RARE DISEASE
Antiphospholipid syndrome
Antiphospholipid syndrome
Antiphospholipid syndrome
Synonyms: APLS, Antiphospholipid antibody syndrome, Classic APLS, Classic antiphospholipid syndrome, Hughes syndrome
Synonyms: APLS, Antiphospholipid antibody syndrome, Classic APLS, Classic antiphospholipid syndrome, Hughes syndrome
Synonyms: APLS, Antiphospholipid antibody syndrome, Classic APLS, Classic antiphospholipid syndrome, Hughes syndrome
Drug discovery
2
drugs
With orphan designations
Overview
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by venous/arterial thrombosis, recurrent pregnancy loss, or placental insufficiency in the presence of persistently elevated antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein-I antibodies). It may occur as a primary condition or secondary to autoimmune diseases like systemic lupus erythematosus. Diagnosis requires clinical events plus antibody positivity on ≥2 tests ≥12 weeks apart. Long-term anticoagulation is the mainstay of thrombotic APS management [1][6][14].
Population
Prevalence: 40-50 cases per 100,000 in the US, with 30-40% occurring in SLE patients [2][17]
Demographics: 3:1 female predominance; peak diagnosis between ages 20-50 [1][10][14]
High-risk profiles: Triple antibody positivity (lupus anticoagulant + IgG anticardiolipin + IgG anti-β2GPI) confers greatest thrombotic risk [3][6]
Therapies
Thrombosis: Lifelong warfarin (INR 2-3) for venous events; arterial thrombosis may require INR 3-4 or combined antiplatelet therapy [3][12][15]
Obstetric: Low-molecular-weight heparin + low-dose aspirin for pregnancy, reducing miscarriage risk from >70% to <30% [3][12][14]
Catastrophic APS: Triple therapy with anticoagulants, corticosteroids, and plasma exchange/IVIG (survival ↑ from 54% to 69%) [8][16]
Categories: rare gynecological and obstetric diseases, rare hematological diseases, rare systemic and rheumatological diseases
Research Papers
2,684 drug discovery papers about Antiphospholipid syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,684 drug discovery papers about Antiphospholipid syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Reported Prevalence of Inherited Thrombophilia in Pregnancy: Impact of Cohort Selection on Screening Implications-A Systematic Review.
Background/Objectives: Inherited thrombophilia (IT) has been extensively investigated as a potential contributor to adverse pregnancy outcomes; however, reported prevalence varies widely across studies. This systematic review aimed to evaluate how cohort selection influences the reported prevalence of inherited thrombophilia in pregnancy and to explore the implications of this variability for clinical interpretation and screening practices. Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and Google Scholar were searched. A total of 5480 records were identified, and 7 observational studies (cohort and case-control) met inclusion criteria. Data were synthesized qualitatively due to heterogeneity. Results: Prevalence ranged from 0% to 14%, depending on population characteristics. The largest cohort study reported an inherited thrombophilia prevalence of 8.1%, comparable to the general population. Higher rates were observed in referral-based and antiphospholipid Syndrome (APS)-associated cohorts, while case-control studies showed no significant differences between affected individuals and controls. Ethnic variability was also observed. Conclusions: These findings should be interpreted as patterns observed across heterogeneous study designs rather than as definitive evidence of causality. Current evidence does not clearly support universal screening in pregnancy; however, the findings should be interpreted cautiously because several included studies were limited by small sample sizes and methodological heterogeneity.
2026-08-12 | Case Report: IVIG as a bridging strategy in high-risk antiphospholipid syndrome with infected cutaneous ulceration and thrombocytopenia.
