Blood cells and Coagulation

HMU English Club

 Blood composition
Our body has 8% of blood:
- 55% plasma
 91.5% H2O
 7% protein (albumin, globulins, fibrinogen)
 Rests: salts, lipids, enzymes, vitamins …
- 45% formed elements
 Erythrocytes (hematocrit)
 Leukocytes
 Platelets
 Blood cell differentiation
• PHSCs (Pluripotent Hematopoiesis Stem Cells)
• RBCs (Red Blood Cells) = Erythrocytes
• WBCs (White Blood Cells) = Leukocytes
• Platelets = Thrombocytes
Blood cell differentiation
Erythrocyte
• Anucleate: No nucleus
• Disc-shaped, biconcave
• Contain hemoglobin
• Function: Transfer O2 and
CO2, Buffering
• Energy: Glucose (Glycolysis
and HMP Shunt)
• Survival time: 120 days
• Normal amount:
- Male: 5.05 ± 0.38 T/l
- Female: 4.66 ± 0.36 T/l
 Erythrocyte - Disorders
• Anemia: classified by
- Hypochromic, Normochromic, Hyperchromic: color
- Microcytosis, Normocytosis, Macrocytosis: size
- Anisocytosis: varying sizes
- Poikilocytosis: varying shapes
- Some kinds of anemia: sickle cell anemia, thalassemia,
megaloblastic anemia …
• Polycythemia: primary polycythemia and secondary
polycythemia
 Leukocyte

