A-57 The Neuropsychological Impact of Antiphospholipid Antibody Syndrome: A Case Study

Abstract Objective Antiphospholipid Antibody Syndrome (APS), also known as Hughes Syndrome, is an autoimmune condition linked to various adverse medical and neurological outcomes affecting 5 in 100,000. APS results from antibodies (aPL) that attack blood proteins that bind to phospholipids (e.g., 2-glycoprotein I and prothrombin), which can cause blood flow problems, increased risk of blood clots, and recurrent vascular thrombotic events. Research suggests APS may lead to various neurologic/medical issues including memory loss, visual disturbances, and dementia. Method Neuropsychological evaluation of 48-year-old female with triple-positive APS and history of bilateral superior parietal chronic ischemic infarctions, multiple bilateral lacunar infarctions, and bilateral encephalomalacia. Reports progressive cognitive changes (< 1 year). Results Neuropsychological evaluation evidenced low average premorbid functioning and currently, extremely low overall cognitive ability. Memory was variable with significant visual and working memory impairment but preserved delayed recall of contextual information. While verbal abilities were intact, deficits were noted in executive functioning, attention, processing speed, visuomotor, visual–spatial, and fine motor skills. Conclusion This 48-year-old woman’s cognitive profile is consistent with findings in the APS literature and is indicative of an early onset major vascular neurocognitive disorder. Retrospective studies suggest that cognitive deficits often precede somatic symptoms of APS and abnormal neuroimaging findings; she presents atypically, as somatic symptoms and abnormal neuroimaging preceded cognitive decline. This case adds to the limited body of neuropsychological data regarding the effects of APS on cognitive functioning, as the pathogenesis of cognitive impairment in APS is unclear and leads to questions regarding differences in, and trajectories of, cognitive deficits in APS.

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The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656023 ◽

1997 ◽

Vol 77 (04) ◽

pp. 624-628 ◽

Cited By ~ 139

Author(s):

Sabine Eichinger ◽

Ingrid Pabinger ◽

Andreas Stümpfien ◽

Mirko Hirschl ◽

Christine Bialonczyk ◽

...

Keyword(s):

Oral Anticoagulant Therapy ◽

Oral Anticoagulants ◽

Factor V Leiden ◽

Multicenter Trial ◽

Observation Time ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Factor V ◽

Increased Risk ◽

Recurrent Vte

SummaryThromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anticoagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% Cl 7.8-17) in patients without factor V Leiden and was 10.6% (95% Cl 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral. anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

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Venous Thromboembolism: A Survey of Oral Anticoagulant Preferences in the Treatment of Challenging Patient Populations

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618804080 ◽

2018 ◽

Vol 24 (9_suppl) ◽

pp. 209S-216S ◽

Cited By ~ 2

Author(s):

Genevieve Claire Moyer ◽

Bethany Samuelson Bannow ◽

Courtney Thornburg ◽

Rachel Rosovsky ◽

Tzu-Fei Wang ◽

...

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulant ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Treatment Options ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Oral Anticoagulant Treatment ◽

Increased Risk ◽

Altered Metabolism

Venous thromboembolism (VTE) is a highly morbid condition with several available oral anticoagulant treatment options. Numerous studies have been published comparing warfarin to direct oral anticoagulants; however, several populations remain underrepresented in these reports. We surveyed members of The Venous ThromboEmbolism Network U.S. working group regarding their oral anticoagulant preferences for the treatment of VTE in different and challenging populations. In individuals with VTE and no other medical comorbidities, respondents preferred either rivaroxaban (48.7%) or apixaban (48.7%). Apixaban (53.3%) was preferred in elderly individuals with an increased risk of bleeding. Warfarin was preferred in individuals with liver or kidney dysfunction (42% and 47%), altered metabolism (>55%), and antiphospholipid antibody syndrome (84.2%). Low-molecular-weight heparin was preferred in individuals with malignancy (56.6%), followed by edoxaban (23.7%). These findings may help guide clinicians when choosing an anticoagulant in these challenging situations and demonstrate the urgent need for additional study in these groups.

