HEMOSTASIS & BLOOD COAGULATION HEMOSTASIS Collective term for all the physiologic mechanism the body uses

s to protect itself from blood loss OBJECTIVES: Stops bleeding from an injured site At the same time maintains blood in fluid state within the vascular compartment Involves synchronized cooperation between several interrelated physiologic systems FORMATION OF TEMPORARY HEMOSTATIC / PLATELET PLUG
PLATELET EVENTS

TEMPORARY PLATELET PLUG DUE TO THE FF

PLATELET ACTIVATION DIRECT

PLATELET AGGREGATION INDIRECT ACTIVATORS

PLATELET ADHESION

PROCOAGULANTS vs. ANTICOAGULANTS ACTIVATOR FAILURE OF HEMOSTASIS - HEMORRHAGE FAILURE TO MAINTAIN FLUIDITY OF BLOOD - THROMBOSIS
COLLAGEN

THROMBIN

The four main systems are: Vascular Platelets Coagulation proper Normal control mechanisms to blood clotting STOPS BLEEDING & MAINTAINS FLUIDITY OF BLOOD
VASCULAR RESPONSE PC

ADP, EPINEPHRINE THROMBOXANE A2

Characteristics of Platelets Round,oval discs 2 4 micrometers in diameter. BM megakaryocytes 150,000 300,000 / microliter Half-life in blood of 8 to 12 days Active Factors in Platelet Cytoplasm Actin & myosin molecules Residuals of endoplasmic reticulum and Golgi apparatus Mitochondria & enzyme systems Enzyme systems that synthesize prostaglandins Fibrin stabilizing factor
COAGULATION PATHWAY

HEMOSTATIC CONTROL MECHANISMS AC

ARREST BLEEDING

PLATELET ACTIVATION PC

COAGULATION PATHWAY PC

Synchronized Cooperation between Interrelated Systems VASCULAR

RESPONSE VASOCONSTRICTION NERVOUS REFLEXES LOCAL MYOGENIC SPASM

EXTRINSIC PATHWAY Activator Tissue thromboplastin

INTRINSIC PATHWAY

LOCAL HUMORAL FACTORS

In vivo activator Collagen, ADP Thrombin

In vitro activator neg charged glass surface Kaolin, ellagic acid

THE VASCULAR RESPONSE

BLEEDING RELEASE OF TISSUE THROMBOPLASTIN EXPOSURE OF SUBENDOTHELIAL COLLAGEN RELEASE OF ADP, Calcium

EPINEPHRINE THROMBOXANE A2

Clotting Factors: Enzymes [ proteins ] or co enzymes that are synthesized independently, mainly in the Liver. They are present in plasma as inactive precursors & must be activated to become biologically functional in the coagulation system. This activation is done via the Intrinsic or Extrinsic pathway or both.

VASCULAR RESPONSE

PLATELET EVENTS

COAGULATION PATHWAY

NORMAL CONTROL MECHANISMS TO BLOOD CLOTTING


COAGULATION MECHANISM EXTRINSIC PATHWAY ACTIVATOR TISSUE THROMBOPLASTIN FACTOR VII ACTIVATED FACTOR VII FACTOR VII COMPLEX ACTIVATED FACTOR VII TISSUE THROMBOPLASTIN CALCIUM PHOSPHOLIPID

Activation of Factor Xa initiates the terminal phase of coagulation. Factor Xa [ Ca+ phospholipid ] reacts with prothrombin to generate thrombin COMMON PATHWAY [ enhanced by Factor V]
FACTOR X - X Activated

Factor V Complex V, Xa, Ca , phospholipid Prothrombin -- Thrombin Fibrinogen - Fibrin Factor XIII Fibrin Polymer

INTRINSIC PATHWAY Begins with Contact activation of contact coagulation factors [ XI , XII ] , by appropriate in vivo / in vitro contact activators. Consequences of activation of Factor XIIa + cofactor HMWK are ff; Activates prekallekrein to kallikrein, which in turn activate more Factor XII. This is a selfamplifying system Activates Factor XI Promotes conversion of plasminogen to plasmin Activated Factor XIa ,activates Factor IX [ Ca ] Factor X activator complex Kallekrein activates bradykinin, initiates partly complement
COAGULATION MECHANISM INTRINSIC PATHWAY ACTIVATORS COLLAGEN,GLASS, ETC F XII - F XIIa F XI - F XIa F IX - FIXa F VIII COMPLEX CALCIUM PHOSPHOLIPID F VIIIa Smoothness Of Endothelium F IXa

THROMBIN- potent procoagulant Converts fibrinogen to fibrin Enhance platelet release reaction Augments activation of factor V & VIII Converts plasminogen to plasmin Activates Protein C Activates factor XIII Pathologic conditions : thrombin cleaves fibrinogen into fragments & split the peptide bonds in a wide range of other proteins FIBRINOGEN Fibrinogen becomes fibrin when thrombin removes the tip of the 2 pairs of peptide chains, releasing Fibrinopeptides A & B... Fibrin monomer [ 97% of the original fibrin molecule ] polymerizes into a stable insoluble fibrin clot in the presence of Factor XIIIa, which causes the crosslinkage of the peptide bonds. Normal Control
Mechanisms To Blood Clotting

Endothelial Surface Factors

Antithrombin III Antithrombin Action of Fibrin

HEPARIN

FIBRINOLYTIC SYSTEM

Proteins Bound to Endothelium

Normal Laminar Flow

THE COMMON PATHWAY Both the intrinsic & extrinsic pathway converge to form the common pathway, that activates plasma prothrombin [ II ] to become the active form Thrombin [ IIa ]

BLOOD CLOT Thrombus blood clot formed inside living blood vessel. The process is called Thrombosis Blood Clot is composed of meshwork of fibrin fibers running in all directions & entrapping blood cells, platelets & plasma. The fibrin fibers also

adhere to damaged surfaces of blood vessels; therefore, the blood clot becomes adherent to any vascular opening & thereby prevents blood loss. CLOT RETRACTION Within a few minutes after a clot is formed, it begins to contract & usually expresses most of the fluid from the clot within 20 to 60 minutes. Platelets are necessary to clot retraction. Failure of clot retraction is an indication that the number of platelets in the circulation is low. As the clot retracts the edges of the broken blood vessel are pulled together, thus contributing still more to the ultimate state of hemostasis. PLASMIN - lysis of blood clots Plasminogen plasma protein called euglobulin, which when activated becomes a substance called Plasmin or fibrinolysin. Plasmin resembles Trypsin [proteolytic enzyme]. It digests the fibrin fibers & also digests other clotting factors.
PLASMINOGEN F XIIa + cofactor Tissue Kinases, Trypsin PLASMIN Factor V & VIII Fibrin Fibrinogen Fibrinogen Breakdown Products Thrombin Plasma, Vascular Kinases

Breakdown Products

Fibrin Breakdown Products

Vitamin K dependent Clotting Factors Vitamin K is synthesized by GIT Vitamin K is necessary in formation of ff clotting factors : Prothrombin [ II ] Factor VII Factor IX Factor X