aPL Abs Research Articles

THE PREVALENCE OF ANTIPHOSPHOLIPID ANTIBODIES AND THEIR CORRELATION WITH CLINICAL, LABORATORY FINDINGS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Objective. To evaluate the prevalence of antiphospholipid antibodies (aPL Abs) in systemic lupus erythematosus (SLE) patients and the relationship between these Abs with clinical and laboratory findings.Methods. Cross-sectional descriptive study on 60 patients newly diagnosed with SLE according to SLICC 2012 criteria, at the Center for Allergy - Clinical Immunology, Bach Mai Hospital from October 2022 to August 2023. The aPL group were defined as positive for at least one aPL. The clinical manifestation and laboratory findings of the positive and negative aPL groups were compared. Results. 37/60 patients (61.67 %) had positive for at least one aPL Abs. The percentage of groups positive for single antibody aCL, LAC, β2GPI, aPL, double and triple antibodies are 46.67%, 30%, 20%, 11.67%, 35%, 18.33%, respectively. We found that positive aPL and LA Abs significantly correlated with chronic kidney disease as compare with negative group. Unfortunately, no significance was found in hematology, neurology, thromboembolism, obstetric pathology, or livedo manifestations between the two groups. Conclusion. 61.7% newly SLE diagnosis was positive for at least one aPL Abs and the presence of these Abs was independently associated with the risk chronic kidney disease in SLE patients.

YKL-40 in serum: a promising biomarker of juvenile SLE and strongly correlated with disease duration.

The biological function of YKL-40 is not well determined in different inflammatory and autoimmune diseases; however, some data highlighted its possible connection with disease activity. We investigated the diagnostic utility of serum YKL-40 in patients with SLE and examined its correlation with disease activity. Additionally, we examined any differences in serum YKL-40 levels between juvenile and adult SLE patients. We included 78 female patients with SLE and 42 controls. The level of YKL-40 in serum was measured by ELISA. The serum YKL-40 level in SLE patients was significantly higher compared to the control group (9 (3) ng/mL vs. 5.5 (0.1) ng/mL; p < 0.001). YKL-40 showed excellent diagnostic utility with an AUC of 1 (p < 0.001) and a cutoff point of 5.6, providing sensitivity and specificity of 100%. YKL-40 was higher in adolescents and those with a positive family history of SLE (p = 0.01 for both) and positively correlated with disease duration (r = 0.45, p < 0.001). YKL-40 level was significantly higher in patients with photosensitivity, fever, vasculitis, blood disorders, positive anti-dsDNA, and APL ab (p < 0.05 for all). Conversely, patients with skin manifestations had a significantly lower YKL-40 (p = 0.004). In juvenile SLE, the AUC was 0.65 and a p-value of 0.01, and at a cutoff value of (8.7) ng/mL, the sensitivity and specificity were 72% and 60%, respectively. YKL-40 in serum could be a promising biomarker in patients with SLE, especially in adolescent-onset cases. It is independently influenced by disease duration, anemia, thrombocytopenia, positive anti-dsDNA, and APL ab features.

Antiphospholipid Antibodies in Pregnancy: Maternal and Neonatal Implications.

Antiphospholipid antibodies (aPL Abs) have long been associated with the occurrence of certain specific pregnancy morbidities, affecting both mother and fetus. Antithrombotic-based prophylactic regimens are the standard of care. Their intensity is modulated by the thrombotic history and has greatly improved the prognosis related to spontaneous morbidity. Observational studies show that this treatment is still associated with the persistence of excess of late-pregnancy placental diseases, calling for new or complementary developments, yet to be validated. Rigorous prospective multicentric validation of clinical and laboratory parameters capable of identifying those women and fetuses at a risk of pejorative evolution, thus early prognosis, is a priority issue. These will make it possible to develop customized treatments and test them. Furthermore, there are still concerns, particularly neurodevelopmental ones, about children born to aPL Ab-positive mothers, and clarification based on regular, more systematic evaluations is required. Even after pregnancy, women with a pure obstetrical antiphospholipid syndrome are at a greater risk of venous and arterial thrombosis over time, and prevention needs to be improved. These women also appear to develop more psychiatric and mood disorders. Central nervous system imaging using high-resolution techniques has shown subtle impairments in the white matter, associated with the most pathogenic aPL Abs and the clinical significance of this is under investigation. These mothers also seem to develop an excess of cancers. The systemic impact of aPL Abs is gradually being suspected, although this requires further evidence, and prevention should be envisaged.

Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data.

The investigation of the prevalence of the IgG and the IgM isotypes of anticardiolipin (aCL) and antib2glycoprotein I (ab2gpI) Abs in healthy Serbian middleaged subjects was the main goal of our study. In addition, we analyzed the potential associations of above-mentioned Abs with serum proteins and lipids/lipoproteins. Forty healthy subjects were included in our study. Obesity (BMI 30 kg/m2) was present in 8/40 (20%) subjects. Titers of analyzed Abs were measured by ELISA. The prevalence of IgG and IgM ab2gpI Abs was 5% and 12.5%, respectively, while the prevalence of IgM aCL was 10%. The IgG ab2gpI Abs were significantly different between subjects with normal triglycerides levels and those with hypertriglyceridemia (Mann-Whitney, P = 0.014). The significant difference in hsCRP concentrations was observed between subjects with the increased levels of the IgM isotype of aCL Abs and those with normal IgM aCL values (Mann-Whitney, P = 0.028). Dyslipidemia and BMI ≥30 were associated with aPL Abs and therefore, the correction of BMI and lipid status might be beneficial in reduction or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy middle-aged subjects. Larger national study is necessary to confirm our findings.

Antiphospholipid antibodies in patients with Graves' orbitopathy: preliminary data.

Graves' orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (-) subgroups of GO patients. Study included consecutive patients with GO (66 with Graves' (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations.

Vox Sanguinis International Forum on Hospital Transfusion Services' Response to COVID‐19: Responses

Question 1Demographics:a. Beer Yaakov, Israel.b. Large academic medical center.c. 956 beds.d. 9034 RBC units issued in 2019, approximately 9000.e. 4831 confirmed SARS‐CoV‐2 cases and 17 deaths (March 31, 2020, 12:40 pm, data from the Israeli Ministry of Health).f. 9,136,000 inhabitants.g. The spread of SARS‐CoV‐2 in Israel is still increasing, but as of yesterday the rate of increase is declining sharply (from almost 30% of samples tested per day at the peak to 12% yesterday).

Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome

Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fashion. CGS21680 also reduces thrombosis in the inferior vena cavae of both control mice and mice administered aPL Abs. The antithrombotic medication dipyridamole is known to potentiate adenosine signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP. Like CGS21680, dipyridamole suppresses aPL Ab-mediated NETosis via the adenosine A2A receptor and mitigates venous thrombosis in mice. In summary, these data suggest an anti-inflammatory therapeutic paradigm in APS, which may extend to thrombotic disease in the general population.

Anti-annexin A5 antibodies and 25-hydroxy-cholecalciferol in female patients with primary antiphospholipid syndrome.

