5. Platelets
• Platelets, also called thrombocytes. They are
component of blood whose function is to stop
bleeding by clumping and clotting.
• The normal platelet count is 150,000-350,000
per microliter of blood.
6. What is coagulation of blood ?
• Coagulation is the process by which blood
forms clots.
• Coagulation or clotting is defined as the
process in which blood loses its fluidity and
becomes a jelly-like mass.
Clotting factors and anticoagulants are made in the
liver. They have the ability to turn on or turn off as
needed.
7. Clotting factors
Factor Name
I Fibrinogen
II Prothrombin
III Tissue Factor or
thromboplastin
IV Ca++
V Proaccelerin
VII Proconvertin
VIII Antihemophilic A
factor
IX Antihemophilic B
factor or
Factor Name
X Stuart or Stuart-
Prower factor
XI Plasma thomboplastin
antecedent
XII Hageman factor,
contact factor
XIII Fibrin stabilizing factor
8. Anticoagulants
(Heparin, Warfarin)
Substances which prevent or postpone coagulation of blood
are called anticoagulants.
Anticoagulants are of three types:
1. Anticoagulants used to prevent blood clotting inside the
body, i.e. in vivo (In the living organism).
2. Anticoagulants used to prevent clotting of blood that is
collected from the body, i.e. in vitro.
3. Anticoagulants used to prevent blood clotting both in
vivo and in vitro.
Anticoagulants and antiplatelet agents are
medicines that reduce blood clotting in an artery,
a vein or the heart.
In vitro anticoagulants: those that remove calcium ions from the blood to prevent
coagulation, such as citrate, oxalate, fluoride, and ethylene diamine tetra acetic
acid (EDTA)
10. HEPARIN
Heparin is a naturally produced anticoagulant in the
body. It is produced by mast cells.
Mechanism of Action of Heparin
• Heparin: It prevents blood clotting by its antithrombin
activity. It directly suppresses the activity of thrombin
(Combines with antithrombin III (a protease inhibitor
present in circulation) and removes thrombin from
circulation). Heparin inhibits the coagulation process by
enhancing the activity of the endogenous inhibitor,
antithrombin by 1000 x.
11. Heparin—Clinical Applications
• Prophylaxis( action taken to prevent disease) and
treatment of Venous thrombosis (DVT)
• Pulmonary Embolism(PE)
• Peripheral arterial embolism
• Prevention of post-op DVT/PE
• Diagnosis and treatment of DIC??
• Prevention of clotting in surgery
• Anticoagulant in blood transfusions and dialysis
12. Clinical uses of heparin
Heparin is used to treat and prevent deep vein
thrombosis, pulmonary embolism, and arterial
thromboembolism. It is also used in the
treatment of heart attacks and unstable
angina. It is given by injection into a
vein. Other uses include inside test
tubes and kidney dialysis machine.
13. Side Effect Of Heparin
• easy bleeding and bruising;
• pain, redness, warmth, irritation, or skin
changes where the medicine was injected;
• itching of your feet; or
• bluish-colored skin.
14. • One unit of heparin(the "Howell unit") is an
amount approximately equivalent to 0.002 mg
of pure heparin.
• Antidote of heparin: Protamine sulfate
15. Warfarin (self study)
• Warfarin, sold under the brand name Coumadin
among other, is a medication that is used as a
blood thinner. It is commonly used to treat blood
clots such as deep vein thrombosis and pulmonary
embolism and to prevent stroke in people who
have atrial fibrillation, valvular heart disease or
artificial heart valves. Less commonly it is used
following ST-segment elevation myocardial
infarction (STEMI) and orthopedic surgery.[4] It is
generally taken by mouth but may also be used by
injection into a vein.
16. Contraindication
• Warfarin is contraindicated in pregnancy, as it passes
through the placental barrier and may cause
bleeding in the fetus; warfarin use during pregnancy
is commonly associated with spontaneous abortion,
stillbirth, neonatal death, and preterm birth.[25]
Coumarins (such as warfarin) are also teratogens,
that is, they cause birth defects; the incidence of
birth defects in infants exposed to warfarin in utero
appears to be around 5%, although higher figures (up
to 30%) have been reported in some studies.[26]
Depending on when exposure occurs during
pregnancy, two distinct combinations of congenital
abnormalities can arise
17. Side Effect Of Warfarin
• Severe bleeding, including heavier than normal
menstrual bleeding
• Red or brown urine
• Black or bloody stool
• Severe headache or stomach pain
• Joint pain, discomfort or swelling, especially after an
injury
• Vomiting of blood or material that looks like coffee
grounds
• Bruising that develops without an injury you remember
• Dizziness or weakness
18. Blood clot
Blood clot is defined as the mass of coagulated
blood which contains RBCs, WBCs and platelets
entrapped in fibrin meshwork. RBCs and WBCs
are not necessary for clotting process. However,
when clot is formed, these cells are trapped in it
along with platelets. The trapped RBCs are
responsible for the red color of the clot.
