COAGULATION
OF BLOOD
Coagulation is defined as the process in which blood loses is
fluidity and becomes a jelly like mass few minutes after it is shed out or
collected in a container.
Factors involved in blood clotting
Factors
1.
Fibrinogen
2. Prothrombin
3. Thromboplastin
4. Calcium
5. Labile factor
6. Accelerin
7. Stable factor
8. Antihemophilic
9. Cristmas
10. Stuart prower
11. Plasma thromboplastin antecedent
12. Hageman
13. Fibrin stabilizing
2. Prothrombin
3. Thromboplastin
4. Calcium
5. Labile factor
6. Accelerin
7. Stable factor
8. Antihemophilic
9. Cristmas
10. Stuart prower
11. Plasma thromboplastin antecedent
12. Hageman
13. Fibrin stabilizing
Mechanism
Enzymes cascade theory
Most of the clotting factors are proteins in the
form of enzymes. Normally all the factors are present in the form of inactive
proenzyme. These proenzyme must be activated into enzymes to enforce clot
formation. It is carried out by a series of proenzyme enzyme conversion
reactions. First one of the series is converted into an active enzyme that
activates the second one which activates the third one this continues till the
final active enzyme thrombin is formed.
Stages of blood clotting
1. Formation of prothrombin activator
2. Conversion of prothrombin into thrombin
3. Conversion of Fibrinogen into fibrin.
1. STAGE 1:- Formation of
prothrombin
Blood clotting commences
with the formationof a substance called prothrombin activator which converts
prothrombin into thrombin.
Formation of prothrombin activator 2 pathways
1. Intrinsic pathways
1.During the injury the
blood vessel is ruptured endothelium is damaged and collagen beneath the endothelium is exposed.
2.When factor 12 Hagrman
comes in contact with the collegen it is converted into activated factor 12 in
the presence of kallirein and high molecular weight kinogen.
3.The activated factor
12 converts factor 11 into activated factor 11 in the presence of high
molecular weight kinogen.
4.The activated factor
11 activates factor 9 in the presence of factor 4 calcium.
5.Activated factor 9
activates factor 10 in the presence of factor 8 and calcium.
6.When platelet comes in
contact with the collagen of damaged blood vessel it gets activated and
releases phospholipids.
7.Now the activated factor
10 reaxts with platelet phospholipid and factor 5 to form prothrombin
activator.
8.This needs the
presence of calcium ions Factor 5 is also activated by positive feedback effect of thrombin
Extrinsic pathway
Pathway
Pathway
1.Tissues that are damaged during injury releases tissue
thromboplastin.
2.Thromboplastin contains proteins phospholipid and glycoprotein
which act as proteolytic enzymes.
3.Glycoprotein and phospholipid components of thromboplastin convert factor 10
into activated factor 10 in the presence of factor 7.
STAGE 2:- CONVERSION OF PROTHROMBIN INTO
THROMBIN
1.Prothrombin activator
that is formed in intrinsic and extrinsic pathway converts prothrombin into
thrombin in the
presence of calcium
2.Once formed thrombin initiates the formation of more thrombin molecules.
3. The initially formed thrombin activates factor 5. Factor 5 in turn accelerates
formation of both extrinsic.
STAGE 3 :- CONVERSION OF FIBRINOGEN INTO FIBRIN
1.Trombin converts
inactive fibrinogen into Activated Fibrinogen due to loss of 2 pairs of polypeptides from each
Fibrinogen molecule.
2.Fibrin monomer polymerizes with other monomer molecules and form loosely
arranged strands of fibrin.
stage coagulation |
BLOOD CLOT
Blood clot is defined as
the mass of coagulation blood which contains RBC WBC and platelets entrapped in
fibrin meshwork.
FIBRINOLYSIS
Lysis of blood clot
inside the blood vessel is called fibrinolysis. It helps to remove the clot
from lumen of the blood vessel. This process requires a substanceccalled
plasmin or fibrinolysis.
ANTICOAGULANTS
1.Anticoagulant used to prevent blood clotting inside. The body in vivo.
2.Anticoagulant used to prevent clotting of blood that is collected from thecbody
in vitro.
3.Anticoagulant used to prevent blood clotting both in vivo and in vitro.