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Motor and cognitive functioning in children treated for idiopathic clubfoot at the age of 3 years

BMC Pediatrics ◽

10.1186/s12887-019-1765-3 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Julia Dillmann ◽

Gudrun Schwarzer ◽

Christian-Dominik Peterlein

Keyword(s):

Cognitive Functioning ◽

Motor Development ◽

Cognitive Abilities ◽

Cognitive Skills ◽

Fine Motor ◽

Idiopathic Clubfoot ◽

Gross Motor ◽

Motor Functioning ◽

Visual Spatial ◽

Increased Risk

Abstract Background Several studies have investigated motor and cognitive skills in infants as well as gross motor abilities in schoolchildren treated for congenital idiopathic clubfoot, mostly indicating specific impairments in those children. However, until now, little is known about the motor and cognitive abilities of preschool children treated for idiopathic clubfoot. Thus, it was the aim of this study to examine gross motor, fine motor and cognitive skills of 3-year-old-children treated for idiopathic clubfoot. Method We tested gross motor, fine motor and cognitive functioning of 10 children treated for idiopathic clubfoot and 10 typically developing children at the age of 40 months (SD = 1) with the Bayley Scales of Infant and Toddler Development. Results The children treated for idiopathic clubfoot showed a slight delay in gross motor development. In particular, they demonstrated difficulties in tiptoeing, walking upstairs and walking downstairs. Moreover, we found some slight deficits in cognitive development, particularly in visual-spatial memory. Discussion Children treated for idiopathic clubfoot appear to have an increased risk of gross motor and spatial cognitive deficits. Orthopedic pediatrics should incorporate measures of gross motor functioning, for example tiptoeing, in their orthopedic setting. Moreover, future studies are needed to clarify whether the observed deficits persist through childhood. If so, some kind of a motor training for children with idiopathic clubfoot might be required.

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The Use of Anti-CD20 Chimeric Monoclonal Antibody, Rituximab in Adult Patients with Treatment Refractory Immune Thrombocytopenia.

Blood ◽

10.1182/blood.v104.11.3950.3950 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3950-3950 ◽

Cited By ~ 4

Author(s):

Jack Jacoub ◽

Wassim Mchlayeh ◽

Imad Tabbara ◽

Harish P. Dave ◽

Robert Siegel ◽

...

Keyword(s):

