Elevated Titers Of Antiphospholipid Antibodies Research Articles

Imaging vitreous cortex hyalocyte response to paracentral acute middle maculopathy (PAMM) using En Face OCT.

Vitreous cortex hyalocytes (VCH) are resident macrophage cells that provide immunosurveillance, respond to tissue injury and inflammation, and help maintain the transparency of the media. In this case report we demonstrate the use of en face optical coherence tomography (OCT) to image VCH in vivo in a patient presenting with PAMM secondary to antiphospholipid syndrome. A 38-year-old female with no known medical history presented with complaints of visual disturbances in the right eye. OCT revealed hyperreflective bands in the IPL and INL nasal to the fovea. A diagnosis of PAMM was made. Work-up revealed elevated titers of antiphospholipid antibodies. En face OCT revealed a decline in the inflammatory activation over a seven-month period as evidenced by changes in VCH distribution and morphology. Our findings suggest that monitoring changes in the distribution and morphology of VCH could have a potential clinical utility for assessing disease severity, predicting recovery, and early recognition of treatment response in various inflammatory ocular pathologies such as PAMM.

O-002. Beneficial Role of sodium nitrate on pregnancy in mice lacking eNOS

To report a series of patients with occlusive retinal vasculitis associated with systemic sclerosis (SSc) and elevated antiphospholipid antibody titers.Case series. Main outcome measures included clinical and fluorescein angiographic findings at presentation and over time.Case 1 - A 61-year-old woman initially diagnosed with idiopathic, bilateral panuveitis and retinal vasculitis causing peripheral nonperfusion was subsequently diagnosed with limited cutaneous systemic sclerosis (lcSSc). Her ocular inflammation and retinal vasculitis were controlled with topical and periocular corticosteroids, but she eventually developed peripheral retinal vascular occlusion that progressed to macular ischemia 11 years after presentation. Repeat serologic evaluation detected interval development of antiphospholipid antibodies. Case 2 – A 58-year-old woman was found to have bilateral peripheral nonperfusion and retinal neovascularization in her right eye. Given her elevated hemoglobin A1c of 8.5%, she was diagnosed with presumed proliferative diabetic retinopathy. Three years after initial presentation, she was diagnosed with lcSSc. Subsequent serum workup detected elevated B2-glycoprotein antibody titers. Her peripheral nonperfusion progressed despite adequate glycemic control, resulting in further neovascularization in each eye. Case 3 – A 40-year-old woman with diffuse cutaneous systemic sclerosis (dcSSc) and elevated titers of anti-cardiolipin antibodies developed multiple branch retinal artery occlusions with subsequent neovascularization of the retina, optic disc, and angle in the right eye.Vision-threatening occlusive retinal vasculitis may develop in select patients with SSc. The presence of elevated anti-phospholipid antibody titers may confer increased risk for this vision-threatening complication.

P-018. Analysis of subpopulation of exosomes in prospective samples before the onset of preeclampsia

To report a series of patients with occlusive retinal vasculitis associated with systemic sclerosis (SSc) and elevated antiphospholipid antibody titers.Case series. Main outcome measures included clinical and fluorescein angiographic findings at presentation and over time.Case 1 - A 61-year-old woman initially diagnosed with idiopathic, bilateral panuveitis and retinal vasculitis causing peripheral nonperfusion was subsequently diagnosed with limited cutaneous systemic sclerosis (lcSSc). Her ocular inflammation and retinal vasculitis were controlled with topical and periocular corticosteroids, but she eventually developed peripheral retinal vascular occlusion that progressed to macular ischemia 11 years after presentation. Repeat serologic evaluation detected interval development of antiphospholipid antibodies. Case 2 – A 58-year-old woman was found to have bilateral peripheral nonperfusion and retinal neovascularization in her right eye. Given her elevated hemoglobin A1c of 8.5%, she was diagnosed with presumed proliferative diabetic retinopathy. Three years after initial presentation, she was diagnosed with lcSSc. Subsequent serum workup detected elevated B2-glycoprotein antibody titers. Her peripheral nonperfusion progressed despite adequate glycemic control, resulting in further neovascularization in each eye. Case 3 – A 40-year-old woman with diffuse cutaneous systemic sclerosis (dcSSc) and elevated titers of anti-cardiolipin antibodies developed multiple branch retinal artery occlusions with subsequent neovascularization of the retina, optic disc, and angle in the right eye.Vision-threatening occlusive retinal vasculitis may develop in select patients with SSc. The presence of elevated anti-phospholipid antibody titers may confer increased risk for this vision-threatening complication.