Severe cutaneous ulceration in antiphospholipid syndrome (APS) with concurrent infection and thrombocytopenia presents a therapeutic dilemma: standard immunosuppression risks worsening infection, while anticoagulation risks hemorrhage. We present a high-risk case successfully managed using intravenous immunoglobulin (IVIG) as a bridging immunomodulatory strategy. A 73-year-old man with triple-positive APS and immune thrombocytopenic purpura (ITP) developed rapidly progressive leg ulcers with clinical features consistent with pyoderma gangrenosum-like disease, complicated by active MRSA and Pseudomonas aeruginosa infection and severe thrombocytopenia (12 × 109/L). Standard therapies were contraindicated: corticosteroids risked worsening infection; anticoagulation risked hemorrhage. The patient received IVIG (0.4 g/kg per dose, every 3 weeks) as primary immunomodulation, concurrent targeted antimicrobial therapy, temporary anticoagulation interruption, and discontinuation of baseline mycophenolate mofetil. Following platelet recovery above 70 × 109/L, therapeutic anticoagulation was resumed with enoxaparin (80 mg subcutaneously twice daily) and aspirin (75 mg daily). Over five months, progressive re-epithelialization culminated in complete healing with platelet recovery. This case supports the feasibility of IVIG as a bridging immunomodulatory strategy in high-risk APS cutaneous disease where standard therapies are contraindicated by concurrent infection and thrombocytopenia. The sequential management approach successfully resolved a clinically challenging scenario. This case illustrates how risk-adapted immunomodulation may enable safe management of complex APS manifestations.
2026-08-10 | Monoclonal Gammopathy of Thrombotic Significance.
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant precursor to multiple myeloma (MM). While development of end-organ damage in MM largely reflects increasing clonal burden, emerging evidence indicates that qualitative properties of the monoclonal immunoglobulins in MGUS can be directly pathogenic, leading to serious organ injury independent of disease burden. This has led to the recognition of a broader spectrum of disorders collectively termed monoclonal gammopathy of clinical significance (MGCS). MGCS can be further subclassified based on the organ system involved; for example, monoclonal gammopathy of renal significance specifically refers to monoclonal immunoglobulin-driven renal injury. Along these lines, we propose monoclonal gammopathy of thrombotic significance (MGTS) as encompassing thrombotic disorders in which there is definitive, mechanistically supported evidence that a monoclonal (M)-protein associated with a clonal plasma or B-cell disorder directly contributes to thrombosis. Based on current evidence, monoclonal protein-induced immune thrombocytopenia and thrombosis is the only disorder that meets our criteria for MGTS. Other thrombotic disorders, such as thrombotic microangiopathy and antiphospholipid syndrome, may occur in the setting of a monoclonal protein and have biologically plausible M-protein-mediated mechanisms; however, direct evidence implicating the M-protein in thrombosis is currently lacking. Accordingly, we provisionally classify these disorders as thrombotic syndromes associated with M-proteins, pending causal validation. We also highlight thrombotic disease associations with multifactorial pathogenesis that should not be classified as MGTS. Broader recognition of MGTS is essential to advance consensus definitions, establish diagnostic criteria, and develop evidence-based management strategies for this clinically important group of disorders.
2026-08-08 | Enhanced type I interferon signature in primary APS patients is associated with thrombocytopenia.
