ABSTRACT
The quality control process is a critical feature of pathology best practice. In addition
to internal quality control processes applied on a test-to-test or day-to-day basis,
the participation of laboratories in external quality assurance programs (QAPs) is
critical to achieving ongoing test accuracy. There are several such programs operating
in the international arena. With respect to thrombophilia, these include the Australia-based
Royal College of Pathologists of Australia QAP, the United Kingdom-based National
External Quality Assessment Service, and the International Thrombophilia External
Quality Assessment Scheme, based in the Netherlands. Although there are some similarities
between the programs, some diversity is also apparent. Each of the programs assess
for the common markers of congenital thrombophilia, such as antithrombin, protein
C, protein S, and activated protein C resistance. Testing of some acquired markers
of thrombophilia, such as lupus anticoagulant, and genetic tests such as factor V
Leiden and prothrombin G20210A mutation, are also available. This report focuses on
some recent trends from these programs.
KEYWORDS
Protein C - protein S - antithrombin - activated protein C resistance - lupus anticoagulant
- laboratory assessment - survey - hemostasis testing - diagnostic practice - quality
control
REFERENCES
1
Bertina R M.
Genetic approach to thrombophilia.
Thromb Haemost.
2001;
86
92-103
2
Simioni P.
The molecular genetics of familial venous thrombosis.
Baillieres Best Pract Res Clin Haematol.
1999;
12
479-503
3
Thiagarajan P, Shapiro S S.
Lupus anticoagulants and antiphospholipid antibodies.
Hematol Oncol Clin North Am.
1998;
12
1167-1192
4
Van Cott E M, Laposata M.
Laboratory evaluation of hypercoagulable states.
Hematol Oncol Clin North Am.
1998;
12
1141-1166
5
Rao A K, Kaplan R, Sheth S.
Inherited thrombophilic states.
Semin Thromb Hemost.
1998;
24(suppl 1)
3-12
6
Field S L, Brighton T A, McNeil H P, Chesterman C N.
Recent insights into antiphospholipid antibody-mediated thrombosis.
Baillieres Best Pract Res Clin Haematol.
1999;
12
407-422
7 Haematology R CPA. QAP contact and program details. Available at: www.rcpaqap.com.au/.
Accessed July 20 2004
8 UK NEQAS: NEQAS contact and other details. Available at: www.ukneqasbc.org/. Accessed
July 20 2004
9 ECAT: ECAT contact and other details. Available at: www.ecat.nl/. Accessed July
20 2004
10 CAP: CAP contact and other details. Available at: www.cap.org/apps/cap.portal.
Accessed July 20 2004
11
Favaloro E J, Smith J, Petinos P, Collecutt M, Street A, Hertzberg M. on behalf of
the RCPA Quality Assurance Program (QAP) in Haematology Scientific Haemostasis Advisory
Panel .
Laboratory testing, diagnosis and management of von Willebrand's disease: Current
practice in Australasia.
Am J Clin Pathol.
1999;
112
712-719
12
Favaloro E J, Smith J, Petinos P, Hertzberg M, Koutts J. on behalf of the RCPA Quality
Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel .
Laboratory testing for von Willebrand's disease: an assessment of current diagnostic
practice and efficacy by means of a multi-laboratory survey.
Thromb Haemost.
1999;
82
1276-1282
13
Favaloro E J, Thom J, Baker R. on behalf of the Australasian Society for Thrombosis
and Haemostasis Emerging Technologies Group .
Assessment of current diagnostic practice and efficacy in testing for von Willebrand's
disease: Results from the second Australasian laboratory survey.
Blood Coagul Fibrinolysis.
2000;
11
729-738
14
Favaloro E J, Bonar R, Sioufi J et al..
Laboratory diagnosis of von Willebrand Disorder: current practice in the Southern
Hemisphere.
Am J Clin Pathol.
2003;
119
882-893
15
Favaloro E J, Bonar R, Kershaw G et al..
Laboratory diagnosis of von Willebrand's disorder: quality and diagnostic improvements
driven by peer review in a multi-laboratory test process.
Haemophilia.
2004;
10
232-242
16
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 Australasia Haematology Quality
Assessment Program.
Semin Thromb Hemost.
2005;
31
49-58
17
Favaloro E J, Wong R, Silvestrini R, McEvoy R, Jovanovich S, Roberts-Thompson P.
A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin
antibody and beta2 -glycoprotein I antibody testing.
Semin Thromb Hemost.
2005;
31
73-84
18 Hertzberg M, McDonald D, Neville S, Favaloro E J. External quality assurance of
DNA testing for thrombophilic mutations. Am J Clin Pathol 2005 (in press)
19
Jennings I, Kitchen S, Woods T AL, Preston F E, Greaves M.
Clinically important inaccuracies in testing for the lupus anticoagulant: an analysis
of results from three surveys of the UK NEQAS for Blood Coagulation.