Stress perfusion Cardiac Magnetic Resonance in Patients with Antiphospholipid Syndrome.

Background:Antiphospholipid syndrome (APS) is characterized by the combination of recurrent arterial and venous thrombotic events and detection of persistently elevated antiphospholipid antibody titers in the serum or plasma. APS clinical manifestations also include non-thrombotic complications from various organ systems, mainly the CNS, kidneys, and heart. Cardiac manifestations of APS include valvulopathy, myocardial infarction and angina (stable, unstable, and Pritzmental angina). A previously published case series of cardiac magnetic resonance (CMR) in patients with APS has revealed a high rate of asymptomatic myocardial necrosis and scarring, but the prevalence of myocardial ischemia identified as CMR perfusion defects prior to development of necrosis is unknown.Aims of the study:To detect CMR imaging markers of myocardial ischemia in APS patients without symptoms of cardiovascular disease (CVD).Methods:We will scan fifty APS patients without symptoms of CVD stress-perfusion CMR in a 1.5 Tesla tomographer, after intravenous infusion of adenosine and gadolinium. In addition to markers of cardiac anatomy and function, we will record imaging markers of ischemia and scarring, namely perfusion defects (PDs), and late gadolinium enhancement (LGE). We will perform parametrics using dedicated software in order to derive each patient’s myocardial perfusion reserve index (MPRI). Scans will be reviewed independently by two experienced reviewers, with evaluation of inter- and intra-observer reliability. Statistical hypotheses will be examined using Student’s test and Pearson’s correlation coefficient, or non-parametric equivalents (Kruskall-Wallis and Spearman) for continuous variables, and Fisher’s exact test for binary variables. Linear or logistic regression analyses will be used to investigate APS-related determinants of subclinical myocardial ischemia.Anticipated benefits:We expect to identify CMR imaging patterns characteristic of APS, which will allow proactive therapeutic interventions for primary prevention of CVD and guide further research into the pathogenesis of APS cardiac manifestations.

SLE and APS

Childhood-onset systemic lupus erythematosus (cSLE) represents 15-20% of all SLE cases and is in general associated with a more aggressive disease course and more rapid damage accrual than adult-onset SLE. Disease expression varies according to ethnicity, with more severe disease course in non-Caucasian ethnic groups. The majority of patients with cSLE develop damage within 5-10 years of disease onset, most frequently involving the musculoskeletal, ocular, renal and central nervous systems. Premature atherosclerosis and osteoporosis have become increasingly prevalent comorbidities in cSLE patients. Treatment of cSLE is challenging and is further complicated by an unpredictable disease course, adolescent noncompliance and long requirement for therapy. New therapeutic regimens combining immunosuppressive agents and targeted B-cell depletion often provide improved disease control and follow the oncologic model of remission induction and maintenance therapy. Management of children with SLE must include also prevention of medication side effects on growth, delayed puberty, development and fertility. Optimal management of an adolescent with SLE should take into account also patient’s quality of life, psychosocial development and organization of successful transition from pediatric to adult care. The antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disease characterized by thromboembolic events, pregnancy morbidity, hematologic, dermatologic, neurologic and other manifestations in the presence of elevated titers of antiphospholipid antibodies (aPL). APS may occur as an isolated clinical entity (primary APS) or in association with autoimmune diseases, infections and malignancies. Multiple pathogenic mechanisms have been proposed by which aPL may predispose to thrombosis including interaction between aPL and endothelial cells, platelets, monocytes, activation of the complement system, and interaction with the proteins involved in the regulation of the coagulation cascade. Management in all patients with APS include avoidance of additional risk factors for thrombosis. Patients with persistently positive aPL, in particular those with lupus anticoagulants (LA), have a high risk for recurrent thrombosis and should receive long-term anticoagulation with warfarin. The standard treatment in APS patients with venous or non-cerebral arterial thromboembolism consist of oral anticoagulation at a target INR of 2.0-3.0. However, it is essential to individualize treatment according to the presence of additional thrombophilic risk factors and the aPL profile (multiple aPL antibodies, high titers of aCL and/or anti-β2GPI, presence of LA). An improved understanding of the pathogenic mechanisms by which aPL induce thrombosis has suggested some innovative treatments such as new anticoagulant and antiplatelet drugs, hydroxychloroquine, statins, complement inhibitors, rituximab and other targeted therapies.

