryoprecipitate,partially purified factor VIII concentrate- Lyophilized concentratepowder  Each unit of Factor VIII infused increases plasma level of recipient by 2% per Kg of body weight.

Source of Factor VIII

 Fresh

whole blood  Fresh frozen plasma  Cryoprecipitate prepared from human plasma  Freeze-dried animal AHG Freeze Freeze-dried human AHG Freeze-

Precautions
  

Nerve Blocks - avoid if not on replacement therapy For infiltration no need for cover of antibiotics Tranexamic acid Prophylaxis - 10 ml of 4.8% aqueous solution, QID for 1 week should be prescribed for patients undergoing regional blocks

Preventive dental care:  Use of fluorides  Fissure sealants  Dietary advice  Regular dental checkups

Surgical procedure
Simple tooth extraction:
Regime I Regime II

1.

Factor VIII of 1. Epsilon Amino between 50-75% is 50caproic acid 5-6 5required. grams every 6th hrly. 2. Preoperative factor 2. Tranexamic acid 1gr VIII, i.v QID for 10 days. 3. Tranexamic acid 1g 3. If bleeding occurs (30mg/kg) QID during this time, a start 24 hrs preoperative dose of factor VIII

Desmopressin Therapy
  

0.3 0.5g/kg i.v just before the surgery, repeat 12 hrly if necessary for upto 4 days. Temporary correction of hemostatic defect. In patients with F VIII inhibitors, it releases - Factor VIIIc - von Willebrands factor - Tissue plasminogen activator from endothelial storage.

For third molar surgeries

    

F VIII replacement Buccal approach to lower 3rd molars Minimal amount of bone should be removed Section teeth for removal whenever possible Extraction socket should be packed with: - Oxidized regenerated cellulose - Absorbable gelatin sponge - Bone wax - Tranexamic acid Acrylic protective splints on palates.

For Major Surgeries

For Major Surgeries: Thorough assessment of the patient PT, APTT, Platelet count, Factor VIII assay, Fibrinogen estimation, Hepatitis B&C, Liver function test, blood grouping.

Von Willebrand disease/ pseudo hemophilia

` ` ` ` ` `

` `

Most common inherited bleeding disorder Due to inherited deficiency of vWF Affects both males & females Inherited as AUTOSOMAL DOMINANT but severe form as sexsexlinked recessive trait like true hemophilia vWF synthesized in endothelium and megakaryocytes Acts as carrier for factor VIII, protecting it from proteolytic degradation, thus deficiency lead to low factor VIII concentration Mediates platelet adhesion to damaged endothelium Mediates platelet aggregation, thus deficiency lead to defective platelet adhesion, which causes secondary deficiency in factor VIII

Von Willebrand disease/ pseudo hemophilia

Types: Type I : Quantitative defect, 80% Type II : Qualitative defect 20% Type III : severe deficiency of vWF

Management of Von Willebrand s disease

Minor procedure Preoperative DDAVPDDAVP-0.3g/kg in 5050-100cc normal saline over 20-30 20mins. 1 hour before surgery OR Type I DDAVP nasal spray (1.5mg/ml) 1-2 1doses in each nostril Repeat every day for 2-3 days after extraction Postoperative Repeat every day for 2-3 days after extraction OR Major procedure Preoperative DDAVP 0.3g/kg in 50-100 cc normal 50saline i.v. over 202030 mins. 1-2 hours 1before surgery (factor VIII level should be 80-100%) 80Postoperative Repeat every day for 5-10 days (factor VIII level 30-50%, 30normal BT)

Type II

Exogenous vWF in cryoprecipitate dose equal to 15-25U/kg 15factor VIII

Maintain F VIII levels at 30% i.e. 15U/kg, 2-3 days 2postoperatively

Exogenous vWF in cryoprecipitate to obtain 80-100% 80levels of factor VIII 1-2 hrs before surgery.

Maintains F VIII levels at 30-50% by 30infusing exogenous factor VIII every 12 hrs for 5-10 days. 5-

DDAVP : 1- Desamino 8- D Arginine, Vasopressin/ Desmopressin Arginine,

HAEMOPHILIA C (FACTOR XI DEFICIENCY)

Inherited as in complete recessive autosomal disorder. ` Cannot activate thrombin-activable fibrinolytic inhibitor(TAFI) thrombinResults in rapid fibrinolysis, which is responsible for bleeding tendency ` Confers to injury related bleeding tendency
`