1. HEPARIN
Heparin is a naturally produced anticoagulant in the body. It is produced
bymast cells which are the wandering cells present immediately outside the
capillaries in many tissues.
mechanism
Uses of Heparin
Heparin is used as an
anticoagulant both in vivo and in vitro.
Clinical use
1.I.V. injection of haparin (0.5 to 1 mg/kg body weight ) postpones clotting for
3 to 4 hours . So it is widely used as an anticoagulant in clinical practice.
2.Heparin is used for many purposes
3.To prevent intravascular blood clotting during surgery.
4.While passing the blood through artificially kidney for dialysis.
5.During cardiac surgery which involves heart lung machine.
6.To preserve the blood before transfusion.
Use in the laboratory
Heparin is also used as anticoagulant in vitro while collecting blood for various
investigations. About 0.1 to 0.2 mg is sufficient for 1 ml of blood. It is
effective for 8 to 12 hours.
2. COUMARIN
Warfarin and dicoumoral are the derivatives of coumarin
Uses
Dicoumoral and warfarin
are the commonly used oral anticoagulants. Warfarin is used to prevent
myocardial infarction strokes and thrombosis.
3. EDTA
Ethylenediaminetetraacetic
acid is a strong anticoagulant. It is available in 2 forms
Disodium salt (Na2 EDTA
Tripotassium salt ( k3 EDTA)
Mechanism
These substances prevent blood clotting by removing calcium from blood.
Uses
EDTA is used as an
anticoagulant both in vivo and in vitro
4. OXALATE COMPOUNDS
Oxalate composed prevent coagulation by forming calcium oxalate which is
precipitated later.
Mechanism
Oxalate combines with calcium and forms insoluble calcium oxalate. Thus oxalate
removes calcium from blood and lack of calcium prevents coagulation.
Uses
Oxalate compounds are
used only as in vitro anticoagulants. 2 mg of mixture is necessary for 1 ml of
blood. Since oxalate is poisonous it cannot be used in vivo.
5. CITRATES
Sdium ammonium and patassium citrates are used as anticoagulants.
Uses
It is used to store
blood in the blood bank
Citrate is also used in laboratory in the form of formal citrate solution for
RBC and platelet counts.
TESTS FOR BLOOD CLOTTING
1. Bleeding time
Bleeding time is the time interval from oozing of blood after a cut or injury
till arrest of bleeding. Usually it is determined by Duke method using blotting
paper or filter paper method. Its normal duration is 3 to 6 minutes. It is
prolonged in purpura.
2. Clotting time
Clotting time is the time interval from oozing of blood after a cut or injury
till the formation of clot. It is usually determined by capillary tube method.
Its normal duration is 3 to 8 minutes. It is prolonged in hemophilia.
3. Prothrombin time
4. Partial prothrombin time
5. International normalized ratio
6. Thrombin time
BLEEDING DISORDERS
1. Hemophilia
Hemophilia is a group of sex linked inhaerited blood disorders characterized by
prolonged clotting time. Usually it affects the males with the females being
the carriers.
Symptoms of hemophilia
1. Spontaneous bleeding
2. Prolonged bleeding due to cuts toot Extraction and surgery.
3. Hemorrhage in gastrointestinal and Urinary tract.
4. Bleeding in joints followed by swelling And pain .
5. Appearance of blood in urine.
Causes
Hemophilia occurs due to
lack of formation of prothrombin activator. That is why the coagulation
time is prolonged. The formation of prothrombin activator is affected due to
the deficiency of factor VIII, IX, XI.
Treatment for hemophilia
Effective therapy for classical hemophilia involves replacement of missing
clotting factor.
2. PURPURA
Purpura is a disorder characterized by prolonged bleeding time.
3. TROMBOSIS
Thrombosis or intravascular blood clotting refers to coagulation of blood
inside the blood vessels. Normally blood does not clot in the blood vessel
because of some factors which are already explained.
Causes
1. Injury to blood vessel
2. Roughened endothelial lining
3. Sluggishness of blood flow
4. Agglutination of RBC
5. Toxic thrombosis
6. Congenital absence of protein C
Complications of
Thrombosis
1. Thrombus
2. Embolism and embolus
3. Ischemia
4. Necrosis and infarction
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