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or obstetric complications due to persistent antiphospholipid antibodies. Type I interferon (IFN) upregulation has been identified as a potential contributor to the pathophysiology of APS, however, the relationship between type I IFN and clinical manifestations of APS still needs to be delineated. The objective of this study was the evaluation of the potential role of type I IFN regarding different APS manifestations. We conducted a retrospective analysis of APS patients who presented to our clinic between 2017 and 2024, focusing on clinical manifestations, recurring events and serological profiles in relation to Siglec-1 expression on monocytes, as a surrogate marker of type I IFN signature. Out of the 218 APS patients included in the study, 123 were diagnosed with primary APS (pAPS) and 95 with secondary APS (sAPS), the latter mostly SLE associated, showing a general higher type I IFN signature as the pAPS cohort. While no significant differences in Siglec-1 expression were observed across most APS manifestations (venous, arterial, mixed and obstetric events), significantly higher type I IFN activity was detected in APS patients with thrombocytopenia compared to those without (p = 0.0061). Moreover, we found an inverse correlation between platelet numbers and Siglec-1 values. Interestingly, the difference in type I IFN signature was confirmed in the pAPS cohort with thrombocytopenia (p = 0.0242). In sAPS, Siglec-1 expression did not differ significantly between patients with and without thrombocytopenia (p = 0.4664). With regard to serological and clinical characteristics, patients with thrombocytopenia exhibited a higher prevalence of triple positivity, elevated levels of anti-cardiolipin IgG antibodies and an increased incidence of recurrent and mixed (arterial/venous) thromboembolic events. To conclude, the data indicate that type I IFN may be a relevant factor for the occurrence of thrombocytopenia in pAPS. Moreover, thrombocytopenia in APS was linked to increased prevalence of triple positivity, higher anti-cardiolipin IgG titres, and higher disease severity, underscoring the importance of closer monitoring in this subgroup. These results warrant validation in prospective studies and could support potential therapeutic targeting of type I IFN in a subset of APS patients.
2026-08-02 | The Dual Role of Uric Acid: Pathological Implications Across Chronic Diseases and Current Approaches to Hyperuricemia Management.
Uric acid is the end product of purine metabolism and plays a dichotomous role in the human body. On one hand, it exerts antioxidant and neuroprotective effects; on the other hand, chronic hyperuricemia has been strongly associated with diseases beyond gout, affecting the cardiovascular, renal, metabolic, autoimmune, and central nervous systems (CNS). Excess uric acid promotes oxidative stress, endothelial damage, neurodegeneration, inflammasome activation, and impairs energy metabolism. It exacerbates autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS), by increasing inflammatory and oxidative damage, leading to greater end-organ damage. The British Society for Rheumatology, European League Against Rheumatism, American College of Rheumatology, and National Institute for Health and Care Excellence (NICE) have all established a "treat-to-target" approach for hyperuricemia with serum urate levels below 6 mg/dL and below 5 mg/dL in severe cases. Allopurinol and Febuxostat, xanthine oxidase inhibitors, are used as first-line pharmacological therapies for the treatment of hyperuricemia, whereas uricosurics and Interleukin-1 (IL-1) inhibitors are preferred in cases of refractory hyperuricemia. Lifestyle modifications, such as the Dietary Approaches to Stop Hypertension (DASH) diet, weight reduction, and smoking cessation, are also recommended for the long-term management of the disease. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, selective urate transport inhibitors, and plant-derived anti-inflammatory compounds have emerged as new treatments with promising responses. This review synthesizes the current literature on the multifaceted role of uric acid and emphasizes its systemic implications in chronic diseases. It also outlines the already established management options and new innovative therapies for managing this disease. Understanding this dichotomous role is essential for adopting a precise management approach that balances the protective and pathological effects of uric acid.
2026-08-13 | Reported Prevalence of Inherited Thrombophilia in Pregnancy: Impact of Cohort Selection on Screening Implications-A Systematic Review.
Background/Objectives: Inherited thrombophilia (IT) has been extensively investigated as a potential contributor to adverse pregnancy outcomes; however, reported prevalence varies widely across studies. This systematic review aimed to evaluate how cohort selection influences the reported prevalence of inherited thrombophilia in pregnancy and to explore the implications of this variability for clinical interpretation and screening practices. Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and Google Scholar were searched. A total of 5480 records were identified, and 7 observational studies (cohort and case-control) met inclusion criteria. Data were synthesized qualitatively due to heterogeneity. Results: Prevalence ranged from 0% to 14%, depending on population characteristics. The largest cohort study reported an inherited thrombophilia prevalence of 8.1%, comparable to the general population. Higher rates were observed in referral-based and antiphospholipid Syndrome (APS)-associated cohorts, while case-control studies showed no significant differences between affected individuals and controls. Ethnic variability was also observed. Conclusions: These findings should be interpreted as patterns observed across heterogeneous study designs rather than as definitive evidence of causality. Current evidence does not clearly support universal screening in pregnancy; however, the findings should be interpreted cautiously because several included studies were limited by small sample sizes and methodological heterogeneity.