IgG accumulates in inhibitory hippocampal neurons of experimental antiphospholipid syndrome

Mice immunized with β2-glycoprotein I (β2GPI) are an experimental model of the antiphospholipid syndrome (eAPS) displaying elevated titers of antiphospholipid antibodies (aPL). We presently studied whether the behavioral hyperactivity in eAPS mice is associated with in vivo binding and accumulation of IgG in the brain. At 6 weeks post immunization eAPS mice had significantly higher levels of aPL (1.32 ± 0.28 and 0.02 ± 0.01 AU, p < 0.001 by t-test) compared to adjuvant immunized controls, as measured by ELISA. Significant hyperactivity in a staircase test in the eAPS mice compared to controls was found in stair-climbing (18.4 ± 0.9 and 12.0 ± 1.7, respectively) and rearing measures (23.5 ± 2.1 and 12.5 ± 1.9, p < 0.01 by t-test). Immunofluorescence staining in eAPS mice revealed significant in vivo accumulation of IgG in cortical and hippocampal neurons which was not seen in controls. Staining for IgG was markedly intense in inhibitory interneurons co-stained for GAD67 in the hippocampus of eAPS mice. The integrity of the blood brain barrier (BBB) evaluated by injection of Evans blue (EB) was impaired in eAPS and adjuvant immunized mice compared to naïve mice. Electrophysiological recordings in hippocampal brain slices showed altered response to paired pulse stimulation as well as dysregulation of carbachol-induced γ- oscillations in eAPS mice compared to control. Penetration into the brain and direct interaction of aPL with inhibitory interneurons in the hippocampus may explain the hyperactive behavior of the eAPS mice. A direct role of aPL in causing CNS dysfunction points to these antibodies as an important therapeutic target in APS.

Antiphospholipid antibodies in neonates with stroke--a unique entity or variant of antiphospholipid syndrome?

YB current affiliation: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Israel YB and MJS contributed equally to the study and should be regarded as joint first authors on this manuscript. Antiphospholipid syndrome (APS) may present with thrombosis and persistently elevated titers of antiphospholipid antibodies (aPL) in the neonatal period. Our aim was to investigate the course and impact of elevated titers of aPL in a cohort of infants presenting with either perinatal arterial ischemic stroke (PAS) or cerebral sinus vein thrombosis (CSVT) during the perinatal period. Sixty-two infants with clinically and radiologically confirmed PAS or CSVT presenting in the neonatal period underwent thrombophilia workup that included Factor V Leiden (FVL), PII20210A mutation, MTHFR 677T polymorphism, protein C, protein S, aPL namely either circulating lupus anticoagulant (CLA), anticardiolipin antibodies (aCL) or anti-β2-glycoprotein-1 (β2GP1). Mothers also underwent thrombophilia workup. Twelve infants with persistently elevated aPL were prospectively followed. Infants with positive aPL showed no concordance with presence of maternal aPL. All children were followed for a median of 3.5 years (range: nine months to 19 years) with repeated aPL testing every three to six months. Anticoagulant therapy initiation and therapy duration varied at the physician's discretion. In 10/12 cases aPL decreased to normal range within 2.5 years; one female with complex thrombophilia risk factors required indefinite prolonged anticoagulation. None of the infants showed recurrent thrombosis or any other APS manifestations, despite lack of prolonged anticoagulation. The presence of aPL may be important in the pathogenesis of cerebral thrombosis in neonates. Nevertheless, the nature of thrombophilia interactions in this period and their therapeutic impact warrants further investigation.

Symmetrical Peripheral Gangrene ComplicatingEscherichia coliSepsis Associated with Antiphospholipid Antibodies in Lupus Nephritis

Antiphospholipid syndrome (APS) is an autoimmune disease that involves vascular thrombosis and pregnancy morbidity associated with elevated titers of antiphospholipid antibodies. APS can affect any organ and has a variety of clinical manifestations. Infections can be associated with thrombotic events in APS, including the potentially fatal subset catastrophic APS. We report a case of extensive symmetrical peripheral gangrene complicating Escherichia coli sepsis associated with antiphospholipid antibodies in a patient with lupus nephritis. (Korean J Med 2014;87:379-382)

A case of antiphospholipid syndrome refractory to secondary anticoagulating prophylaxis after deep vein thrombosis-pulmonary embolism.

