High Titers Of Antiphospholipid Antibodies Research Articles

Mitral Valve Replacement for Enlarged Libman-Sacks Endocarditis in a Patient with Persistent Primary Antiphospholipid Syndrome and Recurrent Stroke: A Case Report.

BACKGROUND Anticardiolipin antibodies in patients with Libman-Sacks endocarditis (LS) are indicative of comorbid antiphospholipid syndrome (APS) and can result in cerebral infarctions. We describe a case of LS and primary APS with recurrent cerebral infarctions despite anticoagulation treatment. The patient underwent surgery for enlarged LS vegetation with high titers of antiphospholipid antibodies. CASE REPORT A 41-year-old Japanese man was admitted to hospital for small cerebral infarction recurrence in a left parietal lesion. At age 35, the patient had suffered multiple cerebral infarctions. He was found to have high serum titers of all 3 antiphospholipid antibodies. Transesophageal echocardiography (TEE) findings were normal. Differential diagnosis ruled out other autoimmune diseases and a clinical diagnosis of primary APS was made. Warfarin anticoagulation was started. When cerebral infarction recurred 6 years after the first episode, serum titers of antiphospholipid antibodies remained high, and TEE showed a 7×8 mm area of mitral vegetation. A TEE results from his first admission revealed a 5×6 mm area of mitral vegetation, which was believed to be related to the current vegetation. As anticoagulation produced no improvement, the mitral valve was replaced with a mechanical valve. Examination of the excised vegetation found it to be consistent with LS. The patient made good progress within 3 years after surgery. CONCLUSIONS LS size can increase despite anticoagulation in cases with high titers of all 3 antiphospholipid antibodies and cerebral infarction. Such patients require ongoing TEE follow-up and surgical treatment should be considered.

Use of plasmapheresis in treatment of patients with unfavorable anamnestic pregnancy outcomes coupled to antiphospholipid antibodies

Aim: to evaluate efficacy of plasmapheresis combined with low molecular weight heparins (LMWH) and acetylsalicylic acid (ASA).Materials and Methods. 327 plasmapheresis sessions were performed for 75 patients: 17 (22.6 %) patients during preparation for pregnancy, 11 (19.0 %) pregnant women in the first trimester, 33 (56.9 %) pregnant women in the second trimester, and 34 (58.6 %) pregnant women in the third trimester. Study inclusion criteria were as follows: high titers of antiphospholipid antibodies (APA) as well as included non-inclusion criteria in pregnant women with miscarriages and unfavorable anamnestic pregnancy outcome. 36 (62.1 %) women had pregnancy loss in anamnesis. All patients received low-dose ASA and LMWH therapy; 15 (25.86 %) pregnant women also received courses of intravenous immunoglobulins in the first and second trimesters.Results. 47 pregnant women had delivery, whereas 10 of women had pregnancy in progress. Term delivery was in 40 (85.1 %) patients, so that 23 (48.9 %) pregnant women had delivery per vias naturales. The average weight of the fetus was 3364.00 ± 393.76 g, height - 52.13 ± 1.82 cm. In 100 % cases, Apgar score was 8 points. 24 (51.1%) pregnant women had delivery via cesarean section. The average blood loss comprised 528.64 ± 166.10 ml. The average fetal weight in group after surgical delivery was 2982.14 ± 582.88 g, average height - 49.14 ± 4.09 cm, the Apgar score - 7.69 ± 0.47 points. Preterm births were observed in 7 (14.9%) cases, all via cesarean section. In 1 case, early fetal death was at gestational age of 8/9 weeks; according to the karyotyping data, a fetal chromosomal abnormality was detected. No severe obstetric complications were observed.Conclusions. Combining plasmapheresis with low dose LMWH and ASA therapy demonstrated high efficacy in treating obstetric APS manifested as high percentage of favorable pregnancy outcomes and low number of obstetric complications.

