Anticoagulation monitoring during cardiopulmonary bypass is a familiar part of cardiac surgery, but it becomes far more complex when the patient has antiphospholipid syndrome. This systematic review, titled “Anticoagulation Monitoring Strategies During Cardiopulmonary Bypass in Patients With Antiphospholipid Syndrome: A Systematic Review,” examines how clinicians have monitored heparin anticoagulation during cardiopulmonary bypass in this uniquely challenging population.
Antiphospholipid syndrome, often abbreviated APS, is an autoimmune prothrombotic disorder associated with arterial thrombosis, venous thrombosis, pregnancy morbidity, and persistent antiphospholipid antibodies. These antibodies include lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2-glycoprotein I antibodies. Although APS is often discussed as a clotting disorder, the perioperative reality is more complicated. Patients with APS undergoing cardiac surgery face risks on both sides of the hemostatic spectrum: thrombosis and bleeding. This balance is especially difficult during procedures requiring cardiopulmonary bypass, where systemic heparinization is essential to prevent clot formation in the bypass circuit.
In routine cardiac surgery, heparin anticoagulation during cardiopulmonary bypass is commonly monitored with activated clotting time, or ACT. Many institutions target an ACT of at least 480 seconds before initiating or continuing bypass. However, in APS, especially when lupus anticoagulant is present, ACT can be prolonged or unstable even before heparin is administered. This is because lupus anticoagulant interferes with phospholipid-dependent coagulation assays. As a result, ACT may not accurately reflect the true anticoagulant effect of heparin. A patient may appear adequately anticoagulated based on ACT while still having uncertain protection against clotting, or ACT values may be difficult to interpret in the context of the patient’s antibody profile, antithrombin activity, hypothermia, hemodilution, and inflammatory status.
The authors performed a systematic search of PubMed, Scopus, and the Cochrane Library through September 2025. They identified 66 unique records, screened 30 full-text articles, and ultimately included 17 studies. The included literature was dominated by case reports and small case series, with only one retrospective cohort study contributing a larger group of patients. Altogether, the review summarized data from 62 patients with APS who underwent cardiovascular surgery using cardiopulmonary bypass and heparin anticoagulation.
The monitoring strategies reported in the literature were heterogeneous. ACT monitoring was reported in 25 patients, Hepcon-guided heparin concentration monitoring in 25 patients, and heparin-ACT titration in 1 patient. Many reports used more than one method. Combinations included ACT with Hepcon, ACT with anti-Xa testing, ACT with viscoelastic testing such as thromboelastography or rotational thromboelastometry, Hepcon with viscoelastic testing, and other multimodal approaches. This diversity reflects the lack of a standardized protocol for APS patients on bypass.
One of the most important findings of the review is that the available data do not support a clear conclusion that one monitoring method is superior to another. The authors specifically caution against interpreting the reported event counts as true incidence rates or comparative outcomes. Across the included patients, 15 perioperative complications were reported. These included thrombotic events, bleeding events, cerebrovascular accidents, and one perioperative death. However, most quantitative outcome data came from a single retrospective cohort study, which limits the strength and generalizability of any comparison between ACT-based monitoring and Hepcon-based monitoring.
The review provides a practical discussion of the advantages and limitations of available anticoagulation monitoring tools. ACT remains widely available, fast, inexpensive, and familiar to cardiac surgery teams, but it may be unreliable in APS because of lupus anticoagulant and other perioperative factors. Heparin-ACT titration offers a more quantitative estimate of heparin dose response than ACT alone, but it is slower and less standardized. Hepcon systems estimate blood heparin concentration and can guide protamine reversal, with potentially less susceptibility to lupus anticoagulant interference, but they require specialized equipment and are more expensive. Anti-Xa testing is considered a high-reliability laboratory measure of heparin activity and is not affected by lupus anticoagulant, but turnaround time can be too slow for real-time intraoperative decision-making. Viscoelastic testing, including TEG and ROTEM, offers a broader picture of clot formation, platelet contribution, fibrinogen status, and fibrinolysis, but it is not specific for heparin effect.
A key theme of this article is that APS anticoagulation management during cardiopulmonary bypass should not depend blindly on a single number. The authors emphasize the need to interpret monitoring results in the context of antibody profile, lupus anticoagulant status, baseline ACT, suspected heparin resistance, antithrombin activity, and the clinical situation in the operating room. For example, unexplained ACT prolongation, discordance between ACT and the surgical field, or concern for heparin resistance may justify adjunctive testing with heparin concentration measurement, anti-Xa assay, or viscoelastic testing.
The article also proposes a conceptual framework for anticoagulation monitoring in APS patients undergoing cardiopulmonary bypass. This framework is not presented as a validated protocol or formal guideline. Instead, it is a hypothesis-generating approach derived from patterns observed in published cases. It begins with preoperative assessment, including confirmation of APS diagnosis, review of antibody profile, baseline ACT, and antithrombin activity. During cardiopulmonary bypass, it encourages avoiding ACT-only decision-making when results may be unreliable and considering multimodal monitoring. During separation from bypass, it highlights careful protamine reversal and avoidance of protamine excess. Postoperatively, the framework emphasizes reassessment of coagulation status, individualized resumption of anticoagulation, and surveillance for thrombosis.
The review’s limitations are substantial and important. Most available studies were case reports, which are vulnerable to publication bias and incomplete outcome reporting. Diagnostic certainty of APS varied between studies, and detailed antibody profiles were often missing. Triple positivity, which is associated with higher thrombotic risk, was not consistently reported. Catastrophic APS was rarely represented. Monitoring protocols, target values, devices, and outcome definitions also varied widely. These limitations prevent formal statistical comparisons and make it impossible to identify a best monitoring strategy from the current literature.
Despite these limitations, the review makes a valuable contribution by organizing a scattered body of evidence into a clearer clinical picture. It confirms that anticoagulation monitoring during cardiopulmonary bypass in APS remains insufficiently standardized, that ACT alone may be unreliable in selected patients, and that multimodal monitoring is commonly used when clinicians encounter uncertainty. The most important message is not that Hepcon, anti-Xa, ACT, or viscoelastic testing should dominate practice, but that APS patients require individualized, context-aware anticoagulation assessment.
For cardiac surgeons, anesthesiologists, perfusionists, hematologists, and perioperative teams, this article highlights a persistent gap in evidence. Patients with antiphospholipid syndrome are at high risk during cardiac surgery, yet the field lacks prospective, APS-specific studies comparing anticoagulation monitoring approaches during cardiopulmonary bypass. Future research should prioritize multicenter registries, standardized reporting of antibody profiles, consistent documentation of ACT and heparin concentration targets, anti-Xa calibration strategies for bypass ranges, viscoelastic testing parameters, thrombotic events, bleeding outcomes, transfusion requirements, re-exploration, and mortality. Until stronger data are available, the safest approach is likely structured clinical reasoning supported by multiple monitoring modalities when ACT reliability is uncertain.
