Anticardiolipin Antibody Positive Patients Research Articles

Analysis of curative effect of Bushenantai recipe combined with progesterone soft capsules in the treatment of recurrent spontaneous abortion

Objective To investigate the clinical effect of progesterone soft capsules combined with Bushenantai recipe in the treatment of anticardiolipin antibody positive recurrent abortion. Methods 98 patients with positive anticardiolipin antibody and recurrent spontaneous abortion were selected, and they were randomly divided into observation group and control group according to the digital table, 49 cases in each group.The control group was given progesterone soft capsules treatment, the observation group was given the combined treatment of Bushenantai recipe and progesterone soft capsules.The medication time, live birth rate and antibody clearance rate were compared between the two groups. Results The treatment time of the observation group was (179.5±12.8)d, which was significantly shorter than (288.6±14.5)d of the control group, the difference was statistically significant(t=6.249, P<0.05). The live birth rate, antibody clearance rate of the observation group were 91.8%, 79.6%, respectively, which were significantly higher than those of the control group(79.6%, 36.7%), the differences were statistically significant(χ2=5.247, 4.998, all P<0.05). The observation group had 3 cases of adverse reactions(6.0%), the control group had 15 cases of adverse reactions (30.6%), the incidence rate of adverse reactions between the two groups had statistically significant difference(χ2=8.250, P<0.05). Conclusion Progesterone soft capsules combined with Bushenantai recipe in the treatment of anticardiolipin antibody positive patients with recurrent spontaneous abortion can shorten the treatment time, improve pregnancy outcome, improve the antibody clearance rate. Key words: Abortion, habitual; Progesterone; Bushenantai recipe

Modulation of an aqueous extract of Chinese medicine prescription Anzi Heji () on ratio of CD4+CD25+FOXP3+ regulatory T cells in anticardiolipin antibody-positive patients with threatened abortion.

To evaluate Chinese medicine prescription, Anzi Heji (, AZHJ), on immune regulation of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in anticardiolipin antibody (ACA)-positive patients with threatened abortion. Twenty-seven ACA-positive female patients with threatened abortion in the study group were treated with an aqueous extract of AZHJ 125 mL, twice daily for 4 consecutive weeks. The results were compared with control group composed by 15 healthy pregnant women. The ratio of CD4+CD25+FOXP3+ Treg in peripheral blood was identified by flow cytometry. The indicators of ACA were detected by enzyme-linked immunosorbent assay, and embryo development was checked by B-ultrasound. Compared with the control group, the ratio of CD4+CD25+FOXP3+ Treg cells in the study group was significantly lower before AZHJ treatment (P<0.01) and significantly increased after AZHJ treatment (P<0.01). After treatment, 20 of 27 patients (85%) showed that ACA indicators turned into negative, and 7 cases of quantitative indicators of ACA titers were significantly decreased (P<0.01). Total efficiency of treating miscarriage by AZHJ was 92.59%. AZHJ can regulate the immune function of pregnant women by increasing number of CD4+CD25+FOXP3+ Tregs.

A retrospective study on IVF outcome in patients with anticardiolipin antibody: effects of methylprednisolone plus low-dose aspirin adjuvant treatment

Patients undergoing in vitro fertilization–embryo transfer have a high prevalence of anticardiolipin antibody (ACA). However, the relationship between ACA and IVF outcome is still controversial. The aim of the present study was to evaluate the potential effect of anticardiolipin antibody on IVF outcome and determine the role of adjuvant treatment in these ACA positive patients. The study included a total of 116 infertile women (116 IVF-ET cycles) positive for ACA, including 56 women pretreated with methylprednisolone plus low-dose aspirin before IVF (treated ACA+ group) and 60 patients without treatment (untreated ACA+ group). In addition, 518 infertile women (518 IVF-ET cycles) negative for ACA were enroled as controls (ACA− group). The results show that ACA+ patients who did not receive any adjuvant treatment showed a significantly lower fertilization rate, less high-quality embryos, as well as a markedly lower pregnancy rate and implantation rate than controls. Moreover, ACA+ patients who received methylprednisolone plus aspirin achieved significantly higher fertilization, pregnancy and implantation rates than untreated ACA+ patients (FR 69.0%, PR 46.4% and IR 25.4% vs. FR 60.0%, PR 33.3% and IR 17.9%, respectively). The overall IVF results in the treated ACA+ group were comparable to patients negative for ACA (PR 53.9% and IR 32.3%). Thus, while the presence of ACA exerts a detrimental effect on IVF outcome, ACA+ patients have a better outcome if given methylprednisolone for immunosuppression and low-dose aspirin as an anti-thrombotic agent.

