Platelets Disc-shape cell fragment with no nucleus Platelets are the cell fragments pinched off from megakaryocytes in red bone marrow Platelets are important in preventing blood loss Platelet plugs Promoting formation and contraction of clots Platelets--Life History Platelets form in bone marrow by following steps: myeloid stem cells eventually become megakaryocytes whose cell fragments form platelets. Short life span (5 to 9 days in bloodstream) They are formed in bone marrow. They remain few days in circulating blood. Aged ones are removed by fixed macrophages in liver and spleen. Normal count: 2-4 lacs per mm3 of blood.

1. Md. Saiful Islam
Dept. of Pharmaceutical Sciences
North South University
Facebook Group: Pharmacy Universe
YouTube Channel: Pharmacy Universe
BLOOD
Platelets, Blood Clotting, Blood Groups

2. Genesis of Blood Cells

3. Platelets (Thrombocytes)
• Disc-shape cell fragment with no nucleus
• Platelets are the cell fragments pinched off from megakaryocytes in red bone
marrow
• Platelets are important in preventing blood loss
– Platelet plugs
– Promoting formation and contraction of clots
Platelets--Life History
• Platelets form in bone marrow by following steps:
– myeloid stem cells eventually become megakaryocytes whose cell fragments
form platelets.
• Short life span (5 to 9 days in bloodstream)
– They are formed in bone marrow.
– They remain few days in circulating blood.
– Aged ones are removed by fixed macrophages in liver and spleen.
– Normal count: 2-4 lacs per mm3 of blood.

4. Platelets
Platelets bleb off of
megakarocytes

5. • Major functions
• Blood coagulation: When blood is shed, the
platelets disintegrate and liberate
thromboplastin, which activates prothrombin
into thrombin.
• Repair of capillary endothelium: While in the
circulation, the platelets adhere to the
damaged cell lining of the capillaries and thus
bring about a speedy repair.

6. Hemostasis
• Hemostasis is stoppage of bleeding in a quick & localized fashion when
blood vessels are damaged.
• Main goal of Hemostasis is to prevent hemorrhage (hemorrhage is loss of a
large amount of blood)
Opposite of hemorrhage  stops bleeding
Too little hemostasis  too much bleeding
Too much hemostasis  thrombi / emboli
Three major steps:
1. Vasoconstriction/ Vascular spasm
2. Platelet plug Temporarily blocks the hole
1. Platelet-derived cytokines further the process
3. Coagulation cascade (= clot formation seals hole until tissues repaired)
1. Two pathways: Extrinsic and Intrinsic
4. After vessel repair, plasmin dissolves the clot

7. Steps of Hemostasis

8. 1)Vascular Spasm
• Damage to blood vessel stimulates pain receptors
• It causes reflex contraction of smooth muscle of small
blood vessels.
• Vascular Spasm can reduce blood loss for several hours
until other mechanisms can take over.
• Vascular Spasm is effective only for small blood vessel
or arteriole.

9. • Platelets store a lot of chemicals in granules
needed for platelet plug formation
–ADP, Ca+2, serotonin, fibrin-stabilizing
factor, & enzymes that produce
thromboxane A2
• There are three steps in the process of
Platelet plug formation
–(i) platelet adhesion
–(ii) platelet release reaction
–(iii) platelet aggregation
2) Platelet plug formation

10. Platelet plug formation: Steps
i. Platelet Adhesion
• Platelets stick to exposed collagen underlying damaged endothelial
cells in vessel wall. When exposed after injury, platelets aggregate at
the site by mediation of von Willebrand factor (vWF) that binds to
both platelet receptors and collagen/subendo cells.
ii. Platelet Release Reaction
• Platelets activated by adhesion
• Extend projections to make contact with each other
• Release thromboxane A2, serotonin & ADP activating other platelets
• Serotonin & thromboxane A2 are vasoconstrictors decreasing blood
flow through the injured vessel. ADP causes stickiness
iii. Platelet Aggregation
• Activated platelets stick together and activate new platelets to form a
mass called a platelet plug
• Plug reinforced by fibrin threads formed during clotting process

11. Platelet Plug Formation
Von Willebrand Factor : A large blood protein that plays an important role in platelet gathering at the site of a wound

