Anticoagulant

1. CLINICAL USE OFANTICOAGULANT
PREPARED BY; BETHEL BEKELE
SUBMITTED TO ;NAOL.
WOLAITA SODO UNIVERSITY COLLAGE OF
MEDICINE AND HEALTH SCIENCE
SCHOOL OF ANESTHESIA

2. Presentation Outline
2
Hemostasis overview.
Mechanism of coagulation.
 Classification of anticoagulants.
 Perioperative considerations of patients receiving
anticoagulants .

3. Brainstorming
3
WHY BLOOD DOES NOT CLOT IN CIRCULATION?
Endothelial surface factor
Velocity of circulation
Natural anticoagulants
 Activation of Fibrinolytic system
Liver removes activated clotting factors

4. HEMOSTASIS OVERVIEW
4
DEFINITION
 Hem = blood
 Stasis = to halt
 It is the process of forming clots in the wall of
damaged blood vessels & preventing blood loss
while maintaining blood in a fluid state with in
the vascular system.
 Spontaneous arrest of bleeding by physiological
process.

5. Mechanism coagulation
5
Hemostasis involves five main steps:
1. Vascular spasm
2. Platelets reaction
3. Formation of platelet plug
4. Blood coagulation
5.Fibrinolysis

6. 1.Vascular spasm
6
 Reduces flow of blood from injured vessel.
Cause:
- Sympathetic reflex
- Release of vasoconstrictors (TXA2 and serotonin)
from platelets that adhere to the walls of damaged
vessels

7. 7

8. Platelet plug formation
8
What is platelet?
 Produced in the bone marrow by fragmentation of the
cytoplasm of megakaryocytes (1000-5000/cell).
 1/3 of marrow output of platelets is trapped in spleen
(splenectomy?)
 Normal count: 150,000-400,000/μL (250,000)
 Life span 7-10 days.
 Removed from circulation by tissue macrophage system
mainly in spleen.
 Thrombopoietin: major regulator of platelet production
(produced by liver and kidney).

9. Cont..
9
Functional characteristics of platelets
 The cell membrane of platelets contains:
 A coat of glycoprotein (receptors) that cause
adherence to injured endothelial cells and exposed
collagen.
 Phospholipids that play an important role in blood
clotting.

10. 2.Platelet plug formation
10
Mechanism:
 Platelet adherence
 Platelet activation
 Platelet aggregation

11. Blood Coagulation
11
The clotting mechanism involves a cascade of
reactions in which clotting factors are activated.
Most of them are plasma proteins synthesized by the
liver (vitamin K is needed for the synthesis of factor
II, VII, IX and X).
They are always present in the plasma in an inactive
form.
When activated they act as proteolytic enzymes
which activate other inactive enzymes.
Several of these steps require Ca²+ and platelet
phospholipid.

12. 12
Factor Name Synthesized Vitamin K Depen Action
Fibrinogen(factor I) Liver Form a clot
Prothrombin(factor
II)
Liver Yes in active form,
activates I, V, VII,
XIII,platelets,
Tissue factor (factor
III)
Vascular wall and
extravascular cell
membranes; released
from traumatized cells
Cofactor of VII
Calcium (factor IV) Diet Promotes clotting
reactions
Proaccelerin(factor
V)
Liver Cofactor of X;
(Unassigne(factor
VI)
Proconvertin(factor
VII)
Liver Yes Activates IX and X
Antihemophiliac(VIII
)
Liver Cofactor to IX
Von Willebrand Endothelial cells Mediates adhesion
Christmas(factor IX) Liver Yes Activates X
Stuart-Prower(factor Liver Yes Activates II,

13. Coagulation Cascade Made Easy
13

14. 14

15. Intrinsic pathway
15
 The initial reaction is the conversion of inactive factor
XII to active factor XIIa.
 Factor XII is activated in vitro by exposing blood to
foreign surface.
 Activation in vivo occurs when blood is exposed to
collagen fibers underlying the endothelium in the
blood vessels.

16. Extrinsic pathway
16
 Requires contact with tissue factors external to blood.
 This occurs when there is trauma to the vascular wall
and surrounding tissues.
 The extrinsic system is triggered by the release of
tissue factor (thromboplastin from damaged tissue),
that activates factor VII.
 The tissue thromboplastin and factor VII activate
factor X.