Vascular antiphospholipid syndrome (VAPS) and obstetric (OAPS) are different entities because some patients only develop thrombosis (without recurrent pregnancy losses) and vice versa. Only two articles have reported that low 25-hydroxy-cholecalciferol (vitamin D3, VD3) levels were not correlated with the presence of conventional antiphospholipid antibodies (aPL Abs: anticardiolipin (aCL), anti-beta2glycoprotein I (aβ2gpI), and lupus anticoagulant (LA)), but no article analyzed the association of VD3 and anti-annexin A5 (aanxA5) Abs. The aim of our study was to investigate the association between VD3, multiple positivity of conventional aPL and aanxA5 Abs levels only in female OAPS vs. VAPS. Our study included 62 consecutive female PAPS patients. Concentrations of Abs were measured by ELISA, while VD3 levels were determined by immunochemiluminescence. Only 10/62 (16.13%) had sufficient (≥ 30ng/ml) VD3 levels, while 48/62 (77.42%) and 4/62 (6.45%) had insufficiency and VD3 deficiency, respectively. Statistically significant VD3 deficiency was noticed in VAPS (vs. OAPS, P = 0.013). A negative correlation between VD3 levels and the age of patients was noticed (r = - 0.493, P = 0.032) only in VAPS subgroup. Multiple positivity of aPL and aanxA5 Abs was not associated with VD3 deficiency. Newly emerging aPL Abs, such as aanxA5 Abs, or their combinations with classical aPL Abs are not associated with VD3 deficiency in neither OAPS nor VAPS patients. Due to its immunomodulatory roles in B-Ly homeostasis, supplementation with VD3 should be considered in APS, at least in subgroup with severe form of the disease, i.e., VAPS.

Detrimental roles of TNF-alpha in the antiphospholipid syndrome and de novo synthesis of antiphospholipid antibodies induced by biopharmaceuticals against TNF-alpha.

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by arterial and/or venous thrombosis and/or recurrent pregnancy losses. Obstetric APS (OAPS) is considered as a distinct entity from vascular APS (VAPS). In the absence of any additional disease, APS is designated as primary (PAPS), while the term secondary APS (SAPS) is used when other diseases are associated. Catastrophic APS (CAPS) is characterized by the rapid development of multiple thrombosis in various vital organs. The presence of antiphospholipid antibodies (aPL Abs) is considered as a laboratory criterion for APS diagnosis. aPL Abs cause an increase in systemic and decidual TNF-alpha levels in experimental model of APS (eAPS), while paradoxically, administration of TNF-alpha blockers has been associated with de novo synthesis of aPL Abs in patients with various autoimmune diseases. While eAPS provides evidence for the fact that application of TNF-alpha blockers has beneficial effects, lack of randomized prospective studies is the main obstacle for consideration of TNF-alpha blockers administration as a therapeutic option not for all, but at least for selected cases of APS patients despite compelling evidence for detrimental roles of TNF-alpha for both VASP and OAPS. This article represents a review of previously published reports on detrimental roles of TNF-alpha in APS, reports on the application of anti-TNF-alpha agents in eAPS and articles that reported de novo synthesis of aPL Abs induced by biopharmaceuticals against TNF-alpha.

Teaching Principles of Endocrinology Using the Tobacco Hornworm

Insects provide an excellent model for examining concepts in endocrinology in the classroom. They are relatively inexpensive to rear, short-lived, and free from animal welfare regulations. Using the tobacco hornworm (Manduca sexta) as a model, we have developed a simple laboratory experiment to demonstrate the role of hormones in development. In this experiment, students will use a readily available agonist to disrupt insect development, preventing metamorphosis. This exercise fits well into the AP lab curriculum and the NGSS LSB.1 objectives.

Antibodies Against Complement Components: Relevance for the Antiphospholipid Syndrome-Biomarkers of the Disease and Biopharmaceuticals.

Laboratory criterion for the diagnosis of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPL Abs). Complement system has a role in mediating aPL Abs-induced thrombosis in animal models. The importance of antibodies against complement components (potential biomarkers of APS) and the importance of antibodies with beneficial anti-complement effects in APS (as biopharmaceuticals) are reviewed. Antibodies against complement components described in APS patients, so far, are anti-C1q and anti-factor H Abs, although anti-factor B Abs and anti-C5a Abs were described in animal models of APS. Clinical studies in APS patients are limited to a small number of case reports. Studies that would confirm potential role of Abs against complement components (as potential biomarkers of APS) are lacking. Lack of randomized clinical trials (that would provide complete data for confirmation of beneficial effects of biopharmaceuticals in complement inhibition) in APS is alarming.