TREATMENT> ` Fresh frozen plasma or factor XI replacement

`

Other Coagulation factors abnormalities

Factor Factor XII Factor X Factor VII Factor V Factor II Inheritance Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive Laboratory defect aPTT,BT,CT prolonged aPTT,CT prolonged Normal aPTT prolonged PT PT and aPTT prolonged PT and aPTT slightly prolonged PT,aPTT,Throm bin normal C/F Nil Mild bleeding Mild bleeding Mild bleeding Mild bleeding

Factor XIII

Mild bleeding

Vitamin K Deficiency & malabsorption

Fat soluble vitamin ` Present in diet and also synthesized by the gut flora ` Absorbed in small gut, in the presence of bile salts ` Acts as a cofactor at a late stage in the synthesis by liver of coagulation factors (II, VII ,IX, and X). ` Gamma carboxylation of glutamate residues of these zymogen proteins confers on them the capacity to bind calcium and to get bound to PL surface. ` Haemorrhagic disease may result from interference with Vitamin K use by > -Anticoagulants -Malabsorption -Obstructive jaundice -Severe liver disease
`

Liver Diseases
The no. of factors may contribute to the haemostatic defect in liver disease. 1. Defective synthesis of clotting factors 2. Increased fibrinolytic activities 3. Intravascular coagulation. 4. Hepatitis. 5. Malabsorption of Vitamin-K due to parenchymatous diseases.

Drugs
Factors influencing susceptibility of the patient to anticoagulant drug. Potentiating
1. 2. 3. 4.

Inhibitory
1. 2. 3. 4.

Salicylate Phenylbutazone Sulphonamides Thyroxine

Barbiturates Chloral hydrate Spironolactone Glutethimide

Disseminated Intravascular Coagulation

Normal

balance of hemostasis is altered Results in the uncontrolled inappropriate formation and lysis of fibrin within the blood vessels Activation of coagulation occurs systemically
y

Rather than locally at site of injury

Fibrin

is deposited diffusely within capillaries, arterioles and venules Clotting proteins, inhibitors and platelets are consumed faster than they are synthesized

Clinical conditions associated with DIC

DIC Laboratory Diagnosis

 Laboratory
 Available

diagnosis is difficult

tests are nonspecific  No single test can establish the definitive diagnosis of DIC  PT, APTT, TT prolonged  Fibrin degradation products are (+)  Platelet count ; platelet function tests abnormal  Schistocytes, thrombocytopenia on peripheral blood smear

DIC Therapy
 Eliminate
 Acute
 Will

underlying cause, if possible

DIC is often self-limited selfdisappear when fibrin is lysed

 Replacement
 Platelets,

therapy

RBC, Cryoprecipitate or fresh frozen

plasma

Diagnosis of bleeding disorders by the screening tests

Platelet count Bleeding APTT APTT time ProthromProthrom- Presumptive bin diagnosis
Norm. Norm. Norm. Norm. Thrombocytopenia von Willebrands disease Thrombocytopathia intrinsic pathway abnormality (FVIII. IX. XI. XII) extrinsicpathway abnormality (FVII) common pathway abnorm. (FI. II. V. X.) - /FXIII deficiency/ milde bleeding disorder

Decreased Prolonged Norm. Norm. Norm./ increased Norm. Prolonged Prolonged Prolonged Norm. Norm. Prolonged

Norm. Norm. Norm.

Norm. Norm. Norm.

Norm. Prolonged Norm.

Prolonged Prolonged Norm.

ANTICOAGULANTS
Three classes
 Heparin

and Low Molecular Weight Heparins (e.g. enoxaparin, dalteparin)  Coumarin Derivatves e.g. Warfarin, Acenocoumarol  Indandione Derivatves e.g. Phenindione

PARENTRAL ANTICOAGULANTS I-Indirect thrombin inhibitors

- So called because they interact with antithrombin to exert their antithrombotic effect.  - Include unfractionated heparin (UFH = heparin) & low molecular weight heparin (LMWH). (LMWH). HEPARIN  - Sulphated mucopolysaccadide with high molecular weight. It is highly acidic carrying an electronegative charge.  Mechanism of action and actions:  1- Anticoagulant activity: both in vitro and in vivo.  -Antithrombin III inhibits clotting factors proteases (activated clotting factors; IIa, IXa, Xa, XIa & XIIa); most importantly IIa, IXa, Xa, XIIa); thrombin (factor IIa) and factor Xa. In absence of heparin, IIa) Xa. these reactions are slow; in the presence of heparin, they heparin, are accelerated 1000 fold.  - Binding causes conformational changes in this inhibitor exposing its active site for more rapid interaction with the protease.