2026-08-12 | Case Report: IVIG as a bridging strategy in high-risk antiphospholipid syndrome with infected cutaneous ulceration and thrombocytopenia.
Severe cutaneous ulceration in antiphospholipid syndrome (APS) with concurrent infection and thrombocytopenia presents a therapeutic dilemma: standard immunosuppression risks worsening infection, while anticoagulation risks hemorrhage. We present a high-risk case successfully managed using intravenous immunoglobulin (IVIG) as a bridging immunomodulatory strategy. A 73-year-old man with triple-positive APS and immune thrombocytopenic purpura (ITP) developed rapidly progressive leg ulcers with clinical features consistent with pyoderma gangrenosum-like disease, complicated by active MRSA and Pseudomonas aeruginosa infection and severe thrombocytopenia (12 × 109/L). Standard therapies were contraindicated: corticosteroids risked worsening infection; anticoagulation risked hemorrhage. The patient received IVIG (0.4 g/kg per dose, every 3 weeks) as primary immunomodulation, concurrent targeted antimicrobial therapy, temporary anticoagulation interruption, and discontinuation of baseline mycophenolate mofetil. Following platelet recovery above 70 × 109/L, therapeutic anticoagulation was resumed with enoxaparin (80 mg subcutaneously twice daily) and aspirin (75 mg daily). Over five months, progressive re-epithelialization culminated in complete healing with platelet recovery. This case supports the feasibility of IVIG as a bridging immunomodulatory strategy in high-risk APS cutaneous disease where standard therapies are contraindicated by concurrent infection and thrombocytopenia. The sequential management approach successfully resolved a clinically challenging scenario. This case illustrates how risk-adapted immunomodulation may enable safe management of complex APS manifestations.
2026-08-10 | Monoclonal Gammopathy of Thrombotic Significance.
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant precursor to multiple myeloma (MM). While development of end-organ damage in MM largely reflects increasing clonal burden, emerging evidence indicates that qualitative properties of the monoclonal immunoglobulins in MGUS can be directly pathogenic, leading to serious organ injury independent of disease burden. This has led to the recognition of a broader spectrum of disorders collectively termed monoclonal gammopathy of clinical significance (MGCS). MGCS can be further subclassified based on the organ system involved; for example, monoclonal gammopathy of renal significance specifically refers to monoclonal immunoglobulin-driven renal injury. Along these lines, we propose monoclonal gammopathy of thrombotic significance (MGTS) as encompassing thrombotic disorders in which there is definitive, mechanistically supported evidence that a monoclonal (M)-protein associated with a clonal plasma or B-cell disorder directly contributes to thrombosis. Based on current evidence, monoclonal protein-induced immune thrombocytopenia and thrombosis is the only disorder that meets our criteria for MGTS. Other thrombotic disorders, such as thrombotic microangiopathy and antiphospholipid syndrome, may occur in the setting of a monoclonal protein and have biologically plausible M-protein-mediated mechanisms; however, direct evidence implicating the M-protein in thrombosis is currently lacking. Accordingly, we provisionally classify these disorders as thrombotic syndromes associated with M-proteins, pending causal validation. We also highlight thrombotic disease associations with multifactorial pathogenesis that should not be classified as MGTS. Broader recognition of MGTS is essential to advance consensus definitions, establish diagnostic criteria, and develop evidence-based management strategies for this clinically important group of disorders.
2026-08-08 | Enhanced type I interferon signature in primary APS patients is associated with thrombocytopenia.
