4. Ideal test of Perioperative Coagulation
• Simple to perform
• Objectivity
• Cut off values
• Discrete
• Reproducible
• Diagnostically specific
• Cost effective
As no current coagulation monitor meets these expectations; therefore,
integrating results from multiple forms of monitoring may provide valuable
diagnostic insight into perioperative coagulopathies.
6. Clotting Time
• Time required for a sample of blood to coagulate in vitro under
standard conditions
• Capillary tube method : Blood is placed in a glass test tube and kept
at 37° C. The method depends on the fact that blood ceases to flow
back and forth in a capillary tube at the first sign of clotting
• Normal value of clotting time is 8 to 15 minutes.
• Non-specific and subjective differences in performance of the test.
7. • Little or no value in predicting excessive hemorrhage after cardiac
surgical procedures.
Use as a preoperative screening test to assess
bleeding risk is not recommended.
8. Prothrombin time &
International Normalized Ratio
• Measures integrity of the extrinsic and common coagulation pathways
• Time taken by the citrated plasma to form a clot in the presence of sufficient
concentration of calcium and tissue thromboplastin
• Normal range is approximately 12 to 14 seconds
• INR was introduced to standardize the PT results across different laboratories
as thromboplastin test reagents differ in sensitivity.
9. PT & INR
• INR is dimensionless
• INR = [Patient PT/Control PT] * ISI
• International Sensitivity Index- Each lab uses reagents with a specific
sensitivity relative to International Reference Preparation
• Standardized
• This allows comparison of the patient’s testing performed at different
times and/or locations
10. Uses of the PT/INR
• Evaluation of unexplained bleeding
• Diagnosing disseminated intravascular coagulation
• Obtaining a baseline value prior to initiating anticoagulation
• Monitoring warfarin therapy
• Assessment of liver synthetic function
11. Causes of prolonged PT
• Vitamin K antagonists – Warfarin
• Vitamin K deficiency –Impaired nutrition, prolonged use of broad
spectrum antibiotics, or fat malabsorption syndromes.
• Liver disease – Decreased production of both vitamin K- dependent
and vitamin K-independent clotting factors.
12. • DIC
• Factor deficiency – Inherited disorders or acquired inhibitors
• Antiphospholipid antibodies – Lupus anticoagulants or
antiphospholipid antibodies.
• Other anticoagulants –
• Heparins (unfractionated or low molecular weight)
• Fondaparinux
• Direct acting anticoagulants : Argatroban, dabigatran, rivaroxaban, apixaban.
13. Activated partial thromboplastin time
• Assesses the integrity of the intrinsic and common pathways of plasma-
mediated hemostasis
• Measures the time required in seconds for clot formation to occur after
mixing a sample of citrated-patient plasma with phospholipid, calcium,
and an activator of the intrinsic pathway of coagulation (i.e., celite,
kaolin, silica, or ellagic acid)
• Normal range : 28 to 32 seconds
14. • Expressed as a ratio with a control plasma sample from the same
laboratory
• Abnormal aPTT is a reflection of most of the coagulation factor
deficiencies except factor VII. The factor concentrations must be
reduced to roughly 30% of baseline values before the test result
becomes is prolonged
• Factors IX and X are most sensitive to heparin effects, and thus the
aPTT is prolonged even at very low heparin levels
15. Uses of the aPTT
• Evaluation of unexplained bleeding
• Diagnosing disseminated intravascular coagulation (DIC)
• Obtaining a baseline value prior to initiating anticoagulation
• Monitoring therapy with unfractionated heparin
• Monitoring therapy with parenteral direct thrombin inhibitors
• Screening tool for haemophilia A & haemophilia B.
16. Causes of prolonged aPTT
• Heparin
• Direct thrombin inhibitors and direct factor Xa inhibitors
• Liver disease
• DIC / von Willebrand disease/ Hemophilia A or B
• Other inherited factor deficiencies
• Hereditary factor XI deficiency (hemophilia C)
• Hereditary deficiencies of factors X, V, prothrombin (factor II), fibrinogen.
17. Fibrinogen level
• Normal fibrinogen values : 160 - 350 mg/dl
• Low levels : Reduced production or increased consumption
• The levels may be normal in a hypercoagulable state such as DIC as
fibrinogen can markedly increase (>700 mg/dl) in response to
surgery and trauma.
• Fibrinogen consumption without DIC : severe bleeding in patients
with blood loss after major trauma.