Inactivation of Thrombin by Heparin-AT Complexes

Heparin
F H S C

Thrombin

AT

Heparin binds to antithrombin and increases the rate of thrombin inactivation

66 5/98 MedSlides.com

II- DIRECT THROMBIN INHIBITORS II Directly bind to the active site of thrombin inhibiting thrombin's downstream effects thus exerting their antithrombotic activity. These (in comparison with UFH) activity. UFH) have equal efficacy, increased bioavailability from the subcutaneous site of injection and less frequent dosing requirements (long half life),

Lepirudin: Lepirudin:


-Is effective in treatment of heparin induced thrombocytopenia and other thromboembolic effects. effects.

Danaparoid: Danaparoid: its anti factor Xa is more than its antithrombin

activity. Advantages over heparin:  - Useful in heparin induced thrombocytopenia (no effect on platelet, also in heparin resistance (deficient antithrombin III).

 The

dose and frequency is controlled by aPTT measurement which is kept at 50 to 80 sec or 1.51.5-2.5 times the patients pretreatment value.  Does not cross Blood brain barrier or placenta (It is anticoagulant of choice in pregnancy).  Half life 1 4 hrs.

ORAL ANTICOAGULANTS ( VIT. K antagonists): -Coumarin anticoagulants include warfarin and dicumarol. Mechanism of anticoagulant activity (effective only in vivo): Inhibits vit. K epoxide reductase enzyme prevention of reactivation of vitamin K (regeneration of the reduced form from the epoxide form) interfere with synthesis of vitamin K Dependent clotting factors (II, VII, IX, X) in liver by blocking carboxylation of several glutamate residues in the above mentioned factors inactive clotting factors Rapidly and completely absorbed from intestine and is 99 % plasma protein bound. It crosses placenta, and is secreted in milk

WARFARIN: MECHANISM OF ACTION

Vitamin K epoxide

Vitamin K reduced

Inactive factors II, VII, IX, and X Proteins S and C

Active factors II, VII, IX, and X Proteins S and C

 Warfarin blocks the reduction of oxidized vitamin K and

thereby prevents the posttranscriptional carboxylation of the above four factors.This carboxylation reaction is essential for the ability of clotting factors to bind to calcium and to get bound to PL ,necessary for coagulation process to succeed.
Has no effect on previously formed thrombus

PLASMA HALF-LIVES OF VITAMIN K-DEPENDENT HALFKPROTEINS

Factor II Factor VII Factor IX Factor X 72h 6h 24h 36h

Though the synthesis of clotting factors diminishes within 2-4 hrs of warfarin 2administration, anticoagulant effect develops gradually over the next 1-3 days as the level of 1clotting factors already present in plasma decline progressively. Thus there is always a delay between administration of drug and anticoagulant effect .

INDICATIONS
and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism)  Prophylaxis and treatment of Atrial fibrillation  Valvular stenosis  Heart valve replacement  Myocardial infarction
 Prophylaxis

MONITORING OF WARFARIN THERAPY

  

Prothrombin time PT ratio INR (International Normalized Ratio)

PROTHROMBIN TIME (PT)

   

Time required for blood to coagulate is called PT Performed by adding a mixture of calcium and thromboplastin to citrated plasma As a control, a normal blood sample is tested continuously PT ratio (PTR) = Patient s PT Control PT

INTERNATIONAL NORMALISED RATIO (INR) (INR)

INR = [PTpt] [PTRef]

ISI

PTpt prothrombin time of patient PTRef prothrombin time of normal pooled sample ISI International Sensitivity Index The International Normalized ratio is a recommended method for reporting prothrombin time results for control of oral anticoagulation (British Community for Standards in Hematology 1990).

How is Warfarin (Coumadin) Monitor and What Dose Do I Take?

 Warfarin

(Coumadin) is monitored by a blood test called an INR (International Normalized Ratio). Warfarin belongs to a category of drugs known as narrow range of effectiveness drugs. This means that there is a very narrow range where the drug is considered therapeutic. For most indications, the INR range is 2.0 to 3.0. For people with mechanical 3.0. heart valve replacements and certain other conditions, the range is 2.5 to 3.5.

When your INR falls within your range (for example, between 2.0 and 3.0), this means that your level is therapeutic . When your INR level goes below the range (for example, 1.5) this means your blood is too thick , and places you at risk for blood clots. In this situation, your healthcare provider will prescribe a higher dose of warfarin for you to take. If your INR goes above your range (for example, 4.5) this means your blood is too thin , and places you at risk for bleeding. In this situation, your healthcare provider will prescribe a lower dose of warfarin for you to take. Because warfarin (Coumadin) affects each person differently, some people will be on small doses of warfarin and some will be on very large doses. Some people will achieve their appropriate INR quickly and others more slowly. The dose of warfarin you need is the one that keeps the INR in the therapeutic range for your condition. Many factors can affect your INR level including a change in diet, a change in medications, the onset of a new illness,or having to stop your warfarin for a procedure.