Moderate versus high-titer persistently anticardiolipin antibody positive patients: Are they clinically different and does high-titer anti-β2-glycoprotein-I antibody positivity offer additional predictive information?

The association between antiphospholipid antibodies (aPL) and clinical events is stronger with a positive lupus anticoagulant (LA) test, higher anticardiolipin antibody (aCL) titers, and/or higher anti-beta(2)-glycoprotein-I antibody (abeta( 2)GPI) titers. The objective of this study was to determine the clinical characteristics of persistently high-titer (> or =80 U) aCL-positive patients compared with those with persistent moderate aCL titers (40-79 U). Second, we analyzed whether high-titer abeta(2)GPI test adds predictive information in persistently moderate-to-high titer aCL-positive patients. In this cross-sectional study, the primary analysis compared the clinical and aPL characteristics of 58 patients with at least two moderate-titer aCL results to another 85 patients with at least two high-titer aCL results. In the secondary analysis of patients with at least two abeta(2)GPI test results, we compared 29 patients with 'aCL 40-79 U and abeta( 2)GPI < 80 U' profiles with 8 patients with 'aCL 40-79U and abeta(2)GPI > or = 80 U', and also compared 27 patients with 'aCL > 80 U and abeta(2)GPI < 80 U' with 32 patients with 'aCL > 80 U and abeta(2)GPI > or = 80 U'. Although aPL-related vascular and pregnancy events were similar between the moderate- and high-titer aCL groups, the number of patients with positive LA tests (RR 2.06, CI 1.38-3.08, p < 0.01) and with at least one non-criteria aPL manifestation (RR 1.66, CI 1.20-2.30, p = 0.0005) were significantly higher in the high-titer aCL group. While magnetic resonance imaging (MRI) white matter changes were statistically more common in the high-titer aCL group (RR 2.03, CI 1.04-3.94, p = 0.02), there was a trend towards increased prevalence of livedo reticularis, cardiac valve disease, and cognitive dysfunction occurring in the high-titer aCL group. The secondary analysis showed that MRI white matter changes, cardiac valve disease, and cognitive dysfunction were proportionally more common in the high-titer abeta( 2)GPI groups, suggesting a linear relationship between non-criteria aPL manifestations and aPL titers. Our results suggest that patients with high aCL titers, compared with those with moderate titers, are more likely to have a positive LA test and a higher prevalence of non-criteria aPL manifestations. Furthermore, high-titer abeta(2)GPI positivity may further increase the prevalence of non-criteria aPL manifestations in moderate- or high-titer aCL-positive patients.

Prognostic impact of anticardiolipin antibodies in women with recurrent miscarriage negative for the lupus anticoagulant

Anticardiolipin antibodies (ACA) are found with increased prevalence in women with unexplained recurrent miscarriage (RM) but their impact on future pregnancy outcome in lupus anticoagulant (LAC) negative patients needs better quantification. The impact of a repeatedly positive ACA test on the chance of live birth in the next pregnancy after adjustment for relevant prognostic factors was studied in 147 RM patients who had been included in placebo-controlled trials of immunotherapy. Patients with LAC were excluded and none of the patients received therapy with anticoagulation or prednisone. 60/147 patients (41%) were repeatedly ACA positive according to cut-off values derived from this study. The adjusted odds ratio (OR) for live birth among ACA positive patients was 0.36 (95% CI 0.2-0.7, P = 0.006). Using cut-off values derived from a normal population, the adjusted OR for live birth among ACA positive patients was 0.48 (95% CI 0.2-1.1, P = 0.10). Positivity for IgM ACA was found to be much stronger correlated to pregnancy outcome than IgG ACA. In RM women not receiving anticoagulation or prednisone, the presence of ACA in the absence of LAC most likely reduces the chance of live birth by 36-48% compared with the absence of both ACA and LAC. This reduction is inferior to what has been reported from studies where no adjustments for prognostic variables were undertaken and LAC positive patients were included.

A Novel Flow Cytometric Annexin A5 Competition Assay for the Diagnosis of Antiphospholipid Syndrome.

