Study of Phosphatidylserine-dependent Anti-prothrombin Antibody in Cerebral Infarction

Okuma, Hirohisa; Kitagawa, Yasuhisa; Ishikawa, Tatsuya; Takagi, Shigeharu

doi:10.2169/internalmedicine.48.2232

Cited by 9 publications

(10 citation statements)

References 8 publications

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“…The majority of the articles were excluded for the following reasons: in eight papers (49,51,(61)(62)(63)(64)(65)68), the OR [95%CI] for thrombosis was not provided and could not be calculated; 10 other studies (47, 48, 50, 53-59) were found not pertinent for the purpose of this review.…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome

Sciascia¹,

Sanna²,

Murru³

et al. 2014

Thromb Haemost

229

164

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Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen (aPS/PT). Although these antibodies have both been associated with antiphospholipid syndrome (APS) and a correlation between the two assays have been reported, it seems that aPT and aPS/PT belong to different populations of autoantibodies. It was our objective to systematically review the available evidence on aPT and aPS/PT antibodies and the risk of thrombosis in APS. Medline-reports published between 1988 and 2013 investigating aPT and aPS/PT as a risk factor for thrombosis were included. Whenever possible, antibody isotype(s) and site of thrombosis were analysed. This systematic review is based on available data from more than 7,000 patients and controls from 38 studies analysing aPT and 10 aPS/PT. Antibodies to prothrombin (both aPT and aPS/PT) increased the risk of thrombosis (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.72-3.5). aPS/PT seemed to represent a stronger risk factor for thrombosis, both arterial and/or venous than aPT (OR 5.11; 95%CI 4.2-6.3 and OR 1.82; 95%CI 1.44-2.75, respectively). In conclusion, routine measurement of aPS/PT (but not aPT) might be useful in establishing the thrombotic risk of patients with previous thrombosis and/or systemic lupus erythematosus. Their inclusion as laboratory criteria for the APS should be indisputably further explored.

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Section: Risk Of Bias Assessmentmentioning

confidence: 99%

Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome

Sciascia¹,

Sanna²,

Murru³

et al. 2014

Thromb Haemost

229

164

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“…The presence of aPS/PT is directly related to thromboembolic events in aPL syndrome, SLE and cerebral infarction [31-40]. The thrombogenic properties of aPS/PT correlate with increased thrombin generation in aPL syndrome, contributing to the understanding of the pathophysiology of thrombophilia in these patients [36].…”

Section: Discussionmentioning

confidence: 99%

“…The correlation between aPS/PT antibodies and clinical manifestations of aPL syndrome and the importance of aPS/PT as a marker for this syndrome are well established. The relationship between aPS/PT antibodies and hypercoagulability state is further strengthened by their increased incidence in cerebral infarction [40]. aPT autoantibodies are prevalent in SLE and aPL syndrome and are associated with thrombosis and pregnancy morbidity [41-44].…”

Section: Introductionmentioning

confidence: 99%

The thrombophilic network of autoantibodies in celiac disease

Lerner

Agmon‐Levin

Shapira

et al. 2013

BMC Med

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BackgroundCeliac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease.MethodsThe serum autoantibody levels were determined in 248 individuals, classified into three groups. Group 1 comprised 70 children with definitive celiac disease (age: 7.04 ±4.3 years, male to female ratio 1.06) and group 2 comprised 88 normal children (age: 6.7 ±4.17 years, male to female ratio 0.87), representing controls. The pediatric populations were compared to group 3, which included 90 adults who were family members (parents) of group 1 (age: 34.6 ±11.35 years, male to female ratio 1.2). Antibodies were checked by enzyme-linked immunosorbent assay.ResultsMean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin G antibodies were 32.4 ±19.4, 3.6 ±2.5 and 16.1 ±15.8 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 45.7%, 0% and 7.8% of groups 1, 2 and 3 respectively positive for the antibody (P <0.01). Mean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin M antibodies were 14.2 ±8.7, 6.7 ±6.4 and 12.4 ±15.5 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 7.1%, 3.4% and 9.9% of groups 1, 2 and 3 positive for the antibody. Mean optical density levels of serum antiprothrombin and antiphospholipid immunoglobulin G antibodies were higher in groups 1 and 3 compared with 2 (P <0.005) and in groups 1 and 2 compared with 3 (P <0.01), respectively. Groups 1, 2 and 3 were positive for antiphospholipid immunoglobulin G antibodies (groups 1 and 2 compared with 3) . Celiac disease sera harbor a higher antiprothrombin immunoglobulin G level compared with controls.ConclusionsIt is suggested that the intestinal injury, endothelial dysfunction, platelet abnormality and enhanced apoptosis recently described in celiac disease are at the origin of the increased exposure of phospholipids or new epitopes representing autoantigens. Those autoantibodies might play a pathogenic role in the thrombophilia associated with celiac disease and represent markers for potential anticoagulant preventive therapy.

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“…Thus, we consider that PS and PI, as well as β 2-GPI aCL and LA, are important in screening for antiphospholipid antibody syndrome and should be regarded as antibodies associated with cerebral infarction [14]. It remains controversial whether the presence of antiphospholipid antibody is associated with an increased risk of recurrent cerebral infarction.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Antiphosphatidyl‐Serine Antibody and Antiphosphatidyl‐Inositol Antibody in Ischemic Stroke Patients

Okuma

Kitagawa

Takagi

2010

Journal of Immunology Research

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Antiphospholipid syndrome is characterized by arterial or venous thrombosis and the presence of antiphospholipid antibodies (aPL). We measured β2-GPI aCL, IgGaCL, LA, antiphosphatidyl-serine antibody (PS), and antiphosphatidyl-inositol antibody (PI) in each patient at one month after the onset of stroke. In addition, carotid artery echography was performed in patients positive for PI or PS. Among the 250 patients, 13.6% (34/250) were positive for either PI or PS, and 6.8% (17/250) were positive for both. Carotid artery echography performed on these 34 patients showed that the frequencies of increased intimal-medial thickness (IMT) of 1.1 mm or more, plaque, and carotid artery stenosis of 50% or more were all significantly higher in patients positive for antinuclear antibody than those negative for the antibody (P < .05). PI and PS are associated with antinuclear antibody and precipitation of atherosclerosis. Ischemic stroke patients with SLE frequently showed a variety of antiphospholipid-protein antibodies.

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Study of Phosphatidylserine-dependent Anti-prothrombin Antibody in Cerebral Infarction

Cited by 9 publications

References 8 publications

Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome

Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome

The thrombophilic network of autoantibodies in celiac disease

Investigation of Antiphosphatidyl‐Serine Antibody and Antiphosphatidyl‐Inositol Antibody in Ischemic Stroke Patients

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