12. 3)Blood Clotting
Blood clotting – It is a process in which liquid blood is changed
into a semisolid mass (a blood clot).
• Clotting is activated by tissue damage or when blood come in
• Clotting is a cascade of reactions in which each clotting factor
activates the next in a fixed sequence resulting in the
formation of fibrin threads
Blood Coagulation Tests
Bleeding time : (Normal Range: 1-6 minutes)
Clotting time : (Normal Range: 6-10 minutes)
Prothrombin time : (Normal: 12 seconds)

13. Blood Coagulation
• Coagulation is a complex process by which blood forms clots.
• It is an important part of hemostasis (the cessation of blood
loss from a damaged vessel), wherein a damaged blood vessel
wall is covered by a platelet and fibrin-containing clot to stop
bleeding and begin repair of the damaged vessel
• So A blood clot consists of
-a plug of platelets
-enmeshed in a network of insoluble fibrin molecules.

14. Overview of the Clotting Cascade
Extrinsic Pathway:
-Chemical outside the blood triggers blood coagulation.
-This pathway is initiated by damaged tissues.
-Damaged tissues leak tissue factor (thromboplastin) into bloodstream.
• Prothrombinase (Prothrombin activator) forms in seconds
Intrinsic Pathway: Activation occurs when
– endothelium is damaged & platelets come in contact with collagen of blood
vessel wall
– Triggered by Hageman factor (found inside blood)
– platelets damaged & release phospholipids
• Requires several minutes for reaction to occur
Final common pathway
• Prothrombinase is formed by either the intrinsic or extrinsic pathway
• Final common pathway produces fibrin threads
– prothrombinase & Ca+2 convert prothrombin into thrombin
– thrombin converts fibrinogen into fibrin threads
– Fibrin threads trap blood cells and proteins
• Clot retraction follows minutes after cascade

15. Factor Common Name
Number
I Fibrinogen
II Prothrombin
III Tissue Factor
IV Ca2+
Va Proaccelerin
VI Does not exist as it was named initially
but later on discovered not to play a part
in blood coagulation
VII Proconvertin
VIII Antihemophilic Factor A
IX Antihemophilic Factor B/ Christmas Factor
X Stuart Factor
XI Antihemophilic factor C/ Plasma
thromboplastin antecedent
XII Hageman factor
XIII Fibrin Stabilizing Factor

18. ** Why blood does not clot inside the blood vessel?
• Blood does not clot inside the blood vessel
because-
– Endothelium of blood vessels are quite smooth
and non water wettable. A rough and water
wettable substance is required for clotting.
– Speed of the blood flow is optimum to prevent
coagulation.
– Presence of natural anticoagulants like heparin,
antithrombin, etc.

19. Clotting disorders
1)Afibrinigenaemia or fibrinogenopenia:
Rare congenital disease characterized by absence of
fibrinogen in blood.
2)Hemophilia:
This is a genetic disease characterized by
unstoppable hemorrhage. This happens due to
absence of a particular clotting factor – VIII or AHG
(Anti-Haemophillic Globulin).

20. 3) Lack of prothrombin or vitamin K:
• Vitamin K helps in the formation of prothrombin in
liver.
• This vitamin is absorbed from the small intestine in
presence of bile salts.
• In the liver disease like liver cirrhosis and other
malignant disease, there is impaired prothrombin
synthesis in the liver.
• Again in some cases, prothrombin synthesis may be
hindered because of inadequate presence of
vitamin K (For example, in obstructive jaundice,
there is lack of bile salts and for this reason,
vitamin K is not properly absorbed).

21. Thrombosis:
• Thrombus is a clot formed within the unbroken blood
vessel.
• It is formed-
- on rough inner lining of Blood Vessels. For example,
cholesterol can abnormally deposit over the vascular
endothelium and turns it narrow, water wettable and rough
and thus results in clotting.
-if blood flows too slowly (stasis) allowing clotting factors to
build up locally & cause coagulation
-Due to damage or injury of the vascular endothelium.
• This phenomenon is known as atherosclerosis and this
gradually lead to coronary thrombosis and other fatal
disorders.