Annexin A5 (A5) is a potent anticoagulant protein that crystallizes over phospholipid surfaces, shielding them from availability for coagulation enzyme reactions. The antiphospholipid antibody (aPL) syndrome (APS) is an autoimmune thrombophilia that is marked by the presence of antibodies against phospholipid-binding proteins and the paradoxical lupus anticoagulant phenomenon. aPL antibodies can promote coagulation by interfering with the crystallization of A5, thereby increasing the exposure of blood to thrombogenic anionic phospholipids. Since a flow cytometric assay for aPL measuring A5 binding to frozen thawed platelets was previously reported, we investigated whether phosphatidylserine-bound polystyrene beads could provide a robust platform for the assay. Beads were incubated with sera from patients with the aPL syndrome and from non-aPL controls. Fluorescence-tagged A5 was added and samples were analyzed by flow cytometry. Similarly treated beads were also used in coagulation assays to determine whether A5 anticoagulant function was also inhibited. Control sera permitted fluorescent labeling of nearly all beads.In contrast, sera from aPL syndrome patients produced a major population of unlabeled beads, sometimes accompanied by a minor population of labeled beads.7 of 13 confirmed aPL syndrome patients, and 7 of 12 anticardiolipin antibody positive patients, demonstrated reduced A5 binding in this assay, while 10 of 10 healthy blood donor controls did not. Dilution of the aPL sera resulted in progressive increase of A5 binding. Reduction of A5 binding appeared to correlate with reduced A5 anticoagulant activity (r=0.42, n=33, p=.01). This assay shows promise for investigating the effects of aPL antibodies on A5 binding and for the clinical diagnosis of the aPL syndrome. [Display omitted] [Display omitted]

Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis.

To assess the presence of anticardiolipin antibodies (ACAs) in patients with chronic hepatitis B virus (HBV) infection, chronic hepatitis D virus (HDV) infection and HBV-related hepatocellular carcinoma (HCC) and to associate this with the incidence of portal vein thrombosis (PVT) in HCC patients. Sixty-five cirrhotic patients with HBV-related HCC, 28 naive patients with chronic HBV infection and 14 naive patients with chronic HDV infection were enrolled prospectively in the study. Thirty-two healthy blood donors were used as controls. The ACAs (immunoglobulin G and immunoglobulin M) were measured using an enzyme-linked immunosorbent assay system. Statistical analysis used non-parametric methodology (chi-squared test, Student t-test and Fisher exact test, P value<0.05). Eleven of the 65 patients with HCC (16.9%) showed a positive ACA titre and 22 of the patients (34%) had PVT. Of these patients, eight (36%) had a positive ACA titre. In contrast, from the 43 patients without PVT, only three (11%) showed a positive titre. From the 28 HBV patients, six (21.5%) had a positive ACA titre, and six out of 14 (42.8%) HDV patients also showed a positive ACA titre. Three of the six ACA positive HBV patients presented an extrahepatic manifestation of the disease. One out of 32 control patients (3%) had positive ACAs. Both chronic HBV and chronic HDV infections are potent stimulants for the production of ACAs. The presence of ACAs in a great proportion of HBV-cirrhosis-related HCC patients with PVT suggests their possible participation in thrombotic mechanisms and in the hypercoagulable state that occurs in advanced liver disease and HCC.

Transcranial Doppler patterns in patients with anticardiolipin antibodies

Purpose: To evaluate cerebral arterial flow patterns in patients with anticardiolipin antibodies (ACL-Ab).Methods: Flow patterns in ACL-Ab positive patients with (n=15) and without (n=13) stroke or transient ischaemic attacks (TIA) were evaluated with transcranial Doppler (TCD). Flow was categorized as normal, focal stenosis, collateral or occlusive. A side to side, (left to right) difference (STSD) in mean flow velocity in any artery exceeding 30% was considered abnormal (aSTSD). The results were compared to those of a control group (n=30) which included age-matched patients with stroke but no ACL-Ab and a second control group (n=30) that included normal healthy adults.Results: Flow patterns were similar in ACL-Ab positive patients with and without clinical evidence for cerebral ischaemia, and aSTSD was the main abnormality identified. This pattern was significantly more common in ACL-Ab positive patients when compared to ACL-Ab negative patients and normal controls. TCD demonstrated an aSTSD in the presence of a normal MRI in two ACL-Ab positive patients with TIA, and in four ACL-Ab positive patients without clinical evidence for cerebral ischaemia.Conclusions: Abnormally increased STSD is commonly found in ACL-Ab positive patients and may precede the occurrence of overt ischaemic events. The significance of such STSD in these patients remains to be clarified.

