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Akankwasa P, Kakooza J, Katongole J, Namutosi E, Lewis C, Okurut E. Antiphospholipid syndrome in pregnancy: A comprehensive review. World J Rheumatol 2025; 12:103837. [DOI: 10.5499/wjr.v12.i2.103837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/17/2025] [Accepted: 01/23/2025] [Indexed: 02/18/2025] Open
Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the presence of antiphospholipid antibodies and is associated with thrombotic events and pregnancy complications. The classification and management of APS has evolved over time. The classification criteria for APS include laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic domains. Management focuses on prevention of thrombotic events and/or anticoagulation as the primary treatment for thrombosis. Postpartum and long-term thromboprophylaxis after delivery are recommended to reduce the risk of thrombotic events. Despite these recommendations, optimal anticoagulation agents and intensity of treatment are still topics of debate. Further research is needed to understand the pathophysiology of APS and improve its management during pregnancy. In this review, we discuss the classification and pathophysiology of APS. Current treatment options and clinical trials are also discussed.
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Affiliation(s)
- Prosper Akankwasa
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - Jackson Kakooza
- Department of Surgery, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - John Katongole
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - Esther Namutosi
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - Catherine Lewis
- Department of Surgery, St. Joseph's Kitovu Hospital, Masaka, Uganda
- Department of Surgery, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States
| | - Emmanuel Okurut
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
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Bitsadze V, Yakubova F, Khizroeva J, Lazarchuk A, Salnikova P, Vorobev A, Tretyakova M, Degtyareva N, Grigoreva K, Gashimova N, Kvaratskheliia M, Makatsariya N, Kudryavtseva E, Tomlenova A, Gris JC, Elalamy I, Ay C, Makatsariya A. Catastrophic Antiphospholipid Syndrome. Int J Mol Sci 2024; 25:668. [PMID: 38203837 PMCID: PMC10779422 DOI: 10.3390/ijms25010668] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 12/26/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a "thrombotic storm". CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates.
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Affiliation(s)
- Victoria Bitsadze
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Fidan Yakubova
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Jamilya Khizroeva
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Arina Lazarchuk
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Polina Salnikova
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Alexander Vorobev
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Maria Tretyakova
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Natalia Degtyareva
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Kristina Grigoreva
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Nilufar Gashimova
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Margaret Kvaratskheliia
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Nataliya Makatsariya
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Ekaterina Kudryavtseva
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Anna Tomlenova
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
| | - Jean-Christophe Gris
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
- Faculty of Pharmaceutical and Biological Sciences, Montpellier University, 34093 Montpellier, France
| | - Ismail Elalamy
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
- Department Hematology and Thrombosis Center, Medicine Sorbonne University, 75012 Paris, France
- Hospital Tenon, 4 Rue de la Chine, 75020 Paris, France
| | - Cihan Ay
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
- Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, 1080 Vienna, Austria
| | - Alexander Makatsariya
- Department of Obstetrics, Gynecology and Perinatal Medicine, N. F. Filatov Clinical Institute of Children’s Health, I. M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (F.Y.); (J.K.); (A.L.); (P.S.); (A.V.); (M.T.); (N.D.); (K.G.); (N.G.); (M.K.); (N.M.); (E.K.); (A.T.); (J.-C.G.); (I.E.); (C.A.)
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Fleetwood T, Cantello R, Comi C. Antiphospholipid Syndrome and the Neurologist: From Pathogenesis to Therapy. Front Neurol 2018; 9:1001. [PMID: 30534110 PMCID: PMC6275383 DOI: 10.3389/fneur.2018.01001] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 11/06/2018] [Indexed: 12/16/2022] Open
Abstract
Antiphospholipid syndrome (APS) is an autoimmune antibody-mediated condition characterized by thrombotic events and/or pregnancy morbidity in association with persistent positivity to antiphospholipid antibodies (aPL). The nervous system is frequently affected, as intracranial vessels are the most frequent site of arterial pathology. Over the course of years, many other neurological conditions not included in the diagnostic criteria, have been associated with APS. The pathogenic mechanisms behind the syndrome are complex and not fully elucidated. aPL enhance thrombosis, interfering with different pathways. Nevertheless, ischemic injury is not always sufficient to explain clinical features of the syndrome and immune-mediated damage has been advocated. This may be particularly relevant in the context of neurological complications. The reason why only a subgroup of patients develop non-criteria nervous system disorders and what determines the clinical phenotype are questions that remain open. The double nature, thrombotic and immunologic, of APS is also reflected by therapeutic strategies. In this review we summarize known neurological manifestations of APS, revisiting pathogenesis and current treatment options.