The antiphospholipid syndrome may induce non-thrombotic internal jugular vein stenosis: two cases report

BackgroundAntiphospholipid syndrome (APS) is associated with a high incidence of thrombotic events, either arterial thrombosis or venous thrombosis. However, APS-related non-thrombotic venous stenosis is rarely reported.Case presentationThis study described two cases of young women with APS-related internal jugular vein stenosis (IJVS) and reviewed current literature on this issue, including clinical features, diagnosis, and treatment.ConclusionsIJVS is a rather rare complication of APS. Two cases were reported for the first time that high titer of antiphospholipid antibodies (aPL) might mediate direct vessel wall damage and further induce venous stenosis despite long-term standardized anticoagulation to prevent thrombus formation. Therefore, dynamic monitoring of autoantibodies and concomitant use of anticoagulants and corticosteroids may be necessary to the management of APS and its complications.

Significance of detecting antiphospholipid antibodies and genetic mutations of hemostasis for in vitro fertilization

A case of pregravid preparation is described for an in vitro fertilization (IVF) attempt in a woman after four previous IVF failures. Considering her personal and family aggravated medical history, including the family anamnesis, the patient underwent a hemostasis examination including a test for genetic mutations. A high titer of antiphospholipid antibodies of various types and multigene mutations associated with thrombophilia were found. For the treatment of acquired and inherited thrombophilia, vitamin-antioxidant and intravenous immunoglobulin therapy was initiated as well as a course of hirudotherapy. After starting of pregnancy throughout the gestation period, anticoagulant therapy by low molecular weight heparins, antiplatelet, and antioxidant therapy was carried out; in parallel, D-dimer, thrombin-antithrombin and platelet aggregation markers of thrombophilia were monitored. Pregnancy successfully ended by childbirth at 39 weeks.

'Non-Criteria' Neurologic Manifestations of Antiphospholipid Syndrome: A Hidden Kingdom to be Discovered.

Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.

Antiphospholipid Antibody-Mediated Thrombotic Mechanisms in Antiphospholipid Syndrome: Towards Pathophysiology-Based Treatment.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a persistently high titer of antiphospholipid antibodies (aPLs). In addition to pregnancy morbidity, arterial and/or venous thrombosis is another clinical feature of APS. Regardless of the type of APS, the thrombi formed by the induction of aPLs can lead to deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and gangrene. Although the concept of APS was introduced approximately 32 years ago, its thrombogenic pathophysiology is still unclear. Therefore, patients are treated with anticoagulant and/or antiplatelet regimens just as in other thrombotic disorders even though the thrombotic pathophysiology is mainly aPLs-mediated. In this review, we provided an update of the cellular, auto-immune and genetic factors known to play important roles in the generation of thrombi. Current successful regimens are also outlined along with potential emerging treatment strategies that may lead to the optimum management of thrombotic APS patients.

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

Ischemic and nonischemic manifestations of antiphospholipid syndrome

Hypercoagulability syndrome is an actual multidisciplinary problem of the last decade. Blood clotting disorders leading to hypercoagulability syndrome may manifest as different diseases in neurology, obstetrics, rheumatology, surgery, including diseases of pregnancy. Antiphospholipid syndrome is the most common form of hypercoagulability syndrome, which often develops at a young age, in children and even infants, with female-male ratio of 5. Causes and pathogenesis of antiphospholipid syndrome are not fully clear. This problem is especially important for pregnant women. Almost a third of refractory pregnancy losses are associated with antiphospholipid antibodies formation. Main manifestations of this condition include thrombotic events during pregnancy and the postpartum period, including cerebral pathology in both mother and child. Central nervous system damage in this condition may have both ischemic (cerebrovascular accident) and nonischemic (primary immune-mediated damage of the nervous system) genesis. The variety of neurological disorders associated with antiphospholipid syndrome is very wide, from cerebrovascular disorders, migraine and migrainous headaches to chorea and seizures. Headaches are the most common reason for pregnant women to seek neurologic help. Pregnancy associated with high titers of antiphospholipid antibodies often end as early gestation stage stillbirth. Children born to mothers with antiphospholipid syndrome in 20% of cases develop neurological symptoms of ischemic and non-ischemic origin. Thus, antiphospholipid syndrome requires special attention for early and timely diagnosis, especially in women planning pregnancy and in pregnant women for the preventing serious complications, both in mother and fetus.

Chorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome.

BackgroundChorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome has been seldom reported.Case reportAn 89-year-old female developed persistent right side chorea associated with high titers of anticardiolipin antibody (antiphospholipid antibosies immunoglobulin (Ig)M, 45 MPL and 112 IgM aCL (MPL) after 3 months) but normal lupus anticoagulants. Her magnetic resonance imaging (MRI) showed no abnormality, but positron emission tomography (PET) demonstrated increased bilateral striatal metabolic activity, more on the left side. Her MRI showed no cause for chorea. The PET scan demonstrated a marked increase in the metabolic activity of the left basal ganglia.DiscussionHer chorea remained unchanged over a 9-month follow-up period. The literature on chorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid syndrome is reviewed.

Chorea Associated with High Titers of Antiphospholipid Antibodies in the Absence of Antiphospholipid Antibody Syndrome

Chorea Associated with High Titers of Antiphospholipid Antibodies in the Absence of Antiphospholipid Antibody Syndrome

Neurological presentations of the antiphospholipid syndrome: three illustrative cases

The antiphospholipid syndrome (APS) is defined by the association of high titers of antiphospholipid antibodies (aPLs) with thrombotic events and/or obstetrical problems. APS can be isolated or associated with immune system diseases. Several central nervous system (CNS) manifestations have been reported in APS, but are still not included in the international diagnostic criteria. We present here three cases of APS revealed by CNS manifestations. The first patient had a primary APS with stroke, dementia, epilepsy and the "so-called" Liebman-Sacks disease, a subacute thrombotic non-bacterial valvulopathy. The second one developed a primary APS with a Sneddon syndrome, while the third case is a neurolupus-associated APS with subacute encephalopathy, chorea, stroke, and epilepsy. The pathogenesis of the APS is related to both prothrombotic and immunologic effects of the aPLs. Long-term anticoagulation by low-weight heparin or warfarin is currently recommended in APS. We propose to search the presence of aPLs in any case of young adults' stroke, unexplained dementia, and acquired chorea.

Atherosclerosis in Primary Antiphospholipid Syndrome: Summary of Clinical and Pathogenic Evidence

The Antiphospholipid Syndrome (APS) was described in the early ‘80s as a combination of thrombosis, thrombocytopenia and recurrent miscarriages associated with persistent high titers of Antiphospholipid Antibodies (aPL). In subsequent years, it became apparent that aPL were also associated with premature atherosclerosis in Systemic Lupus Erythematosus (SLE) and more recently in primary APS (PAPS). The studies exploring atherosclerosis in PAPS were heterogeneous in conception and size, but overall, provided enough evidence that Intima Media Thickness (IMT) of carotid arteries and endothelial function are abnormal in PAPS. In keeping with the general view that atherosclerosis is a low grade inflammatory and “auto”immune disorder characterised by oxidative and nitrative stress, several studies have confirmed similar findings in PAPS, though a specific relation with the severity of atherosclerosis is lacking. Given its development at an earlier age than average, atherosclerosis should be taken into account in the overall management of PAPS patients as it may significantly add to the vascular risk.

Superior vena cava syndrome – changing etiology in the third millennium

Superior vena cava syndrome (SVCS), is diagnosed following different degrees of central venous system obstruction, which traditionally was caused by infections, tumors or fibrosing mediastinitis. Recently the role of SVC thrombosis secondary to indwelling central venous devices or pacemaker leads as well as different hypercoagulable states have drawn much attention. In the current review we present a 58-year-old female patient who underwent recurrent pacemaker replacements due to recurrent infections. The patient was hospitalized with superior vena cava syndrome and multiple thrombi in the upper body circulation. Additionally the evaluation was conducted for thrombophilia, which revealed the presence of high titers of antiphospholipid antibodies, suggesting the concurrent diagnosis of the antiphospholipid syndrome (APS). This case reflects the changes in the etiology of SVCS, and the need for a comprehensive evaluation of patients, in the search for additional factors that may complicate a pacemaker insertion, such as the presence of antiphospholipid antibodies. We review the relevant literature and highlight the importance for an interdisciplinary approach in the treatment of SVCS nowadays.

