During cardiopulmonary bypass (CPB), there is a need to balance anticoagulation to prevent clots on the bypass circuit and restore hemostasis after surgery. The activated clotting time (ACT) is used to monitor the effects of heparin anticoagulation during CPB. Protamine is administered after CPB to neutralize heparin and restore normal coagulation, but can cause hypotension in some patients. Careful monitoring of anticoagulation and hemostasis is important during cardiac surgery requiring CPB.

1. HAEMOSTATIC MONITORING
DURING CARDIOPULMONARY BYPASS

2. Introduction
• The hemostatic management of patients undergoing
cardiac surgery is a complex issue because there exists
the need to maintain a delicate balance between
• Anticoagulation for cardiopulmonary bypass (CPB)
• Hemostasis after CPB.
• These two opposing goals must be managed carefully
and modified with respect to the patient’s initial
hematologic status, specific timing during cardiac
surgery, and desired hemostatic outcome.

3. Introduction
• During CPB, optimal anticoagulation dictates
that coagulation be antagonized and platelets
be prevented from activating so that
microvascular clots do not form on the
extracorporeal circuit.
• After surgery, coagulation abnormalities,
platelet dysfunction, and fibrinolysis can
occur, creating a situation whereby hemostatic
integrity must be restored.

4. Normal coagulation pathway
• The various coagulation factors participate in a
series of activating reactions that end with the
formation of an insoluble clot.
• The whole process of clot formation can be
divided into
Contact phase
Intrinsic pathway
Extrinsic pathway
Common pathway

5. Contact phase
• The damaged vascular surface exposes the
collegen matrix which initiates the surface
activation of coagulation proteins
• Factor XII binds with negatively charged collagen
material and is autoactivated to factor XIIa.
• High molecular weight kininogen ( HMWK) binds
prekallikrein and factor XI to surface.
• Factor XIIa splits factor XI to form factor XIa and
prekallikrein to form kallikrein.

6. Intrinsic pathway
• The net result of intrinsic pathway is
formation of factor Xa from product of surface
activation.
• Factor XIa converts factor IX to form factor IXa
in presence of Ca++.
• Factor IXa then activates factor X in presence
of Ca++ and factor VIIIa.

7. Extrinsic pathway
• Activation of factor X can also be achieved
independently by substances extrinsic to the
vasculature.
• Thromboplastin released from the tissues act
as a cofactor to activate factor X by factor VII,
Ca++ is also required for this process.

8. Common pathway
• Factor Xa split prothrombin to thrombin, Ca++
and factor Va are required for this process.
• Thrombin split the fibrinogen molecule to
form soluble fibrin monomer.
• Factor XIII, activated thrombin, crosslinks
these fibrin strands to form a clot.

9. Fibrinolysis
• Fibrinolysis is dissolution of fibrin.
• It occurs in the proximity of clot and dissolves it
when endothelial healing occurs.
• It is mediated by the serine protease plasmin,
which is prouced from the plasminogen with the
help of tissue plasminogen activator ( t- PA).
• Fibrinolysis is normal response to clot formation
and represent pathological condition, when it
occures systemically.

10. Heparin
• Glucosaminoglycan
• (polysaccharide)
• Found most commonly
in mast cells
Strongestmacromolecular
acid in the body

11. Heparin
• Glucosaminoglycan (polysaccharide)
• Found most commonly in mast cells
• Strongest macromolecular acid in the body Half
life of heparin is dose dependent.
• And Highly variable between patients
Source of Heparin
• First isolated from liver extract (hepatic)
• Porcine intestinal mucosa
• Bovine lung

12. • Heterogeneous mixture of molecules from 3,000
to 40,000 daltons (mean ~ 15,000)
• Batch to batch heparin preparations may have
different activity levels per milligram
• standardized activity levels reported in units
• 100 units = 1 mg

13. Sources of Heparin
• First isolated from liver
extract (hepatic)
• Porcine intestinal
mucosa
• Bovine lung

14. Heparin
• Lower molecular weight
• More cross linked structure
• Longer lasting
• Higher content of binding sites
for ATIII
• Higher doses needed for CPB
• 25-30% less protamine needed
• Higher incidence of delayed
hemorrhage
• Lower incidence of Heparin
indused thrombocytopenia
• Higher molecular weight
• Less cross linking
• Shorter
• Lower content of ATIII
• binding sites
• Lower doses needed
• May need more protamine
• to neutralize
• Lower incidence of heparin
rebound
Bovine spongiform
• encephalopathy
• transmission (mad cow
• disease)
Porcine Bovine