Platelet Count ◽

T Cell ◽

Immune Thrombocytopenia ◽

Cell Lymphoma ◽

Lymphocytic Leukemia ◽

T Cell Lymphoma ◽

High Dose ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Increased Risk

Abstract Introduction: Approximately 20–30% of treated patients with immune thrombocytopenia (IT) will become resistant to standard therapy. Rituximab has been reported to be effective in nearly 50% of such patients. The following report describes our experience using rituximab as both a splenectomy-sparing and salvage intervention in a heterogenous group of IT patients. Patients and Methods: 11 patients were evaluated retrospectively. Their characteristics were as follows: median age of 44 (range 20–79); 6 were female; median IT duration was 2.8 yrs (range 1mo-17yrs); median number of prior treatments was 3 (range 1–8); all patients had received steroids and most, high dose immunoglobulin. Other treatments included anti-RhD, vincristine, danazol, cyclophosphamide, staphylococcal protein-A column, plasmapheresis, mycophenolate mofetil, cyclosporine and autologous stem cell transplantation (ASCT). 6 patients (55%) had been splenectomized. 8 patients had primary idiopathic thrombocytopenic purpura (ITP) including 2 cases of Evan’s syndrome (ES) and 3 had secondary IT associated with antiphospholipid antibody syndrome (APS), cutaneous panniculitis-like T-cell lymphoma and chronic lymphocytic leukemia (CLL). The planned treatment was rituximab 375 mg/m2 i.v. weekly x 4. A complete response (CR) was defined as a rise in platelet count >100 X 109/L for greater than 3 months, partial response (PR) was defined as a rise in platelet count >50 X 109/L and no response (NR) was defined as no change or a rise < 50 X109/L. Results: All patients received the 4 doses of rituximab except 1 patient who achieved CR after 1 dose. Of the 8 primary ITP patients 6 (75%) attained CR, 1 had a transient PR and 1 a NR. All 3 patients with secondary IT reached CR. Overall, 91% of patients responded and 81% had CR. 1 ITP patient was spared a splenectomy and remains in CR at 7 mos. 5 of 6 (83%) splenectomized ITP patients reached CR and the 6th had a brief PR and failed to respond to retreatment. 4 of 5 splenectomized patients remain in CR at 3, 3, 32 and 34 mos, respectively. The last patient is a 44 y/o M with ES for 17 yrs who attained a transient CR with stable hemolysis but relapsed and was retreated 6 mos later with a sustained CR for nearly 3 years while maintained on intermittent rituximab therapy. Notably, he has experienced hypogammaglobulinemia with recurrent pneumonia. The 5th splenectomized patient reaching CR was a 35 y/o M with ES refractory to extensive pretreatment including ASCT and had a transient PR only after rituximab. He was retreated 4 mos later and reached a sustained CR 3 mos from last dose but died from hepatic failure characterized by marked cholestasis with loss of bile ducts of unclear etiology but possibly drug related. Among those with secondary IT is a 27 y/o F with APS who responded after 1 rituximab dose and remains in CR at 12 mos. Both cases of CLL and T-cell lymphoma remain untreated for their primary disease and continue in CR at 6 and 22 mos, respectively. No characteristic predicting response was identified. Rituximab therapy was well tolerated with limited infusional reaction, fatigue and headache occurring in 3 of 10 patients. Conclusion: In contrast to published reports, 81% of our refractory IT patients treated with rituximab had durable responses. Furthermore, it appears retreatment and maintenance therapy may be effective in refractory IT at the expense of possibly an increased risk for infection.

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Recurrent, Spontaneous Esophageal Ruptures Associated With Antiphospholipid Antibody Syndrome: Report of a Case

International Surgery ◽

10.9738/intsurg-d-13-00204.1 ◽

2014 ◽

Vol 99 (6) ◽

pp. 842-845 ◽

Cited By ~ 3

Author(s):

Hiroshi Naitoh ◽

Minoru Fukuchi ◽

Shinsuke Kiriyama ◽

Takaharu Fukasawa ◽

Yuichi Tabe ◽

...

Keyword(s):

Spontaneous Rupture ◽

English Literature ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Esophageal Rupture ◽

Vascular Thrombosis ◽

Spontaneous Esophageal Rupture ◽

Increased Risk ◽

Boerhaave Syndrome ◽

Syndrome Report

Abstract A 52-year-old man was admitted to our hospital with a spontaneous esophageal rupture (Boerhaave syndrome) and was successfully treated. Eight years after the first incident, he was readmitted with a recurrent rupture. Recurrence of Boerhaave syndrome is extremely rare, with only 7 cases reported in the English literature. During treatment, the patient was also diagnosed with antiphospholipid syndrome (APS). Although APS is known to cause a variety of symptoms due to vascular thrombosis, recurrence of Boerhaave syndrome, coincident with APS, has never been reported. The pathogenesis of Boerhaave syndrome has not been clearly determined. This report serves to increase awareness of the risk of APS, which results in an increased risk of spontaneous rupture of the esophagus.

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Procoagulant Microparticles: New Insights and Opportunities in Pregnancy Loss?

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612654 ◽

2001 ◽

Vol 85 (01) ◽

pp. 3-4 ◽

Cited By ~ 15

Author(s):

Ian Greer

Keyword(s):

Pregnancy Complications ◽

Pregnancy Loss ◽

Recurrent Miscarriage ◽

Fetal Loss ◽

Medical Intervention ◽

Coagulation System ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Intrauterine Death ◽

