Israel Medical Association Journal

Background: Antiphospholipid syndrome (APS) is a common form of acquired thrombophilia associated with a high thrombotic risk. Fabry’s disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (GLA) gene and presents with a wide range of clinical manifestations, including a high rate of thrombosis. Previously reported, 45% of FD patients were found to have antiphospholipid autoantibodies.

Objectives: To determine the prevalence of FD in patients with APS.

Methods: We conducted a prospective study. Data were collected from 41 APS patients at our outpatient clinic at Meir Medical Center in Israel. We utilized chemical and genetic analyses to identify FD among APS patients. Dried blood spot (DBS) was used to assess GLA activity in males, and mutational analysis of the GLA gene was performed by sequencing exons and their flanking regions in women.

Results: Among 41 antiphospholipid patients, one male patient was diagnosed with FD. Gal variants were not detected in any of the tested female patients.

Conclusions: We found a low prevalence (2.4%) of FD in APS patients. Larger studies are needed to evaluate the clinical utility and cost-effectiveness of routine FD screening in this population.

Immune thrombocytopenia (ITP), driven by autoantibodies targeting platelet antigens, is an acquired disorder posing considerable challenges, particularly in pregnancy, where its prevalence escalates to 1–3 per 10,000 women, a tenfold increase compared to the general population [1]. Predominantly characterized by a heightened risk of bleeding, particularly during pregnancy, the incidence of significant hemorrhagic events stands at approximately 18%, mostly non-severe [1]. Despite its rarity, thrombosis can manifest as a complication, especially when accompanied by antiphospholipid antibodies, which amplify the propensity for arterial and venous thrombotic events alongside obstetric complications and thrombocytopenia [2,3].

In this case report, we present the case of a young female with primary unexplained infertility, complicated by ITP and antiphospholipid syndrome (APS), predisposing her to increased bleeding and thrombotic risks. During a multidisciplinary consultation, the medical staff navigated the intricate landscape of fertility treatments and pregnancy options, carefully considering the delicate balance between risks and benefits to optimize patient outcomes.

Myelodysplastic syndrome (MDS) is frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory responses of the immune system. The biological linkage between MDS clones and the occurrence of autoimmune manifestations is mirrored by the response of the latter to MDS modifying therapeutic approaches [1]. We encountered a rare case of MDS coexisting with antiphospholipid syndrome (APS), which was effectively treated with a hypomethylating agent followed by allogenic bone marrow transplantation.

Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I (aβ2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS.

We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diagnosis the patient received prenatal counseling and benefited from the optimal treatment of Obs-APS that led to a successful pregnancy. The applicability of this successful experience about outcomes in women with non-criteria, or seronegative, Obs-APS is also evaluated.

 

Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by vascular thrombosis (arterial or venous) and/or pregnancy complications associated with the occurrence of autoantibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and/or anti-β2 glycoprotein-I antibodies confirmed at least twice over a 12 week period according to the 2006 Sydney criteria. Antiphospholipid antibodies are encountered  in the general population with a reported prevalence of 1% to 5%  However, APS is far more infrequent with a prevalence of 40–50/100,000 persons and an incidence of about 5 new patients/100,000 persons. APS can be diagnosed in patients with no apparent clinical or laboratory pathology (primary APS) or it may be related to numerous other conditions, autoimmune diseases (usually systemic lupus erythematosus), malignancies, infections and drugs (secondary APS). Women are at risk for APS since the disease is encountered in both the primary and the secondary state in females more often than in men. In addition, women in their reproductive years can develop APS (either classical or obstetric), and special attention is warranted in pregnant women with a diagnosis of APS. The benefits of hormonal therapy in the form of contraception or hormone replacement treatment should be carefully weighed against the increased risk for vascular complications in women with APS.

Background: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. 

Objectives: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS.

Methods: Using the BioPlex™ 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls. 

Results: Three non-classic aPL were significantly more prevalent among MS patients in comparison to the control group. These antibodies included IgM and IgG against phosphatidylserine-β2GPI (PS-B2), IgG prothrombin complex (PT-PT) and IgM prothrombin (PT). The positive results according to Bonferroni correction are PS-B2 IgG and PT-PT IgG. The remaining aPL profiles did not differ significantly between the two groups.

Conclusions: An association between certain non-classic aPL and MS has been established. The specific role of these autoantibodies in the pathogenesis of the condition remains uncertain.  

 

Methods: We evaluated 11 patients with catastrophic APS – 8 of them with a probable diagnosis of catastrophic APS and 3 with a definite diagnosis – admitted to Beilinson hospital during the period 2003–2011.

Results: Overall venous events numbered 18 and overall arterial events 10. The event duration per patient was 2.6 ± 1.2 weeks (mean ± SD). Deep vein thrombosis of the legs was quite common (7 events), as was venous intraabdominal thrombosis (10 events). Eight patients had microangiopathic anemia with schizocytes seen in the blood smear. The mean ± SD hemoglobin level was 10.3 ± 3.6 g/dl and the mean ± SD creatinine level 0.98 ± 0.78 mg/dl. All our patients had high acute-phase reactant and all had lupus anticoagulant positivity, The most common positive antibodies were immunoglobulin G anticardiolipin (8 patients) and IgG[1] β2-glycoprotein (7 patients). During the events warfarin was stopped and the patients were given intravenous heparin. All the patients received steroids in variable doses. Five patients underwent plasma exchange, two patients received rituximab and two patients intravenous immunoglobulin.

Conclusions: Catastrophic APS, a rare syndrome, is important because of its major morbidity and mortality among young patients.