15. Mechnism of action of Heparin
• Heparin Acts as a catalyst for antithrombin III (ATIII) to accelerate the
neutralization of
– Thrombin
– Xa
– IXa
– XIa
– XIIa
– VIIa/TF complex
Dosage of Heparin
Initial dose for 200 to 400 units/kg
• Maintenance dose 50 to 100 units/kg (administered any where b/w
30 min to 2hour)
• The extracorporeal circulation was primed with bank blood that was
heparinised in the dose of 2500 to 5000 units/unit of blood.

16. Monitoring Heparin Effect
• The anticoagulant effect of heparin should be
monitored functionally before instituting CPB.
• The administration of heparin does not
guarantee that all patients will be adequately
anticoagulated because there are differences
in levels of circulating co-factors and inhibitors
that can alter the pharmacokinetics and
pharmacodynamics of the drug.

17. Dosage during CPB
• Initial dose for 200 to 400 units/kg
• Maintenance dose 50 to 100 units/kg
• (administered any where b/w 30 min to 2hour)
• The extracorporeal circulation was primed with
• bank blood that was heparinised in the dose of
• 2500 to 5000 units/unit of blood

18. Activated clotting time
• Functional tests of heparin activity are related to
the whole blood clotting time.
• The whole blood clotting time required that
whole blood placed in a glass tube, maintained at
37ºC, and manually tilted until blood fluidity was
no longer detected.
• Glass tube containing diatomaceous earth
(celite), kaolin, or a combination of activators.
• The presence of an activator augments the
contact activation phase of coagulation, which
stimulates the intrinsic coagulation pathway.

19. • Detection of ACT values can be performed
manually but is more commonly by
automated method, as in Hemochron and
Hemotec systems

20. Monitoring of ACT
• Bull et al (1975) recommended structured
approach using ACT monitoring.
• They adopted ACT of 480 sec as safe value,
ACT below 180 sec - life threatening
 b/w 180 to 300 sec - questionable
 ≥ 600 - unwise

21. Current Practice
• Gravlee et al have selected following CPB heparin
management protocol
1. Administer heparine 300 units/kg IV
2. Draw an arterial sample for ACT in 3 to 5 min.
3. Give additional heparin to achieve ACT>300 sec during
normothermic CPB & >400 sec for hypothermic <30ºC.
4. Prime extracorporial circuit with 3 units/ml heparin
5. Monitor ACT every 30 min. during CPB.
6. If ACT decreses below desired min. value, doses of 50 to
100 units/kg given.

22. Limitation of ACT
• ACT values may prolonged by following factors
• Hypothermia
• Haemodilutation
• Apotinin : a serine protease inhibitor, is used
for blood conservation during open heart
surgery. Maintain ACT value >750 when
apotinin is used

23. Heparin Resistance
• Heparin resistance is documented by an inability
to raise the ACT to expected levels despite an
adequate dose and plasma concentration of
heparin.
• Clinical conditions associated with heparin
resistance,
• Familial AT-III deficiency
• Ongoing heparin therapy
• Extreme thrombocytosis ( >7,00,00/mm³)
• Septicaemia

24. Adverse Effects of Heparin
• Bleeding
• Deep vein thrombosis
• Heparin indused hyperkalaemia
• Heparin indused thrombocytopenia : it
develops 7 to 14 days after initiation of
heparin, but may develop within 1 or 2 day in
pt with previous exposure to heparin.
• It is likely to be immune mediated (antibody
formed against PF 4/ heparin complex)

25. Alternative to Heparin
• Low molecular weight heparin(LMWH) : Less
capable of inhibiting thrombin, but potent
inhibitors of factor Xa.
• Inhibition of factor Xa prevents thrombos
formation without impairing haemostasis.
• Thus prophylaxis against deep vein thrombosis
can occur with lower incidence of bleeding
complication.

