This document discusses various coagulants and anticoagulants. It describes vitamin K and its uses including in newborns and for overdose of oral anticoagulants. It also discusses other coagulants like fibrinogen, antihemophilic factor, and desmopressin. The document then covers oral anticoagulants like warfarin including its dosing, effects, interactions and newer oral anticoagulants. It provides details about parenteral anticoagulants including heparin, its uses, pharmacokinetics, administration and adverse effects. Low molecular weight heparins and direct thrombin inhibitors are also summarized.

1. Dr.SUMITHA A MBBS.,MD
Assistant professor of Pharmacology

4. COAGULANTS
 1. Vitamin K
 K1 (from plants, : Phytonadione
 fat-soluble) (Phylloquinone)
 K3 (synthetic)
 —Fat-soluble : Menadione,
 —Water-soluble : Menadione sod. bisulfite
 2. Miscellaneous
 Fibrinogen (human)
 Antihaemophilic factor
 Desmopressin
 Adrenochrome monosemicarbazone
 Rutin, Ethamsylate

5. Vitamin k

6. USES OF VITAMIN K
 Prolonged antimicrobial therapy
 Obstructive jaundice,Malabsorption syndrome:vitamin
k 10 mg i.m./day
 Dietary deficiency of vitamin k
 Liver disease:cirrhosis,viral hepatitis
 Newborn:have low levels of clotting factors and
prothrombin –lower capacity to synthesise.
1 mg im vitamin k1 soon after birth.
Menadione vitamin K3 not used.

7. Overdose of oral anticoagulants:
10 mg i.m.followed by 5 mg 4 th hourly.bleeding stops in
6-10 hrs.Normal levels of coagulation after 24 hrs.
Adverse effects:
Menadione-not used in newborns.
Hemolysis,increased bilirubin load.
Competitively Inhibits glucoronidation of bilirubin.

8. OTHER COAGULANTS
 Adrenochrome monosemicarbazone-styptochrome inj
3mg/2 ml inj
 Rutin: cadisper –c 60 mg tab
 Ethamsylate:250-500 mg tds oral /inj
 Desmopressin,Antihaemophilic factor
 Used in hematuria,bleeding after tooth extraction
epistaxis

9. I. Used in vivo
A. Parenteral anticoagulants
(i) Indirect thrombin inhibitors: Heparin, Low
molecular weight heparins, Fondaparinux,
Danaparoid
(ii) Direct thrombin inhibitors: Lepirudin,
Bivalirudin, Argatroban
B. Oral anticoagulants
(i) Coumarin derivatives: Bishydroxycoumarin
Warfarin sod, Acenocoumarol
Ethylbiscoumacetate
ANTICOAGULANTS

10. ii) Indandione derivative: Phenindione.
(iii) Direct factor Xa inhibitors: Rivaroxaban
(iv) Oral direct thrombin inhibitor: Dabigatran
etexilate
II. Used in vitro
A. Heparin:
150 U to prevent clotting of 100 ml blood.
B. Calcium complexing agents: Sodium citrate

11. ORAL ANTICAGULANTS -WARFARIN

12. ORAL ANTICAGULANTS

13. Warfarin Dose
 Prophylaxis and treatment of venous thrombosis and its
extension, pulmonary embolism (PE)
 Initial dose: 2-5 mg PO qDay for 2 days.
 Initiate warfarin on day 1 or 2 of LMWH or
unfractionated heparin therapy and overlap until desired
INR,then discontinue heparin.
 Check INR after 2 days and adjust dose according to
results
 Maintenance dose - 2 and 10 mg/day

16. Adverse effects
 Bleeding-ecchymosis,hematuria,bleeding in git.
 Occurs if INR –Exceeds 4
 INR-International normalised ratio.
 INR-ratio of prothrombin time during treatment with
ora;l anticoagulant with normal value of prothrombin
In healthy people an INR of 1.1 or belowis normal.
2.Teratogenic effects:
Foetal warfarin syndrome- hypoplasia of nose.eye
socket,hand bones ,growth retardation.
3.Alopecia,dermatitis,diarrhoea

18. DRUG INTERACTIONS OF WARFARIN

19. Newer oral anticoagulants
Direct factor Xa inhibitors: Rivaroxaban,apixaban,Edoxaban
Apixaban-10 mg BD for 7 days followed by 5 mg BD.For TREATMENT
OF DVT and PE.
Oral direct thrombin inhibitor: Dabigatran
Etexilate.
Rapid onset and offset of therapeutic effect.
Short half life
No laboratory monitoring required
Lower risk of bleeding
Fewer drug interactions
Antithrombotic efficacy equal to warfarin.

21. Parenteral anticoagulants- Heparin
HEPARIN
Activates plasma ATIII
Heparin-AT III complex
Binds to clotting factors of intrinsic and
common pathways (Xa, IIa, IXa, XIa, XIIa
and XIIIa) and inactivates them

22. A T I I I T hr ombin
5 13 or more saccharide units
Heparin
Lysine
Sites
A T I I I F actor X a
5
Low Molecular Weight Heparin
Lysine
Sites
<13

23. PHARMACOKINETICS
Heparin is not absorbed orally.
If Injected i.v. - acts instantaneously.
After s.c. injection anticoagulant effect
develops after ~60 min.
Bioavailability of s.c. heparin is
inconsistent.
Heparin does not cross blood-brain barrier
or placenta
It is metabolized in liver by heparinase.
Fragments are excreted in urine.

24. Heparin - Clinical Uses
 venous thrombosis and pulmonary embolism
 mural thrombosis after acute MI
 managing unstable angina
 prevention of coronary artery rethrombosis
 treat selected cases of disseminated intravas-
cular coagulation (DIC)
Effective for the prevention and treatment of:

25.  For thromboembolic disorder:
 Continuous IV infusion:
-Initial dose: 5000 units by IV injection
-Maintenance dose: 20,000 to 40,000 units per 24
hours by continuous IV infusion

26. Heparin - Recommendations for Clinical
Use
Pregnancy - heparin is the anticoagulant of
choice
– does not cross the placenta
– no untoward effects in the fetus or
newborn
– given in therapeutic doses - 15,000 U sc 12
hrs to women with prosthetic heart valves
or venous thromboembolism

27. Adverse effects of Heparin
1.Bleeding(most common)
2. Allergy and Anaphylaxis
3. Increased hair loss, alopecia
4. Long term-Osteoporosis, spontaneous fractures
5. Heparin induced thrombocytopenia (HIT)

28. HIT 2-occurs 5-10 days after heparin therapy.
Platelet count drops more than 50%.Antibody mediated
Treatment:Direct thrombin inhibitor

29. Heparin-Contraindications
 Patients who are hypersensitive
 Presence of active bleeding or hemophilia
 Thrombocytopenia
 Severe hypertension
 Intracranial hemorrhage
 Bacterial endocarditis –risk 0f embolism
 Active tuberculosis (risk of hemoptysis)
 Ulcerative lesions of GI tract

30. Heparin-Contraindications
 Large malignancies(risk of bleeding in
central necrosed area of tumour)
 During or after surgery on the brain, spinal
cord or ocular surgery.
History of heparin-induced
thrombocytopenia.

31.  Heparin antagonist:
 Protamine sulphate –Basic in nature,i.v.
 1 mg neutralises 100 U of heparin
 Hypersensitivity reactions can occur.
 Fondaparinux:
 Selectively inhibits factor Xa.
 Pentasaccharide,s.c. Bioavailability 100 %
 Risk of bleeding osteoporosis minimal
 5mg/0.4 ml syringe

33. Low Molecular-Weight Heparins
Enoxaparin 20 (0.2 ml ) prefilled syringe
Dalteparin
Reviparin
Ardeparin,
Nadroparin
Molecular weight -3000-4000
Selectively inhibit factor X a
–they increase the action of ATIII on factor Xa, but
not its action on thrombin.

35. Low Molecular Weight Heparins
 Better s.c.bioavailability(70-90% )
 Do not require routine monitoring of aPTT.
 Risk of osteoporosis is less.
Uses:Prophylaxis and treatment of DVT.
 Unstable angina and MI.
 To maintain patency of cannulae and stents.

36. Direct thrombin inhibitors
 Lepirudin
 Bivalirudin
 Desirudin
 Argatroban
Bivalirudin:
Synthetic congener of anticoagulant hirudin, obtained
from salivary gland of leech.
Binds to catalytic and substrate binding site of thrombin
without binding to antithrombin

37. Direct thrombin inhibitors

38.  Given i.v.-anticoagulant in patients undergoing PCI for
STEMI.
 value in patients at risk of HIT.
 Argatroban:
 Reversibly binds to catalytic site of thrombin.

40.  THANK YOU