Hemostasis,Clotting Disorder and Anticoagulants

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Text of Hemostasis,Clotting Disorder and Anticoagulants

Disorders of coagulation and anticoagulantsDr.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 HEMOSTASISHemostasis, 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 hemostasisPlatelet 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 activatorThe mechanism sets in to play by 1. Trauma to the vascular wall & adjacent tissue2.

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 simultaneouslyEXTRINSIC 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 PATHWAYActivation 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 testsTest 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 HEMOSTASISTESTPlatelet 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 EVALUATIONHISTORY 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 DISORDERS1. VASCULAR DISORDERS CongenitalHeriditary hemorrhagic telangiectasia Ehler Danlos syndrome

AcquiredHenoch schonein purpura Easy bruishing purpura Senile purpura Factitial purpura Scurvy Severe infection Drugs

QUALITATIVE DISORDERS OF PLATELETS1) 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 PlateletsTHROMBOCYTOPENIAS1) 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 DISORDERSClassification 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

HemophiliaClinical 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

B

(Christmas Disease)Christmas disease is a congenital sex-linked hemorrhagic disorder due to absence, reduction or functional