Report of the Obstetric APS Task Force: 13th International Congress on Antiphospholipid Antibodies, 13th April 2010

The Obstetric APS Task Force of the 13th International Congress identified and discussed five general topics within 'Obstetric' Antiphospholipid Syndrome (APS) that contained areas of controversy or uncertainty: recurrent early miscarriage (REM), fetal death, delivery <34 weeks for severe preeclampsia or placental insufficiency, postpartum care, and long-term implications and care. The Task Force concluded that the frequency with which women with REM have a high titer of antiphospholipid antibodies (aPL) or lupus anticoagulant (LA) is somewhat controversial, especially with regard to the diagnostic titers required by the current international criteria for APS. Also, treatment trials involving heparin differ from one another with regard to the patients included and the outcomes achieved. Similarly, the frequency with which women with fetal death or delivery <34 weeks for severe preeclampsia or placental insufficiency have a high titer of aPL or LA is poorly defined, and there is no level I evidence to guide treatment in either group. Suggestions for future studies with regard to both REM and fetal death or delivery <34 weeks for severe preeclampsia or placental insufficiency were discussed and are outlined below. Postpartum and long-term care in women with APS diagnosed solely for obstetric criteria has been largely guided by expert opinion, and systematic evaluations of these populations would be welcome.

462: High antiphospholipid antibody titers are associated with adverse pregnancy outcome in women with antiphospholipid antibody syndrome

S 62 HIGH ANTIPHOSPHOLIPID ANTIBODY TITERS ARE ASSOCIATED WITH ADVE PREGNANCY OUTCOME IN WOMEN WITH ANTIPHOSPHOLIPID ANTIBO SYNDROME MICHAL J. SIMCHEN, RACHEL PAUZNER, GUY ROFE, EYAL SCHIFF, MORDECHAI DULITZKI, Sheba Medical Center, Tel Aviv University, Obstetrics and Gynecology, Ramat Gan, Israel, Sheba Medical Center, Tel Aviv University, Internal Medicine, Rheumatology, Ramat Gan, Israel, Sheba Medical Center, Tel-Aviv University, Ramat Gan, Israel OBJECTIVE: To investigate whether, in patients with antiphospholipid antibody syndrome (APS), high antibody titers predict adverse pregnancy outcome. STUDY DESIGN: Women diagnosed with APS according to strict clinical and laboratory criteria were prospectively followed in pregnancy. Lupus anticoagulant, anticardiolipin antibodies and Beta-2 Glycoprotein 1 levels were measured prior to pregnancy. Women with antibody titers more than 4 times upper limit of normal were termed High Titer (HT) group, while women with lower positive antibody titers were considered Low Titer (LT) group. All women were treated with LMWH 0.7-1 mg/kg/day and aspirin 100 mg daily. Adverse pregnancy outcomes included fetal/neonatal loss, significantly premature birth 32 weeks= gestation, and intrauterine growth restriction (IUGR, 10th percentile). RESULTS: 51 women in 55 pregnancies were prospectively followed, 20 in the HT and 35 in the LT groups. 35% of HT women and 11.4% of LT women had triple antibody positivity (p 0.07). The risks of pregnancy loss, delivery 32 weeks and/or IUGR were all significantly more common in the HT as compared with the LT group. Moreover, among women with high titers, only 35% of pregnancies culminated in appropriately grown, liveborn infants 32 wks gestation, as compared with 77% of pregnancies with low titers (OR 0.17, 95% CI 0.05-0.53). The 2 groups were similar in the proportion of previous pregnancy losses, previous thromboembolic events, primary/secondary APS and concurrent genetic thrombophilias. CONCLUSION: In women with antiphospholipid syndrome, high antibody titers prior to pregnancy define a unique and extremely high-risk group for adverse pregnancy outcome. These women need special prenatal consultation and tight prenatal care.

Splenic marginal zone lymphoma with Evans’ syndrome, autoimmunity, and peripheral gamma/delta T cells