• Fibrinolysis: Lysis of blood clot inside the blood
vessel is called fibrinolysis. It helps to remove the
clot from lumen of the blood vessel.
19. 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
substance called plasmin or fibrinolysin.
• Plasmin is formed from inactivated glycoprotein
called plasminogen. Plasminogen is synthesized
in liver and it is incorporated with other proteins
in the blood clot. Plasminogen is converted into
plasmin by tissue plasminogen activator(tPA). It
is a protein involved in the breakdown of blood
clots.
20. Formation of Plasmin
• Plasmin is formed from inactivated glycoprotein called
plasminogen. Plasminogen is synthesized in liver and it
is incorporated with other proteins in the blood clot.
Plasminogen is converted into plasmin by tissue
plasminogen activator (t-PA), lysosomal enzymes and
thrombin. The t-PA and lysosomal enzymes are
released from damaged tissues and damaged
endothelium. Thrombin is derived from blood. The t-PA
is always inhibited by a substance called t-PA inhibitor.
It is also inhibited by factors V and VIII. Besides t-PA,
there is another plasminogen activator called
urokinase plasminogen activator (u-PA). It is derived
from blood.
24. Side effects Thrombolytic drugs
(self study)
• blood in the urine
• blood in the stool, or black, tarry stools
• constipation
• coughing up blood
• vomiting blood or material that looks like coffee grounds
• nosebleeds
• unexpected or unusually heavy vaginal bleeding
• dizziness
• sudden, severe, or constant headaches
• pain or swelling in the abdomen or stomach
• back pain or backache
• severe or constant muscle pain or stiffness
• stiff, swollen, or painful joints
25. Antiplatelets (aspirin, clopidogrel, and Prasugrel)
Antiplatelets are a group of medicines
that stop blood cells (called platelets)
from sticking together and forming a
blood clot.
26. Basic steps
• Prothrombin activator --> Prothrombin -->
Thrombin --> Fibrinogen --> Fibrin
• Platelets activation: increase expression of
glycoprotein IIb/IIIa (GPIIb/IIIa, also known
as integrin αIIbβ3).
• What increase the above?
Answer: Thromboxane A2, ADP (adenosine
diphosphate), and thrombin.
29. Adenosine diphosphate
• Under normal conditions, platelets circulate in
the blood freely and without interaction with
one another. ADP is stored in
inside platelets and is released upon platelet
activation. ADP interacts with a family of ADP
receptors found on platelets (P2Y12) which
leads to platelet aggregation.
30. What is thromboxane A2?
• Thromboxane A2 is a type of thromboxane that is
produced by activated platelets and has
prothrombotic properties: it stimulates activation of
new platelets as well as increases platelet
aggregation. This is achieved by increasing
expression of the glycoprotein complex GPIIb/IIIa.
31. What is thromboxane?
• Thromboxane is a member of the family
of lipids known as eicosanoids(lipids)
• Thromboxane-A synthase, an enzyme found
in platelets, converts the arachidonic acid to
thromboxane-A2 which activate aggregation
of platelets by increasing the expression of the
glycoprotein complex GPIIb/IIIa.
32. How do Clopidogrel and Aspirin act as
antiplatelete?
• Clopidogrel acts by inhibiting the ADP receptor
on platelet cell membranes. The drug specifically
and irreversibly inhibits the P2Y12 subtype of ADP
receptor, which is important in activation of
platelets and cross-linking by the protein fibrin.
• Aspirin in lower doses(75-150 mg) exert antiplatelet
effect by prevent the formation of thromboxane A2
by inhibiting Thromboxane-A synthase.
33.
34. SIDE EFFECTS (SELF STUDY)
• Side Effect of clopidogrel
• increased bleeding,
• nosebleeds,
• headaches,
• itching, and
• bruising.
35. Side Effect of Asprin
• black, bloody, or tarry stools;
• coughing up blood or vomit that looks like coffee grounds;
• severe nausea, vomiting, or stomach pain;
• fever lasting longer than 3 days;
• swelling, or pain lasting longer than 10 days; or
• hearing problems, ringing in your ears.
• Less serious side effects may include:
• upset stomach, heartburn;
• drowsiness; or
• headache.