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Affiliation(s)
- Thomas Fleetwood
- Section of Neurology, Department of Translational Medicine University of Eastern Piedmont, Novara, Italy
| | - Roberto Cantello
- Section of Neurology, Department of Translational Medicine University of Eastern Piedmont, Novara, Italy
| | - Cristoforo Comi
- Section of Neurology, Department of Translational Medicine University of Eastern Piedmont, Novara, Italy.,Interdisciplinary Research Centre of Autoimmune Diseases University of Eastern Piedmont, Novara, Italy
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Akinshina S, Makatsariya A, Bitsadze V, Khizroeva J, Khamani N. Thromboprophylaxis in pregnant women with thrombophilia and a history of thrombosis. J Perinat Med 2018; 46:893-899. [PMID: 29949514 DOI: 10.1515/jpm-2017-0329] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 03/06/2018] [Indexed: 11/15/2022]
Abstract
Background Despite intensive research, thromboembolism still accounts for significant maternal morbidity and mortality. We examined thrombophilia in patients with thromboembolism during pregnancy and evaluated the efficiency of antithrombotic prophylaxis in patients with thrombophilia for the prevention of recurrent thromboembolism. Materials and methods Sixty-eight women with a history of thromboembolism were managed during pregnancy, in light of their thrombotic history and the result of thrombophilia assessment. Group I (n=50) received prophylaxis with low molecular weight heparin (LMWH)±aspirin (50-100 mg/day) in preconception period or from the 1st trimester, during pregnancy and at least 6 weeks postpartum. Group II (n=18) received LMWH±aspirin from the II to III trimester. Results Thromboses were associated with pregnancy in 27 patients (39.7%), with systemic diseases - in nine (13.2%), oral contraceptives use - 22 (32.3%), immobilization due to surgery and/or trauma, long flight - six (8.9%), septic complications - two (2.9%). Nevertheless, 24.5% of patients had no apparent provoking factor for the development of thrombotic complications. Thirty-seven (54%) patients with venous thromboembolism (VTE) had familial history of VTE, and 25 (36.7%) had personal history of pregnancy complications (fetal loss syndrome, preeclampsia and placental abruption) (P<0.05 vs. control). Thrombophilia was detected in 58 (85.3%). Usual thrombogenic polymorphisms [factor V (FV) Leiden and prothrombin G20210A, heterozygous forms] were revealed in 16 (23.5%) and eight (11.7%) patients, respectively. Antiphospholipid antibodies (aPL) circulation was found in 34 (50%) patients. Non-usual thrombogenic polymorphisms were identified in 44 (64.7%) of the women and hyperhomocysteinemia - in 30 (44.2%). In group I no one had severe obstetric complications. All the patients were delivered at term and all the babies were alive. In group II moderate-to-severe obstetric complications were noted: preeclampsia - in 11 (16.2%), severe preeclampsia - seven (10.3%), preterm delivery - in 18 (26.4%) patients from subgroup II (P<0.05). Conclusions Women with a personal or a family history of thromboembolism and obstetric complications should be screened for thrombophilia. Beginning anticoagulant therapy early in such patients is effective not only for preventing recurring thrombosis but also preventing obstetric complications. Late prophylaxis after the completion of the trophoblast invasion therapy is much less effective.
