Hemostasis:

Hemostasis: Hemo/Stasis Hemo=خونStasis=سکون

مثلث هموستاز: Blood Vessels Platelets Hemostatic Factors

Causes of Bleeding(1) Thrombocytopenia: Primary: ITP Neonatal Isoimmune TAR Syndrome Wiskott-Aldrich Syn. Secondary: *Malignancy *Aplastic Anemia *DIC *Sepsis *HUS *Hypersplenism *Autoimmune(SLE)

Causes of Bleeding(2) Coagulopathy: Primary: vWF Deficiency Hemophilia Platelet dysfunction Secondary: DIC Anticoagulants Vit K deficiency Hepatic Failure Renal Failure Maternal Anticonvulsant

Causes of Bleeding(3) Vascular(Non-Hematologic) Child Abuse Vasculitis Ulcer Varices Ehlers-Danlos Syndrome Telangiectasia Angiodysplasia

تقسیم بندی هموستاز: 1)هموستاز اولیه:چند ثانیه بعد از آسیب عروقی ایجاد میشود و از خونریزی از عروق کوچک و ونولها جلوگیری میکند. 2)هموستاز ثانویه:چند دقیقه بعد از آسیب عروقی ایجاد میشود و از خونریزی از عروق بزرگ جلوگیری میکند.

Differences of Primary and Secondary Hemostasis: Manifestations Primary Hemostasis: Secondary Hemostasis: Onset of Bleeding ImmediateDelayed-hours or days Site of BleedingSuperficialDeep(joints,…) Physical Exams Petechia,Echymosis Hematoma,Hemarthrosis Family History ADAR or X-link R Response to Therapy Immediate; Local pressure Systemic Therapy

Estimation of BT with desired Platelet count BT= Platelet count (minute) 3,850

Vitamin K Related Factors: Factor II Factor VII Factor IX Factor X

Prolonged PTT No clinical bleeding ??? Mild or rare bleeding ??? Frequent,Severe Bleeding ???

Prolonged PTT No clinical bleeding Factor XII, HMWK, PK Mild or rare bleeding Factor XI Frequent,Severe Bleeding Factors VIII and IX

Prolonged PT ???

Prolonged PT Factor VII Deficiency Vitamin K Deficiency(Early) Warfarin anticoagulant ingestion

Prolonged PT and PTT ???

Prolonged PT and PTT Factor II,V,X Deficiency Vitamin K Deficiency(Late) Warfarin anticoagulant ingestion

Prolonged TT ???

Prolonged TT Mild or rare bleeding: Afibrinogenemia Frequent,Severe Bleeding: Dysfibrinogenemia Heparin like inhibitors or heparin administration

Prolonged PT and/or PTT not corrected with normal plasma Specific or nonspecific inhibitor Syndromes

Clot Solubility in 5 M urea Factor XIII deficiency Inhibitor

Secondary Hemostasis Approach: 1)What is diagnosis? 2)What is hemostatic level of Factor? 3)What is blood distribution of factor? 4)Which products contain desired factor? 5)What is half life of coagulation factor?

APPROACH TO COAGULATION DISORDERS

Clinical approach 1.Is the bleeding significant ? 2. Local Vs Systemic ? 3. Platelet Vs Coagulation disorder ? 4. Inherited Vs Acquired ?

1. Demonstration of the defect 2. Identification of the defect(s) 3. Assessment of severity 4. Consequential studies eg. carrier detection 5. Monitoring of treatment Laboratory Approach

1. Platelet count & morphology 2. Bleeding Time(BT) 3. Prothrombin Time(PT) 4. Activated Partial Thromboplastin Time(PTT) 5. Thrombin Time (TT) Screening Tests

Collection of blood sample 1. Minimum circulatory stasis 2. Clean venous puncture 3. Proper anticoagulant 4. Proportion of blood to anticoagulant 5. Separation of plasma and storage 6. Effect of stress, pregnancy, drugs 7. Effect of PCV on the proportion of plasma to anticoagulant

Coagulation factor deficiency/inhibitor Test plus control plasma - 1:1 Repeat PT/APTT > 50% correction –Yes - Factor deficiency –No - inhibitor Prolonged PT/APTT timed incubation abnormally increasing specific inhibitor no change Lupus Anticoagulant

PT TT APTT PT -  APTT, TT, PLC - N HMWK XII PK XI IX VIII VII X V II I * Factor VII deficiency * Anticoagulant therapy

APTT -  PT, TT, PLC - N * Factor deficiency * vWD * Inhibitors * Heparin therapy PT TT APTT HMWK XII PK XI IX VIII VII X V II I

Mixing tests with APTT APTT of test plasma + Aged plasmaAdsorbed plasmaDiagnosis No correctionCorrectedVIII CorrectedNo correctionIX CorrectedCorrectedXI,XII

Prolonged APTT, BT von Willebrand’s disease Ristocetin Induced Platelet Agglutination VIII:C vWF:Ag vWF multimeric analysis Type 1 - Partial deficiency of vWF 2A - Absence of large and interm. multimers 2B - Absence of large multimers 2M- multimers normal, pl. function  2N -  affinity for FVIII 3 - severe deficiency of vWF

PT TT APTT PT, APTT -  TT, PLC - N HMWK XII PK XI IX VIII VII X V II I * Common Pathway Factor deficiency * Vitamin K deficiency * Oral anticoagulant therapy * Liver disease

Mixing tests with PT PT of test plasma + Aged plasmaadsorbed plasmaDiagnosis CorrectedNot corrected X Not correctedCorrected V Not corrected Partial II

PT TT APTT PT, APTT, TT -  PLC - N HMWK XII PK XI IX VIII VII X V II I * Hypo / dysfibrinogenemia * Heparin * Liver disease * Systemic hyperfibrinolysis

PT TT * DIC - FDP - D-dimer - Fibrin monomer APTT APTT, PT,TT all  PLC - low HMWK XII PK XI IX VIII VII X V II I

PT TT APTT PT, APTT-  TT - N PLC -  HMWK XII PK XI IX VIII VII X V II I Massive transfusion with stored blood

Thrombocytopenia Pseudo vs True Bone marrow biopsy to differentiate  production  destruction PT APTT PT, APTT,TT-N PLC -  HMWK XII PK XI IX VIII VII X V II I TT

Factor XIII deficiency Thrombasthenia –congenital –drug induced Disorders of vascular hemostasis Factor XIII - clot solubility PT, APTT, TT, PLC - Normal Platelet function –BT –clot retraction –1 minute platelet count –aggregation Tourniquet test

Asymptomatic Patient Routine screening tests shows prolonged APTT –Inhibitor - lupus anticoagulant –Factor XII deficiency –Mild congenital factor deficiency

Antiphospholipid Antibody Syndrome Criteria by Branch and Silver 1996 Clinical –Recurrent abortion –Recurrent venous thrombosis –Recurrent arterial thrombosis –Persistent thrombocytopenia –Livedo reticularis Laboratory –IgG/IgM anticardiolipin Ab –Lupus anticoagulant Diagnosis –1 clinical + 1 lab criteria –Lab result must be positive on at least 2 occasions more than 3 months apart

Kaolin clotting time Dilute Russel’s viper venom time Platelet neutralization test Tissue thromboplastin inhibition test Lupus Anticoagulant