fondaparinux and Antiphospholipid-Syndrome

Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis with antiphospholipid antibodies. Dysregulation of the complement pathway has been implicated in APS pathophysiology. We report the successful use of eculizumab, an anti-C5 monoclonal antibody, in controlling and preventing recurrent thrombosis in a refractory case of APS. An 18-year-old female was diagnosed with APS after developing extensive, unprovoked deep vein thrombosis (DVT) of axillary, inferior vena cava, and brachiocephalic veins. Thrombophilia evaluation revealed triple-positive lupus anticoagulant, β-2 glycoprotein IgM, IgA, and anticardiolipin antibodies (each >40 U/mL) with persistently positive titers after 12 weeks. She was refractory to multiple anticoagulants alone (enoxaparin, fondaparinux, apixaban, rivaroxaban, and warfarin) with antiplatelet (aspirin and clopidogrel) and adjunctive therapies (hydroxychloroquine, immunosuppression with steroids and rituximab, and plasmapheresis). Despite these, she continued to develop recurrent thrombosis and additionally developed hepatic infarction and pulmonary embolism with failure to decrease titers after 6 weeks of plasma exchange. Following this event, eculizumab (600 mg weekly × 4 weeks followed by 900 mg every 2 weeks) was initiated in combination with fondaparinux, aspirin, clopidogrel, and hydroxychloroquine. She has remained on this regimen without recurrence of thrombosis. Our case suggests that eculizumab may have a role as a therapeutic option in refractory thrombosis in APS.

Topics: Adolescent; Antibodies, Monoclonal, Humanized; Antiphospholipid Syndrome; Aspirin; Clopidogrel; Female; Fondaparinux; Humans; Hydroxychloroquine; Thrombosis

Limited evidence exists to guide the management of recurrent thrombosis occurring despite therapeutic anticoagulation in patients with thrombotic antiphospholipid syndrome (APS). In this case series, fondaparinux, with or without an antiplatelet agent, provided an effective and safe option in three patients with thrombotic APS, all two triple and one single positive for antiphospholipid antibodies, who had recurrent venous and/or arterial thromboembolism. Rituximab was also used in all patients. Recurrent events occurred despite therapeutic anticoagulation, including at high-intensity, with warfarin and subsequent low-molecular-weight heparin. There were no major bleeding events. Adjunctive therapies used for thrombosis included catheter-directed thrombolysis and rituximab.

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Lupus Erythematosus, Systemic; Platelet Aggregation Inhibitors; Rituximab; Thrombosis; Warfarin

We discuss two patients with antiphospholipid syndrome (APS) who presented with critical ischemia of both lower extremities due to arterial microthrombi. They received multimodality therapy emergently: anticoagulation, immunosuppression, and therapeutic plasma exchange (TPE). Then they were maintained on anticoagulation with fondaparinux and immunosuppression with mycophenolate mofetil (MMF), and were followed for 4 years.. Two patients with APS with ischemia and necrosis of their distal lower extremities were treated emergently with anticoagulation (intravenous heparin), immunosuppression (prednisone), and TPE. They were maintained on anticoagulation with fondaparinux and immunosuppression with MMF.. Neither patient had recurrent microthrombotic disease during a 4-year follow-up.. As described in our small cohort, patients with APS who suffer from microthrombotic arterial disease may benefit from maintenance therapy of anticoagulation with fondaparinux and immunosuppression with MMF, an approach which may be worthy of further trial. Fondaparinux does not require attention to diet, monitoring, and cumbersome bridging that is typical of warfarin therapy. MMF provides immunosuppression while sparing the side effects of steroid treatment.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Combined Modality Therapy; Female; Follow-Up Studies; Fondaparinux; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Plasma Exchange; Thrombosis; Treatment Outcome

Topics: Adrenal Cortex Hormones; Antiphospholipid Syndrome; Cyanosis; Diagnosis, Differential; Drug Therapy, Combination; Fondaparinux; Foot Diseases; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Plasmapheresis; Polysaccharides; Venous Thrombosis

The diagnosis of the antiphospholipid syndrome (APS) is based on clinical and biological criteria including the persistent presence of antiphospholipid antibodies and thrombotic events or pregnancy morbidity. Heparins relayed by vitamin K antagonists (VKA) are the gold standard treatment for thrombosis.. We report a 17-year-old man who presented with an initially seronegative antiphospholipid syndrome, in whom the diagnosis was late, only obtained after anticoagulation withdrawing, when a catastrophic antiphospholipid syndrome (CAPS) with cutaneous lesions and disseminated intravascular coagulation syndrome occurred. For personal convenience, this patient was initially treated with fondaparinux followed by a new oral anticoagulant (rivaroxaban) before to return to the conventional VKA treatment.. The "seronegative" APS is a controversial concept reflecting the heterogeneity of antigenic targets for aPL. This diagnosis may be considered after a rigorous work-up, with the help of haemostasis laboratories testing new emerging aPL assays. In APS, the new anticoagulants represent an attractive option needing nevertheless prospective studies to evaluate their safety and efficacy. Lupus anticoagulant detection in patients treated by new oral anticoagulants is not easy by usually recommended coagulation tests.