Clinical features associated with a positive anticardiolipin antibody in Irish patients with systemic lupus erythematosus.

Anticardiolipin antibodies (ACA) are one of a number of autoantibodies found in patients with systemic lupus erythematosus (SLE) and their presence has been associated with clinical features of the antiphospholipid syndrome (APS). The aim of this study was to determine which clinical features are associated with a positive anticardiolipin antibody in Irish patients with SLE. Ninety-five Irish patients with SLE were studied. All were examined thoroughly, had their full history taken, and had case records reviewed. The presence of any clinical feature associated with the APS was noted. Sera from these patients were tested for IgG and IgM ACA. The only significant association found was between a history of venous thrombosis and the presence of ACA, although several other features were more common in ACA positive patients. There were no significant associations with one or other isotype. This study serves as a reminder to consider the possibility of venous thrombosis, and other clinical features, if an SLE patient is positive for ACA.

Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in systemic lupus erythematosus.

We investigated the clinical significance of IgG phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-beta 2-GPI antibodies by ELISA. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies show an unique form of SLE.

Prevalence of lupus anticoagulant in patients with cirrhosis: relationship with beta-2-glycoprotein I plasma levels

We have previously demonstrated that patients with cirrhosis may be positive for lupus anticoagulant and anticardiolipin antibodies. The prevalence and clinical value of antiphospholipid antibodies in cirrhosis have never been described. Besides, it has not yet been determined if serum levels of beta-2-glycoprotein I, which is synthesized by the liver and mediates the interaction between cardiolipin and anticardiolipin antibodies affects lupus anticoagulant detectability in cirrhosis. We evaluated the prevalence of lupus anticoagulant in 63 patients with cirrhosis and related it to beta-2-glycoprotein I serum levels. We also analyzed whether lupus anticoagulant and anticardiolipin antibodies were associated with previous thrombotic complications. Eleven patients (18%) were lupus anticoagulant positive; 14 (22%) had high values of anticardiolipin antibodies. Fourteen patients had a previous history of splanchnic venous thrombosis (n = 9) or thrombophlebitis (n = 5). A significant association between lupus anticoagulant (p = 0.0001), anticardiolipin antibodies (p = 0.0001) and venous thrombosis was found. Patients with severe liver failure had significantly lower beta-2-glycoprotein I levels than those with moderate (p < 0.01) or low (p < 0.001) hepatic insufficiency. Among 14 anticardiolipin antibodies positive patients, six with severe liver failure were lupus anticoagulant negative and had beta-2-glycoprotein I values below 100 micrograms/ml. In four of these, basal values of dilute activated partial thromboplastin time were not modified by the addition of 50 micrograms/ml of exogenous beta-2-glycoprotein I. This study shows that antiphospholipid antibodies are relatively frequent in cirrhosis and that beta-2-glycoprotein I levels are not so low as to affect lupus anticoagulant detectability.(ABSTRACT TRUNCATED AT 250 WORDS)

Umbilical artery and ductal blood flow velocities in patients treated with aspirin and prednisone for presence of anticardiolipin antibody

Fifteen patients with previous pregnancy losses and positive plasma anticardiolipin antibody (ACA) were treated with prednisone (15 mg/day) and aspirin (80 mg/day). We measured Doppler velocimetries of umbilical artery and ductus arteriosus at intervals of 2 to 3 weeks starting from 20 weeks of gestation until delivery. Umbilical artery systolic/diastolic ratios (S/D) and maximum systolic velocities of ductus arteriosus did not differ from normal values. There were no poor outcomes in the treated group. ACA positive patients with previous poor pregnancy outcome when treated with prednisone and aspirin have umbilical artery and ductal flow velocities similar to those of the normal population.

