What have we learned about antiphospholipid syndrome from patients and antiphospholipid carrier cohorts?

Venous or arterial thrombosis or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL) define the antiphospholipid syndrome (APS). In terms of accepted APS criteria, aPL are detected by one coagulation test (lupus anticoagulant; LAC) and two immunoassays (anticardiolipin antibodies and anti-β2-glycoptrotein I antibodies). In patients with APS, a single positive test carries a much lower risk of thrombosis recurrence or new pregnancy loss than does multiple (or triple) positivity. The same holds true for aPL carriers, namely subjects with laboratory tests but without clinical criteria for APS. Thus, very different risk categories exist among patients with APS as well as in carriers of aPL. Triple positivity apparently identifies the pathogenic autoantibody (antidomain I-II of β2-glycoptrotein I); it is in this category of patients that trials on new therapeutic strategies should focus.     

What causes the antiphospholipid syndrome?

The antiphospholipid syndrome (APS) is characterized by unpredictable, sporadic, thrombotic events. The cause of the thrombosis is probably multifactorial and may involve disparate effects of the autoantibodies associated with the syndrome, which are known to interfere with various protein regulators of hemostasis. An integrated theory of pathogenesis that accounts for the diversity of autoantibodies and their effects suggests that cellular inflammation or apoptosis within the vasculature may lead to oxidation or turnover in phospholipid membranes. Thus, normally cryptic, functionally important epitopes of phospholipidbinding proteins are subjected to increased exposure to immune surveillance.     

Susac's syndrome or catastrophic antiphospholipid syndrome?

Susac's syndrome is a microangiopathic disorder of unknown pathogenesis presenting with encephalopathy, hearing loss and branch retinal artery occlusions. The term 'catastrophic' antiphospholipid syndrome (APS) is used to define a subset of the APS characterized by thrombotic microangiopathy with clinical evidence of three or more organ involvement developed in a short period of time. We describe a patient with typical features of Susac's syndrome, that appeared in less than a week, in whom aPL were detected, thus fulfilling criteria for 'probable' catastrophic APS.     

Stroke and antiphospholipid syndrome—antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event

Clinical Rheumatology - Testing for antiphospholipid antibodies could be an important part in determining the cause of a cerebrovascular event (CVE). Currently, it is also unknown whether...     

Is HLA class II susceptibility to primary antiphospholipid syndrome different from susceptibility to secondary antiphospholipid syndrome?

To assess whether the major histocompatibility complex (MHC) profile of patients presenting with primary antiphospholipid syndrome (PAPS) is different from that of patients with secondary antiphospholipid syndrome (SAPS), we studied 123 patients, 34 of whom presented PAPS and 35 SAPS due to systemic lupus erythematosus (SLE), 54 SLE patients without antiphospholipid syndrome (APS), and 166 controls. HLA-DRB1 and DQB1 alleles were typed using amplified DNA hybridized with sequence-specific primers. Compared to controls, PAPS patients exhibited a nonsignificantly increased frequency of DR53-associated alleles, and SAPS patients presented an increased frequency of HLA-DRB1*03 alleles (corrected P = 0.05). In addition, HLA-DRB1*03 alleles were over-represented in SAPS patients presenting anticardiolipin antibody (aCL) (Pc = 0.02), in SLE patients as a whole (Pc < 0.0001), and in SLE patients without APS (Pc = 0.02). The frequency of aCL among SLE patients presenting or not HLA-DRB1*03 alleles was closely similar. A trend to an increase in the frequency of the DQB1*0604 allele (14.3 versus 4.2%, P = 0.03) and of the DQB1*0302 allele (31.4 versus 12.7%, P = 0.01) was observed in SAPS. Taken together, these results indicate that the association of SAPS with HLA-DRB1*03 is due to the association with SLE and is not due to aCL, and suggest that the HLA class II profile of PAPS is different from that of SAPS.     

Do antiphospholipid antibodies develop for a purpose?

There is a growing body of literature suggesting that antiphospholipid antibodies develop for a purpose, that they play several key roles in the innate immune response, and are only rendered pathologic in susceptible people under adverse intravascular conditions. This paper will review evidence that the autoantibodies associated with the antiphospholipid syndrome develop from natural autoantibodies for purposes that are beneficial to host defense, and are only rendered pathologic as a result of adverse intravascular events.     

Which antiphospholipid antibody tests are most useful?

Despite an active international effort to improve diagnosis and treatment of the antiphospholipid syndrome (Hughes syndrome), there remain problems of lack of standardization and lack of prospective and multivariate epidemiologic analysis which restrict the diagnostic and predictive ability of commercially available tests. Nevertheless, current published series provide some data from which strategic approaches can be used to maximize the efficiency and usefulness of available tests. For further updates on new research and developments of interest to physicians and patients with this syndrome, the following web sites may prove helpful: www.slrapls.org, www.hematology.org, www.acforum.org, www.americanheart.org, www.rarediseases.org, www.aarda.org, and www.lupus.org.     