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Affiliation(s)
- Svetlana Akinshina
- Research Associate of the Ob/Gyn, Department of The First Moscow State Medical Sechenov University, Moscow, Russia
| | - Alexander Makatsariya
- Head of Department of Obstetrics and Gynecology #2 of I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Victoria Bitsadze
- Department of Obstetrics and Gynecology #2 of I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Jamilya Khizroeva
- Department of Obstetrics and Gynecology #2 of I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Nadine Khamani
- Department of Obstetrics and Gynecology #2 of I.M. Sechenov First Moscow State Medical University, Moscow, Russia
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Campbell EJ, Clarke AE, Ramsey-Goldman R. Systemic lupus erythematosus: a case-based presentation of renal, neurologic, and hematologic emergencies. Expert Rev Clin Immunol 2018; 14:803-816. [PMID: 30173578 DOI: 10.1080/1744666x.2018.1518132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with systemic manifestations and multiorgan involvement. Although primarily diagnosed, and managed in the outpatient setting, it can occasionally present with life-threatening complications that require rapid assessment and urgent aggressive therapy. Areas covered: In our review, we explore three organ systems that are often affected in SLE, but have the potential to present as medical emergencies; these are the kidney, the central nervous system, and the hematologic system. We take a case-based approach to each clinical scenario, with information given sequentially in order to reflect "real-life" situations where management decisions need to be made with limited information. We review the acute management, pathophysiology, diagnostic approach, and treatment along with a review of the literature, for lupus nephritis presenting as rapidly progressive glomerulonephritis, acute lupus transverse myelitis, and refractory antiphospholipid syndrome. Expert commentary: At the conclusion of each section, we provide an expert commentary regarding each issue, relating to diagnosis, early management, and current evidence behind treatment recommendations.
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Affiliation(s)
- Eric J Campbell
- a Internal Medicine Resident, Department of Medicine, Cumming School of Medicine , University of Calgary , Calgary , Alberta , Canada
| | - Ann E Clarke
- b Professor of Medicine, Division of Rheumatology, The Arthritis Society Chair in Rheumatic Diseases, Cumming School of Medicine , University of Calgary , Calgary , Alberta , Canada
| | - Rosalind Ramsey-Goldman
- c Solovy Arthritis Research Society Professor of Medicine, Department of Medicine/Rheumatology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA
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Assiri AM, Al Zahrani H, ElGohary G. Autologous Hematopoietic Stem Cell Transplantation for Antiphospholipid Syndrome: Case Report and Review of the Literature. EXP CLIN TRANSPLANT 2018; 17:702-705. [PMID: 29633931 DOI: 10.6002/ect.2017.0168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Refractory antiphospholipid syndrome represents a challenge for preventing thrombosis that may occur despite adequate anticoagulation and immunomodulation therapy. Here, we report a 35-year-old male patient who presented with variable venous thromboembolic events. Autologous hematopoietic stem cell transplant was performed after conditioning with cyclophosphamide and antithymocyte globulin. Five years after transplant, the treatment continued to show a successful outcome in preventing new thrombotic events. Autologous hematopoietic stem cell transplant represents a chance for cure from antiphospholipid syndrome despite the paucity of reported data so far.
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Affiliation(s)
- Ali M Assiri
- From the Internal Medicine Department, College of Medicine, Najran University, Saudi Arabia
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Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies. Blood Coagul Fibrinolysis 2017; 27:870-875. [PMID: 27167859 DOI: 10.1097/mbc.0000000000000504] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
We investigated whether changes to fibrinolysis were associated with other manifestations of systemic lupus erythematosus (SLE), including antiphospholipid (APL) antibody status, endothelial damage, and inflammation. Ninety-four patients (36 SLE patients, 58 healthy controls) were recruited from Tasmania, Australia. Circulating levels of plasminogen, α2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured, as well as APL antibodies (including lupus anticoagulant, anticardiolipin, and antibeta-2 glycoprotein-1 antibodies), soluble E-selectin, and interleukin-6. Whereas there was a significant decrease in plasminogen (patient vs. control; median) (210 vs. 444 ng/ml; P < 0.0001) and increase in α2-antiplasmin (0.53 vs. 0.09 μg/ml; P = 0.0007), there was increased t-PA (0.65 vs. 0.40 ng/ml; P = 0.0001) and decreased TAFI (8.8 vs. 10.0 ng/ml; P = 0.002) in SLE patients compared to healthy controls. Plasminogen was significantly associated with α2-antiplasmin (rho = -0.563, P < 0.001); TAFI (rho = 0.410, P = 0.011); soluble E-selectin (rho = 0.531, P = 0.001); and interleukin-6 (rho = 0.489, P = 0.002) in SLE patients; however, APL antibody status was not associated with any of the markers measured. This study has demonstrated that fibrinolysis is significantly altered in patients with SLE compared to controls, and associated with endothelial cell damage and inflammation, but not APL antibody status.
