Most APS evaluations missed the full antibody panel

A large retrospective review across a regional health system found a wide gap between real-world antiphospholipid syndrome testing and the laboratory pattern expected under 2023 ACR/EULAR research guidance. Among 16,679 patients who had antiphospholipid antibody tests collected, 80.70% did not receive the complete set of tests described in those criteria. In practical terms, most patients evaluated for antiphospholipid syndrome were not assessed with the full serologic panel needed to characterize the disorder with confidence.

APS remains a rare but consequential diagnosis because its clinical burden can be severe and, in some cases, life-threatening. The syndrome is tied to thrombosis and pregnancy morbidity, and laboratory testing is often the hinge on which suspicion becomes diagnosis. When testing is partial, the workup can miss a key laboratory signal or leave the clinician with an incomplete picture of autoimmune risk. In a condition where diagnosis depends on combining clinical events with antibody results, fragmented ordering has direct bedside consequences.

Retrospective testing review across a regional system

Investigators used electronic medical records from a regional health system and searched for patients with International Classification of Diseases diagnostic codes linked to APS-associated conditions, signs, symptoms, and/or antiphospholipid antibody testing. The review covered encounters from January 1, 2011, through December 31, 2020, across selected medical and surgical specialty locations. Rather than trying to reclassify patients as having definite APS, the study treated the 2023 ACR/EULAR research framework as a surrogate standard for evaluating laboratory ordering patterns in routine care.

The laboratory elements expected for APS characterization included IgG and IgM anti-cardiolipin antibodies, IgG and IgM anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant testing. Those markers are not interchangeable. Each one samples a different antibody pathway, and missing any component can blunt the diagnostic value of the evaluation. A partial panel may detect some autoimmune activity while leaving clinically relevant serologic evidence undiscovered.

Incomplete ordering was the rule, not the exception

The central finding was stark: 80.70% of patients tested for antiphospholipid antibodies did not receive the full set of antibody assays listed in the 2023 ACR/EULAR research criteria. That rate suggests that incomplete testing was common across this system rather than limited to isolated practice sites or a narrow subset of clinicians.

The gap matters because APS testing is not a single-analyte exercise. Lupus anticoagulant testing, anticardiolipin antibodies, and anti-beta-2 glycoprotein I antibodies each contribute distinct information. If only one or two are ordered, the evaluation may fail to capture the serologic breadth needed to support recognition of APS. In a disease with heterogeneous presentation, incomplete laboratory ordering can slow diagnosis, complicate referrals, and leave patients in a prolonged period of uncertainty.

This is especially relevant in settings where APS enters the differential after thrombosis, pregnancy loss, or other suggestive events. A clinician may intend to evaluate for the syndrome, yet the laboratory order set may stop short of the full panel. The result is not a benign omission. It can steer the workup away from a clearer immunologic classification and toward repeated testing, delayed specialist input, or missed opportunities to align management with thrombotic risk.

Why a full panel matters in APS biology

APS is biologically and clinically more complex than a single antibody result can capture. The disorder involves antiphospholipid antibodies that can interact with coagulation pathways, endothelial function, and platelet activation. Different assays probe different antibody classes and targets, and laboratory interpretation becomes stronger when the full set is available for context. A lone positive result can suggest risk, but a more complete panel improves the chance of identifying the pattern that research criteria are designed to detect.

Because the 2023 ACR/EULAR framework was built for research classification rather than bedside diagnosis, its use in this study deserves careful interpretation. Even so, the criteria offer a useful benchmark for what a complete laboratory evaluation looks like when APS is being considered. In that sense, the findings are less about strict classification and more about whether routine clinical practice is assembling enough data to support thoughtful decision-making.

Testing gaps point to system-level ordering problems

The pattern observed across the health system raises the likelihood of routine ordering drift rather than a rare documentation artifact. When most patients receiving antiphospholipid testing do not have the full panel, the issue may lie in how clinicians order tests, how laboratories bundle assays, or how local workflows guide autoimmune evaluation. Peer comparison could help clinicians see whether their ordering habits differ from those of colleagues in similar settings. Laboratory guidance could also reduce variability by making the full panel easier to request when APS is suspected.

There is also a diagnostic stewardship angle here. APS is uncommon, and rare disorders often suffer from fragmented evaluation because clinicians may remember the condition but not the complete testing sequence. Automated order sets, specialty-specific prompts, or laboratory reflex strategies could reduce missed assays. None of those solutions would replace clinical judgment. They would simply make it less likely that suspicion of APS ends with an incomplete laboratory snapshot.

Incomplete workups can delay recognition of a high-risk disorder

The stakes are high because APS carries morbidity and potential mortality. If testing is incomplete, the clinical team may never assemble the serologic evidence needed to recognize the syndrome or may do so only after a delayed repeat evaluation. For patients with thrombotic events or pregnancy-related complications, that delay can affect how quickly risk is acknowledged and managed.

The study does not claim that every incomplete panel led to a missed APS diagnosis. It does show that the testing pattern, at least in this system, often fell short of the antibody breadth described in current research guidance. For a disorder where laboratory detail matters, that shortfall is clinically meaningful.

Future laboratory guidance will need to address how APS testing is ordered in real practice, not just how it is defined in research documents. The data show a clear gap between intended evaluation and actual testing behavior, and they point toward the need for more consistent ordering standards, local peer review, and better alignment between suspicion and serologic workup.


Reporting by Dr. Clara Evans, DDS, MS, FACS for Medicine World Foundation, with additional data provided by PLOS Medicine.