A qualitative investigation of the experiences of patients living with antiphospholipid antibodies.

OBJECTIVE: Substantial morbidity and mortality affect those with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome (APS), yet patient experiences remain poorly understood. This research investigated patient experiences of aPL/APS diagnosis; effects on daily life; and healthcare and treatment. METHODS: Patients aged ≥18 years with APS per the Revised Sapporo criteria or with ≥1 positive aPL on ≥2 occasions were recruited from a Canadian multidisciplinary APS clinic to participate in semi-structured in-depth interviews. Interviews were conducted virtually and transcribed verbatim for subsequent thematic analysis. RESULTS: Twenty-one patients with aPLs/APS participated; 95.2% were female, mean (SD) age was 45.6 (15.0) years. Most (71.4%) had APS, and 71.4% had aPLs/APS with SLE. Results are presented around patient experiences of aPL/APS diagnosis, effects on daily life, and healthcare and treatment. Participants described medical complications/physical symptoms and the healthcare, lifestyle, and emotional impacts experienced around the time of aPLs/APS diagnosis. In addition to the physical and psychosocial impacts of living with aPLs/APS, patients reported modified leisure activities, altered employment trajectories, and positive and negative impacts on relationships. Impacts on family planning were also a critical component of the aPL/APS lived experience; participants shared experiences of miscarriage, other pregnancy complications, and medication-related challenges (e.g., with low-molecular-weight heparin injections). Challenging aspects of aPL/APS healthcare and treatment were also discussed, particularly related to the lifestyle, physical, and emotional burden of medication use. Although a lack of resources was described, participants expressed trust in healthcare providers when making management decisions or when seeking information. Suggestions for resources included the need for additional medication-related information, examples to help contextualize management behaviours, and additional information for those with aPLs/APS without SLE. CONCLUSION: Patients highlighted how the diverse manifestations of aPLs/APS, accentuated by management-related challenges, impose considerable physical and psychosocial burdens. Results will inform the development of patient resources aligned with patient priorities.

Cognitive dysfunction and associated neuroimaging biomarkers in antiphospholipid syndrome: a systematic review.

OBJECTIVES: Cognitive dysfunction is common in patients with aPL (including primary APS or APS associated with SLE). Neuroimaging biomarkers may contribute to our understanding of mechanisms of cognitive dysfunction in these cohorts. This review aimed to investigate: (i) the prevalence of cognitive dysfunction in studies including neuroimaging biomarkers; and (ii) associations between cognition and neuroimaging biomarkers in patients with APS/aPL. METHODS: We conducted a systematic search of electronic databases PubMed, Science Direct, Scopus and PsycINFO, and included studies with descriptions of neuroimaging findings, cognitive dysfunction or both, in patients with aPL positivity (LA, IgG and IgM aCL and anti-ß2 glycoprotein-I antibodies). RESULTS: Of 120 search results we included 20 eligible studies (6 APS, 4 SLE with APS/aPL and 10 NPSLE). We identified a medium risk of bias in 6/11 (54%) of cohort studies and 44% of case-control studies, as well as marked heterogeneity in cognitive assessment batteries, APS and aPL definitions, and neuroimaging modalities and protocols. The prevalence of cognitive dysfunction ranged between 11 and 60.5%. Structural MRI was the most common imaging modality, reporting cognitive dysfunction to be associated with white matter hyperintensities, ischaemic lesions and cortical atrophy (four with cerebral atrophy, two with white matter hyperintensities and two with cerebral infarcts). CONCLUSION: Our findings confirm that cognitive impairment is commonly found in patients with aPL (including APS, SLE and NPSLE). The risk of bias, and heterogeneity in the cognitive and neuroimaging biomarkers reported does not allow for definitive conclusions.

Self-perceived quality of life of primary antiphospholipid syndrome patients using vitamin K antagonist.

