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STAT Lupus Testing?

From Ben Troyer at Med Central Health System:  Should lupus anticoagulant testing be offered on a STAT basis? Our LA test volume is pretty low—we average 3–5 requests per week. We make the test available as a STAT, but I’m not sure that this is necessary or appropriate. I’d appreciate any input. Thanks!

Hi, Ben, great question. At our institution we run LA profiles nearly every day, so the question rarely comes up, however we have a pretty high volume so we are able to save resources by batching. I’m trying to imagine a compelling clinical situation that would require an immediate LA diagnosis, but I can’t really come up with anything plausible. As you know, the ISTH-recommended approach to LA testing is to confirm a positive result after a 12-weeks’ interval to establish chronicity. Transient LA has little clinical consequence. The recommended time frame seems to make STAT testing unnecessary. I invite comments from our participants.

Comments (8)
Lupus Anticoagulant
Joyce Low
Sep 4, 2014 11:27pm

If the lab uses a lupus insensitive APTT reagent as recommen
If the lab uses a lupus insensitive APTT reagent as recommended by many including George and Dave, there would be fewer patients to be investigated for LA and perhaps remove the need for STAT LA testing. I am also a bit surprised at the suggestion of missing a FV inhibitor. I do know that FV inhibitors can give lupus like results but I would have thought that the abnormal PT that accompanies a FV inhibitor (at least in the ones that I have seen) would suggest something other than a LA or FVIII inhibitor. Plus the presence of bleeding would suggest that the problem is not LA.

Dave McGlasson
Sep 4, 2014 10:49am

Tony brings up a good point. In a case of a factor V inhibit
Tony brings up a good point. In a case of a factor V inhibitor that initially looked like an LA, if we hadn’t identified the inhibitor instead of an LA presence we may have lost the subject. In an article from McGlasson D et al: Clin Lab Sci. 1990 3:119–21 we described a 55 YO white male who presented with atypical laboratory results and a spontaneous, acquired inhibitor against factor V in response to treatment with Keflex. The atypical results were obtained in a test that was usually specific for LA, the platelet neutralization procedure (PNP). With this assay and lack of correction with mixing studies, we witnessed results that looked like a factor VIII inhibitor or a lupus cofactor prolongation. When we saw the PNP correction we realized that the blood components we were giving him would not work. Researching the literature we discovered a paper by Chediak J, et al. Successful management of bleeding in a patient with FV inhibitor by platelet transfusions. Blood 1980;56:835-41. After administering platelet transfusions his bleeding was managed. Even though the PNP is not used anymore in a lot of settings a factor
V inhibitor can cause a lot of confusion with other tests supposedly specific for the presence of an LA and should probably be ruled out especially when a subject is hemorrhaging. We know bleeding does not usually occur with LA, but it does happen. When this patient’s blood was used in a wet workshop at an international antiphospholipid conference the identification was about 50/50 depending which reagents and confirmatory assays were used.

Tonytang
Sep 3, 2014 5:14pm

Most of the time, surgeons request the LA assay just to vali
Most of the time, surgeons request the LA assay just to validate an unexplained APTT prolongation. They need to exclude the bleeding risk of patients undergoing surgery, for these patients, positive LA results commonly predict nothing.

VadimKo
Sep 2, 2014 1:02pm

Dear Ali Sadeghi-Khomami,

your belief regarding LA testin
Dear Ali Sadeghi-Khomami,

your belief regarding LA testing and pregnancy is not supported clinically: “…which patients should be selected for laboratory testing? …pregnant women without histories of complications [or one time miscarriage] should not be screened for these tests to identify high-risk pregnancies. These assays carry significant rates of false positivity… In one group of young women who served as healthy controls for a study, 18.2% had elevated levels of aCL Abs and 12.8% tested positive for LA. Obtaining a positive aPL test result in an otherwise disease-free individual has the major downside of opening the door to possibility of unnecessary anticoagulant prophylaxis with the potential of hemorrhagic complications…” Cited from: Dos and don’ts in diagnosing antiphospholipid syndrome, ASH Education Book, December, 2012 http://asheducationbook.hematologylibrary.org/content/2012/1/455
Recently, Italian doctors showed that aspirin did not improve pregnancy outcome in pregnant women with laboratory-only criteria of AFS. Instead, higher incidence of pregnancy loss was noticed in treated group:
Del Ross T, et al. Treatment of 139 pregnancies in antiphospholipid-positive women not fulfilling criteria for antiphospholipid syndrome: A retrospective study. J Rheumatol 2013;40:425-9. http://www.ncbi.nlm.nih.gov/pubmed/23418380
more about thromboprophylaxis in this scenario in:
Metjian A, Lim W. ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis? Hematology Am Soc Hematol Educ Program. 2009:247-9. http://asheducationbook.hematologylibrary.org/content/2009/1/247.

Ali Sadeghi-Khomami
Sep 2, 2014 11:58am

I am not sure about thrombotic risks in general but I think
I am not sure about thrombotic risks in general but I think pregnancy complications due to lupus anticoagulants need serious medical attention. I believe some prophylactic actions are warranted to save pregnancy even if LA diagnosis is not confirmed according to the guidelines. Under this scenario, I consider LA testing more as risk factor predictor than diagnosis per se.
Actually, predictive value of LA testing accompanied with clinical symptoms could be very meaningful even in the first time event.

Vadim Kotousov
Sep 2, 2014 10:31am

And one more source of false LA positivity; elevated C-react
And one more source of false LA positivity; elevated C-reactive protein in inflammation:
“CRP was also significantly higher in patients positive for LA than in patients without LA irrespective of the presence of DVT (p<0.001).”
Sidelmann JJ, et al. Lupus anticoagulant is significantly associated with inflammatory reactions in patients with suspected deep vein thrombosis. Scand J Clin Lab Invest 2007;67: 270-9. http://www.ncbi.nlm.nih.gov/pubmed/17454841

Schouwers SM, et al. Lupus anticoagulant (LAC) testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results? Thromb Res 2010; 125:102-4.
van Rossum AP, et al. False prolongation of the activated partial thromboplastin time (aPTT) in inflammatory patients: interference of C-reactive protein. BJH 2012 http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08990.x/full
Inflammation is strongly associated with lupus anticoagulant positivity independent of known autoimmune disease and recent venous or arterial thrombosis. http://www.abstracts2view.com/eular/view.php?nu=EULAR14L_THU0029

Vadim Kostousov
Sep 2, 2014 8:45am

About false positive LA and anticoagulation:
Tripodi A,

About false positive LA and anticoagulation:
Tripodi A, et al: False-negative or false-positive: laboratory diagnosis of lupus anticoagulant at the time of commencement of anticoagulant: a rebuttal , JTH 2011 http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2011.04284.x/pdf
Martinuzzo ME et al. Frequent false-positive results of lupus anticoagulant tests in plasmas of patients receiving the new oral anticoagulants and enoxaparin. Int J Lab Hematol. 2014;36:144-50. http://www.ncbi.nlm.nih.gov/pubmed/24034808

Vadim Kostousov
Sep 2, 2014 8:41am

I agree that routine or STAT testing for LA only would rathe
I agree that routine or STAT testing for LA only would rather cause more problems then “problem-solvings” due to high false positive results:
“…Isolated LA positivity is significantly more frequent in subjects without clinical events or may be false-positive especially if identified as “mild inpotency”, if it is found in elderly patients or if it is diagnosed for the first time…”
Update of the guidelines for lupus anticoagulant detection. JTH 2009
http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2009.03555.x/pdf

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