Dear Editor, Several theories have tried to explain the occurrence of autoantibodies in lymphoid malignancies. Autoimmune phenomena like Evans’ syndrome, lupus anticoagulants, autoimmune thrombocytopenia, and autoimmune hemolytic anemias are frequently associated with lymphomas [4, 5]. Recently, systemic lupus erythematosus (SLE) was associated with an increased risk of diffuse large B cell and marginal zone lymphomas [3]. Splenic marginal zone lymphoma (SMZL) is an indolent B cell lymphoma, which generally presents splenomegaly and involvement of both bone marrow and peripheral blood. In this report, we describe a patient with autoimmunity and bone marrow infiltration that probably broke the mechanisms of central tolerance in bone marrow producing the emergency of new auto-reactive clones and autoantibodies. A 60-year-old man had a 12-month history of B symptoms. Physical examination was unremarkable, except for the presence of massive splenomegaly. A computerized tomograhpy (CT) scan of the abdomen confirmed splenomegaly and visualized enlarged lymph nodes in retroperitoneum (Fig. 1). Blood smear and peripheral blood immunophenotype suggest SMZL with villous lymphocytes. The patient underwent laparotomy for splenectomy, lymph node, and bone marrow biopsies. Histology corresponds to SMZL. Follow-up studies detected the persistence of lymphoid neoplastic cells (1.4%) and a γδ T cell population (TCR γδ CD2+, CD3+, CD5 low+, CD7+, CD8 low+/−, CD16 −/+ CD56+, CD57 +/−) that represented 12% of the cells in peripheral blood. Five months after diagnosis, the patient presented with abdominal discomfort. On a CT scan, abdominal adenopatic progression was observed and the two populations (3.4% of SMZL and 4.9% of γδ T cells) persisted in peripheral blood. The patient received eight cycles of chemotherapy with cyclophosphamide–doxorubicin–vincristin–prednisone regime, resulting in radiological remission. At this moment, flow cytometry of peripheral blood revealed 0.0026% of tumor cells and 13.75% of γδ T cells. Four months after chemotherapy, the patient was admitted to the hospital with a recurrence of SZML. He showed, besides, respiratory insufficiency and Evans’ syndrome, associated with high titers of antiphospholipid antibodies, lupus anticoagulant and prolonged partial tromboplastin time, high levels of immune complexes, and low levels of both immunoglobulins and C3 and C4 fractions of complement. Antinuclear, antineutrophil cytoplasmic, anticardiolipin, antiplatelets, anti-HLA I, and antiEPCR antibodies were also detected. CT scan ascertained the presence of pulmonary emphysema and hepatomegaly, without associated enlarged lymph nodes. Peripheral blood flow-cytometry indicated an increase in the neoplastic B cell population (50%) and a decrease of γδ T cells (5%). The bone marrow biopsy confirmed lymphoid infiltration (SMZL 35% and γδ T cells 4%) by immunophenotype. Ann Hematol (2009) 88:177–178 DOI 10.1007/s00277-008-0555-z

Homocysteine and antiphospholipid antibodies in a woman undergoing ovarian follicular stimulation: Prospective clinical and laboratory evaluation

This is the case of a 28-year-old woman in apparently good health, who had an ischemic stroke and significant proteinuria developed during her first attempt of in vitro fertilization. She was evaluated for inherited and acquired thrombophilia and tested positive for high titer of antiphospholipid antibodies and mild hyperhomocysteinemia. The potential thrombotic risks associated with in vitro fertilization will be discussed.

Chorea and Rapidly Progressive Subcortical Dementia in Antiphospholipid Syndrome

Antiphospholipid antibodies are associated with a variety of neurologic manifestations, both in patients with and without concomitant systemic lupus erythematosus. We report a patient in whom chorea and rapidly progressive subcortical dementia developed in the setting of persistently high titers of antiphospholipid antibodies. While some manifestations of antiphospholipid syndrome can be clearly linked to vascular thrombosis, it is not known whether this is also true for patients affected with chorea, dementia, or both. In our patient, serial magnetic resonance imaging showed the progressive development of deep white matter lesions but no cortical infarcts. The development of widespread pulmonary arterial thrombosis and acute cerebral ischemia, evidenced clinically and on diffusion-weighted magnetic resonance imaging of the brain, provided indirect evidence for a thrombotic pathogenesis for this patient's neurologic disease. Anticoagulation should be considered as an adjunct to the treatment of patients with antiphospholipid antibodies and chorea or subcortical dementia.

Antiphospholipid syndrome and the idiotypic network.

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 +/- 5.0 s vs. 22.4 +/- 1.7 s, in the non-immunized mice). Mice immunized with TM1B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS.(ABSTRACT TRUNCATED AT 250 WORDS)