Double positivity of the IgG isotype of both anticardiolipin and anti-β2gpI antibodies is associated with the highest number of vascular impairment parameters in patients with primary antiphospholipid syndrome: preliminary data.

Although numerous studies investigated the association between homocysteine (Hcy), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and apolipoproteins (apos) with thrombosis and/or recurrent pregnancy losses, studies that analyzed the abovementioned parameters and multiple positivity of antiphospholipid antibodies (aPL Abs) in patients with primary antiphospholipid syndrome (PAPS) are lacking. Therefore, the aim of this study was to analyze the presence of various combinations of the abovementioned parameters and their associations with clinical and/or serological features of PAPS. High-pressure liquid chromatography (HPLC) was used for determination of Hcy, while apoAI, apoB, and lipoprotein (Lp) (a) concentrations were estimated by immunonephelometry. High-sensitivity C-reactive protein (hsCRP) was measured by immunoturbidimetry. Apo (a), TNF-α, and aPL Abs were measured by ELISA. Various combinations of analyzed parameters (Hcy/CRP/TNF/apoAI/apoB/apo (a)/Lp (a)) were not associated with a single presence of either aPL Abs. Double positivity for both isotypes of anticardiolipin (aCL) Abs (IgG + IgM) was associated with the increased apoB levels. The presence of the IgG isotype of both aCL + anti-beta2 glycoprotein I (aβ2gpI) Abs was associated with the highest number of analyzed parameters (i.e., increased levels of hsCRP, Lp (a), and apo (a)). The presence of the IgG isotype of both aCL + aβ2gpI Abs was associated with the highest number of vascular impairment parameters in patients with PAPS, and this combination confers the highest risk for the recurrence of thrombotic episodes. This is the first report that analyzed the association between various combinations of vascular impairment parameters with multiple aPL Ab positivity. Our results provide a rationale for further investigations of therapeutic approaches for PAPS patients.

The IgG and IgM isotypes of anti-annexin A5 antibodies: relevance for primary antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by the presence of thromboses and/or recurrent pregnancy losses (RPL). The persistent presence of antiphospholipid antibodies (aPL Abs): IgG and/or IgM isotypes of the anticardiolipin and/or anti-β2 glycoprotein I antibodies and lupus anticoagulant is mandatory for the laboratory diagnosis of APS. Due to the heating debate on the relevance of the IgM isotype of aPL Abs as a laboratory criterion defining APS, the focus of this article was to analyze whether both the IgG and IgM isotype of anti-annexin A5 Abs have equal relevance for clinical and serological features of patients with primary APS (PAPS). The IgG isotype of anti-annexin A5 Abs is associated with RPL in PAPS patients, although it is not elucidated whether these Abs are the cause or the consequence of RPL in PAPS. No data that could substantiate the association of the IgG and/or the IgM isotypes of anti-annexin A5 Abs with the presence of arterial and/or venous thromboses and/or their main complications in PAPS is available so far. However, the presence of clinical manifestations of the PAPS is increasing with the multiple positivity for aPL Abs and the IgM isotype of anti-annexin A5 Abs. The importance of the IgM isotype of anti-annexin A5 Abs in PAPS needs further elucidation due to the facts that majority of the available articles did not differentiate between both isotypes or only investigated the IgG isotype of anti-annexin A5 Abs.

Antiphospholipid Antibodies and Renal Impairment Parameters in Diabetic Nephropathy: Preliminary Data.

