From Charles Nakar, Indiana Hemophilia and Thrombosis Center: I would like your opinion on the laboratory results below regarding a patient who recently switched providers with a history of deep venous thrombosis due to May-Thurner syndrome and possible antiphospholipid antibody syndrome. He had positive anticardiolipin antibody (ACL) screens and a positive STA-clot (x1) during the acute event and recovery but full and separated quantitative ACLs were negative.
He is currently not on anticoagulation therapy. Initially not only the ACL and Sta-clot were positive but also the anti-phosphatidylserine antibodies was equivocal (IgA 30, N 20–30, IgG 12, N 10–20) and the DRVVT normalized screen/confirm ratio (DRVVT ratio) was positive on repeated testing between 1.3–1.7 (N = <1.2). On evaluation in my clinic these are the results:
| Tests: LUPUS W/O THERAPY PANEL | ||
| PHOSPHATIDL SERUM IGA |
3 |
Means phosphatidyl serine |
| PHOSPHATIDL SERUM IGG |
3 |
|
| PHOSPHATIDL SERUM IGM |
0 |
|
| CARDIOLIPIN IGA AB |
6 APL |
|
| CARDIOLIPIN IGG AB |
9 GPL |
|
| CARDIOLIPIN IGM AB |
2 MPL |
|
| Tests: BETA-2 GLYCOPROTEIN I AUTOANTIBODIES | ||
| BETA 2 IGA |
9 SAU |
0–20 |
| BETA 2 IGG |
4 SGU |
0–20 |
| BETA 2 IGM |
4 SMU |
0–20 |
| Tests: PARTIAL THROMBOPLASTIN TIME, ACTIVATED |
|
|
| PARTIAL THROMBOPLASTIN TIME, ACTIVATED |
28.4 SEC |
22.1–33.0 |
| Tests: PROTHROMBIN TIME WITH INR |
|
|
| INR |
1.02 RATIO |
|
| PROTHROMBIN TIME |
11.1 SEC |
9.5–11.9 |
| Tests: STACLOT LA REFLEX | ||
| STACLOT LA REFLEX |
NEGATIVE |
|
| Tests: DRVVT RATIO | ||
| DRVVT RATIO |
[H] 1.5 |
<1.3 |
| DILUTE PROTIME |
30.9 SECS |
26.3–37.9 |
| DRVVT SCREEN |
[H] 50 SECS |
<45 |
| APTT LA |
[H] 55.5 SECS |
31.6–45.9 |
| INTERPRETATION SEE NOTE | ||
| No evidence of antiphospholipid antibodies. | ||
| No evidence of a lupus anticoagulant. | ||
| Mildly prolonged aPTT LA. | ||
| The negative STACLOT-LA essentially excludes the presence of a lupus anticoagulant. | ||
| The prolonged aPTT-LA may be due to factor deficiency, anticoagulation therapy (i.e. heparin), factor-specific inhibitor, or lupus anticoagulant. | ||
I called both labs to get the exact results of the Sta-clot tests. The previous (acute)positive Sta-clot report was 55.8 s, 42 s, a 13.8 s difference. The current negative Sta-clot is 56.3 s, 49.2 s, a 7.1 s difference.
Hi, Charles, and thanks for the complete report. In summary, the patient’s ACL results, DRVVT ratio, and StaClot LA results were positive during the acute thrombotic episode, but only the DRVVT ratio was positive during convalescence. The beta-2-glycoprotein 1 was performed only during convalescence and was negative, and the IgA anti-phosphatidylserine antibody result, which provides little diagnostic value, was positive during the acute episode.
Based on the convalescent DRVVT ratio, one could conclude the patient possesses a chronic lupus anticoagulant, as it is not necessary for the DRVVT and StaClot-LA results to match. However, the interpretation depends on how long after the acute specimen the convalescent specimen was collected. The International Society on Thrombosis and Hemostasis standard requires a 12-week interval. If the convalescent specimen were collected within the 12-week period, the DRVVT normalized ratio may be merely detecting a waning antibody that is no longer detected by the StaClot LA and the other assays, and has no clinical consequence. Conversely, if the second specimen was collected more than 12 weeks from the acute episode, it would be safe to conclude LA is present and the physician may wish to initiate anticoagulant therapy. Thank you for this case, which illustrates the complexity of antiphospholipid antibody results and the difficulty we face in their interpretation.
Hi Charles, I’m not sure why you have excluded LA on the sec
Hi Charles, I’m not sure why you have excluded LA on the second sample, given that the dRVVT screen, dRVVT ratio and APTT LA were all prolonged. Did you perform any mixing studies? If not, then you cannot exclude some sort of inhibitor such as LA. The Staclot LA result was also prolonged? In such a case, a difference of 7 sec, although below the ‘magic’ cut-off of 8 sec, would definitely not exclude LA. You may, for example, have a case of a strong LA masquerading as a negative LA (see: Favaloro et al. JTH. 2010;8: 282831).