Bleeding tendency

Normal haemostasis Factors involved in normal haemostasis

Bleeding: Clinical Features

Local - Vs - General, spontaneous . . Hematoma & Joint bleed Coagulation Skin/Mucosal Petechiae & Purpura PLT wound / surgical bleeding Immediate - (PLT) Delayed - (Coagulation)

Hemostasis
BV Injury
Tissue Factor

Lab Tests
CBC-Plt BT,(CT) PT PTT

Neural

Blood Vessel Constriction

Platelet Aggregation Primary hemostatic plug Platelet Activation

Coagulation Cascade

Reduced Blood flow

Fibrin formation

Plt Study
Stable Hemostatic Plug

Morphology Function Antibody

Platelet

Coagulation

Petechiae, Purpura

Hematoma, Joint bl.

Primary Hemostatic Disorders

Defect of platelet plug formation platelets small vessels or capillaries plasma proteins required for adhesion to subendothelium

Primary Hemostatic Disorders

Vascular defect - fragility Petechiae, purpura, ecchymoses senile purpura vitamin C deficiency (scurvy) connective tissue disorders Osler-Weber-Rendu syndrome hereditary malformations

Senile Purpura

Primary Hemostatic Disorders

Vascular defect - cont. Infectious and hypersensitivity vasculitides - Rickettsial and meningococcal infections - Henoch-Schonlein purpura (immune)

Primary Hemostatic Disorders

Platelet disorders: platelets (thrombocytopenia) petechiae spontaneous bleeding after trauma CNS bleeding (severe plt) Platelet dysfunction mucocutaneous bleeding Prolonged bleeding time (BT)

Bleeding Time Test

Timer is started upon incision

Bleeding time = time to complete cessation of free blood flow from incision

Thrombocytopenia Causes

Marrow injury/failure - aplastic or myelophthesic anemia - drugs, infections - megaloblastic anemia, PNH Decreased survival - immune (ITP, drugs, infections) - nonimmune (DIC, TTP)

Idiopathic Thrombocytopenic Purpura (ITP)

Acute - children (post infection) Chronic - adults ( females, 20-40 yrs) - autoimmune disorder - antiplatelet antibodies (IgG against platelet glycoproteins) - IgG coated platelets removed by spleen ( platelet survival)

Platelet dysfunction:

Primary Hemostatic Disorders

Inherited - autosomal recessive Bernard-Soulier disease - large platelets - lack of glycoproteins (1b-IX complex) - failure of platelet adhesion Glanzmanns thrombasthenia - normal platelet morphology - lack of glycoproteins (IIb-IIIa complex)

Primary Hemostatic Disorders

Platelet dysfunction: Acquired - common Aspirin and NSAID - cyclo-oxygenase inhibitors - lack of thromboxane A2 and PGE - failure of platelet aggregation Systemic disorders - i.e.

Primary Hemostatic Disorders

Plasma proteins required for adhesion to subendothelium: von Willebrand disease - quantitative or qualitative deficiency of vWF molecule - binds to exposed subendothelial collagen - mediates initial platelet adhesion

Secondary Hemostasis

Consolidates initial platelet plug into stable clot Disorders - deficiencies of plasma clotting factors Clinical - bleeding from large vessels into joints (hemarthroses), muscles, deep soft tissues (hematomas, large ecchymoses)

Laboratory findings: Normal bleeding time, platelet count Prolonged prothrombin time (PT) deficiencies of II, V, VII, X Prolonged activated partial thromboplastin time (aPTT) all factors except VII, XIII Mixing studies - normal plasma

Secondary Hemostatic Disorders

Screening Tests of Blood Coagulation

Factor VIII Deficiency

Classic hemophilia (hemophilia

A) X-linked disorder (affects 1 males) Most common hereditary disease with severe bleeding 30% new mutations (not hereditary)

Factor VIII Deficiency

Classic hemophilia - cont. Clinically severe if <1% circulating factor VIII (moderate 1-5%, mild 5-75%) Abnormal aPTT Diagnosis - factor assays Treatment - factor VIII concentrate - cryoprecipitate (less desirable)

Factor IX Deficiency
Christmas disease (hemophilia B) X-linked recessive disorder Indistinguishable from classic hemophilia Requires evaluation of factor VIII and IX activity levels to diagnose Treatment - factor IX concentrate

Secondary Hemostatic Disorders

Acquired coagulation disorder: Vitamin K deficiency - neonates - decreased intestinal flora and dietary intake - oral anticoagulants (coumadin) - fat malabsorption syndromes Required for factors II, VII, IX, X

von Willebrands Disease Autosomal dominant (or recessive) Primary defect - platelet adhesion (prolonged bleeding time) Secondary defect - deficiency of factor VIII; normally stabilizes factor VIII in

