18/08/2011 1 Whole blood aggregometry using the Multiplate analyser for the diagnosis of HIT Marie-Christine Morel-Kopp, Chee Wee Tan and Christopher Ward Northern Blood Research Centre, Haematology Department, Royal North Shore Hospital - Australia Intermediate/high clinical probability Positive Negative, high clinical probability Positive Suspected HIT Cuker A, J Thromb Haemost 2011 Low clinical probability HIT likely HIT indeterminate HIT unlikely – continue heparin, consider alternative diagnosis Negative Obtain functional assay Discontinue heparin, start alternative anticoagulant Obtain immunologic assay Negative, high clinical probability HIT diagnostic and management algorithm 4T score Low (1-3) 4T score Intermediate (4-5) 4T score High (6-8) HDAA negative HDAA positive HDAA negative HDAA positive HDAA positive HDAA negative OD <1.0 OD >1.0 OD <1.0 OD >1.0 AA not indicated AA not indicated Consider AA AA indicated AA indicated AA not indicated AA: Alternative Anticoagulant HDAA Heparin-Dependant Antibody Assay Suspected HIT Ruf et al, Thromb Haemost 2011 HIT diagnostic algorithm HIT diagnosis Clinical assessment: 4T’s score Laboratory investigation first step: rapid antibody detection (high sensitivity) second step: platelet functional assay to identify the pathological antibodies (high specificity) Not practical to test all samples by functional only
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18/08/2011
1
Whole blood aggregometry using the Multiplate analyser for the
diagnosis of HIT
Marie-Christine Morel-Kopp, Chee Wee Tan and Christopher Ward
Northern Blood Research Centre, Haematology Department, Royal North Shore Hospital - Australia
Intermediate/high clinical probability
Positive Negative, high clinical probability
Positive
Suspected HIT
Cuker A, J Thromb Haemost 2011
Low clinical probability
HIT likely HIT indeterminate HIT unlikely – continue heparin, consider alternative
diagnosis
Negative
Obtain functional assay
Discontinue heparin, start alternative anticoagulant
Obtain immunologic assay
Negative, high clinical probability
HIT diagnostic and management algorithm
4T scoreLow (1-3)
4T scoreIntermediate
(4-5)
4T scoreHigh (6-8)
HDAA negative
HDAA positive
HDAA negative
HDAA positive
HDAA positive
HDAAnegative
OD <1.0 OD >1.0 OD <1.0 OD >1.0
AA not indicated
AA not indicated
Consider AA
AA indicated
AA indicated
AA not indicated
AA: Alternative AnticoagulantHDAA Heparin-Dependant Antibody Assay
ISTH experts recommend no further testing if OD<1.00
HIT conclusion - 1
Rapid antibody detection assaysGel-based assays :
• expansive • low specificity, 100% more false positive than IgG ELISAs
especially with the “new” PaGIA (Diamed)
ELISAS IgGAM vs IgG :
• Same sensitivity• Higher specificity for IgG only assays
IgG ELISAS and OD cut-off:
• SSC recommendations: no functional testing for OD <1.00• 7 HIT positive cases in our cohort with 0.5 < OD <1.0
HIT conclusion - 2
Importance of functional assays:
• HIT diagnosis → heparin cessation, switch to alternative anticoagulants (danaparoid, lepirudin),
• Problems: more expensive and more likely to cause bleeding
• Failure to diagnose HIT or misdiagnosis of patient with thrombocytopenia unrelated to heparin may result in significant morbidity or mortality
SRA can also gives false positive result even with a positivity cut-off raised to >50% release AND false negative
Use laboratory result (including functional results) and clinical judgement for diagnosis and patient’s management
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Negative
70%
SRA-WBIALTA
HIT ?
PaGIA
IgG ElisaIgGAM Elisa
HIT-Thr
HIT: The Iceberg Model
By Warkentin TJ
HIT conclusion - 3WBIA is easy to performWBIA has a rapid turn-around time Only a small volume of unprocessed blood required per test (microcuvette now available 175 ul of blood only)Test sensitivity increased by using selected donors (high responders) and collecting blood in hirudin tube (not citrate)WBIA is a practical alternative for haematology laboratories that do not perform functional assays and rely only on PaGIA or ELISA for HIT diagnosis or have to wait an extended time to receive the SRA result and has been acknowledged as such by the “HIT International Experts”
HIT and WBIA: donor testing
Using a pool of HIT positive samples diluted ¼, we can compare bloods and select good responders
V: 17.0V: 12.7 V: 11.3
V: 10.2
V: 9.1
Plt: 312 Plt: 226 Plt: 212
V: 9.7
Plt: 175 Plt: 182Plt: 153Plt: 106
V: 12.2
Plt: 203
LT: 2.2 LT: 2.2 LT: 1.9 LT: 3.5
LT: 3.5 LT: 4.0 LT: 4.4
V: 10.6
LT: 4.0
200 AU
0 AU
18/08/2011
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Thank You
All clinicians and scientists from:
QueenslandPeter MolleeConnie SolanoSarah Just
NSWChristopher WardChee Wee TanTimothy BrightonJoanne Joseph Dea Prawitha Anita GhevondianGeoffrey KershawJoyce Lo