PURPOSE: Primary antiphospholipid syndrome (PAPS) is a chronic autoimmune disorder clinically characterized by thromboembolic events or obstetric complications. Prolonged anticoagulation therapy with vitamin K antagonists (VKA) is the treatment of choice for PAPS patients with thrombosis. However, the efficacy of VKA therapy depends on laboratory monitoring, dose adjustment, adequate lifestyle and adherence to treatment. Difficulties with VKA therapy can affect patients' self-perceived health related quality of life (HRQOL). This study aims to evaluate PAPS patients' HRQOL, therapy adherence and knowledge of treatment. METHODS: A general Medical Outcome Study Short Form-36 (SF-36) and the Duke Anticoagulation Satisfaction Scale (DASS) were used to access APS-patients self-perceived HRQOL. Treatment adherence was measured by the Treatment Measure Adhesion (TMA) - oral anticoagulant version instrument, and knowledge of VKA treatment was measured using the MedTake test. RESULTS: 66 PAPS patients using VKA were assessed. 63% of them were female; the mean age was 41.9 years old, approximately 60% had unprovoked venous thrombosis and one third of the patients had recurrent thrombotic events. The most impacted domain of DASS was "psychological impacts" and the factors associated to anticoagulation related poor HRQOL were: female sex, presence of arterial thrombosis and INR lability. Using the SF-36 instrument, PAPS-patients self-perceived HRQOL was poorer than that of the general Brazilian population and was associated with female sex and presence of cardiovascular risk factors. CONCLUSION: Despite the high adherence to treatment and knowledge of VKA therapy, self-perceived HRQOL is poor in patients with PAPS and is mainly affected by VKA therapy. Searching for better treatment options is warranted.

The assessment of patients with the antiphospholipid antibody syndrome: where are we now?

The antiphospholipid antibody syndrome (APS), a chronic autoimmune thrombophilia with an increased mortality and morbidity, has been recognized for more than three decades. Unlike other autoimmune rheumatic conditions such as systemic lupus erythematosus, myositis and Sjögren's syndrome, relatively few attempts have been made to develop activity, damage or disease-specific quality of life indices for APS. In this review of the literature, we consider those attempts that have been made to develop assessment tools for patients with APS, but also reflect upon the nature of the condition, to discuss, in particular, whether an activity index is appropriate for this disease.

Fatigue in adults with primary antiphospholipid syndrome: findings from a mixed-methods study.

OBJECTIVE: This study aimed to explore the experience and impact of fatigue in adults with primary antiphospholipid syndrome (pAPS). METHODS: This sequential, explanatory mixed-methods study enrolled adults with a six-month or more history of pAPS. Consenting participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FS), Multi-Dimensional Perceived Social Support Scale, Patient Health Questionnaire (PHQ9), Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQMETS). Relationships between FS and other variables were explored with multiple linear regression. Interviews were conducted with a subgroup of participants, and the data were analysed thematically. RESULTS: A total of 103 participants were recruited (Mage = 50.3 years; standard deviation = 10.1 years; 18 males). Of these, 62% reported severe fatigue. Greater fatigue was associated with lower mood, physical inactivity, poorer sleep quality and lower perceived social support. The best-fit model explained 56% of the variance in FS (adjusted R2 = 0.560, F(3, 74) = 33.65, p > 0.001) and included PHQ9 and IPAQMETS as significant predictors, and PSQI as a non-significant predictor. Twenty participants completed interviews. Three key themes were identified: characteristics of fatigue, impact on life and coping strategies. CONCLUSION: Fatigue was a common symptom of pAPS and challenging to manage. Other factors, particularly mood and physical activity, influenced fatigue. Evidence-based self-management interventions are needed.

Frequency of psychological alterations in primary antiphospholipid syndrome: preliminary study.

Objectives To detect the frequency of psychological alterations in primary antiphospholipid syndrome patients. Methods Thirty-six primary antiphospholipid syndrome patients were analyzed by a psychological interview using a standard protocol and review of medical charts. Clinical manifestations, associated comorbidities, antiphospholipid antibodies, and treatment were also evaluated. Results The mean age was 44.2 ± 10.8 years, 29 (80%) were women and 29 (80%) were of Caucasian race. The mean duration of disease was 7.3 ± 5.2 years. The frequency of the presence of psychological alterations was 97.1%. Family dependence was observed in 14 (40%), memory loss in 12 (34.3%), social losses in 12 (34.3%), sexual limitations in seven (20%), sadness in six (17.1%), severe speech limitation in four (11.4%), anxiety in three (8.6%), learning difficulty in two (5.7%), generalized phobia in two (5.7%), suicide ideation in one (2.6%), agoraphobia in one (2.6%), and obsessive-compulsive disorder in one (2.6%). Conclusion This study demonstrated that almost all primary antiphospholipid syndrome patients have psychological alterations. These data reinforce the need for psychological evaluation in primary antiphospholipid syndrome patients.

The relationship between social support and health-related quality of life in patients with antiphospholipid (hughes) syndrome.

