aPL Tests Research Articles

The hidden world of anti-phospholipid antibodies and female infertility: A literature appraisal.

Even though the association of anti-phospholipid antibodies (aPL) with infertility is debated, infertile women are commonly screened for aPL. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing (i) the association between aPL and infertility, (ii) the positivity rate of criteria and non-criteria aPL in women with infertility, (iii) the association between aPL and assisted reproduction technologies (ART) outcome, (iv) the efficacy of medical treatments on ART outcome, and (v) the effects of ART on thrombotic risk. A total of 46 papers were considered; several limitations emerged: (i) wide heterogeneity in study populations, (ii) non-prospective design in 90% of studies, and (iii) aPL cutoffs not conforming to international guidelines in more than 75% of studies; aPL positivity not confirmed in 89% of studies. Most studies evinced an association between infertility and anti-β2GPI antibodies and almost all non-criteria aPL. The association rate with infertility was below 50% for lupus anti-coagulant, anti-cardiolipin antibodies (aCL), and anti-phosphatidic acid antibodies. According to our estimates, overall positivity rates of criteria and non-criteria aPL tests are 6% and 3% among infertile women, 1% and 2% among controls, respectively. A significant difference in the positivity rate of patients versus controls emerged for aCL only. Five of 18 studies reported a detrimental effect of aPL on ART outcome. Only one of the six studies assessing the effects of treatment on ART outcome among aPL-positive infertile women reported a benefit. All relevant studies reported no increase in the rate of thrombosis among aPL-positive women undergoing ART.

Recognition and management of antiphospholipid syndrome.

This article summarizes the recent developments in the recognition and management of antiphospholipid syndrome (APS). Five Task Forces, created as part of the 14th International Congress on antiphospholipid antibodies (aPL), published their systematic reviews. 'For the recognition of APS': the assessment of aPL profile is crucial for risk stratification; lupus anticoagulant positivity, especially in the context of 'triple aPL positivity' displays the highest risk; a panel of criteria and noncriteria aPL tests may help better risk-stratify the aPL-positive in the future. 'For the management of APS': direct oral anticoagulants are not currently recommended; statins ameliorate the proinflammator/thrombotic markers, whereas hydroxychloroquine reduces the risk of thrombosis in experimental models and lupus patients, which justify their use as an adjunctive treatment in refractory cases; B-cell inhibition may have a role in difficult-to-treat patients with hematologic and microthrombotic/angiopathic manifestations; and complement and mammalian targets of rapamycin complex pathway inhibition are promising targets in APS. Warfarin, heparin, and/or antiplatelet drugs are the standard of care for aPL-positive patients. Recent studies suggest novel approaches that target new coagulation and immunomodulatory pathways; mechanistic and/or controlled clinical studies are needed to determine the effectiveness of these novel approaches.

Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts.

Solar Array Degradation in a High-Fluence, High-Temperature Environment

Spacecraft powered by solar arrays are at risk of significant degradation when operating in high-irradiance, high-temperature environments on extended missions. Testing of common solar array adhesives in the John Hopkins University/Applied Physics Laboratory Combined Environment Test Chamber has identified a potential degradation mechanism. In addition, the APL testing separates the effects of thermal, UV, and charged particle fluence. Experimental design and experimental results are discussed in detail with funding support from the NASA Solar Probe Plus project.

Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio

Background: There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. Methods: A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-β₂-glycoprotein-I (anti-β₂GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Results: Persistent anti-β₂GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-β₂GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-β₂GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. Conclusions: Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β₂GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs.

Determination of clinically significant tests for antiphospholipid antibodies and cutoff levels for obstetric antiphospholipid syndrome.

The objective of this paper is to determine which kinds of assays for antiphospholipid antibodies (aPL) should be tested for clinical practice for patients with recurrent pregnancy loss (RPL). We studied 560 patients with a history of RPL prospectively. We determined the obstetric significance of 11 commercially available tested assays for lupus anticoagulant (LA)-aPTT StaClot, phosphatidylserine-dependent antiprothrombin (aPS/PT) IgG, IgM, classical cardiolipin (CL) IgG, IgM, CL IgG, IgM, IgA, and β2glycoprotein I (β2GPI) IgG, IgM, IgA Phadia. Obstetric significance was defined as the potential for anticoagulant therapy to improve the subsequent live birth rate, or a difference in the live birth rate between positive and negative untreated cases. The LA-aPTT StaClot assay and aPS/PT IgG assay, but not CL IgG, were found to have obstetric significance. Our conventional tests covered positive cases with the aPS/PT IgM and classical CL IgG assays. The results of the LA-aPTT StaClot, LA-aPTT and LA-RVVT assays showed different distributions, although strong or moderate correlation was observed. LA-aPTT StaClot and aPS/PT IgG might be suitable for use in routine practice for patients with RPL. Each test for aPL should be ascertained for obstetric significance, because similar assays may have different outcomes.