• Granulocytes (basophils,
eosinophils, neutrophils)
• Monocytes
• Lymphocytes
• Function: Defense
against infections
• Normal amount: 4.0 - 10.
G/l
Basophil & Mast Cells
• Rarely seen
• Contain heparin (anti-
coagulation), histamine
(vasolidator), serotonin and
bradykinin …
• Can bind IgE to memberane
• Function: Mediates allergic
reaction
 Eosinophil
• 3.2 ± 2.6%
• Bilobate nucleus
• Contain enzymes
(oxidase, peroxidase,
histaminase and
arylsulfatase …)
• Function: Defends against
helminthic and protozoan,
phagocytosis for antigen -
antibody complexes
Neutrophil
• 57.4 ± 8.4%
• Multilobed nucleus
• Contain enzymes and oxidizing
agents for phagocytosis
(lysozymes, myeloperoxydase,
hydrogen peroxide …)
• Acute inflammatory response
 Monocyte
• 3.8 ± 0.5%
• Largest WBCs
• Differentiates into
macrophages in
tissues (Kupffer cells,
ie)
• Function:
Phagocytosis and
Antigen presentation
Macrophage
• Phagocytosis (bacteria,
damaged cells and
tissues)
• Antigen presentation:
present antigen products
in the surface to activate
B lymphocytes
• Long life in tissues
 Lymphocyte
• Small, round,
densely staining
nucleus
• B lymphocytes
• T lymphocytes
Lymphocyte
• B Lymphocyte: Part of humoral
immune system. Activated by
antigens, they differentiate into
plasmoblast, then plasma cells.
They produce antibodies. Some can
remember. Live in many years.
• Plasma cell: Off-center nucleus,
clock-face chromatin distribution,
abundant RER and well-developed
Golgi apparatus.
• T Lymphocyte: Mediates cellular
immune response. Mature in
thymus gland. Differentiate into
cytotoxic T cells, helper T cells and
suppressor T cells.
 Dendritic cells
• Professional APCs
• Called Langerhans
cells in skin
• Express MHC II and
Fc receptor on
surface
• Main inducers of 1o
antibody response
Platelet
• Fragments of cell without
nucleus
• Contain mitochondria,
enzymes, thrombosthenin,
thromboplastin …
• Function: Coagulation
• Normal amount: 150 - 300
G/l
 Coagulation factors
Factor Description
I Fibrinogen (plasma)
II Prothrombin (plasma)
III Thromboplastin (tissue)
IV Ca2+ (plasma)
V Proaccelerin (plasma)
VI (Unassigned)
VII Proconvertin (plasma)
VIII Anti-hemophilia A factor (plasma)
IX Anti-hemophilia B factor (plasma)
X Stuart - Prower factor (plasma)
XI Prothromboplastin, Anti-hemophilia C factor (plasma)
XII Activates prekallikrein and fibrinolysis (plasma)
XIII Fibrin-stabilizing factor (plasma)
Platelets Thromboplastin (platelets)
 Coagulation process
1. Vascular constriction: smooth muscles, nervous reaction, platelets
release thromboxane A2 and serotonin.
2. Formation of the Platelet Plug: A continuous process of releasing
ADP, attracting platelets, releasing serotonin, thromboxane A2 and
prostaglandin E2.
3. Formation of Blood Clots: 2 pathways of coagulation to prevent
blood from flowing.
4. Lysis of Blood Clots: Platelets release thrombosthenin to constrict
the firbin clot and start the lysis of blood clots. Damaged tissues
release plasminogen activator to convert plasminogen into plasmin,
a proteolytic enzyme. After lysis of blood clots, plasmin is inhibited
by 2 - antiplasmin and becomes inactive.
 Coagulation
cascade
• There are 2 pathways
of coagulation: Intrinsic
pathway (PTT) and
Extrinsic pathway (PT)
• PTT: occurs as blood
contacts with rough
surfaces or damaged.
Activated platelets
cause coagulation.
• PT: damaged tissues
release factor III to
activate factor VII,
cause coagulation.
 Coagulation factor inhibitors
and fibrinolysis
• Thrombomodulin combines with thrombin to inactivate it. This
complex thrombomodulin - thrombin also activates Protein C, which
will inactivate factor Va and VIIIa.
• Fibrin network adsorbs 85 - 90% thrombin. The rest is binded with
Antithrombin III and becomes inactive.
• Heparin combines with antithrombin III to form a complex that could
inactivate factor IXa, Xa, XIa and XIIa.
• Tissue plasminogen activator (tPA) is a secreted serine protease
which converts plasminogen to plasmin. This tPA is used in clinic to
treat coronary thrombosis.
• 2 - macroglobulin has the same effect with the complex heparin -
antithrombin III. It inactivates coagulation factors and prevents them
from proteolysis.
 Coagulation disorders
• Vitamin K deficiency: Lack of vitamin K (due to cirrhosis, hepatitis,
etc.) would lead to decrease of coagulation factors II, VII, IX and X.
• Hemophilia: 3 types A, B and C. Type A (lack of factor VIII) and B
(lack of factor IX) are X-linked. Type C (lack of factor XI) is
autosomal. Patients with hemophilia often have long bleeding even
if the wound is small. Also have spontaneous bleeding.
• Thrombocytopenia: Often causes bleeding. An amount of platelets
under 50 G/l can cause death.
• Thrombus and Emboli: An abnormal blood clot formed in blood
vessels is called a thrombus. When it seperates and flows in the
blood flow, it is called an embolus. Emboli start at greater vessels
and flow to smaller vessels, then stuck there.
• Disseminated Intravascular Coagulation (DIC)
Relationship of Clotting cascade, Kinin
cascade and Complement cascade
 References
• Guyton’s Textbook of Medical Physiology, 2006 - Elsevier Inc.
• Sinh lý học, 2007 - Bộ môn Sinh lý, Trường Đại học Y Hà Nội
• Basic Histology: Text & Atlas, 11th edition - McGraw Hill
• Mô học, 2007 - Bộ môn Mô phôi, Trường Đại học Y Hà Nội
• http://wikipedia.org
Thank you for listening!
Question: A child falls and bumps her head on the floor.
Tissue factor is exposed beneath the endothelium of
traumatic blood vessels. Which of the following
procoagulation proteins bind to tissue factor and initiates
the clotting cascade? (question 19, page 114)
A. Factor V
B. Factor VII
C. Factor X
D. Fibrinogen
E. Prothrombin
The correct answer is B

The extrinsic pathway of clotting begins with tissue factor

binding to Factor VII or Factor VIIa. All other clotting proteins
require proteolytic cleavage to become active; however,
Factor VII has a low level of activity in its inactive form and
can act with tissue factor and phospholipids to initiate the
clotting cascade. In the extrinsic pathway, Factor VII cleaves
Factor X to Xa (choice C), which acts in concert with Factor V
(choice A) to cleave prothrombin to thrombin (choice E). The
final step in the coagulation pathway is the cleavage of
fibrinogen to fibrin by thrombin (choice D). Fibrin polymerizes
and cross-links, thereby forming a hemostatic net of insoluble
protein.