22. Embolism:
• In some times, the thrombus or intravascular clot can get dislodged and float
via blood circulation.
• This mobile thrombus or clot is known as embolus. The disorder then can be
called as embolism.
• Embolism can be classified as whether it enters the circulation
in arteries or veins.
• Arterial embolism is a sudden interruption of blood flow to an organ or body
part due to an embolus adhering to the wall of an artery and blocks the flow
of blood.
• A venous embolism is a blood clot that forms within a vein. Assuming a
normal circulation, a embolus formed in a systemic vein will always impact in
the lungs (pulmonary embolus), after passing through the right side of the
heart.

23. Purpura:
• Purpura (from Latin: purpura,
meaning "purple") is the
appearance of red or purple
discolorations on the skin that
do not blanch on applying
pressure.
• They are caused
by bleeding underneath the
skin.
• It is due to platelet deficiency.

24. BLOOD GROUPING

25. History of Blood Groups and Blood Transfusions
•Experiments with blood transfusions have been carried
out for hundreds of years. Many patients have died and
it was not until 1901, when the Austrian Karl
Landsteiner discovered human blood groups, that
blood transfusions became safer.
• He found that mixing blood from two individuals can
lead to blood clumping. The clumped RBCs can crack
and cause toxic reactions. This can be fatal.
http://nobelprize.org/medicine/educational/landsteiner/readmore.html

26. • Karl Landsteiner discovered that blood clumping was an
immunological reaction which occurs when the receiver of
a blood transfusion has antibodies against the donor blood
cells.
•Karl Landsteiner's work made it possible to determine blood
types and thus paved the way for blood transfusions to be
carried out safely. For this discovery he was awarded the
Nobel Prize in Physiology or Medicine in 1930.
History of Blood Groups and Blood Transfusions (Cont.)

27. •The differences in human blood are due to the presence or
absence of certain protein molecules called antigens and
antibodies.
•The antigens are located on the surface of the RBCs and the
antibodies are in the blood plasma.
•Individuals have different types and combinations of these
molecules.
•The blood group you belong to depends on what you have
inherited from your parents.
What are the different blood groups?

28. • There are more than 20 genetically determined blood group
systems known today
• The AB0 and Rhesus (Rh) systems are the most important ones
used for blood transfusions.
• Not all blood groups are compatible with each other. Mixing
incompatible blood groups leads to blood clumping or agglutination,
which is dangerous for individuals.
What are the different blood groups?

29. According to the ABO blood typing system
there are four different kinds of blood
types: A, B, AB or O (null).
ABO blood grouping system

30. Blood group A
If you belong to the blood group
A, you have A antigens on the
surface of your RBCs and B
antibodies in your blood plasma.
Blood group B
If you belong to the blood group
B, you have B antigens on the
surface of your RBCs and A
antibodies in your blood plasma.
AB0 blood grouping system

31. Blood group AB
If you belong to the blood group AB,
you have both A and B antigens on the
surface of your RBCs and no A or B
antibodies at all in your blood plasma.
Blood group O
If you belong to the blood group O (null), you
have neither A or B antigens on the surface of
your RBCs but you have both A and B antibodies
in your blood plasma.

32. ABO Blood Groups

33. Well, it gets more complicated here, because there's another antigen to be
considered - the Rh antigen.
Some of us have it, some of us don't.
If it is present, the blood is RhD positive, if not it's RhD negative.
So, for example, some people in group A will have it, and will therefore be
classed as A+ (or A positive).
While the ones that don't, are A- (or A negative).
And so it goes for groups B, AB and O.
The Rhesus (Rh) System

34. • Rh antigens are transmembrane proteins with loops exposed at the
surface of red blood cells.
• They appear to be used for the transport of carbon dioxide and/or
ammonia across the plasma membrane.
• They are named for the rhesus monkey in which they were first
discovered.
• RBCs that are "Rh positive" express the antigen designated D.
• 85% of the population is RhD positive, the other 15% of the population is
running around with RhD negative blood.
The Rhesus (Rh) System (Cont.)

35. • A person with Rh- blood can develop Rh antibodies in the blood plasma
if he or she receives blood from a person with Rh+ blood, whose Rh
antigens can trigger the production of Rh antibodies.
•A person with Rh+ blood can receive blood from a person with Rh-
blood without any problems.

36. People with blood group O are
called "universal donors" and
people with blood group AB are
called "universal receivers."
Blood transfusions – who can receive
blood from
whom?

