ABSTRACT
The presence of lupus anticoagulants (LA) in plasma is a strong risk factor for thromboembolism
and fetal loss. Because of this, demand for testing for LA is increasing, but the
performance of clinical laboratories in terms of its detection is still a matter of
concern. This is due in part to the lack of specific tests but also to the lack of
standardization and application of the diagnostic criteria. The aim of this article
is to review the diagnostic criteria and the many issues that may affect test results.
KEYWORDS
Thrombophilia testing - antiphospholipid syndrome - thrombosis - fetal loss
REFERENCES
1
Brandt J T, Triplett D A, Alving B, Scharrer I.
Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee
on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation
Committee of the ISTH.
Thromb Haemost.
1995;
74
1185-1190
2
Roussi J, Roisin J P, Goguel A.
Lupus anticoagulants. First French interlaboratory Etalonorm survey.
Am J Clin Pathol.
1996;
105
788-793
3
Arnout J.
Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants.
Thromb Haemost.
2001;
86
83-91
4
Favaloro E J, Bonar R, Sioufi J et al..
Multilaboratory testing of thrombophilia: current and past practice in Australasia
as assessed through the Royal College of Pathologists of the Australasia Quality Assurance
Programs for Hematology.
Semin Thromb Hemost.
2005;
31
49-58
5
Favaloro E J, Bonar R, Duncan E et al..
(on behalf of the RCPA QAP in Haematology Haemostasis Committee). Identification of
factor inhibitors by diagnostic haemostasis laboratories: a large multicenter evaluation.
Thromb Haemost.
2006;
96
73-78
6
Jennings I, Kitchen S, Woods T A, Preston F E, Greaves M.
Potentially clinically important inaccuracies in testing for the lupus anticoagulant:
an analysis of results from three surveys of the UK National External Quality Assessment
Scheme (NEQAS) for Blood Coagulation.
Thromb Haemost.
1997;
77
934-937
7
Arnout J, Meijer P, Vermylen J.
Lupus anticoagulant testing in Europe: an analysis of results from the first European
Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal
antibodies against human beta2-glycoprotein I.
Thromb Haemost.
1999;
81
929-934
8
Tripodi A, Biasiolo A, Chantarangkul V, Pengo V.
Lupus anticoagulant (LA) testing: performance of clinical laboratories assessed by
a national survey using lyophilized affinity-purified immunoglobulin with LA activity.
Clin Chem.
2003;
49
1608-1614
9
Pengo V, Biasiolo A, Gresele P et al..
on behalf of participating centers of Italian Federation of Thrombosis Centers (FCSA).
Survey on lupus anticoagulant diagnosis by central evaluation of positive plasma samples.
J Thromb Haemost.
2007;
5
925-930
10
Kelsey P R, Stevenson K J, Poller L.
The diagnosis of lupus anticoagulants by the activated partial thromboplastin time;
the central role of phosphatidyl serine.
Thromb Haemost.
1984;
52
172-175
11
Exner T, Rickard K A, Kronenberg H.
A sensitive test demonstrating lupus anticoagulant and its behavioural patterns.
Br J Haematol.
1978;
40
143-151
12
Denis-Magdelaine A, Flahault A, Verdy E.
Sensitivity of sixteen APTT reagents for the presence of lupus anticoagulants.
Haemostasis.
1995;
25
98-105
13
Adcock D M, Marlar R A.
Activated partial thromboplastin time reagent sensitivity to the presence of the lupus
anticoagulant.
Arch Pathol Lab Med.
1992;
116
837-840
14
Brancaccio V, Ames P R, Glynn J, Iannaccone L, Mackie I J.
A rapid screen for lupus anticoagulant with good discrimination from oral anticoagulants,
congenital factor deficiency and heparin, is provided by comparing a sensitive and
an insensitive APTT reagent.
Blood Coagul Fibrinolysis.
1997;
8
155-160
15
Rauch J, Tannenbaum M, Janoff A S.
Distinguishing plasma lupus anticoagulants from anti-factor antibodies using hexagonal
(II) phase phospholipids.
Thromb Haemost.
1989;
62
892-896
16
Triplett D A, Barna L K, Unger G A.
A hexagonal (II) phase phospholipid neutralization assay for lupus anticoagulant identification.
Thromb Haemost.
1993;
70
787-793
17
Brandt J T, Barna L K, Triplett D A.
Laboratory identification of lupus anticoagulants: results of the Second International
Workshop for Identification of Lupus Anticoagulants. On behalf of the Subcommittee
on Lupus Anticoagulants/Antiphospholipid Antibodies of the ISTH.
Thromb Haemost.
1995;
74
1597-1603
18
Tripodi A, Mancuso M E, Chantarangkul V et al..
Lupus anticoagulants and their relationship with the inhibitors against coagulation
factor VIII: considerations on the differentiation between the 2 circulating anticoagulants.
Clin Chem.