OBJECTIVE: Antiphospholipid (Hughes) syndrome (APS) is recognised as a systemic autoimmune disease defined by recurrent thromboembolic events and/or pregnancy morbidity. Little is known about the psychological burden of this long-term condition. This study aims to explore the relationship between social support and health-related quality of life (HRQoL) in patients with APS. METHODS: A total of 270 patients with a clinical diagnosis of APS participated in a cross-sectional online questionnaire survey. Data included demographics, disease-related information, social support and HRQoL. RESULTS: Both perceived and ideal social support were associated with HRQoL in APS. Patients reported receiving insufficient social support. Perceived emotional support was related to physical functioning (B = 7.77, p = .006, 95% CI: 2.25, 13.29); perceived instrumental support was associated with bodily pain (B = 17.52, p <  .001, 95% CI: 11.15, 23.90) and perceived informational support with physical and social functioning (B = -6.30, p = .05, 95% CI: -12.52, -0.08; B = 8.06, p = .02, 95% CI: 1.17, 14.94). Ideal emotional support was related to physical and social functioning (B = 5.80, p = .04, 95% CI: 0.26, 11.34; B = 7.53, p = .04, 95% CI: 0.55, 14.51); ideal instrumental support was associated with mental health (B = 4.73, p = .03, 95% CI: 0.38, 9.07) and ideal informational support with vitality (B = 5.85, p = .01, 95% CI: 1.23, 10.46). CONCLUSION: Social support was linked to HRQoL in patients with APS. Insufficient social support was associated with limitations in various HRQoL domains. Increasing social support especially through provision of disease-specific education might contribute to improving HRQoL in patients with APS. Patient-tailored interventions addressing psychosocial aspects of living with APS are needed to improve patients' psychological and physical status.

Annexin A2, autoimmunity, anxiety and depression.

OBJECTIVES: Antiphospholipid syndrome (APS) is associated with neurological manifestations and one of the novel autoantigens associated with this disease is Annexin A2 (ANXA2). In this work we have examined the effect of high levels of autoantibodies to ANXA2 on the brain in a mouse model. METHODS: Recombinant ANXA2 emulsified in adjuvant was used to immunize mice while mice immunized with adjuvant only served as controls. At peak antibody levels the animal underwent behavioral and cognitive tests and their brains were examined for ANXA2 immunoglobulin G (IgG) and expression of ANXA2 and the closely linked protein p11. RESULTS: Very high levels of anti-ANXA2 antibodies (Abs) were associated with reduced anxiety in the open field 13.14% ± 0.89% of the time in the center compared to 8.64% ± 0.91% observed in the control mice (p < 0.001 by t-test). A forced swim test found significantly less depression manifested by immobility in the ANXA2 group. The changes in behavior were accompanied by a significant reduction in serum corticosteroid levels of ANXA2 group compared to controls. Moreover, higher levels of total IgG and p11 expression were found in ANXA2 group brains. Lower levels of circulating anti-ANXA2 Abs were not associated with behavioral changes. CONCLUSIONS: We have established an animal model with high levels of anti-ANXA2 Abs which induced IgG accumulation in the brain and specific anxiolytic and anti-depressive effects. This model promises to further our understanding of autoimmune disease such as APS and to provide better understanding of the role of the ANXA2-p11 complex in the brain.

Impairment of quality of life in patients with antiphospholipid syndrome.

OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). CONCLUSION: Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient's perspective and to provide patients with the support they need.

Experiencing pregnancy in the context of lupus and antiphospholipid syndrome: a grounded theory.

OBJECTIVE: To understand the meanings attributed to pregnancy in the context of Lupus and antiphospholipid syndrome by women and healthcare professionals. METHOD: Qualitative research, using Symbolic Interactionism as a theoretical framework and Grounded Theory, a constructivist perspective. Data were collected between January and August 2022, through online interviews with 27 women with Lupus located on the social network Facebook and in-person or remote interviews with 12 healthcare professionals. RESULTS: The theoretical model constructed has two categories: "Equal conditions, distinct experiences: experiencing the gestational process" shows that obstetric complications and lack of connection with healthcare professionals trigger negative meanings to the experience; and "Therapeutic management interfering in the attribution of meanings to the experience", demonstrates that the way women interact with healthcare professionals and how they manage treatment favors a positive reframing. FINAL CONSIDERATIONS: The meanings attributed to pregnancy are elaborated and modified according to the interpretation of previous and current experiences, healthcare trajectory and interactions with healthcare professionals. Previous guidance, planning, bonding and trust in healthcare professionals enable positive meanings, while obstetric complications, unqualified assistance and lack of bonding with professionals provide negative meanings.