Combined Primary and Secondary Hemostatic Disorders

Von Willebrands Disease

Clinical - often mild - excessive bleeding from wounds - spontaneous bleeding from mucous membranes Different types - quantity or loss of selective multimers Diagnosis - ristocetin induced plt aggregation or multimer

von Willebrand Factor multimeric analysis

Disseminated Intravascular Coagulation Primary - platelet consumption ( bleeding time, platelets) Secondary - factor consumption ( PT, aPTT) Major pathologic processes obstetric complications, neoplasms, infection (sepsis),

Combined Primary and Secondary Hemostatic Disorders

Disseminated Intravascular Coagulation

Thromboplastic substances

Multiple initiating factors Tissue factor Widespread

endothelial injury

Activates extrinsic pathway

platelet aggregation Activates intrinsic pathwa

Microvascular thrombosis
Clotting factor Tissue injury, consumption Fibrinolysis Hemolytic anemia Fibrin split products Bleeding plasmin

Disseminated Intravascular Thrombosis (DIC)

Acute DIC - bleeding - i.e. major trauma - give fresh frozen plasma Chronic DIC - thrombosis - i.e. cancer - give heparin or anticoagulant

Severe Liver Disease Primary - dysfunctional platelets and/or thrombocytopenia ( BT) Secondary - decrease in all coagulation factors except vWF ( PT, aPTT) Vitamin K will promote synthesis of factors II, VII, IX, X

Combined Primary and Secondary Hemostatic Disorders

Summary Hemostatic Disorders

BT Plt PT

PTT
1o hemostasis 2o Factor VIII/IX deficiency 2o Vitamin K deficiency - - -

 Approach to bleeding disorders Personal history of bleeding With surgery Tonsillectomy, circumcision Epistaxis a Immediate bleeding after trauma or surgery suggest platelet or severe protein deficiency. Bleeding 2-5 days post trauma or surgery suggest plasma protein deficiency .

 Family history X linked Autosomal al * Drug history Oral anticoagulant, Heparin, Aspirin * Physical examination

Initial lab works CBC : Platelet count PT (INR) APTT Bleeding time

Bleeding Ecchymoses Petechiae Hemarthroses Hematomas

Signs and Symptoms of Coagulation Disorders

Petechiae

Platelets versus Coags

Petechiaeplatelets low or dysfunctional Ecchymoses, hematomas, hemarthrosesseen more frequently with low clotting factors or dysfunction Bleeding can be seen with either

Hematom a

Hemarthrosis

Hematom a

Ecchymosis

 Management : Always be on the safe side Dont do invasive procedures if you are in doubt. Always check with haematology/ internal medicine. Check the above tests if normal you can proceed Remember some cases of bleeding tendency might go first to you, like AML with gingival hyper trophy. Always check Drugs

HEPARIN THERAPY
Enhances activity of AT III Parenteral administration required Onset of action immediate Monitor aPTT Lower dose may work in patients without active thrombosis

HEPARIN THERAPY
Low Molecular Weight HeparinAdvantages
Less heterogeneous than heparin Less inhibition of platelet function Longer half life - Can give 1-2x/day Much less thrombocytopenia ? safer, equally effective

HEPARIN
Low Molecular Weight HeparinDisadvantages
Bleeding-? Less than with heparin (probably not) Most cross react with heparin RE: thrombocytopenia Each preparation is different Less overall experience with the drug

COUMADIN (warfarin)
Mechanism of Action
Inhibits Vitamin K dependent carboxylase activity Prevents reduction of Vitamin K Humans secrete des--carboxyglutamic acid, an inactive protein DOES NOT AFFECT PROTEINS ALREADY SYNTHESIZED Monitor using prothrombin time Multiple interactions with other drugs Antidote-Vitamin K

 What do if no help if INR< 1.5 safe to do procedures, so if patient on Warfarin , stop Warfarin 2 days before surgery. Heparin stop if unfractionated 2 hours before SX. If low MW Heparin 4-6 hours stop surgery

 Platelet defect: Count : Thrombocytopenia = low platelet count Thrombocytosis = High platelet count Safe procedure if platelet count above 50,000. Thrombosthenia : The count is normal but the function is abnormal.

 Systemic illnesses can predispose to bleeding like liver diseases, Chronic renal failure.

 Depending on the underlying cause abnormalities of the platelet should be corrected before any procedure . How to correct depends on the underlying cause either with platelets transfusion or other modalities to increase the count ,like steroids , IVIg in ITP.

 If on Aspirin please stop Aspirin at least one week before SX. If urgent please check bleeding time if prolonged please give platelets. Which should be 1-2 hour before SX.

 For congenital causes of bleeding please contact haemtology.

leukaemias
Can predispose to bleeding due to 1- low platelets count 2- DIC 3-Hyerviscosity syndrome. Oral manifestations of acute leukaemia Includes : gingival hypertrophy, bleeding , and ulcers.

Oral manifestations of leukaemia