Antiphospholipid antibodies (aPL Abs) represented an independent factor that was associated with the occurrence and/or progression of nephropathy in patients with antiphospholipid syndrome, but their role in diabetic nephropathy is not elucidated. Therefore, we evaluated the association of aPL Abs with the renal impairment parameters in patients with diabetic nephropathy. Concentrations of analyzed antibodies were measured by enzyme-linked immunosorbent assay. Cystatin C and anticardiolipin (aCL) antibodies of the immunoglobulin (Ig) G ( r = .349, P = .004) and the IgM isotype ( r = .316, P = .009) were in positive correlation. The IgG isotype of the aCL Abs was in positive correlation with creatinine ( r = .252, P = .038), urea ( r = .241, P = .048), and uric acid ( r = .271, P = .025). The concentrations of the IgG isotype of the aCL Abs were significantly different between subgroups of patients with diabetic polyneuropathy and patients without this clinical finding (Mann-Whitney, P = .033). This is the first report on positive correlation between aCL Abs and renal impairment parameters. Larger studies are necessary for elucidation whether this association is involved in further progression of the disease.

SAT0009 The Prevalence and Patterns of Antiphospholipid Antibodies in SLE and Non-Sle Patients with END Stage Renal Disease

BackgroundElevated levels of antiphospholipid antibodies (aPL Abs) have been reported in over 30% of lupus (SLE) patients, and are associated with an increased risk of thrombosis. However, not all aPL...

THU0016 The Relationship between Infection and Anti-Phospholipid Syndrome: A Systemic Review of CASE Reports

BackgroundThe coexistence of infection and anti-phospholipid syndrome (APS) has been increasingly reported in the literature under the assumption that infection may be a triggering factor for the development of APS.ObjectivesTo...

Adiponectin, Non-Esterified Fatty Acids and Antiphospholipid Antibodies in Type II Diabetes Mellitus

Adiponectin, Non-Esterified Fatty Acids and Antiphospholipid Antibodies in Type II Diabetes MellitusThe importance of the association of antiphospholipid antibodies (aPL Abs) with the features of type II diabetes mellitus has not yet been elucidated. The aim of this work was to investigate the association of aPL Abs with adiponectin and non-esterified fatty acids (NEFA) in type II diabetes mellitus patients without micro and/or macrovascular complications, and to analyze the differences between the male and female patients with regard to the abovementioned parameters. Male patients with type II diabetes mellitus showed a positive correlation between NEFA concentrations and anti-oxLDL antibodies (r=0.334, p=0.019). A weak, but statistically significant correlation between adiponectin concentrations and the IgM isotype of anti-annexin A5 antibodies was found in type II diabetes mellitus patients (r=0.285, p=0.011). The presence of a positive correlation between NEFA and anti-oxLDL antibodies might be useful in the detection of patients with premature atherosclerosis in type II diabetes mellitus patients without any micro and/or macrovascular complications among type II diabetes mellitus patients.

Annexin A2 Deficient Mice Are Resistant to Pathogenic Effects of Antiphospholipid Antibodies in Vivo