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or obstetric complications due to persistent antiphospholipid antibodies. Type I interferon (IFN) upregulation has been identified as a potential contributor to the pathophysiology of APS, however, the relationship between type I IFN and clinical manifestations of APS still needs to be delineated. The objective of this study was the evaluation of the potential role of type I IFN regarding different APS manifestations. We conducted a retrospective analysis of APS patients who presented to our clinic between 2017 and 2024, focusing on clinical manifestations, recurring events and serological profiles in relation to Siglec-1 expression on monocytes, as a surrogate marker of type I IFN signature. Out of the 218 APS patients included in the study, 123 were diagnosed with primary APS (pAPS) and 95 with secondary APS (sAPS), the latter mostly SLE associated, showing a general higher type I IFN signature as the pAPS cohort. While no significant differences in Siglec-1 expression were observed across most APS manifestations (venous, arterial, mixed and obstetric events), significantly higher type I IFN activity was detected in APS patients with thrombocytopenia compared to those without (p = 0.0061). Moreover, we found an inverse correlation between platelet numbers and Siglec-1 values. Interestingly, the difference in type I IFN signature was confirmed in the pAPS cohort with thrombocytopenia (p = 0.0242). In sAPS, Siglec-1 expression did not differ significantly between patients with and without thrombocytopenia (p = 0.4664). With regard to serological and clinical characteristics, patients with thrombocytopenia exhibited a higher prevalence of triple positivity, elevated levels of anti-cardiolipin IgG antibodies and an increased incidence of recurrent and mixed (arterial/venous) thromboembolic events. To conclude, the data indicate that type I IFN may be a relevant factor for the occurrence of thrombocytopenia in pAPS. Moreover, thrombocytopenia in APS was linked to increased prevalence of triple positivity, higher anti-cardiolipin IgG titres, and higher disease severity, underscoring the importance of closer monitoring in this subgroup. These results warrant validation in prospective studies and could support potential therapeutic targeting of type I IFN in a subset of APS patients.
2026-08-02 | The Dual Role of Uric Acid: Pathological Implications Across Chronic Diseases and Current Approaches to Hyperuricemia Management.
Uric acid is the end product of purine metabolism and plays a dichotomous role in the human body. On one hand, it exerts antioxidant and neuroprotective effects; on the other hand, chronic hyperuricemia has been strongly associated with diseases beyond gout, affecting the cardiovascular, renal, metabolic, autoimmune, and central nervous systems (CNS). Excess uric acid promotes oxidative stress, endothelial damage, neurodegeneration, inflammasome activation, and impairs energy metabolism. It exacerbates autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS), by increasing inflammatory and oxidative damage, leading to greater end-organ damage. The British Society for Rheumatology, European League Against Rheumatism, American College of Rheumatology, and National Institute for Health and Care Excellence (NICE) have all established a "treat-to-target" approach for hyperuricemia with serum urate levels below 6 mg/dL and below 5 mg/dL in severe cases. Allopurinol and Febuxostat, xanthine oxidase inhibitors, are used as first-line pharmacological therapies for the treatment of hyperuricemia, whereas uricosurics and Interleukin-1 (IL-1) inhibitors are preferred in cases of refractory hyperuricemia. Lifestyle modifications, such as the Dietary Approaches to Stop Hypertension (DASH) diet, weight reduction, and smoking cessation, are also recommended for the long-term management of the disease. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, selective urate transport inhibitors, and plant-derived anti-inflammatory compounds have emerged as new treatments with promising responses. This review synthesizes the current literature on the multifaceted role of uric acid and emphasizes its systemic implications in chronic diseases. It also outlines the already established management options and new innovative therapies for managing this disease. Understanding this dichotomous role is essential for adopting a precise management approach that balances the protective and pathological effects of uric acid.
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Drug Discovery Landscape
2 orphan drug designations for Antiphospholipid syndrome.
2 orphan drug designations for Antiphospholipid syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
certolizumab pegol | antibodies | FDA | 2026-03-02 | — | UCB, Inc. |
Hydroxychloroquine | small molecules | EMA | 2017-01-12 | — | Cristina Belizna |
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