Obsessive-compulsive behavior as presenting symptom of primary antiphospholipid syndrome.

OBJECTIVE: This study aimed to improve understanding and treatment of psychiatric symptoms in antiphospholipid syndrome (APS) and to present an approach to the medical management of patients presenting with obsessive-compulsive disorder (OCD) with suspected neurovascular pathology. METHOD: A 15-year-old boy presented with severe OCD of recent onset. An infarct of the caudate nucleus was identified as the initial presentation of primary APS. This case report includes a selective literature review of the neuropsychiatric correlates of APS. RESULTS: The patient had OCD for 3 months with increasing symptoms resulting in admission for psychiatric reasons. After referral to the emergency department 3 weeks later, an infarct of the caudate nucleus was documented using magnetic resonance images of the brain, and APS was diagnosed based on additional laboratory findings. Anticoagulant treatment (enoxaparin and phenprocoumon) in this patient was effective in reducing obsessive-compulsive symptom severity. CONCLUSION: OCD may present as a neuropsychiatric manifestation of APS. The present observations are consistent with a thrombotic mechanism for neurologic or psychiatric symptoms in APS. In general, routine medical workup for childhood OCD is not indicated, but a comprehensive psychiatric, medical, and family history taking and physical examination are essential, particularly if OCD is of recent onset. The role of anticoagulant therapy in neuropsychiatric manifestations of APS without the presence of a cerebral infarct requires further research.

Factors and comorbidities associated with first neuropsychiatric event in systemic lupus erythematosus: does a risk profile exist? A large multicentre retrospective cross-sectional study on 959 Italian patients.

OBJECTIVE: To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE. METHODS: A number of generic (not strictly SLE related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated. RESULTS: Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors [mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001] were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement. CONCLUSIONS: In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus.

A patient with bipolar disorder and antiphospholipid syndrome.

Antiphospholipidsyndrome (APS) is an autoimmune disorder which causes a hyper-coagulable state characterized by recurrent thrombosis. It has a diverse range of central nervous system manifestations. We describe a case of a 61 year old man with bipolar disorder and APS, and we compare this to a previously reported case. Additionally, we reviewed literature regarding APS-related markers and the relationship of APS to other psychiatric and neurologic illnesses. We discuss possible mechanisms for an association between APS and bipolar disorder. We encourage clinicians to be aware of this possible relationship and have proposed research strategies.

Recurrent miscarriage and thrombophilia: an update.

PURPOSE OF REVIEW: Acquired and inherited thrombophilia is an important research avenue in the recurrent miscarriage field. The optimum treatment for patients with recurrent miscarriage and a confirmed thrombophilia remains a contentious issue. We aim to appraise and explore the latest research in the field of thrombophilia and recurrent miscarriage in this review. RECENT FINDINGS: Antiphospholipid syndrome (APS) is the only proven thrombophilia that is associated with adverse pregnancy outcomes. Research involving inherited thrombophilia and recurrent miscarriage is limited to small observational studies with small and heterogeneous populations. Aspirin and heparin therapy are frequently prescribed for APS, yet there is no robust evidence for the most efficacious regime. The combination of inherited hypercoagulability and environmental factors in association with recurrent miscarriage has recently been explored as an aid to identify high-risk individuals. SUMMARY: The cause of recurrent miscarriage is multifactorial and appropriate treatment continues to be a challenge. Laboratory tests need to be standardized and well designed multicentre research trials are essential to expand on the current knowledge base with the aim to produce strong evidence-based medicine.

Primary antiphospholipid antibody syndrome presenting with encephalopathy, psychosis and seizures.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events, miscarriages and thrombocytopenia with persistently positive antiphospholipid antibodies.( 1,2 ) APS may be isolated (primary APS) or associated to a connective tissue disease, most often systemic lupus erythematosus (SLE).( 1,2 ) APS usually affects young patients before the fifth decade( 3 ) with stroke being the commonest neurological manifestation.( 4 ) Various other neurological manifestations are being recognized in patients with APS including migraine, epilepsy, multi-infarct dementia and chorea.( 2 ) The pathological process underlying the neurological manifestations remains obscure.( 1,2 ) Herein we report a case of primary APS presenting with a group of unusual neurological manifestations in a 68-year-old woman.

Pathological gambling and primary antiphospholipid (Hughes) syndrome: a unique neuropsychiatric association.