Quality in hemostasis and thrombosis - part IV.

bleeding symptoms, macrothrombocytopenia, mild spontaneous platelet aggregation, positive RIPA at 0.3 and 0.4 mg/mL, von Willebrand factor (VWF) ristocetin cofactor (VWF:RCo) to antigen (VWF:Ag) ratio of T located at nucleotide 3805 in the g.DNA of the patient’s GP1BA gene, resulting in a Trp to Leu amino acid change at residue 246 (p.W246L). This mutation was absent in his unaffected mother and also in the 100 controls and was predicted as damaging by in silico analysis. The residue W246 is located within the VWF binding region and exists in a strongly conserved position in the phylogenetic tree, which is expected to be unable to tolerate substitutions without changing its functional characteristics. These findings argue strongly in favor of the view that this substitution does not represent a polymorphism, and therefore, is responsible for the PT-VWD phenotype of the patient. The accompanying editorial by Othman and Emsley 5 highlights the importance of this new work, and it alsoextends the analysis of the proposed mutation by molecular modeling. The second editorial, 7 along with the accompanying highlighted articles, 8,9 deal with recent initiatives in the standardization and harmonization of antiphospholipid antibody (aPL) testing, essential for the appropriate diagnosis and management of patients with antiphospholipid syndrome (APS) and other hypercoagulable states. 14 The leading issues in aPL testing include high vulnerability to preanalytical, analytical as well as postanalytical problems, the heterogeneous sensitivity of tests and reagents, high intermethod and interlaboratory variability, the clinically meaningful rate of false-negative and false-positive results, an absence of

Diagnosing Antiphospholipid Antibody Syndrome: A Review of the Criterion for Definite APS

Antiphospholipid Antibody Syndrome (APS) is a highly prevalent cause of antibody-mediated thrombosis manifesting in venous thrombosis (DVT and PE), arterial thrombosis (most commonly stroke), and pregnancy complications. The diagnosis of definite APS requires both clinical and laboratory criterion as established by the working group of the International Congress on Antiphospholipid Antibodies (based on expert opinion). Since thrombosis and pregnancy loss are common in the general population, and antiphospholipid antibodies (aPL) occurs in a small percentage of the healthy public, it is important to demonstrate antibody persistence in patients who have the proper clinical indications in order to avoid misdiagnosis. Unfortunately, laboratory testing in this area lacks standardization, resulting in wide inter-laboratory variance. However, due to the commercialization of tests and automation, inter-laboratory variance has improved. Data on several new non-criterion tests suggest that they may improve the specificity or risk stratification for thrombosis. A new guidance document on aPL testing strives to achieve better consistency, but much work remains to be done in the area of standardization.

The participations of the physicians on the diagnosis and treatments of antiphospholipid related pregnancy morbidities in Japan: from the result of nationwide survey.

Thromboses and pregnancy morbidities are major pathologies of antiphospholipid syndrome (APS). In general, rheumatologists or hematologists see APS thrombosis patients, and they often give advices for the treatments of APS-related pregnancy morbidities, such as measurements and interpretations of antiphospholipid antibodies(aPL). To survey the approaches of physicians in Japan to the diagnosis and treatment of aPL-associated pregnancy morbidities. The study group on the Health and Labour Sciences Research Grants sent a questionnaire to 550 board members of the Japan College of Rheumatology and the Japanese Society on Thrombosis and Hemostasis, and analyzed the responses. The number of valid responses was 157 (28.5%). The number of pregnant women who were diagnosed as having APS was 118.7 patients/year in 53 of 157 hospitals (33.8%). With respect to aPL measurements, 128 out of 157 hospitals (81.5%) determined one or more anticardiolipin antibodies or β2GPI-dependent anticardiolipin antibodies with one or more lupus anticoagulants; however aPL tests of only 2 hospitals (1.3%) covered all aPLs defined in the classification criteria. The obstetricians were responsible for treatments in 33.1% to 42.3% of the hospitals. The treatment methods or duration of treatments did not reach to the general consensus. The number of cases of aPL-related pregnancy complications that physicians have intervened was relatively small. There are considerable patients that are not diagnosed as having the disease due to insufficient aPL examinations. There were less involvement of physicians to the diagnosis and treatment of pregnant women with aPLs.

