slides blod clot

Hemostasis
- prevention of blood loss
Mechanism of hemostasis
1. vascular spasm
2. formation of platelet plug
3. formation of blood clot
4. growth of fibrous tissue
Vasoconstriction
Vessel wall contracts after wounding
Causes of contraction
1. nervous reflex
2. myogenic spasm
3. release of local humoral factors
Thromboxane A2 – release from platelets
Platelet plug formation
Physical and chemical properties of platelets
-minute oval discs 2 -4 micrometers
-cytoplasmic factors
1. actin and moysin molecules
2. thrombosthenin
3. calcium in ER and golgi app
4. enzymes producing prostaglandin
5. fibrin stabilizing factors
6. growth factors
Mechanism
Contact with damaged vascular wall – collagen and endothelial cells
Platelets swell with pseudopods
Contractile proteins contract
Release of granules with multiple active factors
Adp and thromboxane A2 activate other platelets becoming sticky
Additional platelets adhering to original platelets
Formation of plug
Importance of platelet plug
Platelet plug is enough to stop bleeding from small vascular rent
Minute rupture of small blood vessel occurs everyday
Decrease in platelet count can result to small hemorrhages in skin and other tissues
Blood coagulation in ruptured blood vessel
Begins to develop in 15-20 seconds (severe)
1 – 2 mins. If minor trauma
Activator substances released from
traumatized vascular wall
platelets
blood proteins
Clot is formed in 3-6 mins.
Clot retraction occurs after 20 mins to an hour
Clot retraction is a function of platelets
Fibrous tissue organization of dissolution
2 courses that can occur after a clot is formed
1. invaded by fibroblasts
2. it can dissolved
Growth factor
Mechanism of blood coagulation
Presence of procoagulant and anticoagulant
General mechanism
1. formation of prothrombin activator
2. conversion of prothrombin to thrombin
3. conversion of fibrinogen to fibrin fibers
Convertion of prothrombin to thrombin
prothrombin
Prothrombin activator Ca++

thrombin

fibrinogen fibrinogen monomer

Thrombin activated fibrin fibers
Fibrin-stabilaizing
Factor

cross-linked fibrin fibers
formation of clot
Clot is a meshwork of fibrin fibers entrapping blood cells, platelets and plasma
Clot retraction – contracts minutes after clot is formed
-- expresses fluid out in 20-60 mins
-- serum—plasma devoid of clotting factors
-- function of platelets – release of
thrombosthenin
actin myosin
initiation of coagulation
2 ways of forming prothrombin activator
1. by extrinsic pathway – trauma to vascular wall
and surrounding tissue
2. by intrinsic pathway – trauma to blood itself

facilitated by plasma protein– blood clotting factors
-- inactive forms of proteolytic enzymes
Extrinsic pathway
Tissue trauma
Tissue factor
VII
VIIa
X activated X
Ca++ Ca++
V
prothrombin activator
platelet phospholipid

prothrombin thrombin

Ca++
Intrinsic pathway
BLOOD TRAUMA OR CONTACT WITH COLLAGEN

XII activated XII
HMW kinogen,prekallikrein
XI activated XI
Ca++
IX activated X
VIII
Thrombin Ca++ Ca++
VIIIa
X activated X prothrombin activator
platelet thrombin
phospholipid V
prothrombin thrombin
Ca++

Role of calcium
Except for first 2 steps calcium ions are required in cascading reaction
Absence of calcium ions- no clot formation
Calcium ion level can be reduced to prevent clot formation
Citrate ion – deionize cacium
Oxalate ion -- precipitate calcium
Prevention of clotting
Endothelial surface factors
1. smoothness of the endothelial lining
2. layer of glycocalyx
3. thrombomodulin – binds thrombin – complex –
activates protein C that inhibits
factor V and VIII
Antithrombin action of fibrin and antithrombin III
- fibrin traps most thrombin
- unabsorbed thrombin neutralized by antithrombin III

Heparin – produce by basophilic mast cell
-- powerful anticoagulant – on its own it is weak - -combines with antithrombin III increasing efficacy as
anticoagulant

lysis of blood clot
Plasminogen – plasma protein - activated becomes plasmin
Plasmin – enzyme digesting fibrin fibers and other factors
Tissue plasminogen activator – release by injured tissue
and activates plasminogen trapped in the
clot
conditions that cause bleeding
Deficiency of any one of the blood clotting factors
Most common conditions
1. vitamin K deficiency
2. hemophilia
3. thrombocytopenia
Vit. K
MOST BLOOD CLOTTING FACTORS ARE FORMED IN THE LIVER
AFFECTION OF THE LIVER MAY LEAD TO BLEEDING PROBLEM
ROLE OF VITAMIN k
--NECESSARY IN SYNTHESIS OF: FACTORS II,VII,IX,X
--NORMALLY PRODUCE BY BACTERIA IN INTESTINE
-- FAT SOLUBLE THUS ABSORBED WITH FATS
-- BILE NEEDED FOR FAT ABSORPTION
-- FAILURE OF BILE TO PASS THRU INTESTINE THUS
CAN AFFECT ABSORPTION OF VIT. K
Hemophilia
Bleeding disorder occurring in male
Deficiency in factor VIII in 85% of cases
Others cause by deficiency of factor IX
Transmitted by way of X chromosomes as a
recessive trait
bleeding occurs after trauma
treatment – transfusion of factor VIII
thrombocytopenia
Very low quantity of platelets
Bleeding usually from small venules and capillaries
Manifests as small punctate hemorrhage
Spontaneous bleeding - <50,000>