37. • AGGLUTINATION PROCESS IN TRANSFISION
REACTION:
• For a blood transfusion to be successful, AB0 and Rh blood groups must be
compatible between the donor blood and the patient blood.
• If they are not (When bloods are mismatched so that anti-A or anti-B plasma
agglutinins are mixed with RBC that contain A or B agglutinogens, respectively),the
red blood cells from the donated blood will clump or agglutinate as a result of the
agglutinins attaching themselves to the RBC.
• Because of the agglutinins Have 2 binding sites (IgG type) or 10 binding sites (IgM
type).A single agglutinins can attach to two or more RBC at the same time, there
by causing the cells to be bound together by agglutinin. This causes the cells to
clump, which is the process of agglutination
• The agglutinated red cells can clog blood vessels and stop the circulation of the
blood to various parts of the body.
• The agglutinated red blood cells also crack and its contents leak out in the body.
The red blood cells contain hemoglobin which becomes toxic when outside the
cell. This can have fatal consequences for the patient.
• This clumping could lead to death

38. Agglutination Reaction

39. If a person with A+ blood receives B+ blood,The B
antibodies in the A+ blood (Receiver) attack the foreign red
blood cells by binding to them. The B antibodies in the A+
blood (Receiver) bind the antigens in the B+ blood
(Donor)and agglutination occurs. This is dangerous because
the agglutinated red blood cells break after a while and their
contents leak out and become toxic.
Why A person with A+ve blood cannot receive from B+ve donor?

40. •
O negative is universal donor
• A universal donor is someone who can donate blood to anyone else,
with a few rare exceptions. People with the O-ve blood type have
traditionally been considered universal blood cell donors.
• The antibodies in the receiver’s blood attack the donors antigen
(foreign red blood cells) by binding to them.
• But Type O blood produces no antigen but both "anti-A" and "anti-B"
antibodies.
• If a person with type A blood received a transfusion with type B
blood, the recipient's "anti-B" antibodies would attack the B blood
cells.
• However, if the same person received type O blood, the "anti-B"
antibodies have no target antigen and thus would not attack the O
blood cells. This is also true for B blood type recipients.

41. •
AB is universal Receiver
• Blood group AB is a universal receiver because they can receive
blood from any blood group. However, they can only donate
blood to other people with blood group AB.
• But Group AB – has both A and B antigens on red cells,but
neither A nor B antibody in the plasma.
• Normally the antibodies in the receiver’s blood attack the
donors antigen (foreign red blood cells) by binding to them.
• So type AB can receive blood from any group as there is no
antibody present in receivers blood to attack donors antigen .

42. Erythroblastosis Fetalis
• Erythroblastosis fetalis, also known as hemolytic disease of the newborn, is
a disease in the fetus or newborn which is characterized by high
erythroblast count in fetus.
• It is caused by transplacental transmission of maternal antibody, usually
resulting from maternal and fetal blood group incompatibility.
• Rh incompatibility may develop when a woman with Rh-negative blood
becomes pregnant by a man with Rh-positive blood and conceives a fetus
with Rh-positive blood.
• Red blood cells (RBCs) from the fetus leak across the placenta and enter the
woman's circulation throughout pregnancy with the greatest transfer
occurring at delivery.
• This transfer stimulates maternal antibody production against the Rh factor,
Maternal antibodies against fetal red blood cell antigens pass through the
placenta into the fetus, where an excessive destruction of fetal red blood
cells occurs.

43. Erythroblastosis Fetalis

44. Erythroblastosis Fetalis
• The baby becomes anemic and hypoxic .The baby's body tries to
compensate for the anemia by releasing immature red blood cells,
called erythroblasts, from the bone marrow.
• The overproduction of erythroblasts can cause the liver and spleen to
become enlarged, potentially causing liver damage or a ruptured
spleen.
• Since the blood lacks clotting factors, excessive bleeding can be a
complication.
• When such hemolysis begins during pregnancy, stillbirth may result. the
pregnant woman will generally notice a decrease in fetal
movement.Brain damage and death may result if blood transfusions are
not performed.
• While there is little danger of damage to the fetus during the first pregnancy,
by the second pregnancy sufficient antibodies will have accumulated in the
mother’s bloodstream to cause increasing danger of hemolytic disease.

45. Find out
• Why Erythroblastosis Fetalis is fatal for second
pregnancy?

46. THANK YOU