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Islam MA, Alam F, Sasongko TH, Husin A, Abdullah S, Gan SH, Wong KK. Antiplatelet and anticoagulant agents for preventing recurrence of peripheral vascular thrombosis in patients with Antiphospholipid syndrome. Hippokratia 2016. [DOI: 10.1002/14651858.cd012198] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Md. Asiful Islam
- Universiti Sains Malaysia; Human Genome Centre, School of Medical Sciences, Health Campus; Jalan Raja Perempuan Zainab II, Kubang Kerian Kota Bharu Kelantan Malaysia 16150
| | - Fahmida Alam
- Universiti Sains Malaysia; Human Genome Centre, School of Medical Sciences, Health Campus; Jalan Raja Perempuan Zainab II, Kubang Kerian Kota Bharu Kelantan Malaysia 16150
| | - Teguh H Sasongko
- Universiti Sains Malaysia; Human Genome Centre, School of Medical Sciences, Health Campus; Jalan Raja Perempuan Zainab II, Kubang Kerian Kota Bharu Kelantan Malaysia 16150
| | - Azlan Husin
- Universiti Sains Malaysia; Department of Internal Medicine, School of Medical Sciences, Health Campus; Jalan Raja Perempuan Zainab II, Kubang Kerian Kota Bharu Malaysia
| | - Sarimah Abdullah
- Universiti Sains Malaysia; Unit of Biostatistics and Research Methodology; Jalan Raja Perempuan Zainab II, Kubang Kerian Kota Bharu Kelantan Malaysia 16150
| | - Siew Hua Gan
- Universiti Sains Malaysia; Human Genome Centre, School of Medical Sciences, Health Campus; Jalan Raja Perempuan Zainab II, Kubang Kerian Kota Bharu Kelantan Malaysia 16150
| | - Kah Keng Wong
- Universiti Sains Malaysia; Department of Immunology, School of Medical Sciences, Health Campus; 16150 Kubang Kerian Kota Bharu Malaysia
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Aĭsina RB, Mukhametova LI, Ostriakova EV, Seredavkina NV, Patrushev LI, Patrusheva NL, Reshetniak TM, Gulin DA, Gershkovich KB, Nasonov EL, Varfolomeev SD. [Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen level and thrombosis in patients with antiphospholipid syndrome]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2014; 60:72-93. [PMID: 24749249 DOI: 10.18097/pbmc20146001072] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The frequency of venous and arterial thromboses and plasminogen level were investigated in 78 patients with antiphospholipid syndrome (APS), 35 of whom with systemic lupus erythematosus (SLE+APS) and 43 - with primary APS (PAPS). The levels and genotype of plasminogen activator inhibitor type 1 (PAI-1) were determined in 45 patients with APS, of whom 21 patients with SLE + APS and 24 patients with PAPS. A control group included 10 healthy individuals without autoimmune disease signs and thromboses on period of investigation and in past history. It was shown for the first time that for one third of 67 patients with APS and thromboses high positive levels of antiphospholipid antibodies (aPL) are associated with low plasminogen levels. The levels of PAI-1 antigen measured by ELIZA method, which detects active, latent and bound with plasminogen activator PAI-1, were opposed with frequency of thromboses in APS patients. Correlation between the high and increased levels of PAI-1 and high positive aPL levels was found for one third of 43 patients with APS and thrombosis. One of the possible mechanisms of this interconnection was considered. It was shown that arterial and, to a more extent, venous thromboses are associated with the 4G/5G polymorphism of PAI-1 gene and high plasma level of the inhibitor in 79% of APS patients. At the presence of the 4G allele patients with SLE+APS had higher PAI-1 levels than patients with PAPS. The obtained results show that measuring the levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of PAI-1 gene which is associated with thromboses may have the practical significance for identification of high risk of thrombosis in APS patients.
