introduction

2. Thrombosis and
Anticoagulation
Ahmed ElshebinyAhmed Elshebiny
University of MenoufyiaUniversity of Menoufyia

3. Thrombosis
 Arterial
 Venous
 Risk factors
 Thrombophilia

4. VTE, PE
 10% of hospital deaths may be due to PE
 PE is the most common preventable cause of
death in hospitals
 Thromboprophylaxis is highly effective and
cost – effective
 All medical and surgical admitted patients
must be assessed for thrombotic risk and
given appropriate thromboprophylaxis

5. Risk factors for VTE
 Patients
factors
 Disease or
surgical
procedure

6. Coagulation factors

7. Coagulation

8. Coagulation cascade

9. Fibrin formation

10. Investigations of coagulation system
 Coagulation tests use citrate as anticoagulant
 Adding tissue factor(thromboplastin and calcium) …… PT…
measures VII , X, V, prothrombin and fibrinogen
 Adding a surface activator like Kaolin (phospholipid) to
mimic platelet membrane and calcium….. PTT…..VIII,
IX,X,XI,V , in addition to prothrmbin and fibrinogen( Classic
Intrinsic)
 Adding Thrmbin…. Thrombin Time TT
 Correction tests
 Factor assays
 Fibrinogen and FDPs

11. Natural inhibitors of coagulation
 Antithrombin
 Activated
protein C
 Protein S
 Others

12. Antithrombin and its deficiency
 Action
 Hereditary and acquired
 Concentrates available

13. Acquired antithrombin difficiency
 Neonates
 Pregnancy and its states
 Trauma , major surgery
 Liver disease
 Kidney disease (NS)
 Sepsis
 Consumptive coagulopathies
 Bone marrow transplantation (Veno-occlusive
disease)
 Drugs (heparin, oral contraceptives, asparaginase)

14. Hereditary antithrombin difficiency
 Early onset of thrombosis
 Types (I and II)
 Different gene mutations and antithrombin
activities

15. Protein C and S

16. DIC

17. Anticoagulants
Anticoagulants
Indirect thrombin Inhibitors Direct thrombin inhibitors
Heparin LMW heparin Fondaparinux Parentral oral
Vitamin k antagonists
Classic oral
Warfarin
PhendionPhenendionee
Hirudin
Lepirudin
Bivalirudin
Enoxparin
Dalteparin
danaparinoiDanaparoidd
Dabigatran

18. Anticoagulants

19. Heparin
 1937
 Heterogenous mixture of sulfated MPs
 Its binds to endothelial cell surface and plasma
proteins
 Its activity depends on endogenous antithrombin
 Heparin functions as a cofactor for the antithrombin-
protease reaction without being consumed
 Monitor heparin
 Has Antidote

20. Adverse effects of Heparin
 Bleeding
 Allergy
 Increased loss of hair and reversible alopecia
 Long term use is associated with osteoporosis
and spontaneous fractures and
minralocorticoid deficiency
 Heparin induced thrombocytopenia (HIT)

21. Heparin induced Thrombocytopenia(HIT(
 A hypercoagulable state in in 1-4 % of patients
treated with UFH for a minimum of 7 days
 More in surgical patients , less in pregnant, more
with bovine heparin than porcine
 Lower in LMW heparins
 Morbidity and mortality due to thrombotic events
 In all patients receiving heparin ------ monitor
platelets ---if decreased in the time frame of immune
cause ---- stop heparin and add direct thrombin
inhibitor or fondaparinux
 Don’t introduce warfarin alone

22. Contra-indications of heparin
 HIT, hypertension (severe), hemophilia
 Erosions (ulcers of GIT)
 Purpura
 Active bleeding- active T.B., abortion (threatened),
advanced liver and kidney disease- visceral cancer
 Recent surgery in brain, eye, spinal cord (planned
Lumbar puncture) or renal biopsy
 Infective endocarditic
 Never administer IM

23. LMW heparins
 Enoxparin(clexane)
 Daltparin(fragmin)

24. LMW heparin characteristics
 Duration
 Bleeding
 Control of dosing

25. Doses of Heparins
 UFH bolus 80-100 U/ kg then 15-22/Kg/hr
 Enoxparin ( 30 mg / 12 or 40 mg /d prophylactic ….
If therapeutic 1 mg /kg /12 hr or 1.5 mg/kg/ d in
selected patients)
 Dalataparin( prophylactic dose 5000 U/d…. Full
dose is 200 U/kg / d for venous or 120 U/kg /12 hr in
ACS)
 Use LMW with caution in renal insufficiency and in
patients > 150 kg ….. Monitor with anti-Xa level

26. Reversal of the action of heparin
 Discontinue heparin
 Protamine sulfate
 Avoid excess protamine
 Protamine can’t reverse fondaparinux
 What about LMW ?

27. Fondaparinux
 Synthetic pentasaccharide
 Long acting, once daily
 Effective
 Acts through antithrombin resulting in
efficient inactivation of factor Xa
 Appears not to cross react with HIT
antibodies

28. factor Xa inhibitors
 Fondaparinux
 Rivaroxaban (oral)

29. Indirect thrombin inhibitors

30. Direct Thrombin inhibitors
 Hirudin
 Lepirudin (kidney)
 Bivalirudin (reversible), less bleeding
 Argatroban (Liver)
 Monitor by PTT

31. Vitamin K antagonists
 Coumarins (Warfarin)
( Marevan)
 Inandiones (phenendione)
( Dindevan)

32. Target INR and Indications
 2.5
 3.5

33. Bleeding during anticoagulation
 INR 3-6
 4-6
 6-8 without bleeding or minor
 > 8 without bleeding or minor
 > 8 major bleeding

34. Anticoagulation during pregnancy

35. New orally active anti-coagulant drugs
 Direct thrombin
 Xa inhibitors

36. References
 Current diagnosis and treatment (Medicine) 2010
 Kumar and Clark’s Clinical Medicine 2009
 E-medicine- online textbook/Hematology Specialty
 Harrison’s online textbook 2008
 Zehnder James L, "Chapter 34. Drugs Used in
Disorders of Coagulation" Katzung BG: Basic
& Clinical Pharmacology, 11e