Topics: Adolescent; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Disseminated Intravascular Coagulation; Factor Xa Inhibitors; Fondaparinux; Humans; Male; Morpholines; Polysaccharides; Rivaroxaban; Thiophenes

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

Topics: Adult; Antibodies, Monoclonal, Murine-Derived; Anticoagulants; Antiphospholipid Syndrome; Fondaparinux; Humans; Immunologic Factors; Male; Necrosis; Plasma Exchange; Polysaccharides; Rituximab; Skin; Skin Diseases, Vascular; Treatment Outcome

To describe the course and management of thrombotic storm in 8 children.. Clinical data were collected and analyzed for consecutive children diagnosed with thrombotic storm, aged 6 months to 21 years inclusive, in the context of a single-institution prospective inception cohort study. Thrombotic storm was defined as newly diagnosed multisite venous thromboembolism (VTE) with acute thrombus progression despite conventional or higher than conventional dosing of heparin or low molecular weight heparin. All evaluations and therapies were ordered by the treating physicians in the context of clinical decision making.. Eight of the 178 children with VTE enrolled in the cohort between March 2006 and November 2009 were diagnosed with thrombotic storm. Antiphospholipid antibodies were acutely positive in 6 children, of whom heparin-induced thrombocytopenia was confirmed by serotonin release assay in 2 and atypical in 1. One child died. Five children received a direct thrombin inhibitor, titrated to achieve normalization of markedly elevated D-dimer levels. All children were transitioned to fondaparinux or enoxaparin before receiving extended anticoagulation with warfarin. Immunomodulatory therapy was instituted in all children. During follow-up (median duration, 3 years; range, 2-6 years), 3 of the 7 surviving children experienced recurrent VTE, and 4 children had clinically significant postthrombotic syndrome.. Thrombotic storm is an infrequent but potentially fatal presentation of VTE in children. Administration of direct thrombin inhibitors and immune modulation can achieve quiescence, although long-term adverse outcomes are common.

Topics: Adolescent; Anticoagulants; Antiphospholipid Syndrome; Child; Child, Preschool; Cytokines; Enoxaparin; Fatal Outcome; Female; Fondaparinux; Humans; Immunomodulation; Male; Polysaccharides; Prospective Studies; Venous Thromboembolism; Young Adult

Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for initial thrombosis are antiphospholipid syndrome and heterozygous mutation for prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was effective, but discontinuation of warfarin after 12 months resulted in recurrence of thrombosis. Unfractionated heparin (UFH) was initiated during the acute period, but heparin-induced thrombocytopenia developed. Transition from UFH to fondaparinux resulted in successful anticoagulation for a period of platelet recovery. We report a case of HIT developing with a background of prothrombotic genetic risk factors and antiphospholipid syndrome. This case study highlights several difficulties in pediatric HIT cases.

Topics: Anticoagulants; Antiphospholipid Syndrome; Child; Drug Substitution; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Mutation; Polysaccharides; Prothrombin; Risk Factors; Thrombocytopenia; Venous Thrombosis; Warfarin

Topics: Antibody Formation; Anticoagulants; Antiphospholipid Syndrome; Fondaparinux; Heparin; Humans; Platelet Activation; Polysaccharides; Thrombocytopenia

Topics: Aged; Aged, 80 and over; Anticoagulants; Antiphospholipid Syndrome; Dermatitis, Allergic Contact; Drug Tolerance; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Skin

To describe the clinical characteristics, management, and outcomes of patients with heparin-induced thrombocytopenia with thrombosis (HITTS) or without thrombosis (HIT) who also had an elevated baseline activated partial thromboplastin time (aPTT) due to antiphospholipid antibody syndrome (APS).. Four patients with HIT/HITTS and an elevated baseline aPTT due to APS were identified. Two patients had venous thrombosis, 1 had limb ischemia, and 1 had isolated HIT. All 4 were managed with a weight-based fixed dose of argatroban without laboratory monitoring. None of the patients had thrombotic or bleeding complications once therapy was initiated.. Management of patients with HIT/HITTS and an abnormal baseline aPTT due to APS is problematic. We review alternative management strategies, such as monitoring direct thrombin inhibitors with the ecarin clotting time or thrombin inhibition time or using an alternative anticoagulant, such as fondaparinux. As of March 13, 2006, none of these management strategies has been evaluated in a clinical trial for this patient population. We report the successful use of weight-based, fixed-dose argatroban without laboratory monitoring in patients with APS.. Use of a fixed-dose argatroban regimen without laboratory monitoring is a potential management strategy for patients with HIT/HITTS and an elevated baseline aPTT due to APS.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Arginine; Female; Fondaparinux; Heparin; Humans; Middle Aged; Partial Thromboplastin Time; Pipecolic Acids; Polysaccharides; Sulfonamides; Thrombocytopenia; Thrombosis

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia