normal aptt with actin-fs avoids intrinsic pathway factors ...€¦ · results n=140 (fviii, fix...
TRANSCRIPT
R.Li, C.Swaelens, F.Vandermijnsbrugge, B.Cantinieaux BSTH Laboratory of haematology, Porte de Hal, Antwerp
Institut Jules Bordet and CHU Saint-Pierre, ULB 23/11/2012
Normal aPTT with Actin-FS avoids intrinsic pathway factors assays in the presence of an isolated prolongation of aPTT (Platelin-LS)
without hemorrhagic history
Institut J. Bordet
Introduction
Reagent Platelin-LS
Coagulometer MDA II aPTT assays
Lupus anticoagulant LA Heparin therapy
Intrinsic pathway factor deficiency
Sensitivity
Introduction
An isolated prolonged
aPTT paediatric
Pre-operative screening
Bleeding related
Non-bleeding related
FVIII, FIX, FXI deficiency
FXII or contact factor
deficiency, Inhibitor like
LA
Introduction
aPTT with Actin FS
An isolated prolonged
aPTT with
Platelin LS
Normal aPTT
Prolonged aPTT
A mixing aPTT study
Corrected aPTT
Non corrected
aPTT
FVIII, FIX, FXI FXII deficiency
LA FXII deficiency
LA
FVIII, FIX, FXI, FXII deficiency
Aim
aPTT with
Actin FS An isolated
prolonged aPTT with
Platelin LS A mixing aPTT study
Non-bleeding related
FXII or contact factor deficiency,
Inhibitor like LA
Bleeding related
FVIII, FIX, FXI deficiency
Differential diagnosis
An algorithm for a prolonged aPTT
Prothrombin time, Fibrinogen and Thrombin time
At first time a prolonged
aPTT with Platelin LS
Abnormal PT, Fibrinogen and TT
Normal PT, Fibrinogen and TT
New sample to confirm this prolonged aPTT and to continue further investigations
aPTT with Actin FS and
A mixing aPTT (1:1 without incubation)
Follow other algorithms
Materials and Methods
� The quantitative determinations of FVIII, FIX, FXI and FXII were performed
in using one stage factor clotting assay in the week. - firstly with Platelin LS in two dilutions,
- secondly with Actin FS if a suspicion of a nonspecific inhibitor detected
by Platelin LS with a non-parallel curve.
� LA assays (PTT-LA and dRVVT) were done in the week.
Materials and Methods � During 4 years, from 2008 to 2011,
among 9048 paediatric patients: an isolated prolonged aPTT in 308 (3.4%) outpatients in their haemostasis’ screening before surgical intervention
� 156 pateints with 161 samples: confirmed this prolongation of aPTT
Median age: 3 years-old, 1 to 15 years-old
including 13 neonatal samples (age < 6 months) � Further investigations including :FVIII, FIX, FXI, FXII and LA
with the limitation of the plasma volume
-- in 140 samples: FVIII, FIX and FXI were performed
-- in 131 samples : FVIII, FIX, FXI and FXII were performed -- in 88 samples: LA assays were performed
Materials and Methods � cut-off values
-- aPTT with Platelin LS, aPTT with Actin FS and mixing aPTT cut-off values were established locally (N=50).
-- FVIII, FIX, FXI and F XII
50 % – 200%
-- LA cut-off values were established according to the international recommendation
� Statistics
Sensitivity, Specificity, Postive Predicitive Value, Negative Predictive Value and
p value were analysed by Fisher’s exact test
Results With the further investigation of factor clotting and LA assays : Explanation of the prolonged aPTT: 101/161 (63%)
� Factor deficiencies: 43 -- for FVIII, FIX and FXI: 17/140 (12%) -- isolated : 10 -- multiple deficiencies: 7 (5 neonatal cases) -- for FVIII, FIX, FXI and FXII: 31/131 (24%) -- isolated FXII: 26 -- multiple deficiencies : 5 (3 neonatal cases) � LA: 88
-- Positive: 64 /88 (73%) -- Negative: 24
Results
N=140 (FVIII, FIX and FXI ) Factor Deficiencies (N=17)
% Sensitivity Specificity PPV NPV P value
Prolonged Actin-FS 59 93 53 94 <0,0001
Corrected mixing aPTT 59 29 10 84 0,2328
Prolonged Actin-FS and
Corrected mixing aPTT 29 96 50 91 0,0025
Table 1 The statistical values of an aPTT with Actin FS and a mixing aPTT study for the detection of FVIII, FIX or FXI deficiencies by Fisher’s exact test.
N=140 (FVIII, FIX and FXI )
Bleeding related
Non-bleeding related
N=17 FVIII, FIX, FXI
deficiencies
N=123 FVIII, FIX, FXI
normal
Results
Table 2 The statistical values of an aPTT with Actin FS and a mixing aPTT study for the detection of FVIII, FIX , FXI or FXII deficiencies by Fisher’s exact test.
N=131 (F VIII, IX, FXI and XII ) Factor Deficiencies (N=43)
% Sensitivity Specificity PPV NPV P value
Prolonged ActinFS 28 92 63 72 0,0034
Corrected mixing aPTT 74 38 37 75 0,1225
Prolonged ActinFS and
Corrected mixing aPTT 14 95 60 69 0,0634
N=131 (FVIII, FIX, FXI and FXII)
N=43 FVIII, FIX, FXI, FXII
deficiencies
N=88 FVIII, FIX, FXI, FXII
normal
Results Table 3. The levels of intrinsic pathway factor deficiencies with normal Actin FS
Normal Actin FS Factor Deficiencies 16,4-36,2 F VIII F IX F XI F XII
secondes % % % % Case 1 33,8 48 Case 2 30,4 41 Case 3 32,7 46 Case 4 33,1 37 Case 5 32,1 38 Case 6 35,4 43 Case 7 34,1 32 24 of 26 cases (92%) normal 22 - 48
Results
N= 88 (LA) Positive LA (N=64)
% Sensitivity Specificity PPV NPV P value
Non-corrected mixing aPTT 55 88 92 42 0,0003
Normal Actin-FS 94 21 76 56 0,0584
Non-corrected mixing aPTT
and normal Actin-FS 50 96 97 42 <0,0001
Table 4. The statistical values of an aPTT with Actin-FS and a mixing aPTT study for the LA detection.
A prolonged aPTT with Actin FS was found in 4 of 64 positive LA samples.
N=88 (LA)
N=64 Positive LA
N=24 Negative LA
Conclusions
Face to an isolated prolongation of aPTT without hemorrhagic or family history,
� A normal aPTT with Actin-FS permitted: -- to exclude a FVIII, FIX or FXI deficiency lower than 30%,
-- to explain an isolated prolonged aPTT (Platelin-LS)
by either a FXII deficiency or the presence of LA ,
so it was not necessary to perform the factor clotting assays in this case. � A mixing aPTT study
-- a non-corrected mixing aPTT was useful to suggest the presence of LA,
-- a corrected mixing aPTT was useless to detect a factor deficiency.