Thromb Haemost.
1997;
77
934-937
20
Preston F E, Kitchen S, Jennings I, Woods T A.
A UK National External Quality Assessment scheme (UK NEQAS) for molecular genetic
testing for the diagnosis of familial thrombophilia.
Thromb Haemost.
1999;
82
1556-1557
21
Jennings I, Kitchen S, Woods T A, Preston F E.
Normalization does not improve between-laboratory agreement but may improve specificity
of some assays for activated protein C resistance.
Blood Coagul Fibrinolysis.
1999;
10
451-453
22
Jennings I, Kitchen S, Cooper P C, Rimmer J E, Woods T A, Preston F E.
Further evidence that activated protein C resistance affects protein C coagulant activity
assays.
Thromb Haemost.
2000;
83
171-172
23
Jennings I, Greaves M, Mackie I J, Kitchen S, Woods T A, Preston F E.
UK National External Quality Assessment Scheme for Blood Coagulation. Lupus anticoagulant
testing: improvements in performance in a UK NEQAS proficiency testing exercise after
dissemination of national guidelines on laboratory methods.
Br J Haematol.
2002;
119
364-369
24
Jennings I, Kitchen S, Smith J, Woods T A, Preston F E.
Between-centre agreement in homocysteine assays: experience from the UK NEQAS proficiency
testing scheme.
Thromb Haemost.
2002;
87
921-922
25
Jennings I, Kitchen S, Cooper P, Makris M, Preston F E.
Sensitivity of functional protein S assays to protein S deficiency: a comparative
study of three commercial kits.
J Thromb Haemost.
2003;
1
1112-1114
26
Jennings I, Kitchen S, Woods T AL, Preston F E.
Multilaboratory testing in thrombophilia through the United Kingdom National External
Quality Assessment Service (Blood Coagulation) Quality Assurance Program.
Semin Thromb Hemost.
2005;
31
66-72
27
Meijer P, De Maat M PM, Kluft C, Haverkate F, Van Houwelingen H C.
Assessment of the long-term analytical performance of field methods in haemostasis
by evaluation of results of an external quality assessment programme.
Clin Chem.
2002;
48
1011-1015
28
Meijer P, Kluft C, Haverkate F, De Maat M P.
The long-term within- and between-laboratory variability for assay of antithrombin,
and proteins C and S: results derived from the external quality assessment program
for thrombophilia screening of the ECAT Foundation.
J Thromb Haemost.
2003;
1
748-753
29
Meijer P, Haverkate F.
External quality assessment and the laboratory diagnosis of thrombophilia.
Semin Thromb Hemost.
2005;
31
59-65
30
Favaloro E J, Orsag I, Bukuya M, McDonald D.
A nine-year retrospective assessment of laboratory testing for activated protein C
resistance: Evolution of a novel approach to thrombophilia investigations.
Pathology.
2002;
34
348-355
31
Favaloro E J, Mirochnik O, McDonald D.
Functional activated protein C resistance assays: correlation with factor V DNA analysis
is better with RVVT- than APTT-based assays.
Br J Biomed Sci.
1999;
56
23-33
32
Favaloro E J, Silvestrini R, Mohammed A.
Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation
and limited consensus by participants of external Quality Assurance Programs signals
a cautious approach.
Pathology.
1999;
31
142-147
33
Favaloro E J, Silvestrini R.
Assessing the utility of anticardiolipin antibody assays: a cautious approach is suggested
by high variation and limited consensus in multi-laboratory testing.
Am J Clin Pathol.
2002;
118
548-557
34
Tincani A, Allegri F, Sanmarco M et al..
Anticardiolipin antibody assay: a methodological analysis for a better consensus in
routine determinations: a cooperative project of the European Antiphospholipid Forum.
Thromb Haemost.
2001;
86
575-583
35
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
36
Galli M, Barbui T.
Antiphospholipid syndrome: clinical and diagnostic utility of laboratory tests.
Semin Thromb Hemost.
2005;
31
17-24
37
Lutz C T, Foster P A, Noll W W et al..
Multicenter evaluation of PCR methods for the detection of factor V Leiden (R506Q)
genotypes.
Clin Chem.
1998;
44
1356-1358
38
Tripodi A, Peyvandi F, Chantarangkul V, Menegatti M, Mannucci P M.
Relatively poor performance of clinical laboratories for DNA analyses in the detection
of two thrombophilic mutations-a cause for concern.
Thromb Haemost.
2002;
88
690-691
39
Favaloro E J.
Diagnostic issues in thrombophilia: a laboratory scientist's view.
Semin Thromb Hemost.
2005;
31
11-16
Dr. E. J Favaloro
Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR)
WSAHS, Westmead, New South Wales, 2145, Australia
Email: emmanuel@icpmr.wsahs.nsw.gov.au