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Abd-Elsayed AA, Lisco SJ, Alsidawi S, Bonomo J. Simultaneous antiphospholipid syndrome and heparin-induced thrombocytopenia in a single patient. A & A CASE REPORTS 2014; 2:9-10. [PMID: 25612260 DOI: 10.1097/acc.0b013e3182a1afc9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Antiphospholipid syndrome and heparin-induced thrombocytopenia are immune-mediated thrombotic conditions initiated by 2 distinct antibodies each targeting a discrete protein-antigen complex. Although produced by 2 different types of antibodies, they are similar in their autoimmune and pathophysiologic mechanisms. We present a case with simultaneous antiphospholipid syndrome and heparin-induced thrombocytopenia syndromes that sheds light on the correlation between these 2 syndromes.
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Affiliation(s)
- Alaa A Abd-Elsayed
- From the *Department of Anesthesiology, University of Cincinnati, Cincinnati, Ohio; †Department of Anesthesiology, University of Nebraska, Omaha, Nebraska; and Departments of ‡Internal Medicine and §Emergency Medicine, University of Cincinnati, Cincinnati, Ohio
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Bakshi J, Stevens R. Rituximab therapy for recurrent thromboembolic disease in antiphospholipid syndrome. Lupus 2013; 22:865-7. [DOI: 10.1177/0961203313491023] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- J Bakshi
- Rheumatology Department, Buckinghamshire Hospital NHS, Buckinghamshire, UK
| | - R Stevens
- Rheumatology Department, Buckinghamshire Hospital NHS, Buckinghamshire, UK
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Martínez-Zamora MA, Tassies D, Carmona F, Espinosa G, Cervera R, Reverter JC, Balasch J. Clot lysis time and thrombin activatable fibrinolysis inhibitor in severe preeclampsia with or without associated antiphospholipid antibodies. J Reprod Immunol 2010; 86:133-40. [DOI: 10.1016/j.jri.2010.05.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2010] [Revised: 05/18/2010] [Accepted: 05/18/2010] [Indexed: 10/19/2022]
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Martínez-Zamora MA, Creus M, Tassies D, Bové A, Reverter JC, Carmona F, Balasch J. Thrombin activatable fibrinolysis inhibitor and clot lysis time in women with recurrent miscarriage associated with the antiphospholipid syndrome. Fertil Steril 2010; 94:2437-40. [DOI: 10.1016/j.fertnstert.2010.02.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2009] [Revised: 02/09/2010] [Accepted: 02/15/2010] [Indexed: 11/26/2022]
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Martinez-Zamora MA, Tassies D, Carmona F, Espinosa G, Cervera R, Reverter JC, Balasch J. ORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and Thrombosis. Am J Reprod Immunol 2009; 62:381-9. [DOI: 10.1111/j.1600-0897.2009.00751.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
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Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood 2009; 114:3074-83. [PMID: 19628708 DOI: 10.1182/blood-2008-11-188698] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Antiphospholipid (aPL) antibodies recognize receptor-bound beta(2) glycoprotein I (beta(2)GPI) on target cells, and induce an intracellular signaling and a procoagulant/proinflammatory phenotype that leads to thrombosis. Evidence indicates that annexin A2 (A2), a receptor for tissue plasminogen activator and plasminogen, binds beta(2)GPI on target cells. However, whether A2 mediates pathogenic effects of aPL antibodies in vivo is unknown. In this work, we studied the effects of human aPL antibodies in A2-deficient (A2(-/-)) mice. A2(-/-) and A2(+/+) mice were injected with immunoglobulin G (IgG) isolated from either a patient with antiphospholipid syndrome (IgG-APS), a healthy control subject (IgG-normal human serum), a monoclonal anti-beta(2)GPI antibody (4C5), an anti-A2 monoclonal antibody, or monoclonal antibody of irrelevant specificity as control. We found that, after IgG-APS or 4C5 injections and vascular injury, mean thrombus size was significantly smaller and tissue factor activity was significantly less in A2(-/-) mice compared with A2(+/+) mice. The expression of vascular cell adhesion molecule-1 induced by IgG-APS or 4C5 in explanted A2(-/-) aorta was also significantly reduced compared with A2(+/+) mice. Interestingly, anti-A2 monoclonal antibody significantly decreased aPL-induced expression of intercellular cell adhesion molecule-1, E-selectin, and tissue factor activity on cultured endothelial cells. Together, these data indicate for the first time that A2 mediates the pathogenic effects of aPL antibodies in vivo and in vitro APS.
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