17. HEMOSTATIC FUNCTION TESTS
17
 Bleeding time
 Clotting time
 Prothrombin time
 Activated clotting time

18. BLEEDING TIME (B.T)
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Definition - time interval between the skin puncture and
spontaneous unassisted stoppage of bleeding.
Normal bleeding time 1 – 5 min.
Measures platelet function: adhesion, aggregation

19. CLOTTING TIME ( C.T )
19
Definition-time interval between entry of blood into
glass capillary tube or a syringe and formation of fibrin
threads.
Normal Clotting Time 3 – 6 min.

20. PROTHROMBIN TIME (P.T)
20
 It measures the time to strand formation via a short
sequence of reactions involving TF,
VII,X,V,II(prothrombin) & I (fibrinogen)
 Low prothrombin suggest Vit. K def. and liver and
biliary diseases.
 Prolonged suggests deficiency of factor II, V, VII, and
X.
 It is most sensitive to decrease in factor 7
 Normal P.T ; 15 – 20 sec.

21. INR ratio
21
 Developed by WHO using an IRP(international reference
preparation) to which all the thromboplastins can be
compared.
 Recommended as a patient value can be expressed as a
ratio by normalizing it to IRP.
ISI of IRP : 1

22. Cont..
22
 An INR of 1.0 means that the patient PT is normal.
 An INR greater than 1.0 means the clotting time is
elevated.
 INR of greater than 5 or 5.5 = unacceptable high risk of
bleeding, whereas if the INR=0.5 then there is a high
chance of having a clot.
 Normal range for a healthy person is 0.9–1.3, and for
people on warfarin therapy, 2.0–3.0, although the target
INR may be higher in particular situations, such as for
those with a mechanical heart valve.

23. Partial thromboplastin time(PTT)
23
 reflects the time to fibrin strand formation via the
classical intrinsic pathway of coagulation
 A contact activator is added hence the name aPTT
 Normal : 25-35 sec
 most sensitive to factor VIII & IX

24. ACTIVATED CLOTTING TIME
24
 Tests the ability of blood to clot in a test tube and is
dependent on factors that are all intrinsic to blood .
 Used to monitor heparin therapy in operating room.
 Normal: 90-120sec
 The presence of activator augments the contact
activation phase of coagulation, which stimulates the
intrinsic coagulation pathway.

25. CLASSIFICATION OF
ANTICOAGULANTS
25
 Oral Anticoagulants.
 Parenteral Anticoagulants.
 Anti platelets.

26. Oral Anticoagulants
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 Warfarin
 Dicumarol
 Phenprocoumon
 Acenocumarol
 Indandione Derivatives

27. Parenteral Anticoagulants
27
 Heparin
 Low molecular weight Heparin (LMWH)
 Danaproid
 Parenteral Direct Thrombin Inhibitors -
-Lepirudine - bivalirudin
- Argatroban - desirudin

28. ANTI PLATELETS
28
 Aspirin and NSAIDS
 Thienopyridine derivatives
-clopedogrel
 Platelet GP IIb/IIIa antagonists

29. Therapeutically use of anticoagulants
29
 used DVT and DIC
 pulmonary embolism and hemodialysis
 extra corporeal circulation
Unstable angina
retinal vein thrombosis

30. Prophylactic use
30
 DVT
 patients with IHD
 stroke
 atrial fibrillation -RHD
 cardiac failure
 mechanical heart valves
 immobility
 orthopedic surgeries
 previous history of VTE

31. Why all the anesthesiologists are
concerned about anticoagulation?
31
Because
 Either the Patients may be on anticoagulants, who need
to be pricked for general anesthesia or neuraxial
blockade.
 Patient may be at high risk of developing VTE –
anticoagulants to be given prophylactically.

32. Perioperative Considerations and
Management of Patients Receiving
Anticoagulants
32
 Anticoagulants are commonly prescribed for patients
at risk of arterial or venous thromboembolism.
 The most common indications are atrial fibrillation,
venous thromboembolism, and presence of mechanical
heart valves.
 Perioperative management of anticoagulant therapy
poses a major problem.

33. High risk
33
 High bleeding risk procedures include coronary artery
bypass surgery, kidney biopsy, and any procedure
lasting >45 minutes.
 In general, the anticoagulant must be discontinued if
the surgical bleeding risk is high.

