Addressing the gaps in anti-phospholipid syndrome management

28 Feb 2020

Although the antiphospholipid syndrome (APS) is a low prevalence autoimmune disorder, it is currently considered the most frequent acquired thrombophilia, accounting for 10% to 20% of recurrent miscarriages and, up to one-fifth of strokes in people under age 50.1 APS encapsulates a heterogeneous set of clinical manifestations, characterized by the presence of antiphospholipid antibodies (aPL). However, the lack of standardization in testing for aPL remains a significant concern towards diagnosing APS. Dr. Savino Sciascia from the Centre of Research of Immunopathology and Rare Disease (CMID), University of Turin, Italy, addressed the current gaps in APS and the potential approaches for the management of the disease, at the International Conference of Chinese Rheumatologists (ICCR) 2019, organized by the Hong Kong Society of Rheumatology.

APS is a systemic autoimmune disorder with heterogeneous clinical manifestations.1 To date, there is no single test to diagnose APS, and clinical diagnosis relies on performing a panel of different antibodies. Characterizing patients with APS requires fulfilling at least one clinical and one laboratory classification criteria from the updated Sapporo recommendations. According to this updated version, the so-called “Sydney classification criteria”, the number of false-positive cases can be reduced by increasing the time interval between two positive tests (from 6 to at least 12 weeks).  

However, when applying the Sydney classification criteria in clinical practice, physicians might run the risk of either undertreating or over-treating the patient. “What I want to stress here is the fact that classification and diagnosis are two completely different settings. Classification criteria, I personally feel, perfectly apply for research purposes,” stated Dr. Savino Sciascia.

During an interview with Omnihealth Practice, Dr. Sciascia further stressed the advantages of the classification in clinical research, by stating “The classification criteria are perfect for identifying homogeneous subgroup of patients among subjects suspected for APS, and when we want to run an observational or a clinical study.” Dr. Sciascia pointed out that despite these benefits, there is still an absence of sufficient clinical trials in the field. He explained, "One of the main challenges for future research in this field is to design practical clinical trials, including randomized trials, enrolling a heterogeneous group of APS patients who exhibit many different forms of the disease and aPL profile.” 

In addition, APS patients may exhibit many different forms of the disease (e.g. arterial and/or venous thrombosis, recurrent pregnancy morbidity) and different aPL profiles. Besides, it is worth stressing that the presence of aPL in asymptomatic individuals (aPL carriers) does not confirm the diagnosis of APS. These asymptomatic individuals may eventually develop APS over time. Dr. Sciascia emphasized the importance of incorporating additional steps for primary prevention to reduce the risk of aPL carriers to develop thrombosis or pregnancy complications during his interview with Omnihealth Practice.  “The new treatment goal in the field of APS is to prevent the development of full-blown syndrome in asymptomatic individuals who are only positive for aPL. Therefore, the rate of thrombosis or pregnancy-related morbidity can be reduced by the early identification of seropositive individuals and consequent risk-based management,” commented Dr. Sciascia.

He further expanded on his thoughts by sharing that the conventional aPL screening might be not be sufficient to optimize the APS disease management. Dr. Sciascia commented, “How we treat patients with APS needs to change. We need to consider the role of detecting aPL not only as a biomarker for a diseases but, most practically, as risk factor for developing some clinical manifestations, mainly thrombosis and pregnancy morbidity.”

Necessarily, evidence-based recommendations based on the stratification of high-risk profile are required to treat APS. Thus, identifying the factors associated with prominent clinical manifestation related to APS, such as thrombotic, cardiovascular and obstetric events, are crucial for the disease burden management. A significant risk factor is the presence of high-risk aPL profile. Conventional aPL screening includes testing for lupus anticoagulant, anticardiolipin antibodies or antibeta2 glycoprotein I antibodies. Importantly, the European League against Rheumatic Diseases (EULAR) characterizes patients with triple-positive aPL profile as high risk for thrombosis.

Building on this principle of aPL profiling, Dr. Sciascia and his team developed and validated the Global APS score (GAPSS), determining a predictive model for developing clinical manifestations by analyzing the risk factors for thrombosis and pregnancy loss. For example, when applied to 143 pregnant women suspected for APS, the rate of uneventful pregnancy was significantly lower in women with GAPPS ≥12, suggesting that high risk subjects as identified by GAPSS might benefit from tailored therapeutic management.

Better standardization of both clinical and laboratory criteria is required for the current diagnosis of APS. Future classification criteria should take into account the expanding scenario of upcoming clinical and laboratory profiles. Besides, APS management strategies need to be specific, and feasible for everyday clinical practice. Future APS management ideally consists of a comprehensive panel of tests to assess the aPL profile and tailor the therapeutic choices.

  1. Sciascia S et al. Novel diagnostic and therapeutic frontiers in thrombotic antiphospholipid syndrome. Intern Emerg Med. 2017;12(1):1-7.2
  2. Miyakis S et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
  3. Pengo V et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011;118(17):4714-4718.
  4. Sciascia S et al.The global antiphospholipid syndrome score in primary APS. Rheumatology. 2015;54(1):134-138.