HEMOSTASIS

Dr. Taj

Antithrombogenic Thrombogenic

Vessel injury

(Favors fluid blood) (Favors clotting)

OBJECTIVES

At the end of the lecture you should be able to describe…..What is hemostasisWhat are the steps of hemostasisThe 2 pathways of coagulationThe role of platelets in hemostasisBleeding & clothing disorders

HEMOSTASIS

From an injured blood vessel is the

Prevention of blood loss

Or Stoppage of bleeding

Or Arrest of bleeding from a broken blood vessel

STEPS OF HEMOSTASIS

Vascular Spasm

Formation of platelet plug

Blood Coagulation

Clot Retraction

VASCULAR SPASM(Vascular Constriction)

Factors Nervous reflexes Local myogenic spasm Local humoral factor

For smaller vessels Platelets Thrombokanc A2

Importance Censhing injuries Intense spasm No lethal loss of

blood

FORMATION OF PLATELET PLUG

Importance of platelet plug small vascular damage

BLOOD COAGULATION Formation Of Clot

Blood clotting is the transformation of blood from a liquid into a solid gel form

Pathways Intrinsic Extrinsic

Initiated by: Activator substances from traumatized vascular wall, plts & blood proteins

Begins to develop in 15-20 sec Minor trauma 1-2 min. Severe trauma

physical events of Clotting process

PLATELETS Formed by fragmentation from megakaryoctyes

PLATELETS

Contractile, adhesive, cell fragments. Store coagulation factors & enzymes Surface Binding sites for fibrinogen Surface Glycoprotein Antigens-HPA1.

SHAPE: MINUTE ROUND OR OVAL DISCSSIZE: 1-4 um IN DIAMETERHALF LIFE: 8-12 DAYSCOUNT: 150,000 – 300,000/ microlitrer

•ACTIN AND MYOSIN ACTIN AND MYOSIN MOLECULESMOLECULES

•THROMBESTHENINTHROMBESTHENIN•ENDOPLASMIC RETICULUM ENDOPLASMIC RETICULUM

AND GOLGI APPARATUSAND GOLGI APPARATUS•MITOCHONDRIAMITOCHONDRIA•ENZYME SYSTEMS FOR ENZYME SYSTEMS FOR

SYNTHESIS OF SYNTHESIS OF PROSTAGLANDINSPROSTAGLANDINS

•FIBRIN STABILIZING FIBRIN STABILIZING FACTORFACTOR

•GROWTH FACTORGROWTH FACTOR

FUNCTIONAL CHARACTERISTICS:

MECHANISM

Formation of Prothrombin activator

complex

Conversion of prothrombin into

thrombin

Conversion of fibrinogen into fibrin

INITIATION OF COAGULATION

Formation Of Prothrombin Activator Complex

2 WaysBy Extrinsic pathway trauma to vascular

wall and surrounding tissues

By Intrinsic pathway trauma to the blood

Is the rate - limiting factor

CONVERISON OF PRTHROMBIN TO THROMBIN

By Prothrombin Activator Complex

ProthrombinPlasma protein (Alpha2 globulin)Mol. Wt. - 68,700Plasma conc. - 15 mg/dlUnstable proteinSynthesized by liverVitamin-K is required for synthesis

CONVERSION OF FIBRINOGEN TO FIBRIN

Formation Of Clot

FibrinogenMol. Wt. – 340,000Plasma conc. – 100 – 700 mg/dlSynthesized in liver

ACTION OF THROMBIN ON FIBRONOGEN TO FORM FIBRIN

BLOOD CLOT

A meshwork of fibrin fibres running in all directions and entrapping blood cells, platelets and plasma

CLOT RETRACTION

When clot contracts, it expresses most of the fluid from the clot within 20-60 min. Serum

