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The Journal of Clinical Investigation Jun 2024Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune...
Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune disease known as antiphospholipid syndrome (APS). The understanding of neutrophil metabolism has advanced tremendously in the past decade, and accumulating evidence suggests that a variety of metabolic pathways guide neutrophil activities in health and disease. Our previous work characterizing the transcriptome of APS neutrophils revealed that genes related to glycolysis, glycogenolysis, and the pentose phosphate pathway (PPP) were significantly upregulated. Here, we found that APS patient neutrophils used glycolysis more avidly than healthy control neutrophils, especially when the neutrophils were from APS patients with a history of microvascular disease. In vitro, inhibiting either glycolysis or the PPP tempered phorbol myristate acetate- and APS IgG-induced NETosis, but not NETosis triggered by a calcium ionophore. In mice, inhibiting either glycolysis or the PPP reduced neutrophil reactive oxygen species production and suppressed APS IgG-induced NETosis ex vivo. When APS-associated thrombosis was evaluated in mice, inhibiting either glycolysis or the PPP markedly suppressed thrombosis and circulating NET remnants. In summary, these data identify a potential role for restraining neutrophil glucose flux in the treatment of APS.
PubMed: 38869951
DOI: 10.1172/JCI169893 -
International Journal of... Apr 2024Patients with human immunodeficiency virus (HIV) infection have an increased likelihood of venous thromboembolism (VTE) owing to factors such as acquired protein C and S...
Patients with human immunodeficiency virus (HIV) infection have an increased likelihood of venous thromboembolism (VTE) owing to factors such as acquired protein C and S deficiency, antiphospholipid antibody syndrome, and heightened levels of pro-inflammatory cytokines. This case report highlights an exceptionally uncommon occurrence of deep venous thrombosis in an HIV-infected patient receiving a therapeutic dose of enoxaparin. This underscores the need for cautious consideration of the risk of VTE in HIV-infected individuals, even with preventive or therapeutic anticoagulant treatment. Further research is recommended to investigate HIV as a potential risk factor of prophylactic anticoagulation.
PubMed: 38868809
DOI: 10.18502/ijhoscr.v18i2.15379 -
Clinical Case Reports Jun 2024Our case depicts a challenging diagnosis of catastrophic antiphospholipid syndrome in a young patient with a heterogenous presentation with extensive clinical course, a...
Our case depicts a challenging diagnosis of catastrophic antiphospholipid syndrome in a young patient with a heterogenous presentation with extensive clinical course, a wide range of investigations, including multimodality imaging, and multidisciplinary expertise, to initiate prompt treatment addressing multiorgan thrombotic injury.
PubMed: 38868115
DOI: 10.1002/ccr3.9061 -
Transfusion Medicine and Hemotherapy :... Jun 2024The transplantation of highly sensitized patients remains a major obstacle. Immunized patients wait longer for a transplant if not prioritized, and if transplanted,...
Successful Desensitization with Imlifidase and Daratumumab in a Highly Immunized, Crossmatch Positive, Blood Group-Incompatible Living-Donor Re-Transplant Recipient with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.
INTRODUCTION
The transplantation of highly sensitized patients remains a major obstacle. Immunized patients wait longer for a transplant if not prioritized, and if transplanted, their transplant outcome is worse.
CASE PRESENTATION
We report a successful AB0- and HLA-incompatible living donor kidney transplantation in a 35-year-old female patient with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The patient had a positive T- and B-cell complement-dependent cytotoxicity (CDC) crossmatch and previous graft loss due to renal vein thrombosis. We treated the patient with intravenous immunoglobulins, rituximab, horse anti-thymocyte globulin, daratumumab, and imlifidase, besides standard immunosuppression. All IgG antibodies were sensitive to imlifidase treatment. Besides donor-specific HLA antibodies, anti-dsDNA antibodies and antiphospholipid antibodies were cleaved. The patient initially had delayed graft function. Two kidney biopsies (day 7 and day 14) revealed acute tubular necrosis without signs of HLA antibody-mediated rejection. On posttransplant day 30, hemodialysis was stopped, and creatinine levels declined over the next weeks to a baseline creatinine of about 1.7 mg/dL after 12 months.
CONCLUSION
In this case, a novel multimodal treatment strategy including daratumumab and imlifidase enabled successful kidney transplantation for a highly immunized patient with antiphospholipid antibodies.
PubMed: 38867806
DOI: 10.1159/000538513 -
Research and Practice in Thrombosis and... May 2024Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in...
Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.
PubMed: 38854821
DOI: 10.1016/j.rpth.2024.102432 -
Cureus May 2024Cerebral venous thrombosis (CVT) is a cerebrovascular condition characterized by cerebral venous sinus thrombosis, resulting in venous infarction. The condition can...
Multifaceted Cerebral Venous Thrombosis With Extensive Intra-cerebral Hemorrhage in a Young Man With Mitral Valve Replacement Due to Thrombosis and IgA Nephropathy: A Challenging Case Report From Saudi Arabia.