26. • Dematan sulfate : It accelerates the inhibition of
thrombosis by heparin cofactor II.
• Hirudin : isolated from medicinal leeches & inhibits
thrombin without requiring AT III.
• Used in pt with HIT
• Defibrinogenating agents
 Ancrod : It lyses fibrinogen thus preventing formation
of fibrin polymers.
 Streptokinase and Urokinase : these thrombolytic
agents are capable of producing defibrinogenation,
increased plasmin formation can lead to
hyperfibrinolysis.

27. Heparin Coated Surfaces
• Binding of heparin to the internal surface of
CPB circuit, the need for systemic
heparinisation during CPB may be reduced.
• The use of heparin coated circuit in
combination with full systemic heparinisation
has been shown to better then uncoated
circuit in terms of platelet preservation and
postoperative bleeding

28. Hemostasis
• Hemostasis is the body’s response to vascular
injury.
• The three major components of hemostasis
include
• Vascular endothelium
• Platelets, which determine primary
hemostasis, and
• The coagulation cascade glycoproteins, which
determine secondary hemostasis

29. Protamine
• Protamine has been mainstay of heparin
neutralization for more then 3 decades.
• It is derived from the sperms of salmon fish
• A polycationic protein
• Bind with heparin to produce stable
precipitate which has no anticoagulant
property.
• It has mild anticoagulant effect independent
of heparin.

30. Dosage of Protamine
• At the end of CPB, the remaining heparin in
circulation should be neutralized in order to
restore normal coagulation.
• 1 to 1.3 mg of protamine is administered for each
100 units of heparin.
• The amount of heparin neutralized is taken as the
total dose of heparin administered during CPB or
initial dose of heparin.
• Simple & no need of ACT measurment.
• Disadvantage - excessive or under neutralization
of heparin.

31. Protamine Reaction
• Haemodynamic compromise following protamine
administration during cardiac surgery is well known &
documented.
• Characterised by
 Increase in PA & CVP
 Decrease in left atrial & systemic arterial pressure.
• Possible causes are
 Pharmacologial histamin release
 Anaphylactoid reaction
 True anaphylaxis mediated by specific antiprotamine
Ig.

32. • Protamine should not administered faster then 5
mg/min.
• Or average dose not >200mg in 40 min.
• Most anaesthesiologists prefer to give a bolus of 25 to
50mg & then carefully observe haemodynamics for
short period of time.
• If no change is observed, another bolus is
administered.
• The site of administration should be left side of
circulation (LA,aorta) or peripheral vein with
subsequent dilution.
• Pt with know food allergy to fish avoid protamine.

33. Other Agent
• Platelet factor 4 : neutralized heparin’s inhibition of factor Xa & thrombin.
• Recombinant PF4 has effectively neutralise heparin effect & useful
alternative to protanime.
• Aprotinin : serine protease & kallikrein inhibitor with ability to preserve
platelet function & inhibit fibrinolysis.
• Desmopressin acetate : releases coagulation system mediators from
vascular endothelium ( eg factor VIII,factor XII,prostacyclin & t-PA).
• Dose of 0.3 µg/kg by IV, IM or subcutaneous route.
• Epsillon aninocapnoic acid & tranexamic acid: these are antifibrinolytic
agent.
• EACA is used to treat excessive bleeding after CPB.
• TA has also show reduced chest drainage & blood transfusion requirment.

34. Evaluation of coagulation
abnormalities
Test for coagulation
mechanisms
 Whole blood clotting time
 ACT
 Protamine titration test
 PT
 APPT
Test for platlet function
 Platelet count
 Bleeding time
 Platelet aggregation &
adhesion
 Test for fibrinolysis
 Fibrinogen & fibrin
degradation product
 Thromboelastograph

35. Reference
• Kaplan’s cardiac anaesthesia 5th edition
• Clinical practice of cardiac anaesthesia- Deepak k.
Tempe
• Management of coagulation during
cardiopulmonary bypass -Continuing Education in
Anaesthesia, Critical Care & Pain Volume 7
Number 6 2007
• Monitoring anticoagulation and hemostasis in
cardiac surgery- Anesthesiology Clin N Am21
(2003) 511 – 526

36. Thank you