Antiphospholipid syndrome (APS) is an acquired systemic autoimmune disorder characterized by a combination of clinical criteria, including vascular thrombosis or pregnancy morbidity and elevated antiphospholipid antibody titers. It is one of the causes of deep vein thrombosis and pulmonary embolism that can be critical due to the mortality risk. Overall recurrence of thromboembolism is very low with adequate anticoagulation prophylaxis. The most effective treatment to prevent recurrent thrombosis is long-term anticoagulation. We report on a 17-year-old male with APS, who manifested blue toe syndrome, deep vein thrombosis, pulmonary thromboembolism, and cerebral infarction despite adequate long-term anticoagulation therapy.

PReS13-SPK-1592: Pediatric aspects of antiphospholipid syndrome

The antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disease characterized by thromboembolic events, pregnancy morbidity, hematologic, dermatologic, neurologic and other manifestations in the presence of elevated titers of antiphospholipid antibodies (aPL). In recent years, APS has been increasingly recognized in various pediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way.

Acyl-CoA:lysocardiolipin acyltransferase (Lycat): a potent pathogenic factor in antiphospholipid syndrome (APS)-related recurrent pregnancy failure

To validate a novel model system to study the pathogenesis of recurrent miscarriages in APS patients. Experimental animal study. Elevated titers of antiphospholipid antibodies (aPL) have a close association with many obstetric disorders. Cadiolipin (CL), a major phospholipid of mitochondria, regulates membrane permeability and potential. Remodeling enzyme Lycat is required for both CL maturation and repair of damaged acyl chains. At present, APS animal models were generally created by immunization of exogenous antigens. This study presents the first genetic model in which elevated Lycat leads to a drastic rise of aPL, concomitant with a high rate of in utero fetal loss. Mice over-expressing Lycat were generated by BAC transgenesis (Tg). Fertility were compared between Tg and WT mice. Mutant implantation sites were sectioned for histology, anti-phospho-H3 IF, TUNEL and in situ hybridization. Altered global gene expression of the mutant conceptus was first tested by NextGENe RNA-seq technology, followed by Q-PCR. Serum aPL were tested by ELISA. At least 3 samples were included in each assay for each genotype. Unpaired student's t-test was performed between WT and Tg groups. All Tg female mice showed elevated aPL, whose levels are positively correlated to the severity of fetal loss. Pregnant Tg females produced fewer pups than the controls (Tg, 2.3±0.2, v.s. WT, 8.5±1.4; p<0.01). Degenerating conceptus revealed faulty extraembryonic structures involving trophoblast giant cells, chorion and amnion. As a result, the embryos developmentally arrested by E7.5. Absence of EOMES, Hand1, PL1 and Tpbp indicates defective trophoblast differentiation; while altered expression of Gas1 and Foxh1 suggests mis-instructed embryogenesis. Decreased synthesis of hemoglobins by decidual cells indicates severe oxygen starvation in the mutants. Pathogenic effects of elevated Lycat are multifold, in which oxygen homeostasis, trophoblast differentiation and embryo growth are all affected.

Severe Abdominal Pain as a Presenting Symptom of Probable Catastrophic Antiphospholipid Syndrome

Catastrophic antiphospholipid syndrome (APS) in pediatric medicine is rare. We report 3 adolescents who presented with acute onset of severe abdominal pain as the first manifestation of probable catastrophic APS. The 3 patients, 2 male patients and 1 female patient were 14 to 18 years old. One had been diagnosed with systemic lupus erythematosus in the past, but the other 2 had no previous relevant medical history. All presented with excruciating abdominal pain without additional symptoms. Physical examination was noncontributory. Laboratory results were remarkable for high inflammatory markers. Abdominal ultrasonography was normal, and abdominal computed tomography scan showed nonspecific findings of liver infiltration. Only computed tomography angiography revealed evidence of extensive multiorgan thrombosis. All patients had elevated titers of antiphospholipid antibodies. The patients were treated with full heparinization, high-dose steroids, and intravenous immunoglobulin with a resolution of symptoms. One patient was resistant to the treatment and was treated with rituximab. In conclusion, severe acute abdominal pain can be the first manifestation of a thromboembolic event owing to catastrophic APS even in previously healthy adolescents. Diagnosis requires a high index of suspicion with prompt evaluation and treatment to prevent severe morbidity and mortality.

Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset

BackgroundThe primary objective of this study was to determine if elevated antiphospholipid antibody titers were correlated with the presence of preeclampsia/eclampsia, systemic lupus erythematosus (SLE), placental insufficiency, and a prolonged length of stay (PLOS), in women who delivered throughout Florida, USA.MethodsCross-sectional analyses were conducted using a statewide hospital database. Prevalence odds ratios (OR) were calculated to quantify the association between elevated antiphospholipid antibody titers and four outcomes in 141,286 women who delivered in Florida in 2001. The possibility that the relationship between elevated antiphospholipid antibody titers and the outcomes of preeclampsia/eclampsia, placental insufficiency, and PLOS, may have been modified by the presence of SLE was evaluated in a multiple logistic regression model by creating a composite interaction term.ResultsWomen with elevated antiphospholipid antibody titers (n = 88) were older, more likely to be of white race and not on Medicaid than women who did not have elevated antiphospholipid antibody titers. Women who had elevated antiphospholipid antibody titers had an increased adjusted odds ratio for preeclampsia and eclampsia, (OR = 2.93 p = 0.0015), SLE (OR = 61.24 p < 0.0001), placental insufficiency (OR = 4.58 p = 0.0003), and PLOS (OR = 3.93 p < 0.0001). Patients who had both an elevated antiphospholipid antibody titer and SLE were significantly more likely than the comparison group (women without an elevated titer who did not have SLE) to have the outcomes of preeclampsia, placental insufficiency and PLOS.ConclusionThis exploratory epidemiologic investigation found moderate to very strong associations between elevated antiphospholipid antibody titers and four important outcomes in a large sample of women.

Recurrent Intestinal Perforation Associated with Thrombosis of Inferior Vena Cava: Uncommon Presentation of Antiphospholipid Syndrome

To the Editor: Antiphospholipid syndrome (APS) is characterized by a state of hypercoagulability potentially resulting in thrombosis of all segments of the vascular bed1,2, fetal loss, and moderate thrombocytopenia3,4. APS is associated with elevated titers of antiphospholipid antibodies (aPL) and/or lupus anticoagulant (LAC)5,6. Gastrointestinal manifestations are rarely observed (about 1.5% of patients) and intestinal infarction, resulting from mesenteric vessel thrombosis, has been infrequently reported3. The presentation may be acute (acute abdomen), often preceded by intestinal angina1. Rarely, thrombosis of large vessels (aorta and inferior vena cava) has also been reported in association with aPL7. We describe a case of recurrent ...

A case of catastrophic antiphospholipid syndrome presenting with acute respiratory distress syndrome as the initial manifestation

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss, accompanied by elevated titers of antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome (CAPS) is a small subset of APS characterized by widespread systemic thrombotic disease with multiorgan failure. We herein describe an autopsy case of CAPS who developed severe respiratory failure due to acute respiratory distress syndrome (ARDS) as the initial manifestation. Patients with APS may exhibit a broad spectrum of pulmonary diseases. ARDS is the common pulmonary complication in CAPS, although it rarely occurs in APS. Some mechanisms of ARDS in CAPS have been postulated but the precise mechanism is still not clearly understood. It is important to understand that APS or CAPS could be a cause of ARDS since ARDS might develop as the initial manifestation of APS or CAPS as seen in our case. Our case is interesting in that severe respiratory failure due to ARDS was the initial presentation of CAPS.

Cutaneous Leg Ulcer Mimicking Pyoderma Gangrenosum in Patient with Secondary Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is characterized by vascular thrombosis in association with elevated titers of antiphospholipid antibodies. Leg ulcers are a considered to be a cutaneous manifestation of APS due to thrombosis of small to medium sized vessels. We report a case of necrotic non-healing, ankle ulcers mimicking pyoderma gangrenosum associated with APS in 50-year-old man. He had a past history of autoimmune thrombocytopenia and cerebral infarction. Laboratory findings showed a circulating lupus anticoagulant, positive anticardiolipin antibodies as well as anti-dsDNA and anti-Sm antibodies. Skin biopsy of ulcer lesions showed thrombotic vasculopathy of medium sized vessels with minimal leukocyte infiltration. Ulcers were successfully treated with surgical debridement and subsequent skin graft along with anticoagulation therapy.