Cerebral venous thrombosis (CVT) is a cerebrovascular condition characterized by cerebral venous sinus thrombosis, resulting in venous infarction. The condition can manifest through a range of signs and symptoms such as headaches, benign intracranial hypertension, subarachnoid hemorrhage, localized neurological deficits, seizures, unexplained changes in consciousness, and meningoencephalitis. Its causes are linked to numerous different conditions and factors. We report a complicated case and course of antiphospholipid antibody syndrome in a young patient. The case began two years prior, involving a 33-year-old man who had chronic kidney disease due to IgA nephropathy, pneumonia, and a large mass on his native mitral valve. He developed deep vein thrombosis (DVT) in his upper limb, for which he was prescribed warfarin. He was transferred to our hospital with a five-day history of severe headaches followed by a decrease in consciousness and seizures requiring intubation. He was found to have a subdural hematoma with a high international normalized ratio (INR). He underwent hematoma evacuation and a right decompressive craniotomy. CT of the brain via CT venography revealed intracerebral haemorrhage along with ischemic infarction in the right frontal-parietal and temporal lobes and cerebral venous thrombosis. He was treated with heparin infusion but later developed heparin-induced thrombocytopenia (HIT) and was switched to fondaparinux. Plasma exchange and intravenous methylprednisolone were given. His hospital course was complicated by recurrent infections, a new left intraparenchymal hemorrhage with intraventricular extension, and the need for extra ventricular drainage (EVD). The diagnosis of antiphospholipid antibody syndrome was confirmed. This case report provides invaluable insights into managing a complex scenario that requires balanced decisions between anticoagulation in the context of severe ICH and the necessity of immunosuppressive therapy. The emphasis is on the significance of using a personalized and multidisciplinary strategy to address CVT situations and their issues.
PubMed: 38854275
DOI: 10.7759/cureus.60016 -
Cureus May 2024Antiphospholipid syndrome (APLS) is an established cause of thrombosis and hypercoagulability. However, the clinical characteristics of those with APLS or patients with...
BACKGROUND
Antiphospholipid syndrome (APLS) is an established cause of thrombosis and hypercoagulability. However, the clinical characteristics of those with APLS or patients with positive antiphospholipid antibodies (APLA) in the embolic stroke of undetermined source (ESUS) have not been well studied.
METHODS
A retrospective analysis was conducted between January 1, 2010, and December 31, 2020, across all three Mayo Clinic sites. Patients who were included in the study were tested for APLA and had a diagnosis of ESUS. Baseline characteristics, radiographic parameters, and outcome data were collected and compared between those who tested positive for APLS or had positive APLA and those who were negative.
RESULTS
A total of 206 patients were included in the study. Eight (4%) patients were diagnosed with APLS, and 21 (10%) patients had positive APLA. On comparing those with a diagnosis of APLS and those without, patients with APLS were found to be significantly older (75 years old ± 9 vs. 58 years old ± 14, p = 0.001) and were more likely to have a history of cancer (50% vs. 13%, p = 0.012). Those with positive APLA had similar findings of being older (67 years old ±13 vs. 58 years old ± 14 p = 0.003) and more likely to have a history of cancer (29% vs. 8.4% p = 0.027). Radiographically, those with APLS had a higher white matter disease burden (Fazekas score median 2 (IQR 1.5-3) vs. median 1 (IQR 1-2), p = 0.028).
CONCLUSION
Both APLS and positive APLA are associated with older age and a history of malignancy. These findings highlight the importance of considering a hypercoagulable evaluation even in the elderly ESUS population.
PubMed: 38854238
DOI: 10.7759/cureus.59891 -
Ugeskrift For Laeger May 2024Individuals with antiphospholipid syndrome (APS) have antibodies directed against phospholipid-binding proteins (aPL). The condition is most associated with an increased... (Review)
Review
Individuals with antiphospholipid syndrome (APS) have antibodies directed against phospholipid-binding proteins (aPL). The condition is most associated with an increased risk of thromboembolism and obstetric complications. The 2023 classification criteria for APS include six clinical domains (venous thromboembolism, arterial thrombosis, microvascular events, obstetric events, cardiac valve, thrombocytopaenia) and two laboratory domains (lupus anticoagulant, and anti-cardiolipin or anti-β2-glycoprotein-I antibodies). Diagnosis and treatment of APS are specialist tasks and are summarised in this review.
Topics: Antiphospholipid Syndrome; Humans; Antibodies, Antiphospholipid; Pregnancy; Female; Anticoagulants; Thrombosis
PubMed: 38847311
DOI: 10.61409/V11230715 -
Autoimmunity Dec 2024The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately...
The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRβ repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.
Topics: Humans; Antiphospholipid Syndrome; Female; Pregnancy; Biomarkers; Adult; Receptors, Antigen, T-Cell; Lupus Erythematosus, Systemic; Pregnancy Complications
PubMed: 38836341
DOI: 10.1080/08916934.2024.2360490 -
Cureus May 2024Thrombotic microangiopathy (TMA) is a rare yet potentially life-threatening condition. The diagnosis is difficult as there are other conditions presenting with features...
Thrombotic microangiopathy (TMA) is a rare yet potentially life-threatening condition. The diagnosis is difficult as there are other conditions presenting with features akin to TMA during the peripartum period such as eclampsia, preeclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and antiphospholipid syndrome. A 28-year-old woman with no significant past medical history developed TMA following a massive hemorrhage after an emergency cesarean section at 41 weeks of gestation. This case was finally diagnosed as postpartum hemorrhage (PPH)-associated TMA. The patient fully recovered after plasma exchange therapy. We posit the value of accumulating case reports, given that the documentation on the efficacy of plasma exchange in PPH-associated TMA is limited.
PubMed: 38832165
DOI: 10.7759/cureus.59623