News Item

December 29, 2009 -- New guidelines for Lupus Anticoagulant diagnosis announced at the 2009 ISTH meeting

Announcement:
The Scientific and Standardization Committee (SSC) on Lupus Anticoagulant (LA), which met at the XXIInd Congress of the International Society on Thrombosis and Haemostasis (ISTH) this past July in Boston, presented new recommended guidelines regarding proper detection of LA within the context of antiphospholipid syndrome (aPS) diagnosis.

Why the New Guidelines?

• The new guidelines simplified those made 14 years ago.

• Since then, there has been an international External Quality Assessment Programme report showing that dRVVT is the most robust test for LA detection and confirmation.

• A separate published report states that a positive result from a dRVVT assay is specific for detection of LA in patients suspected of possessing high risk for prothrombotic events.

What are the New Guidelines?
The newly clarified diagnostic criteria are as follows: 

When patients have either a high probability of aPS based on personal history, or an unexplained elevated aPTT during the course of routine examination, two tests must be performed in both a screening and confirmation regime: 

First, a dilute Russell’s viper venom time run on a double centrifuged plasma sample.  If the sample is to be stored for later analysis, it should be quickly frozen. 

Second test, a sensitive aPTT (low phospholipid levels, only micronized silica as the activator).

Interpretation:
LA is positive if one of the two aforementioned assays provides a positive result.  Mixing studies with normal pooled plasma are then performed and a thrombin time (TT) determined.  If the TT is significantly prolonged, then LA cannot be conclusively determined, because interference from inadequately neutralized heparin may be present.  If the TT is normal, then a different confirmatory test is attempted by increasing the phospholipid concentration in the original aPTT screening test by using bilayer or hexagonal (II) phase phospholipids. 

TT assays are known to be affected by monoclonal gammopathy of unknown significance (MGUS), a condition related to the most common bone cancer affecting adults, multiple myeloma.  TTs are also affected by the presence of direct thrombin inhibitors (DTI) such as hirudin, melagatran, argatroban, and dabigatran.  Patients suspected of MGUS or on DTIs must be accounted for before performing the TT.

For all procedures, the results are expressed as a simple ratio of patient to normal PNP, rather than the less straightforward index of circulating anticoagulant calculation that had been recommended previously.

Significance of the new guidelines?:
Overall, these guidelines are favorable for Stago and our customers for the following reasons:

• We already sell kits for screening and confirmation of LA by the dRVVT test (cat nos. 00333, 00334, and 00339). 

• We not only sell a sensitive aPTT marketed for LA detection activated by micronized silica (00599), but also a high quality adapted aPTT reagent containing a sensitive level of phospholipids (Staclot® LA, item no. 00594, 00600).  Additionally, Staclot® LA is an integrated test that utilizes both aPTT methodology as well as a mixing study protocol.  Of even more significance to its sensitivity for LA is the use of hexagonal phase PL within the test system for differentiation of normal vs. LA positive samples.

• Due to the presence of a heparin neutralizer in the Staclot® LA product, there is no interference from heparin up to 1 IU/ml. 

• Our package inserts already provide the calculation for the normalized ratio, which is provided again here:

 

*Screen ratio = Screen clotting time (CT) of the patient / Screen CT of the reference pool.
               *Confirm ratio = Confirm CT of the patient / Confirm CT of the reference pool.

References:
1.         Pengo, V., Tripodi, A., Reber, G., Rand, J. H., Ortel, T. L., Galli, M. & de Groot, P. G. (2009) J Thromb Haemost.
2.         Brandt, J. T., Triplett, D. A., Alving, B. & Scharrer, I. (1995) Thromb Haemost 74, 1185-90.
3.         Arnout, J., Meijer, P. & Vermylen, J. (1999) Thromb Haemost 81, 929-34.
4.         Galli, M., Finazzi, G., Bevers, E. M. & Barbui, T. (1995) Blood 86, 617-23.
5.         Rosner, E., Pauzner, R., Lusky, A., Modan, M. & Many, A. (1987) Thromb Haemost 57, 144-7.
6.         Urbanus, R. T., Derksen, R. H. & de Groot, P. G. (2008) Blood Rev 22, 93-105.
7.         Zangari M, Saghafifar F. et al. The Blood Coagulation Mechanism in Multiple Myeloma. Seminars in Thrombosis & Hemostasis 2003;29:275-281.
8.         National Cancer Institute. http:/seer.cancer.gov/faststats/html/inc_mulmy.html