When a person first starts taking warfarin (Coumadin) the INR level tends to fluctuate up and down until the correct dose of warfarin is found that keeps your INR level stable. It is therefore very important to get your INR level checked frequently. In general, when you first start warfarin you will need to get your INR level checked 2 to 3 times a week for the first two weeks, then one to two times a week for two weeks, then every other week, then once a month. This may vary, depending on how your INR levels are. If the INR level becomes stable quickly, you will go for INR blood tests less often, if the INR level does not become stable, you will need to go for INR blood tests more often. When your INR level is too high or too low, you often will not feel any symptoms. This is why it is so important to get your INR blood tests done regularly!

PERIODONTAL CONSIDERATION
1) Consult the patient physician to determine the nature of the underlying medical problem and the degree of required anticoagulation. 2) A)INFILTRATION ANAESHESIA,SCALING AND ROOT PLANNING may be done-if INR less than done3. B)BLOCK ANAESTHESIA,MINOR PERIODONTAL SURGERY AND SIMPLE EXTRACTION-if INR less than 2 to 2.5 EXTRACTIONC)COMPLEX SURGERY OR MULTIPLE EXTRACTIONS may require INR less than 1.5 to 2.

3) Often, the anticoagulant is discontinued for 2 to 3 days before periodontal treatment(clearance half life of warfarin is 36-42 hours), and INR is checked on the day of therapy.If INR is within acceptable target range,the procedure is done and anticoagulant resumed immediately after treatment. 4)Careful technique and complete wound closure are paramount. For all procedures, application of pressure can minimize hemorrhage. 5)Use of oxidized cellulose, micrifibrillar collagen, topical thrombin,and tranexamic acid should be considered for persistent bleeding.

SIDE EFFECTS
Hemorrhage  Skin necrosis  Purple toe syndrome  Microembolization  Teratogenecity Agranulocytosis, leukopenia, diarrhoea, nausea, anorexia.


Periodontal Procedures
Periodontal health is critically important because of two principal reasons: 1) Hyperemic gingiva contributes to spontaneous and induced gingival bleeding 2) Periodontitis is a leading cause of tooth morbidity, necessitating extraction  Oral hygiene neglect due to fear of toothbrushinduced bleeding  Oral physiotherapy can be accomplished  Periodontal probing and supragingival scaling and polishing can be done routinely.  Careful subgingival scaling with fine scalers

Severely inflamed and swollen tissues are best treated initially with or by gross debridement with a cavitron or hand instruments to allow gingival shrinkage prior to deep scaling

chlorhexidine oral rinses

Periodontal surgical procedures warrant elevating circulating factor levels to 50% and use of posttreatment antifibrinolytics

83

Dabigatran and rivaroxaban, new oral anticoagulants. new approaches in dentistry J Clin Exp Dent. 2010;2(1):e1-5. 2010;2(1):e1

New generation of antithrombotic agents not related to coumarin are dabigatran etexilate (Pradaxa ) and rivaroxaban (Xarelto ). Anticoagulant DABIGATRAN is the first direct thrombin inhibitor, orally available. Specifically and available. reversibly inhibits thrombin, so the duration of action is predictable. The anticoagulant effect correlates well with plasma drug concentrations, which implies an effective anticoagulation with low bleeding risk without major problems of interactions with other drugs.

Rivaroxaban is first oral anticoagulant inhibitor of factor Xa

(F Xa). It produces a predictable and reversible inhibition of F Xa activity with ability to inhibit clot-bound F Xa. The emergence of new oral anticoagulants, such as dabigatran and rivaroxaban, has in recent years appear as a substitute of coumarin anticoagulants and have the potential to change the standards of clinical practice in the prevention of deep vein thrombosis and pulmonary embolism. The use

of dabigatran and rivaroxaban does not require continuous monitoring of INR.

Furthermore, dabigatran and rivaroxaban, unlike warfarin or acenocoumarol, have no drug interactions with NSAIDs or with most first-choice antimicrobials used in the dental office, so it is a dental management safer and easier for the professional in the oral cavity.

References
     

PRINCIPLES OF INTERNAL MEDICINE, HARRISON S, 15TH EDITION. BURKET S ORAL MEDICINE 10TH EDITION CONCISE MEDICAL PHYSIOLOGY, CHOUDHARI, 9th EDITION. CLINICAL PERIODONTOLOGY,CARANZZA,10TH EDITION. ESSENTIAL OF MEDICAL PHARMACOLOGY, K.D.TRIPATHI,6TH EDITION. JOURNAL OF CLINICAL AND EXPERIMENTAL DENTISTRY 2010;2(1)