18. Tests of fibrinolysis :
Fibrin degradation products & D‐Dimer
• FDP assay detects degradation products of fibrin (cross-linked or
uncross-linked) and fibrinogen
• Excessive fibrinolysis results in elevated FDPs in conditions such as
advanced liver disease, exogenous thrombolysis (streptokinase),
fibrinolysis with CPB and DIC
19. • A rise in FDP cannot differentiate between primary and secondary
fibrinolysis as it is elevated in both conditions
• The D-dimer is specific for degradation products of cross-linked fibrin
• D-dimer reflects widespread lysis of the cross-linked fibrin of an
established thrombus : DIC, deep venous thrombosis and pulmonary
embolism
• Non specific (negative predictive value)
21. Activated Clotting Time
• First described by Hattersley in 1966.
• Most common POC test to measure heparin anticoagulation.
• Automated variation of the Lee-White CT that uses an activator such
as celite or kaolin to activate clotting via intrinsic pathway in a test
tube.
• Automated systems : Hemochron (International Technidyne Inc.,
Edison, NJ, USA) and Hemotec (Medtronic Hemotec, Parker, CO,
USA).
22. • Normal range : 80-120s
• CPB : >480s or > 2.5-3 times the baseline value
• OP-CABG : 250-300s
• ECMO : 180-240s
23. Advantages
• Point-of- care in operating room; simple, safe, and cost- effective
• Linear response at high heparin concentration.
• Ability to titrate heparin and protamine dosages more accurately :
reductions in blood loss and transfusion requirements.
Niinikoski J, Laato M, Laaksonen V, et al. Use of activated clotting time to monitor
anticoagulation during cardiac surgery. Scand J Thorac Cardiovasc Surg. 1984;18:57.
24. Limitations:
• Poor correlation : Anti-Xa measures of heparin activity, or with heparin
concentration during CPB. This is especially true of paediatric patients
whose consumption of heparin is increased.
• Return of the ACT to baseline is not an absolute validation of complete
heparin neutralization.
Despotis GJ, Summerfield AL, Joist JH, et al: Comparison of activated coagulation time and
whole blood heparin measurements with laboratory plasma anti-Xa heparin concentration
in patients having cardiac operations. J Thorac Cardiovasc Surg 108:1076-1082, 1994
Miller BE, Mochizuki T, Levy JH, et al. Predicting and treating coagulopathies after
cardiopulmonary bypass in children. Anesth Analg 1997; 85: 1196 – 202
26. Heparin Sensitivity & Individualized Heparin Dosing
• Different concentrations of endogenous heparin-binding proteins :
vitronectin and PF4.
• This variability seems to be greater when measuring the ACT.
• Critical to use functional monitor of heparin anticoagulation in
cardiac surgical patient.
• In vitro techniques have been introduced to measure patient dose –
response to heparin. These assays measure the sensitivity to a
known quantity of heparin and generate a dose–response curve that
enables calculation of the heparin dose required to attain the target
anticoagulation.
27. • Blood loss and transfusion requirements in cardiac surgical patients
can be reduced with more accurate control of heparin anticoagulation
and its reversal.
Jobes DR, Aitken GL, Shaffer GW. Increased accuracy and precision of
heparin and protamine dosing reduces blood loss and transfusion in
patients undergoing primary cardiac operations. J Thorac Cardiovasc
Surg 1995; 110: 36 – 45
28.
29.
30. • Automated Dose-Response systems
• The Hemochron RxDX (International Technidyne Corp.) system : ACT-based HDR assay
- Lower protamine doses & significantly reduced transfusions and chest tube drainage.
• Hepcon (Medtronic) HDR : constructs a three-point HDR curve using the baseline, 1.5,
& 2.5 IU/ml heparin. From this curve, extrapolation to the desired ACT or heparin
concentration yields the indicated dose of heparin.
• These dose – response assays are used less frequently than weight-based
heparin dosing since the latter technique is faster, less expensive, and
extremely safe when monitored.
• It is not clear that individualized heparin dosing alone, in the absence of
individualized protamine dosing, affects perioperative blood loss and
transfusions in cardiac surgery.
31. Heparin Concentration Monitoring
• CPB changes the sensitivity of ACT to heparin. Heparin concentration
monitoring has been suggested as an alternative or supplemental
means to confirm adequate anticoagulation.
• The most common point-of-care laboratory technique that measures
whole-blood heparin concentration is a protamine titration assay
called Hepcon (Medtronic, Parker, CO).
• The maintenance of a stable heparin concentraion rather than a
specific ACT level usually results in administration of larger doses of
heparin because the hemodilution and hypothermia during CPB
increase the sensitivity of the ACT to heparin.
32. • Heparin concentration monitoring and higher heparin doses
have been shown to result in better preservation of coagulation
cascade proteins and less postoperative bleeding but the use of
heparin concentration monitoring has not supplanted ACT-
based monitoring as standard of care.
