HEMOSTASIS Dr. Taj Antithrombogenic Thrombogenic Vessel injury (Favors fluid blood) (Favors clotting)
Jan 05, 2016
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