Antiphospholipid antibodies: what is new in 2022 / Détection des anticorps antiphospholipides : actualités en 2022

Antiphospholipid syndrome (APS) is a clinicobiological entity defined by the association of thrombotic events and/or obstetric complications and the presence of persistent antiphospholipid antibodies (aPLs) detected by coagulation tests (lupus anticoagulant, LAC) and/or immunological assays (anticardiolipin and anti-glycoprotein-beta-I antibodies). The increased use of direct oral anticoagulants (DOAC) for the treatment of venous thromboembolism (VTE) is now a challenge for hematology laboratories for the diagnosis of APS. DOAC interfere with LAC screening and confirmation tests resulting in a risk of false positive results. To avoid these interferences, several solutions are suggested. Some of them rely on the use of DOAC-reversal systems (activated charcoal tablet, filter system) others on the use of reagents insensitive to DOAC presence in the sample. Detection of anti-phosphatidylserine/prothrombin antibodies may be helpful because they are strongly associated to the presence of LAC and are increasingly recognized as a useful tool in the diagnosis and prognosis of APS. Finally, positivity of LA in the setting of a viral infection is frequent and not specific to APS. During the Covid-19 pandemic, many patients developed arterial and VTE that could suggest testing for aPLs. The association between LAC and a risk of VTE or in-hospital mortality in hospitalized Covid-19 patients was not demonstrated. Moreover, aPLs do not persist after Covid-19. Currently, testing for aPLs in Covid-19 patients is not recommended.

Le syndrome des antiphospholipides (SAPL) est une entité clinico-biologique définie par l'association de manifestations thrombotiques et/ou de complications obstétricales et la présence persistante d'anticorps antiphospholipides (aPLs) détectés par des tests de coagulation (lupus anticoagulant, LA) et/ou par des tests immunologiques (anticorps anti-cardiolipine et anticorps anti-ß2-glycoprotéine-I). L'essor des anticoagulants oraux directs (AOD) dans la prise en charge des évènements thrombotiques veineux (ETV) constitue aujourd'hui un défi pour les laboratoires d'hémostase dans le cadre du diagnostic du SAPL. Les AOD interfèrent avec les tests de dépistage et de confirmation du LA occasionnant des faux positifs. Afin de se soustraire à ces interférences plusieurs solutions sont proposées. Certaines reposent sur l'utilisation de système neutralisant l'AOD (pastille de charbon activé, système de filtre) d'autres sur l'utilisation de réactifs insensibles à la présence d'AOD. On peut également faire appel aux anticorps anti-phosphatidylsérine/prothrombine très corrélés à la présence de LA et constituant un outil de plus en plus reconnu dans le diagnostic biologique du SAPL et son pronostic. Enfin, la positivité des aPLs dans un contexte infectieux est fréquente et non spécifique du SAPL. Au cours de la pandémie Covid-19, de nombreux patients ont présentés des ETV et artériels qui ont pu motiver la recherche d'aPLs. L'association entre LA et le risque d'ETV ou la mortalité hospitalière chez les patients Covid-19 hospitalisés n'a pas été démontrée. De plus, il ne semble pas qu'il y ait de persistance de ces aPLs après la Covid-19. A ce jour, la recherche d'aPLs chez les patients atteint de Covid-19 n'est pas recommandée.

Lupus Anticoagulant Single Positivity During the Acute Phase of COVID-19 Is Not Associated With Venous Thromboembolism or In-Hospital Mortality.

OBJECTIVE: The clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19. METHODS: This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19. RESULTS: Two hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-ß2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-ß2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively). CONCLUSION: Patients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.