Despotis GJ, Joist JH, Hogue CW Jr, et al: More effective suppression of hemostatic system
activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood
concentra- tions rather than ACT. Thromb Haemost 76:902-908, 1996
33. Monitoring Platelet Function
• Thrombocytopenia
- Hemodilution
- Sequestration
- Spallation
• Platelet dysfunction
- More common
- Extra-corporeal circuit trauma
- Pharmacologic therapy
- Hypothermia
- Cardiotomy suctioning
- Use of bubble oxgenators
- Non coated extracorporeal circuit
35. Platelet count
• Integral component in assessing coagulation abnormalities, a first test in
evaluating primary hemostasis
• It only reflects the quantity of platelets in numbers and provides no
information about their function.
• Normal range : 150,000-440,000/mm3
• Thrombocytopenia : Counts < 150,000/mm3
• Surgical bleeding : 40,000-70,000/mm3.
• Spontaneous bleeding : 10,000-20,000/mm3.
36. • A satisfactory platelet plug will not be formed if the platelets
are too low and/or if they are functionally inert
• Platelet count is crucial in evaluating for heparin-induced
thrombocytopenia on patients who are on prolonged heparin
therapy.
• False low platelet counts : Platelet clumping and sample
haemodilution.
37. Bleeding Time
• Clinical test which assesses platelet endothelial interaction without involving the
clotting mechanism
• Ivy’s method for BT: Place a cuff around the upper arm and inflate to 40 mm Hg.
After cleaning the forearm make two puncture marks in the skin. Remove the blood
oozing from the wound every 15 seconds with filter paper without pressing on the
skin until bleeding ceases. (Normal BT : 4 - 10 mins)
• Limitations: poor reproducibility, time needed to perform the test, and potential for
scarring.
• Confounding variables: skin temperature, skin thickness, age, ethnicity, anatomic
test location, etc.
39. Applications
• Diagnosing and treating perioperative coagulopathy
• Within 15 to 30 minutes
• On-site information- integrity of the coagulation system, the platelet
function, fibrinogen function, and fibrinolysis.
• Decreased blood loss
• Decreased rate of transfusion of allogenic blood products
40.
41. Thrombelastography (TEG)
• A viscoelastic point of care hemostatic assay
• Provides a graphic presentation of clot formation & lysis
42. • Whole blood test
• Measures hemostasis
Clot initiation through clot lysis
Net effect of components
• Reflects balance of the hemostatic system
• Utility of TEG Analysis
Demonstrates all phases of hemostasis
• Initial fibrin formation
• Fibrin-platelet plug construction
• Clot lysis
Identifies imbalances in the hemostatic system
• Risk of bleeding
• Risk of thrombotic event
Hemostasis Monitoring
43. TEG Technology : How It Works
• Cup oscillates
• Pin is attached to a
torsion wire
• Clot binds pin to cup
• Degree of pin movement
is a function of clot
kinetics
• Magnitude of pin motion
is a function of the
mechanical properties of
the clot
• System generates a
hemostasis profile
• From initial formation
to lysis
44. TEG Tracing and Clotting Process
Reaction time,
first significant
clot formation
Achievement
of certain clot
firmness
Maximum amplitude –
maximum strength of
clot
Kinetics
of clot
development
LY30
Percent lysis
30 minutes
after MA
46. Clotting
Time
R
The latency period from the time that the blood was placed in the TEG® analyzer until initial fibrin
formation(2mm). Represents enzymatic reaction.
7-14 min
(1-3 min)
Clot
Kinetics
K
A measure of the speed to reach 20 mm amplitude. Represents clot kinetics. Represesnts fibrinogen
levels and function.
3-6 min
Alpha
A measure of the rapidity of fibrin build-up and cross-linking (clot strengthening). Represents fibrinogen
levels and function.
45-55o
Clot
Strength
MA
A direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa.
Represents maximum platelet function.
50-60 mm
G A transformation of MA into dyn/cm2 (5000MA)/
(96-MA)
Coagulati
on Index
CI A linear combination of R, K, alpha, MA.
Clot
Stability
LY30
EPL
A measure of the rate of amplitude reduction 30 min.after MA.
Estimates % lysis based on amplitude reduction after MA.
<7.5%
<15%
49. TEG modifications : Rapid TEG
• Uses recombinant human tissue factor as an activator to accelerate the
rate of thrombin formation and thus the formation of fibrin and stable
clot.
• Rapid TEG has been used to a great degree in trauma settings because the
added tissue factor activator shortens the R time to less than 1 minute,
and the time to obtain the MA is usually 20 minutes.
• Disadvantage : Loss of some sensitivity to the coagulation factor
component of the standard R time.
• Studies in trauma indicate the utility of TEG in diagnosing trauma-induced
coagulopathy, as well as accelerated fibrinolysis, which has been used in a
risk prediction model with correlations with mortality rates in trauma.