2005;
51
1883-1885
19
Chantarangkul V, Tripodi A, Arbini A, Mannucci P M.
Silica clotting time (SCT) as a screening and confirmatory test for detection of the
lupus anticoagulants.
Thromb Res.
1992;
67
355-365
20
Arnout J, Vanrusselt M, Huybrechts E, Vermylen J.
Optimization of the dilute prothrombin time for the detection of the lupus anticoagulant
by use of a recombinant tissue thromboplastin.
Br J Haematol.
1994;
87
94-99
21
Thiagarajan P, Pengo V, Shapiro S S.
The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants.
Blood.
1986;
68
869-874
22
Galli M, Finazzi G, Bevers E M, Barbui T.
Kaolin clotting time and dilute Russell viper venom time distinguish between prothrombin-dependent
and beta 2-glycoprotein I-dependent antiphospholipid antibodies.
Blood.
1995;
86
617-623
23
Pengo V, Biasiolo A, Rampazzo P, Brocco T.
dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity
of anti-beta2-glycoprotein I autoantibodies.
Thromb Haemost.
1999;
81
256-258
24
Moore G W, Savidge G F.
Heterogeneity of Russell viper venom affects the sensitivity of the dilute Russell
viper venom time to lupus anticoagulants.
Blood Coagul Fibrinolysis.
2004;
15
279-282
25
Gardiner C, MacKie I J, Malia R G et al..
The importance of locally derived reference ranges and standardized calculation of
dilute Russell viper venom time results in screening for lupus anticoagulant.
Br J Haematol.
2000;
111
1230-1235
26
Jacobsen E M, Barna-Cler L, Taylor J M, Triplett D A, Wisloff F.
The lupus ratio test; an interlaboratory study on the detection of lupus anticoagulants
by an APTT-based, integrated, and semi-quantitative test. Fifth International Survey
of Lupus Anticoagulants ISLA 5.
Thromb Haemost.
2000;
83
704-708
27
Rosner E, Pauzner R, Lusky A, Modan M, Many A.
Detection and quantitative evaluation of lupus circulating anticoagulant activity.
Thromb Haemost.
1987;
57
144-147
28
Tripodi A, Chantarangkul V, Clerici M, Mannucci P M.
Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment.
Performance of dilute Russell viper venom test and silica clotting time in comparison
with Staclot LA.
Thromb Haemost.
2002;
88
583-586
29
Triplett D A, Brandt J T, Kaczor D, Schaeffer J.
Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin
inhibition procedure with a new platelet neutralization procedure.
Am J Clin Pathol.
1983;
79
678-682
30 Feinstein D I.
Acquired disorders of hemostasis . In: Colman RW, Hirsh J, Marder VJ, Salzman EW Hemostasis and Thrombosis. Basic Principles
and Clinical Practice. Third ed. Philadelphia, PA; Lippincott 1994: 881-905
31
Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E.
The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference
on Antithrombotic and Thrombolytic Therapy.
, [Erratum in: Chest 2005;127:415–416]
Chest.
2004;
126(3, Suppl)
204S-233S
32
Triplett D A, Stocker K F, Unger G A, Barna L K.
The textarin/ecarin ratio: a confirmatory test for lupus anticoagulants.
Thromb Haemost.
1993;
70
925-931
33
Chantarangkul V, Tripodi A, Clerici M, Bressi C, Mannucci P M.
Laboratory diagnosis of lupus anticoagulants; effect of residual platelets in plasma,
assessed by Staclot LA and silica clotting time.
Thromb Haemost.
2002;
87
854-858
34
Sletnes K E, Gravem K, Wisloff F.
Preparation of plasma for the detection of lupus anticoagulants and antiphospholipid
antibodies.
Thromb Res.
1992;
66
43-53
35
Exner T.
Conceptions and misconceptions in testing for lupus anticoagulants.
J Autoimmun.
2000;
15
179-183
36
Favaloro E J.
Preanalytical variables in coagulation testing.
Blood Coagul Fibrinolysis.
2007;
18
86-89
37
Galli M, Luciani D, Bertolini G, Barbui T.
Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin
antibodies in the antiphospholipid syndrome: a systematic review of the literature.
Blood.
2003;
101
1827-1832
38
Rai R S, Regan L, Clifford K et al..
Antiphospholipid antibodies and beta2-glycoprotein I in 500 women with recurrent miscarriage:
results of a comprehensive screening approach.
Hum Reprod.
1995;
10
2001-2005
39
de Laat B, Wu X X, van Lummel M, Derksen R H, de Groot P G, Rand J H.
Correlation between antiphospholipid antibodies that recognize domain I of beta2-glycoprotein
I and a reduction in the anticoagulant activity of annexin A5.
Blood.
2007;
109
1490-1494
Dr. Armando Tripodi
Via Pace 9, 20122 Milan
Italy
Email: armando.tripodi@unimi.it