34. Low risk
34
 Low bleeding risk procedures include dental
extractions, minor skin surgery, cholecystectomy,
carpal tunnel repair, and abdominal hysterectomy.
 Individuals undergoing selected low bleeding risk
surgery often can continue their anticoagulant.

35. Cont..
35
 Rebound hypercoagulability may occur following
abrupt cessation of anticoagulation.
 whereas perioperative anticoagulation increases the
risk of bleeding for many invasive and surgical
procedures.
 The consequences of hematoma formation following
neuraxial blockade can be catastrophic for the patient
and include permanent paraplegia.

36. 36
It is coumarin derivative which is oral anticoagulant
commonly used to treat and prevent blood clot.
MOA: inhibits vitamin k epoxide reductase complex this
can deplete functional vitamin k reserves and reduces
synthesis of clotting factor.
Onset :is typically24 to 72 hour.
peak therapeutic effect is seen 5 to 7 days
Protein binding :99%
Warfarin

37. Anesthetic management warfarin
37
 Anesthetic management of patients anti coagulated
perioperative with warfarin depends on dosage and
timing of initiation of therapy.
 The PT and INR of patients on chronic oral
anticoagulants requires 3–5 days to normalize after
discontinuation of anticoagulant therapy.

38. Cont..
38
 Warfarin is stopped 4–5 days preoperatively
(±bridging therapy) and INR should be within
reference range before initiation of regional anesthesia.
 Remove the indwelling neuraxial catheters when the
INR is <1.5 to assure that adequate levels of Vitamin
K-dependent factors are present.
 With INR >1.5 but <3 removal of neuraxial catheters
should be done with caution and neurological status
assessed until INR has been stabilized (levels <1.5).

39. Dose of warfarin - reduced
39
 Old age
 Females
 Weight <45kg
 liver, cardiac and renal disease
 Excessive surgical blood loss

40. HEPARIN
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 Heparin is a naturally occurring mucopolysaccharide
with molecular size of 5000–25,000 Daltons.
 It exists in its unfractionated form or fractionated form.

41. Unfractionated heparin
41
 It is a mucopolysaccharide with an average molecular
weight of 15,000–18,000 daltons.
 It acts by binding reversibly to antithrombin III,
accelerating its action on coagulation factors XII, XI,
X, IX, plasmin, and thrombin.
 UFH indirectly inhibits thrombin and factor Xa by
binding to ATIII causing a conformational shape
change which signficantly increases its activity.
 It also inhibits platelet activation by fibrin.

42. Cont..
42
 Unfractionated heparin (UFH) is administered
parenteral both subcutaneous (S/C) for its prophylaxis
and as a continuous intravenous (IV) infusion when
used therapeutically.
 IV heparin is usually given as a bolus of 100 U/kg
followed by approximately 1000 U/h titrated to
achieve an activated partial thromboplastin time
(aPTT) of 1.5–2.5 times the control.
 The effect of heparin is reversed using protamine in
the dose of 1 mg for 100 U of UFH.

43. Anesthetic management Unfractionated
heparin
43
 Anesthetic management of patients receiving UFH
should start with review of medical records to
determine any concurrent medications that influence
clotting mechanisms.
 There is no contraindication to regional anesthesia
with 5000 units twice daily S/C UFH (prophylaxis).
 Risk of bleeding are reduced by delaying
heparinization until block completion, but may be
increased in debilitated patients following prolonged
heparin therapy.

44. Low molecular weight heparin
44
 LMWH include dalteparin, enoxaparin, and reviparin.
 It is prepared via controlled chemical or enzymatic
cleavage of UFH in depolymerization reaction.
 This process yiel fragments of lower molecular weight
and more predictable action than UFH.
 LMWH has an average molecular weight of 2000–
10,000 daltons with a greater ability to inhibit factor
Xa, than thrombin.

45. Cont..
45
 LMWH has 100% bioavailability and reaches peak
levels 2–4 h after S/C administration.
 It has a half-life of 3–4 h, and is eliminated primarily
via renal clearance, necessitating dose reduction in
patients with renal insufficiency.
 Factor Xa levels are used to monitor the effects of
LMWH; ideally, factor Xa levels should be obtained 4
h after the administration of LMWH.