Antiphospholipid antibody testing for the antiphospholipid syndrome: a comprehensive practical review including a synopsis of challenges and recent guidelines

The antiphospholipid (antibody) syndrome (APS) is an autoimmune condition characterised by a wide range of clinical features, but primarily identified as thrombotic and/or obstetric related adverse events. APS is associated with the presence of antiphospholipid antibodies (aPL), including the so-called lupus anticoagulant (LA). These aPL are heterogeneous in nature, detected with varying sensitivity and specificity by a diverse range of laboratory tests. All these tests are unfortunately imperfect, suffer from poor assay reproducibility (inter-method and inter-laboratory) and a lack of standardisation and harmonisation. Clinicians and laboratory personnel may struggle to keep abreast of these factors, as well as the expanding range of available aPL tests, and consequent result interpretation. Therefore, APS remains a significant diagnostic challenge for many clinicians across a wide range of clinical specialities, due to these issues related to laboratory testing as well as the ever-expanding range of reported clinical manifestations. This review is primarily focussed on issues related to laboratory testing for APS in regards to the currently available assays, and summarises recent international consensus guidelines for aPL testing, both for the liquid phase functional LA assays and the solid phase assays (anticardiolipin and anti-beta-2-Glycoprotein-I).

Antiphosphatidylserine antibodies as diagnostic indicators of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune condition that is diagnosed by the presence of at least one of the clinical manifestations (thrombosis and/or pregnancy failure) and one of antiphospholipid antibodies (aPL) laboratory tests. The most relevant aPL are lupus anticoagulant (LA), anti-beta2 glycoprotein I (aβ2GPI) and anticardiolipin (aCL). The clinical significance of other antibodies like anti-phosphatidylserine antibodies (aPS) is still under investigation. The aim of the study was to assess the diagnostic value of aPS antibodies, and to compare their utility to that of other aPL antibodies. We conducted a prospective observational study consisting of 212 patients with suspected thrombosis, pregnancy failure, or unexplained, prolonged clotting time. Data on demography, clinical presentation and autoantibody levels were assessed. Descriptive analysis, accuracy analysis, sensitivity, specificity, predictive value and likelihood ratio were calculated for aPS in comparison to other aPL. The diagnostic value of aPS versus other aPL antibodies revealed the high specificity of aPS (87%), with 70% of aPS-positive patients being confirmed APS. When the aPS test was used as a single test, it was effective for detection of confirmed APS cases (p < 0.01). Among 28 confirmed primary APS cases, 75% of patients were positive for aPS (p < 0.003). Moreover, by using aPS we detected three additional confirmed APS cases and another three probable cases. Our findings reveal a significant association between aPS and APS, especially when used to diagnosis clinical cases with other negative aPL tests. There is an independent association between aPS and primary APS. In addition, these results demonstrated the advantages of using aPS as a diagnostic test for APS.

Identification and treatment of APS renal involvement.

Renal involvement in antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-related APS, includes renal artery stenosis or thrombosis, renal infarction, renal vein thrombosis and a small-vessel vaso-occlusive nephropathy defined as "antiphospholipid antibody (aPL)-associated nephropathy." aPL-associated nephropathy is characterized by acute lesions, thrombotic microangiopathy, and chronic lesions such as fibrous intimal hyperplasia, organizing thrombi with or without recanalization, fibrous occlusions of arteries or arterioles and focal cortical atrophy. Systemic hypertension, hematuria, proteinuria (ranging from mild to nephrotic level) and renal insufficiency represent the major clinical manifestations associated with aPL-associated nephropathy. Similar renal histologic and clinical characteristics have been described among all different groups of patients with positive aPL (primary APS, SLE-related APS, catastrophic APS and SLE/non-APS with positive aPL). In patients with aPL-associated nephropathy lesions in the absence of other causes associated with similar histological characteristics, aPL testing needs to be considered.

Antiphospholipid scoring: significance in diagnosis and prognosis.

Recently our group introduced the "antiphospholipid score" (aPL-S), a quantitative marker that represents aPL profile. We have validated its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis. The study comprised two independent sets of patients with autoimmune diseases. In the first set of patients (n=233), the aPL-S was established by analyzing aPL profiles. In the second set of patients (n=411), the predictive value of the aPL-S for thrombosis was evaluated. To define aPL-S, we calculated the relative risks (approximated by odds ratios (ORs)) of having APS manifestations (thrombosis and/or pregnancy morbidity) for each of the aPL tests and devised an original formula in which aPL-S was determined by OR: aPL-S=5 × exp ([OR] -5)/4. The receiver operating characteristic (ROC) curve showed a hyperbolic pattern and the area under the ROC curve value was 0.752 (0.686 for revised Sapporo criteria), implying that aPL-S is a potential quantitative marker for APS diagnosis. The OR for thrombosis in patients with a high aPL-S (≥ 30) was 5.27 (95% confidence interval (95% CI) 2.32-11.95, p<0.0001). By multivariate analysis, an aPL-S of ≥ 30 appeared to be an independent risk factor for thrombosis (hazard ratio 3.144 (95% CI 1.383-7.150), p=0.006). The aPL-S is a useful quantitative index for diagnosing APS and may be a predictive marker for thrombosis in autoimmune diseases.