Background: Thrombosis is an important cause of morbidity and mortality in Antiphospholipid Syndrome (APS) and in SLE patients with antiphospholipid antibodies (aPL). APL recognize β2 glycoprotein I (β2GPI)-bound to receptor (s) in endothelial cells (EC) and other target cells (i.e. platelets, monocytes) and trigger an intracellular signalling and a pro-coagulant and pro-inflammatory phenotype [i e.expression of tissue factor (TF), vascular cell adhesion molecule-1 (VCAM-1)] that lead to thrombosis. There is in vitro evidence that annexin A2 (A2), a receptor for tissue plasminogen activator (tPA) and plasminogen – and possibly other proteins such as toll-like receptors or the receptor for apolipoprotein E2′ - may be binding β2GPI on the membrane of target cells. Here, we examined the involvement of A2 in aPL-mediated pathogenic effects in vivo. We studied the effects of aPL Abs on thrombus formation, VCAM-1 expression in aortas of mice, and TF function in carotid artery homogenates in annexin A2 deficient (−/−) mice.Methods: A2 (−/−) mice and the corresponding wild-type (WT) mice, in groups of 10, were injected i.p. twice (0 and 48 hours later) with IgG from a patient with APS (IgG-APS) or with control IgG (IgG-NHS). Seventy-two hours after the first injection, several procedures were done in each mice:dynamics of thrombus formation (thrombus size),TF function in homogenates of carotid arteries, and c) VCAM-1 expression in the aortas using quantum dot nano crystals and two-photon excitation laser scanning microscopy.In addition, we examined the effect of an anti-A2 antibody on aPL-induced expression of intercellular cell-adhesion molecule (ICAM-1), E-selectin and TF acvitity on cultured endothelial cells (EC).Results: The titers of aCL and anti-β2GPI Abs in the sera of the mice at the time of surgery were medium-high positive in A2 (−/−) mice and in wild type mice injected with IgG-APS. Thrombus sizes were significantly larger in WT mice injected with IgG-APS when compared to similar type of mice treated with IgG-NHS (p=0.003). The size of thrombus in A2 (−/−) mice injected with IgG-APS was significantly smaller than mean thrombus size in WT mice injected with IgG-APS (p:0.0005). However, thrombus size in A2 (−/−) mice was larger in mice injected with IgG-APS when compared to same type of mice treated with control IgG-NHS (p=0.003), indicating a partial but significant abrogation of the thrombogenic effect. TF activity was significantly larger in WT mice treated with IgG-APS when compared to mice injected with IgG-NHS. Importantly, TF activity in carotid arteries homogenates of annexin A2 (−/−) mice injected with IgG-APS was significantly decreased (by 52%) when compared to wild type mice treated with IgG-APS. The expression of VCAM-1 in aorta of annexin A2 (−/−) ex vivo was also significantly reduced compared to LPS-treated mice (positive control) (p= 0.01). Interestingly, anti-A2 antibody significantly decreased aPL-induced expression of ICAM-1, E-sel and TF on cultured EC.Conclusions: Altogether these data indicate for the first time that A2 is involved in vivo pathogenic effects of aPL Abs. These findings may have important implications to devise new targeted and more specific therapeutic approaches to block the pathogenic effects of aPL Abs in patients with APS and SLE.

Antiphospholipid Antibodies and the Antiphospholipid Syndrome: Pathogenic Mechanisms

Antiphospholipid antibodies (Abs) are associated with thrombosis and are a risk factor for recurrent pregnancy loss and obstetric complications in patients with the antiphospholipid syndrome. It is generally accepted that the major autoantigen for aPL Abs is beta (2) glycoprotein I, which mediates the binding of aPL Abs to target cells (i.e., endothelial cells, monocytes, platelets, trophoblasts, etc.) leading to thrombosis and fetal loss. This article addresses molecular events triggered by aPL Abs on endothelial cells, platelets, and monocytes and complement activation, as well as a review of the current knowledge with regard to the putative receptor(s) recognized by aPL Abs on target cells as well as novel mechanisms that involve fibrinolytic processes. A section is devoted to the description of thrombotic and inflammatory processes that lead to obstetric complications mediated by aPL Abs. Based on experimental evidence using in vitro and in vivo models, new targeted therapies for treatment and/or prevention of thrombosis and pregnancy loss in antiphospholipid syndrome are proposed.

Novel therapies for the antiphospholipid syndrome

Antiphospholipid antibodies (aPL Abs) are associated with thrombosis in patients with the antiphospholipid syndrome (APS). There is strong evidence that aPL Abs are pathogenic in vivo from studies in animal models. Furthermore, there are now convincing data indicating that activation of complement is involved in those processes. This report addresses current modalities of treatment, as well as recent findings with respect to molecular events triggered by aPL Abs on endothelial cells, platelets, monocytes and complement activation. A separate section addresses recent findings with regard to the putative receptor(s) recognized by aPL Abs on target cells. Based on experimental evidence using in vitro and in vivo models, new targeted therapies for treatment and/or prevention of thrombosis in APS are proposed and discussed.