Do antiphospholipid antibodies cause preeclampsia and HELLP syndrome?

Antiphospholipid syndrome (APS) is associated with adverse pregnancy outcomes including preeclampsia, recurrent early pregnancy loss, fetal death, and intrauterine growth restriction. Approximately one third of women with APS will develop preeclampsia during pregnancy. The association between antiphospholipid antibodies (aPL) in the absence of the clinical syndrome and preeclampsia is less clear, and a causal relationship has not yet been proven. Testing for aPL should be considered in women with early-onset (< 34 weeks) severe preeclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, especially when additional clinical features of APS are present. Prospective testing for aPL in women at risk for preeclampsia is not recommended. Current evidence does not justify inclusion of preeclampsia as a major criterion for APS, but preeclampsia could reasonably be included as a secondary or minor criterion in diagnosis when a patient has other clinical features of APS.     

Cardiac manifestations in primary antiphospholipid syndrome and their association to antiphospholipid antibodies’ types and titers—cross-sectional study of Serbian cohort

Clinical Rheumatology - Antiphospholipid syndrome (APS) is multisystem autoimmune coagulopathy with antiphospholipid antibodies (aPL) in its ground, manifested as a primary disease (PAPS) or in the...     

Arterial compliance: is it reduced in antiphospholipid syndrome?

To assess vascular compliance in patients with antiphospholipid syndrome (APS), or antiphospholipid antibodies (aPLs) positivity in comparison to healthy people and diabetes mellitus patients. Twenty-five patients with APS or aPLs, 33 healthy people (HP), 28 patients with diabetes mellitus (DM) underwent pulse wave analysis. Data calculated included the small artery elasticity (SAE), large artery elasticity (LAE) and systemic vascular resistance (SVR). Statistical analysis was performed as appropriate. The patient group was divided into two subgroups: APS-1 with warfarin treatment, and APS-2 without warfarin treatment. All patients and healthy subjects were matched by gender, body mass index and lipid profiles. Patients in APS-1 group were significantly younger in comparison to three other groups. After the adjustment for age, we found that SAE in APS-1 group did not differ from SAE in the HP group (6.4+/-1.8 ml/mmHg x 100 and 5.54+/-3.4 ml/mmHg x 100, respectively, P>0.05). In contrast, SAE in the group APS-2 was significantly lower (3.41+/-1.2 ml/mmHg x 100) than in the APS-1 and was almost equal to SAE in the DM group (4.2+/-2.37 ml/mmHg x 100). The SAE in the APS-2, DM and HP groups was inversely correlated with age, whereas in the APS-1 group we did not find such correlation. This pilot study showed abnormal small vascular elasticity in the patients with positive aPL, relative to the healthy subjects. The APS patients, treated with warfarin had the normal vascular function. This data support the hypothesis that APS may be associated with diffuse changes in the arterial wall, and may be a risk factor for atherosclerotic disease.     

Catastrophic antiphospholipid syndrome: is life-long anticoagulation therapy required?

Clinical Rheumatology - Catastrophic antiphospholipid syndrome (CAPS) is an unusual complication of antiphospholipid syndrome (APS) occurring in about 1% of patients. If left untreated, mortality...     

Primary antiphospholipid syndrome with and without Sneddon��s syndrome

The main objective of this study was to compare clinical and laboratory data obtained from patients with primary antiphospholipid syndrome (PAPS) with and without Sneddon’s syndrome (SS). A transverse study with 54 (85.2% female) PAPS patients (Sapporo criteria) was performed. Demographic, drug use, and antiphospholipid antibodies data were evaluated, as well as clinical and laboratory findings of SS. Patients were subdivided into one of two groups: PAPS with SS and PAPS without SS. Both groups were similar with respect to age (p = 0.05), gender (p = 0.34), race (p = 0.31), weight (p = 0.93), height (p = 0.27), and body mass index (p = 0.75); however, the SS group exhibited higher disease duration (96.0 ± 54.9 vs. 55.2 ± 52.0 months, p = 0.01). By definition, all PAPS with SS patients suffer from stroke, an arterial event; the frequency of stroke events (28.5 vs. 7.5%, p = 0.04), as well as of limb ischemia (100 vs. 30.0%, p < 0.0001) was higher in this group than in the PAPS without SS group. On the other hand, patients in the PAPS without SS group had more venous events, such as deep venous thrombosis, than those in the PAPS with SS group (80.0 vs. 50.0%, p = 0.03). In conclusion, an understanding of the relationship between APS and SS is important in order to identify a subgroup for which more rigorous accompaniment and therapy may be necessary.