Autoantibody profiling in APS.

The international consensus for the classification of antiphospholipid syndrome (APS) requires clinical and laboratory criteria to be considered at an equal level for diagnosing APS. Thus, detection of antiphospholipid antibodies (aPL) being a hallmark of APS has been the object of intensive investigation over the past 40 years. However, appropriate detection of aPL still remains a laboratory challenge due to their heterogeneity comprising autoantibodies reactive to different phospholipid-binding plasma proteins, such as beta-2 glycoprotein I (β2GPI) and prothrombin. The relevance of aPL interacting with phospholipids other than cardiolipin (CL, diphosphatidylglycerol), such as phosphatidylserine (PS), remains elusive with regard to the diagnosis of APS. Recently, the concept of aPL profiling has been introduced to assess the risk of thrombotic complications in patients with APS. New assay techniques, apart from enzyme-linked immunosorbent assays (ELISAs) recommended by the international consensus for the classification of APS, have been proposed for multiplexing of aPL testing. Line immunoassays (LIAs) employing a novel hydrophobic solid phase for the simultaneous detection of different aPL seem to be an intriguing alternative. We evaluated a novel multiplex LIA employing a hydrophobic membrane coated with different phospholipid (PL)-binding proteins or PLs. The performance characteristics of this new multiplexing assay technique demonstrated its usefulness for aPL profiling.

Antiphospholipid antibodies and infertility.

Since the late 1980s some publications have proposed that antiphospholipid antibodies (aPL) may have some relationship with infertility, considering reported deleterious effects that aPL exert on trophoblast proliferation and growth. Although not included in current classification criteria for antiphospholipid syndrome, many physicians investigate for aPL in patients with a history of infertility, including antibodies not listed in classification criteria, and most of those patients will receive anticoagulant therapy if any of those antibodies have a result considered positive. A review of literature was conducted searching for studies that investigated the association of aPL and infertility and if aPL positivity alters in vitro fertilization (IVF) outcome. The definition of infertility, routine work-up to exclude other causes of infertility, definition of IVF failure as inclusion criteria and control populations were heterogeneous among studies. Most of them enrolled women over 40 years of age, and exclusion of other confounding factors was also inconsistent. Of 29 studies that assessed aPL positivity rates in infertile women, the majority had small sample sizes, implying a lack of power, and 13 (44.8%) reported higher frequency of aPL in infertile patients compared to controls, but most of them investigated a panel of non-criteria aPL tests, whose clinical significance is highly controversial. Only two studies investigated all three criteria tests, and medium-high titer of anticardiolipin cut-off conforming to international guidelines was used in one study. Considering IVF outcome, there was also disparity in this definition: few studies assessed the live birth rate, others the implantation rate. Of 14 publications that addressed the relationship between aPL and IVF outcome, only two described a detrimental effect of these autoantibodies. In conclusion, available data do not support an association between aPL and infertility, and aPL positivity does not seem to influence IVF outcome. Well-designed clinical studies recruiting women with a clear diagnosis of infertility and a high-risk aPL profile should be performed to test whether clinically relevant aPL do-or not-exert an effect on human fertility.

Pre-eclampsia as a manifestation of antiphospholipid syndrome: assessing the current status.

The presence of antiphospholipid antibodies is considered a risk factor for pre-eclampsia. Two meta-analyses and a number of case-control and cohort studies have found associations between pre-eclampsia and lupus anticoagulant, anticardiolipin, and/or anti-β2 glycoprotein I. However, existing literature is inconsistent, with varying severity of pre-eclampsia phenotype examined, differing aPL titer cutoffs used to define positive status, and an overwhelming lack of repeat confirmatory aPL testing. This calls into question the link between aPLs and pre-eclampsia, or at least makes it less well defined. There is evidence for a mechanistic pathway between aPLs and adverse pregnancy outcomes (APOs) including pre-eclampsia via the complement pathway. Complement appears to be overactive in pregnancies affected by APOs. A mouse model has show that the fetal wastage caused by treatment with human aPLs can be salvaged by either creating genetic knockouts along the complement, TNF-alpha, and tissue factor pathways or be treating mice with monoclonal antibodies blocking key complement factors. Thus, this is worth further investigation to clarify the likely association of aPLs and pre-eclampsia in humans, as well is to further evaluate the interaction with complement in human pregnancies.