Neuropsychiatric conditions are common in patients with primary antiphospholipid syndrome (APS) with or without vascular thrombosis of the central nervous system. There are frequent descriptions of memory alterations, cognition and mood disorders, such as depression, anxiety, and even conditions of mania and psychosis preceding the diagnosis of primary APS. However, this study is the first to present primary or secondary APS associated with habit or impulse control disorders. The authors describe the case of a 53-year-old male patient who had been a pathological gambler since adulthood and who has had APS for more than 20 years. We describe the case and review its characteristics, criteria for diagnosis and treatment offered for patients with this specific subtype of impulse disorder.

[Neurological and psychiatric manifestations of systemic lupus erythematosus and antiphospholipid syndrome]. / A szisztémás lupus erythematosus és az antifoszfolipid-szindróma neurológiai és pszichiátriai szövodményei.

Neurological or psychiatric symptoms are present in 60% of the cases with systemic lupus erythematosus. Direct lesions of nervous system are associated with the presence of antibodies, vasculitis, thrombosis and impairments mediated by cytokines. Damages caused by injuries of other organs or those due to therapy are known as indirect causes. In the complex pathogenesis the primary cause is neuronal dysfunction mediated by autoantibodies, vasculopathia and coagulopathia. Until now, more than 20 antibodies have been identified in association with damages of the nervous system. These antibodies may impair neurons or astrocytes and may promote thrombotic processes in vessels of the brain. Activation of endothelial cells and disturbance of blood-brain barrier are also pathogenic factors. In patients with systemic lupus erythematosus the most frequent psychiatric manifestations are organic psychosyndrome, particularly deterioration of cognitive functions, and depression, while the most common neurological syndromes are epilepsy and ischemic stroke. In the pathogenesis of antiphospholipid syndrome ß2-glycoprotein I plays the most important role; binding to its antibody the complex may interact with cells and modify haemostatic actions. The most frequent neurological manifestations of antiphospholipid syndrome are headache and ischemic stroke.

[Neuropsychiatric manifestations of systemic lupus erythematosus]. / Neuropsihijatrijska ocitovanja sistemskog eritemskog lupusa.

Neurologic and psychiatric disorder is reported in up to 70% of patients with systemic lupus erythematosus (SLE). New classification criteria for neuropsychiatric SLE define 19 syndromes with characteristic clinical features, laboratory findings and imaging. Better diagnostic possibilities, particularly imaging methods reveal new data on some conditions: demyelinating disorders in patients with SLE, neuropsychiatric disorders associated with antiphospholipid syndrome. Based on neuropsychological examination the diagnosis of cognitive dysfunction, most common psychiatric impairment, is more often established.

Mania: psychiatric manifestations of the antiphospholipid syndrome.

BACKGROUND: Antiphospholipid syndrome (APS) is a prothrombotic condition characterized by recurrent vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies. Central nervous system (CNS) involvement is a prominent feature of APS, and many neurological manifestations have been described in published reports. There are limited data on psychiatric syndromes occurring in association with APS, and there have been no previous reports of mania associated with APS. METHOD: The authors present the case of a 31-year-old man who experienced an acute manic episode in association with APS. They review the literature on psychiatric manifestations of APS, discuss potential mechanisms of CNS pathogenesis, and consider diagnostic and treatment implications of the co-occurrence of APS and psychiatric symptoms.

Explaining "unexplained" perinatal loss: experiences of women with antiphospholipid syndrome.

OBJECTIVE: To explore women's experiences of 1 or more perinatal losses associated with antiphospholipid syndrome (APS) and describe their perceptions about losses related to this disorder and its effects on both their outlook and subsequent childbearing. SUBJECTS: The participants included thirty-eight 18- to 50-year-old women from 5 countries, who were members of general and APS online perinatal support groups and had 1 or more perinatal losses associated with APS. METHODS: The respondents were recruited from various online perinatal loss support groups, using convenience and snowball sampling. Semistructured e-mail interviews were conducted, using the qualitative technique of phenomenology. RESULTS: Two major themes that emerged from the data are existence in bewilderment and persistence in the quest for knowledge and information. The first theme has 2 subthemes: delayed diagnosis and living in uncertainty. CONCLUSION: Women with APS and related perinatal losses perceive the need to persist in seeking scientific knowledge because the information they receive from healthcare providers is limited and unclear. Evidence-based medical and nursing education about antiphospholipid antibody syndrome is necessary to improve clinical practice and thereby the perinatal outcome and the ill effects of this condition for women during and after the childbearing period.