46. Cont..
46
 LMWH is indicated for
-thromboprophylaxis
-treatment of DVT/pulmonary embolism
-myocardial infarction.
 LMWH has been demonstrated to be efficacious as a
bridge therapy for patients anticoagulated with
warfarin including
-parturients,
-patients with prosthetic heart valves
- preexisting hypercoagulable condition.

47. Properties of LMWH differ from
UFH in the following ways
47
1. Lack of monitoring of anticoagulant response (anti-Xa
level not predictive of risk)
2. Prolonged elimination half-life
3. Anti-Xa activity present 12 h postinjection
4. Unpredictable response to protamine

48. Anesthetic management LMWH
48
 There is increased risk of hematoma with concomitant
use of hemostasis altering medications.
 Altered coagulation can occur with preoperative
LMWH thromboprophylaxis and
 it is recommended that deep-PNB/neuraxial placement
be delayed 10–12 h after the last dose.
 In patients receiving therapeutic LMWH, delay of 24 h
(minimum) is recommended to ensure adequate
hemostasis at the time of regional anesthesia

49. Cont..
49
 It is not recommended to perform neuraxial/deep-PNB
techniques in patients receiving LMWH 2 h
preoperatively
 because needle placement would occur at peak
anticoagulant activity.
 Management of postoperative LMWH
thromboprophylaxis and neuraxial/deep-PNB
techniques is based upon:
1. Time to first postoperative dose
2. Total daily dose
3. Dosing schedule

50. 50
Postoperative LMWH
 Regional technique can be given
 Removal of catheter to be done – depending on total daily
dose and timing
Twice-daily prophylactic dosing
 There is increased risk of spinal hematoma
 first dose of LMWH should be administered 24 hrs
postoperatively not earlier than 12 hrs
 Indwelling catheters should be removed prior to initiation
of LMWH thromboprophylaxis
 LMWH should be delayed for 4 hours after catheter
removal

51. Antiplatelet medications
51
 Aspirin and other NSAID drugs when administered alone
during perioperative period are not considered a
contraindication to regional anesthesia.
 In patients on combination therapy with medication that
affect coagulation, clinicians should be conscious about
neuraxial and deep-PNB techniques due to increased risk of
bleeding.
 Cyclooxygenase 2 inhibitors have shown minimal effect on
platelet function, consider safe for patients receiving
regional anesthesia, and without additive effects in the
presence of anticoagulation therapy.

52. Summary of clinical ASRA guidelines and
protocols 2020
52
Drug Recommendations
Warfarin Discontinue chronic warfarin therapy 4-5 days before spinal procedure
and evaluate INR. INR should be within the normal
range at the time of procedure to ensure adequate levels of all Vitamin
K-dependent factors. After operation, daily INR
assessment with catheter removal occurring with INR -.1.5
LMWH Delay procedure at least 12 h from the last dose of thromboprophylaxis
LMWH dose. For “treatment” dosing of LMWH, at
least 24 h should elapse before procedure. LMWH should not be
administered within 24 h after the procedure. Indwelling
epidural catheters should be maintained only with once daily dosing of
LMWH and strict avoidance of additional hemostasis
altering medications, including NSAIDs

53. Cont…
53
Unfractionated
subcutaneous
heparin
There are no contraindications to a neuraxial procedure if total daily
dose is 10,000 units. For higher dosing regimens, increase
neurological monitoring and cautiously co-administer antiplatelet
medications
Unfractionated
intravenous
heparin
Delay needle/catheter placement 2-4 h after last dose, document normal
aPTT. Heparin may be restarted 1 h after procedure.
Sustained heparinization with an indwelling neuraxial catheter
associated with increased risk; monitor neurological status
aggressively
Antiplatelet
medications
No contraindications with aspirin or other NSAIDs.

54. Reference
54
1. Regional Anesthesia in the Patient Receiving
Antithrombotic or Thrombolytic Therapy
2. American Society of Regional Anesthesia and Pain
Medicine Evidence-Based Guidelines (Fourth Edition)
(Regional Anesth Pain Med 2018;43: 263–309)
3. Miller’s anesthesia
4. Stoeltings pharmacology and physiology in anesthesia
practice 5th edition
5. clinical anaesthesia : Paul G Barash

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Thank you