Triple positive antiphospholipid antibody profile in outpatients with tests for lupus anticoagulants.

A triple positive antiphospholipid (aPL) antibody profile [two positive serum IgG aPL antibodies along with one positive functional plasma lupus anticoagulant (LAC) test result] is associated with an increased risk for thrombosis, whereas patients with single positive test results may have little to no increased risk. The frequency of triple positivity in outpatients with various combinations of LAC test results is unclear. We extracted from our database all LAC test results [dilute Russell viper venom times (dRVVT) and silica clotting times (SCT)] that had concomitant serum IgG aPL testing [both serum anti β2-glycoprotein I (anti-β2GPI) and anti-cardiolipin (aCL) antibodies]. There were 3195 patients without a prolonged prothrombin time. Double antibody positivity was found in 1% (31/2955) of those with normal functional LAC test results, in 16.0% (31/81) of those with a positive dRVVT, in 12.7% (10/79) of those with a positive SCT, and in 56.3% (45/80) of those with both tests positive (p<0.001). A triple positive aPL antibody profile was found in 28.3% (68/240) of those with at least one positive LAC test result. We conclude that 28% of patients with elevated LAC tests have a triple positive aPL antibody profile and patients with two positive LAC tests have a higher prevalence of a triple positive profile than do those with one positive LAC test result.

The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review

BackgroundAround 10% of all thrombotic cerebrovascular events (CVE) occur in young population and in a large proportion of those the trigger remains undetermined. Antiphospholipid antibodies (aPL) are recognised risk factors...

Antiphospholipid antibody testing and standardization.

The laboratory criteria that define patients with antiphospholipid syndrome (APS) include lupus anticoagulant (LAC), anticardiolipin antibodies and anti-β2 glycoprotein I antibodies (aβ2GPI). All assays show methodological shortcomings and the combination of the three tests, each with different sensitivity and specificity, and hence, differences in clinical utility make the laboratory diagnosis of APS challenging. Consensus guidelines and proposals for antiphospholipid antibodies (aPL) testing have been published in the last 20 years and have led to a substantial improvement. Despite efforts so far, standardization is not reached yet, but progress has been made. On-going efforts to reduce the interlaboratory/interassay variations remain important; even an absolute standardization cannot be feasibly achieved. Taking into account the methodological shortcomings of the means we have available, more detailed guidelines may help in adequate performance of aPL testing. This review will focus on the efforts and achievements in standardization and on the weaknesses and strengths of the current available laboratory methods.

Antiphospholipid antibodies in neonates with stroke--a unique entity or variant of antiphospholipid syndrome?

YB current affiliation: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Israel YB and MJS contributed equally to the study and should be regarded as joint first authors on this manuscript. Antiphospholipid syndrome (APS) may present with thrombosis and persistently elevated titers of antiphospholipid antibodies (aPL) in the neonatal period. Our aim was to investigate the course and impact of elevated titers of aPL in a cohort of infants presenting with either perinatal arterial ischemic stroke (PAS) or cerebral sinus vein thrombosis (CSVT) during the perinatal period. Sixty-two infants with clinically and radiologically confirmed PAS or CSVT presenting in the neonatal period underwent thrombophilia workup that included Factor V Leiden (FVL), PII20210A mutation, MTHFR 677T polymorphism, protein C, protein S, aPL namely either circulating lupus anticoagulant (CLA), anticardiolipin antibodies (aCL) or anti-β2-glycoprotein-1 (β2GP1). Mothers also underwent thrombophilia workup. Twelve infants with persistently elevated aPL were prospectively followed. Infants with positive aPL showed no concordance with presence of maternal aPL. All children were followed for a median of 3.5 years (range: nine months to 19 years) with repeated aPL testing every three to six months. Anticoagulant therapy initiation and therapy duration varied at the physician's discretion. In 10/12 cases aPL decreased to normal range within 2.5 years; one female with complex thrombophilia risk factors required indefinite prolonged anticoagulation. None of the infants showed recurrent thrombosis or any other APS manifestations, despite lack of prolonged anticoagulation. The presence of aPL may be important in the pathogenesis of cerebral thrombosis in neonates. Nevertheless, the nature of thrombophilia interactions in this period and their therapeutic impact warrants further investigation.