Increased Risk

SummaryIn recent years, prothrombotic states have been not only associated with an increased risk of venous thrombosis, but also with pregnancy complications. In particular there is good evidence linking antiphospholipid antibody syndrome, which is associated with increased thrombin generation (1), to recurrent miscarriage. The importance of procoagulant changes in the pathophysiology of recurrent miscarriage is emphasised by the fact that treatment with heparin and low dose aspirin will substantially improve the likelihood of a successful pregnancy (2). Essentially, this is the only successful medical intervention in the treatment of miscarriage. There are also data now accumulating that link congenital thrombophilia to pregnancy complications such as miscarriage, pre-eclampsia, intra-uterine growth restriction, abruption and intrauterine death (3, 4). Furthermore, recent data have shown that acquired changes in the coagulation system, such as the acquired activated protein C resistance of pregnancy is also associated with an increased risk of pre-eclampsia (5). These data collectively suggest that procoagulant changes in general, rather than congenital or acquired thrombophilia in particular are associated with the development of pregnancy complications including fetal loss. However, in the majority of cases of fetal loss no cause is found and we cannot easily link these events to a procoagulant problem in the mother. In this issue of the Thrombosis and Haemostasis, Laude et al. (6) report, for the first time, the association between circulating procoagulant microparticles and pregnancy loss so providing a new insight into potential mechanisms.

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Graves' Disease Associated with Cerebrovascular Disease and Antiphospholipid Antibody Syndrome

International Journal of Endocrinology ◽

10.1155/2010/624152 ◽

2010 ◽

Vol 2010 ◽

pp. 1-3 ◽

Cited By ~ 5

Author(s):

Ines Khochtali ◽

Nadia Hamza ◽

Elyes Gassab ◽

Asma Baba ◽

Maha Kacem ◽

...

Keyword(s):

Cerebrovascular Disease ◽

Antiphospholipid Antibodies ◽

Graves Disease ◽

Thyroid Disorders ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Simultaneous Presence ◽

Increased Risk

Thyroid disorders are commonly associated with coagulopathy. Patients with hyperthyroidism have increased risk for developing thromboembolic accidents, which are favoured by a simultaneous presence of antiphospholipid antibodies syndrome. in this paper, we describe the case of a patient with Graves' disease, who developed strokes with antiphospholipid antibodies syndrome.

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Mesothelioma-associated antiphospholipid antibody syndrome presenting with cutaneous infarction and neuropathy

British Journal of Dermatology ◽

10.1046/j.1365-2133.1998.02289.x ◽

1998 ◽

Vol 138 (6) ◽

pp. 1092-1094 ◽

Cited By ~ 10

Author(s):

Tucker ◽

Coulson ◽

Salman ◽

Kendra ◽

Johnson

Keyword(s):

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome

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Plasma Levels of Lipoprotein(a) Are Elevated in Patients with the Antiphospholipid Antibody Syndrome

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642454 ◽

1994 ◽

Vol 71 (04) ◽

pp. 424-427 ◽

Cited By ~ 42

Author(s):

Masahide Yamazaki ◽

Hidesaku Asakura ◽

Hiroshi Jokaji ◽

Masanori Saito ◽

Chika Uotani ◽

...

Keyword(s):

Plasma Levels ◽

Active Form ◽

Plasminogen Activator Inhibitor ◽

Arterial System ◽

Control Group ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Lipoprotein A ◽

Soluble Thrombomodulin ◽

Relationship Of

SummaryThe mechanisms underlying clinical abnormalities associated with the antiphospholipid antibody syndrome (APAS) have not been elucidated. We measured plasma levels of lipoprotein(a) [Lp(a)], the active form of plasminogen activator inhibitor (active PAI), thrombin-antithrombin III complex (TAT) and soluble thrombomodulin (TM), to investigate the relationship of these factors to thrombotic events in APAS. Mean plasma levels of Lp(a), TAT, active PAI and TM were all significantly higher in patients with aPL than in a control group of subjects. Plasma levels of Lp(a) and active PAI were significantly higher in patients with aPL and arterial thromboses than in patients with aPL but only venous thromboses. There was a significant correlation between plasma levels of Lp(a) and active PAI in patients with aPL. These findings suggest that patients with aPL are in hypercoagulable state. High levels of Lp(a) in plasma may impair the fibrinolytic system resulting in thromboses, especially in the arterial system.

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