2. Anticoagulant
When Blood is collected, it clots after sometime. The a
nticoagulants are the chemical agents which prevent t
he clotting of Blood when mixed with Blood in proper
proportion.
Purpose of using anticoagulants:
- For study of various constituents of Blood component
s.
- Study of coagulation(clotting of Blood).
- Preservation of Blood in Blood Bank.
3.
4. Coagulation Phase
Two major pathways
Intrinsic pathway
Extrinsic pathway
Both converge at a common point
13 soluble factors are involved in clotting
Biosynthesis of these factors are dependent on
Vitamin K1 and K2
Normally inactive and sequentially activated
Hereditary lack of clotting factors lead to
hemophilia -A
5.
6.
7. Classification of anticoagulant
1.Calcium chelator
Bind with Calcium
Oxalates
It is following forms:-
-Ammonium Oxalate
-Potassium Oxalate
- Double Oxalate
EDTA (Ethylenediaminetetraacetiac
id)
Tri-sodium citrate etc.
2. Non-calcium chelator
Do not bind with Calciu
m
Heparin
Warfarin etc.
Most of the anticoagulants used in laboratory act by bind
ing with calcium and prevent clotting of blood since calc
ium ion is essential for many of the steps in coagulation
mechanism.
8.
9. Classification according to Route o
f administration:
Parenteral Anticoagulants:
1.Heparin
2.Hirudin
3.Lepirudin
Oral Anticoagulants:
1.Warfarin
2.Dicoumarol
3.Acenocoumarol
10. E.D.T.A.(Ethylenediamine tetra-acetic a
cid)
It is the most commonly used anticoagulant in Haematology lab becau
se E.D.T.A. is the most powerful calcium chelating (binding) agent we h
ave. It gives the best preservation to the cell morphology therefore E.
D.T.A. is the preferred anticoagulant for all cell count and blood smear
preparation.
E.D.T.A. is used in two different forms:-
Di-sodium E.D.T.A. salt (Versene)
Di-potassium E.D.T.A. salt (Sequestrene)
11. Excess of EDTA
Excess of EDTA affects both red blood cells
and leukocytes causing shrinkage and deg
enerative changes.
Excess of EDTA ( in case of 2 mg/ml) may c
ause significant decrease in packed cell vol
ume(PCV) and increase in mean cell haem
oglobin concentration (MCHC).
Platelets swell and disintegrate due to the
excess of EDTA and artificially high platelet
s count may be obtained due to disintegra
ted platelets.
12. Heparin
It is a natural anticoagulant and is nor
mally present in the blood in small a
mount and highly acidic. This is the b
est anticoagulant for open heart surg
ery and it causes minimum haemolysi
s.
It is very expensive.
It produce black back ground in the s
mear so it is not use for smear prepar
ation.
14. Warfarin
It is an oral medication
It rapidly and completely absorbed from the intes
tine and is 99% plasma protein bound.
It crosses placenta and is secreted in milk.
The commercial preparation of warfarin is a mixtu
re of both dextrorotatory and levorotatory enanti
omers.
15. Mechanism of action
Descarboxy Prothrombin Prothrombin
Reduced Vitamin K Oxidized Vitamin K
NADHNAD
Warfarin
Normally, vitamin K is converted to vitamin K epoxide in the liver.
→This epoxide is then reduced by the enzyme epoxide reductase.
→The reduced form of vitamin K epoxide is necessary for the synthesis of m
any coagulation factors (II, VII, IX and X, as well as protein C and protein S).
→Warfarin inhibits the enzyme epoxide reductase in the liver, thereby inhib
iting coagulation.
16. Warfarin Side Effect
Severe Side effects:
• Severe bleeding
• Bleeding from the rectum or black stool
• Skin conditions such as hives, a rash or itching
• Swelling of the face, throat, mouth, legs, feet or hands
• Bruising that comes about without an injury you remember
• Chest pain or pressure
• Nausea or vomiting
• Fever or flu-like symptoms
• Joint or muscle aches
• Diarrhea
• Difficulty moving
• Numbness of tingling in any part of your body
• Painful erection lasting four hours or longer
17. Anticoagulant used in Blood Bank
ACD (Acid Citrate Dextrose)
CPD ( Citrate Phosphate Dextrose )
CPDA (Citrate Phosphate Dextrose Adeni
ne)
18. Anticoagulants
CURRENT DRUGS
Unfractionated Heparin______________
Low Molecular Weight Heparin________
Lepirudin (DTI)____________________
Bivalirudin (DTI) ___________________
Argatroban(DTI)____________________
Danaparoid_______________________
Drotrecogin Alfa____________________
Vitamin K antagonists (Warfarin)_______
NEW/ in DEVELOPMENT DRUGS
Fondaparinux_____________________
Idraparinux_______________________
SSR 126517______________________
Rivaroxaban______________________
Apixaban_________________________
LY517717________________________
YM150__________________________
DU-176b_________________________
Betrixaban________________________
Ximelagatran*_____________________
Dabigatran etexilate________________
*taken off the market Italics are Oral Drugs
Inhibit clotting factor activation reactions in the blood
TARGETED FACTOR
Antithrombin (indirectly Xa and IIa)
Antithrombin (indirectly Xa and IIa)
Thrombin (IIa)
Thrombin (IIa)
Thrombin (IIa)
Antithrombin
Va, VIIIa
Prothrombin (II), VII, IX, X
Xa
Xa
Xa
Xa
Xa
Xa
Xa
Xa
Xa
Thrombin (IIa)
Thrombin (IIa)