Haemostatic monitoring during cardio bypass

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