SERUM CANNOT CLOT ROLE OF PLTS IN CLOT

FORMATION VICIOUS CIRCLE OF CLOT

FORMATION

Clotting Factors

EXTRINSIC MECHNANISM

FOR INITIATING CLOTTING

INTRINSIC MECHNANISM

FOR INITIATING CLOTTING

ROLE OF THROMBIN IN HEMOSTASIS

ROLE OF CALCIUM IONS IN CLOTTING

No Ca++ No Clotting Blood samples are prevented from

clotting by adding:Citrate ions Deionization of Ca++

Oxalate ions ppt the Ca++

LYSIS OF BLOOD CLOTS PLASMIN

Plasminogen / Profibrinolysin

T-PA

Plasmin or Fibrinolysin

Lysis of clot

INTRAVASCULAR ANTICOAGULANTS

1. Endothelial Surface Factors Smoothness of Endothelium Glycocalyx Layers Thrombomodulin Protein

2. Antithrombin action of Fibrin and Antithrombin III

85-90 % Thrombin binds with Fibrin 10-15 % Thrombin binds with Antithrombin III

INTRAVASCULAR ANTICOAGULANTS

3. Heparin - vely charged conjugated polysaccharide

Increase the effectiveness of Antithrombin III Produced by

Mast cells Basophil cells

Most widely used anticoagulant clinically e.g. in stroke

4. Alpha2 – Macrogobulin Acts as a binding agent for several coagulation

factors

BLEEDING & CLOTTING DISORDERS

A. Liver diseases & Vitamin-K

deficiency

B. Hemophilia

C. Thrombocytopenia

BLEEDING DISORDERS

A. Liver diseases & Vitamin-K deficiency

e.g. Hepatitis, Cirrhosis Decreased formation of clotting factors

Icnreased clotting time

Vitamin K dependent factors Prothrombin, Factor VII, IX, X

HEMOPHILIA

HEMOPHILIA AClassic Hemophilia85 % casesDef. Of factor VIII

HEMOPHILIA B15 % casesDef. Of factor IX

THROMBOCYTOPENIA

PLT count upto 50,000 ul Less than 10,000 ------ Fatal ETIOLOGY Decreased production

Aplastic anemiaLeukemiaDrugs Infections (HIV, Measles)

HEMOPHILIA

Genetic disorders Transmitted by female chromosome as

recessive trait Occurs exclusively in male Females are

carriers Types

Hemophilia AHemophilia B

HEMOPHILIA

Clinical FeaturesEasy bruising, massive bleeding after trauma

or operation, hemorrhages in jointsFactor VIII

Small Comp. Hemophilia A Large Comp. Von-Willebrand’s disease

RxInjection of factor VIII (Hemophilia A)Injection of factor IX (Hemophilia B)

THROMBOCYTOPENIA

Increased destruction ITP Drugs Infections

Clinical Features Easy brusability Epistaxis Gum bleeding Hemorrhage after minor trauma Petechiae/Ecchumosis

THROMBOCYTOPENIA

DiagnosisPLT decreasedB.T increased

RxRx of the underlying causePLT concentratesFresh whole blood

transfusionSplenectomy

THANK YOU

ANTI COAGULANTS FOR CLINICAL USE

Heparin ---------- Subcutaneous or intramuscular

Warfarin --------- Oral

THROMOEMBOLIC CONDITIONS

Thrombus Abnormal clot that develops in a blood vessel

Embolus Freely flowing clots Emboli from Lf heart or large arteries ------------ Emboli from Rt heart or venous system ----------

Etiology Roughened Endothelia surface Sluggish flow of blood

Rx Use of genetically engineered t-PA Use of streptokinase

FEMORAL THROMBOSIS & MASSIVE PULMONARY EMBOLISM

Prolonged Immobilization

Propping the knees with

underlying pillows

Intravascular clot

Grows up and down

Clot disengages

Venous blood

Massive pulmonary embolism

DISSEMINATED INTRAVASCULAR COAGULATION

Results fromPresence of large amounts of traumatized or dying

tissue in the bodyReleases tissue thromboplastinClots are small and numerous Seen in Septicemic shock

BLEEDING DISORDERSA. Vitamin-K Fat soluble vitamin Required by liver for formation 4 clotting factors Sources

Diet Sythesized in the intestinal tract by bacteria

Deficiency Malabsorption syndromes Biliary obstruction Broad spectrum antibiotics Dietary def (in Neonates) Rx.: Treat the underlying cause Vit K injections