Blood Coagulation

Dr. Samra Bashir

 Learning Objectives
• What is blood coagulation and its significance?
• How this process takes place?
• What are the mechanisms which inhibit clot formation under normal
conditions?
• What are the disorders resulting from abnormal hemostasis?
• What are anticoagulants and what are their clinical implications?
 Blood Coagulation
• The 3rd step in hemostasis
• Clot formation begins within 15-20 seconds if trauma to the vascular
wall is severe or 1-2 minutes if the trauma has been minor
• Chemicals involved in the process of blood coagulation are called as
clotting factors
• Clotting factors are derived from damaged wall of the blood vessel,
platelets and from blood.
 Clotting factors
Factor Name of the factor Source
I Fibrinogen Liver
II Prothrombin (Zymogen) Liver
III Tissue factor/tissue thromboplastin Endothelial cells
IV Calcium Diet and bones
V Proaccelerin/Labile factor Endothelial cells. platelets
VII
Factor Proconvertin/Stable
Name of the factor factor (Zymogen) Liver
Source
VIII Antihemophilic factor/Antihemophilic factor A Liver
IX Christmas factor/ Antihemophilic factor B (Zymogen) Liver
X Stuart-Prower factor (Zymogen) Liver
XI Plasma thromboplastin antecedent/ antihemophilic factor C Liver
(Zymogen)
XII Hageman factor, contact factor, glass factor (Zymogen) Liver
XIII Fibrin Stabilizing factor Liver and platelets
 Clotting factors
Additional factors
1. Von Willebrand factors (vWB) - causes platelets adhesion and
carries clotting factor VIII in the blood
2. Fitzgerald factors/ high molecular wt. kininogen
3. Fletcher factor/ prekallikrein
4. Platelet phospholipids (PF3)
 Clotting mechanism
(formation of fibrin)
Blood coagulation is completed in 3 stages.
1. Formation of prothrombin activator
• Intrinsic pathway: Only clotting factors present
in the blood participate in this pathway.
Clotting time= 2-6 min
• Extrinsic pathway: Tissue factor is also
involved in this pathway in addition to some
factors present in the blood. Clotting time= 15
sec
2. Conversion of prothrombin into thrombin Final common pathway
3. Conversion of fibrinogen into fibrin.
Clotting Pathway/Clotting Cascade
Kallikrein
HMW- kininogen

Tissue damage
Extrinsic
III (TF)
VII VIIa
Ca++
• The intravenous blood is collected in a test tube from a patient for
some diagnostic purpose. Which pathway is mainly responsible for
the clotting of blood in this case
a. Intrinsic pathway
b. Extrinsic pathway
 Fibrin polymerization

Thrombin Thrombin
Fibrinogen Fibrin Fibrin polymer (soluble)
monomer

Factor XIII

Crossed liked fibrin

polymer (insoluble)
 Clot retraction
• Role of Actin, myosin and thrombosthenin (platelet
contractile proteins)
• In an hour of clot formation or so, clot retraction
takes place
• It compresses fibrin meshwork and serum squeeze
out (Clot solidification)
• Clot size is reduced by 40%
• Edges of damaged blood vessel are pulled together
• Fibroblasts and endothelial cells repair the blood
vessel
 Lysis of Clot
1. Plasminogen or pro-
fibrinolysin (plasma
protein) is responsible
for clot lysis
2. Plasminogen trapped in
the clot is gradually
activated by tPA a few
days after clot formation
3. tPA is released by
damaged tissue and
endothelium
 Clinical uses of tPA
As thrombolytic therapy in
• to treat stroke caused by clot in
cerebral blood vessels.
• to prevent death from a heart
attack (acute myocardial
infarction)
• Alteplase is also used to treat a
blood clot in the lung (pulmonary
embolism).
• Administer alteplase within 3 hrs
of onset of symptoms
 Abnormalities of Hemostatic
mechanisms
• Conditions that cause excessive bleeding
1. Liver diseases
2. Vitamin K deficiency
3. Hemophilia
4. Von Willebrand disease
5. Thrombocytopenic purpura
• Thromboembolic conditions
 Abnormalities of Hemostatic
mechanisms
• Conditions that cause excessive bleeding
1. Liver diseases – hepatitis, cirrhosis, etc
2. Vitamin K deficiency – (needed for Factor II, VII, IX and X formation in the liver)
 Intestinal bacteria are most important source of vitamin K
 Deficiency can occur in
- neonates
- gastrointestinal diseases
-failure of liver to secrete bile (liver disease or bile duct obstruction)
Treatment: Vitamin K injection to neonates or surgical patients with liver or
gastrointestinal disease.
 Abnormalities of Hemostatic
mechanisms
3. Hemophilia: bleeding disorder that occurs almost exclusively in males.
• X linked recessive disorder
• 1 in every 10,000 males suffer from hemophilia in US
• 85% are deficient in factor VIII (hemophilia A or classic hemophilia)
• 15% are deficient in factor IX (Hemophilia B or Christmas disease)
• No spontaneous bleeding takes place
• Bleeding is associated only with trauma
• Degree of bleeding may vary from person to person and severity of trauma required to
cause severe bleeding may also vary.

4. Von-Willebrand disease: Deficiency of Von Willebrand factor

Treatment: Injection of purified factor VIII in case of sever prolong bleeding

 Abnormalities of Hemostatic
mechanisms
5. Thrombocytopenic purpura:
• Normal platelet count 150,000-400,000/µl
• Bleeding occurs when platelet count falls below 50,000/µl
• Platelet count less than 10,000/µl is lethal
• Spontaneous bleeding occurs from many capillaries and
venules
• Skin shows formation of many small purplish patches –
thrombocytopenic purpura
Treatment:
1. Transfusion of fresh whole blood
2. Splenectomy
 Thromboembolic conditions
• Formation of abnormal clot in a blood vessel – Thrombus
• Clot detached from its site of formation and flowing free in the blood
– Emboli

Causes:
1. Roughened Endothelium/atherosclerosis
2. Slow blood flow
 Thromboembolic conditions
Common Conditions resulting from
thromboembolism:
1. Femoral venous thrombosis
2. Pulmonary embolism
3. Ischemic stroke

Treatment:
Tissue plasminogen activator (tPA)
 Where to study from?
Essentials of medical Physiology, Jaypee Publishers

Chapter. 18