270 Severity of respiratory distress syndrome in neonates of mothers with elevated antiphospholipid antibody titers

270 Severity of respiratory distress syndrome in neonates of mothers with elevated antiphospholipid antibody titers

Catastrophic antiphospholipid syndrome: Remission following leg amputation in 2 cases

Objective: The antiphospholipid syndrome is characterized by venous and arterial thrombotic events that are often recurrent, thrombocytopenia, recurrent fetal loss, and elevated titers of antiphospholipid antibodies. A subtype of patients with a particularly overwhelming clinical picture has been termed catastrophic antiphospholipid syndrome (CAPS). In this report, we present 2 patients who exhibited a similar multisystem disorder associated with gangrenous changes in the lower extremities. Methods: Two patients with CAPS are presented, highlighting the impact of this disorder on the patients and the response to various therapeutic modalities. Results: Both patients had pulmonary, cardiac, cutaneous, and neurologic findings consistent with CAPS. In addition, they had large purulent leg ulcers associated with livedo reticularis. Amputation of the legs in each case induced remission of the systemic illness. Conclusions: We believe that infection plays a significant role in the pathogenesis and amplification of the antiphospholipid syndrome. In certain patients, this association probably is mediated via immune mechanisms, which also enhance the genesis of atherosclerosis. After the foci of infection (suppurative leg ulcers) were removed, the underlying illness improved. These case studies provide an opportunity to study the interrelationship between several confounding factors that converge and lead to the development of this autoimmune condition. Semin Arthritis Rheum 31:127-132. Copyright © 2001 by W.B. Saunders Company

Impairments of the protein C system and fibrinolysis in infection-associated stroke.

Infection/inflammation appears to be an important predisposing risk factor for brain infarction, but little is known regarding underlying molecular mechanisms. We examined the hypothesis that patients with brain infarction preceded by infection/inflammation within 1 week could be identified by a distinctive procoagulant laboratory profile characterized by abnormalities in the protein C system and endogenous fibrinolysis. We performed a case-control study examining the relationship between preceding systemic infectious/inflammatory syndromes and selected immunohematologic variables in 36 patients with acute brain infarction and 81 control subjects (community control subjects [n = 47] and hospitalized nonstroke neurological patient controls [n = 34]). The stroke group had a lower mean level of the circulating antithrombotic enzyme activated protein C (APC) (4.33 +/- 0.34% [log-transformed percentage of control value, mean +/- SD]) than community control subjects (4.51 +/- 0.27%, P < .02) or hospitalized neurological patient controls (4.57 +/- 0.31%, P < .005). The lowest circulating APC levels were found in the stroke group with antecedent infection/inflammation within 1 week preceding index brain infarction (4.23 +/- 0.4%, n = 12). Within the stroke group, circulating APC levels were inversely related to IgG isotype anticardiolipin antibody titers (r = -.55, P < .001). Only the stroke group with infection/inflammation within 1 week had elevated plasma C4b binding protein compared with control subjects (141 +/- 61% versus 112 +/- 44%, P < .05). Stroke patients with antecedent infection/inflammation had a distinctively lower ratio of active tissue plasminogen activator to plasminogen activator inhibitor (0.11 +/- 0.04, n = 9) than other stroke patients (0.19 +/- 0.06, n = 9, P < .01) and control subjects (0.22 +/- 0.16, n = 17, P < .02). Impairments in the protein C pathway and endogenous fibrinolysis may contribute to the increased risk for brain infarction after recent (< or = 1 week) infection/inflammation. A decrease in the circulating anticoagulant APC may be related to elevated antiphospholipid antibody titers.

Frequent Hemodialysis Graft Thrombosis: Association With Antiphospholipid Antibodies

We present two cases of patients with systemic lupus erythematosus and end-stage renal disease. Both were on hemodialysis and had multiple arteriovenous graft thromboses associated with the presence of antiphospholipid antibodies. A review of patients with end-stage renal disease secondary to systemic lupus erythematosus reveals that all had borderline or frankly elevated antiphospholipid antibody titers, and four of the seven patients had multiple graft thromboses. Possible etiologic and pathophysiologic mechanisms are discussed.