Prospective study of anticardiolipin antibodies in immunized and untreated women with recurrent spontaneous abortions

To investigate whether active leukocyte immunization increases levels of anticardiolipin antibodies in women with recurrent spontaneous abortions. To assess the impact of anticardiolipin antibodies on pregnancy outcome in these women. Patients who had received various treatments in an ongoing randomized trial were studied prospectively. A department of clinical immunology investigating women with recurrent spontaneous abortions from all over Denmark. Eighty-nine patients with unexplained recurrent spontaneous abortions whose pregnancies had been completed during the course of the trial. After randomization, 44 patients were actively immunized with husband's or third party leukocytes, and 27 patients received placebo. Eighteen patients received anticoagulation therapy in pregnancy. Changes in levels of immunoglobulin (Ig)M class and IgG class anticardiolipin antibodies after active immunization. Frequency of new miscarriages in patients who were positive or negative for anticardiolipin antibodies. Neither IgM nor IgG anticardiolipin antibodies changed significantly after active immunization (P greater than 0.2). The interim results of the immunization trial showed a success rate of 68% in the treated group versus 56% in the placebo group (not significantly different). Relative risk of miscarriage in anticardiolipin antibody-positive patients compared with anticardiolipin antibody-negative patients was 1.3 (95% confidence interval 0.7 to 2.2; P = 0.4) in the combined study groups. Patients eligible for active immunization did not exhibit significant changes in anticardiolipin antibody levels subsequent to the treatment. The treatment did not seem to provide any overall benefit with respect to pregnancy outcome. Prospectively, the risk of miscarriage in patients positive for anticardiolipin antibodies was not significantly increased.

Specificity of antibodies to single-stranded (ss) DNA in SLE patients with anti-phospholipid syndrome.

Although the concept of anti-phospholipid syndrome has been proposed in patients with SLE and other rheumatic diseases, the immunological mechanism is still controversial. Recently, the crossreactivity between anti-cardiolipin antibody and anti-ssDNA antibodies has been discussed in relation to this syndrome. In the present study, the specificity such as the avidity and the crossreactivity of anti-ssDNA antibodies was examined to find a clue to clarify the question why all of anti-cardiolipin antibody positive patients do not have any specific clinical features, thrombosis and spontaneous abortion. The avidity of IgG anti-ssDNA antibodies was examined by salt elution studies in solid phase ELISA. The avidity of anti-ssDNA antibodies tended to be lower in 10 patients with specific features than in other 10 patients without those features. The crossreactivity of affinity purified IgG anti-ssDNA antibodies was investigated by competitive ELISA. Purified anti-ssDNA antibodies from 4 patients without specific features were slightly inhibited by negatively charged phospholipids, cardiolipin and phosphatidylserine, whereas purified anti-ssDNA antibodies from 2 patients with specific features, who were considered to have anti-phospholipid syndrome, were little inhibited by these phospholipids. The above results suggest that the specificity of anti-ssDNA antibodies appears, at least partly, in different manners whether specific features are present or absent in anti-cardiolipin antibody positive patients. Moreover, anti-ssDNA antibodies and anti-phospholipid antibodies may form separate groups of antibodies in patients with anti-phospholipid syndrome.

Lupus anticoagulant: clinical significance in anticardiolipin positive patients with systemic lupus erythematosus.

The significance of anticardiolipin antibodies and the lupus anticoagulant was studied in 58 consecutive patients with systemic lupus erythematosus. On 85 occasions serum IgG and IgM anticardiolipin antibodies were measured by an enzyme linked immunosorbent assay (ELISA), and simultaneous plasma samples tested for lupus anticoagulant activity. The most significant association with clinical events (previous thrombosis or thrombocytopenia occurring in 11/58 patients) was with prolonged tissue thromboplastin inhibition time (TTIT) followed by prolonged kaolin cephalin clotting time (KCCT) then raised IgG anticardiolipin antibody concentrations and dilute Russell's viper venom time. Although IgG anticardiolipin antibodies or KCCT were the most sensitive tests in identifying this group, the TTIT was the most specific (98%). Nine patients were IgG anticardiolipin antibody positive and lupus anticoagulant negative, of whom one had thrombocytopenia but none had thrombosis. The presence of a lupus anticoagulant in anticardiolipin antibody positive patients increases specificity for certain adverse clinical events.

Clinical manifestations in anticardiolipin antibody-positive patients with progressive systemic sclerosis

Anticardiolipin antibody-positive patients with progressive systemic sclerosis were analyzed. Elevated anticardiolipin antibody titers were observed in 13 of 40 cases (33%). Anticardiolipin antibody titer was significantly higher in patients with progressive systemic sclerosis type 1 than in those with type 2 or type 3. Occurrence of anticardiolipin antibody was significantly more frequent in patients positive for anti-nRNP antibodies, rheumatoid factor, or thrombocytopenia. In contrast, patients with proximal scleroderma, scarring, or esophageal hypomotility were positive for anticardiolipin antibody less frequently. These results suggest that anticardiolipin antibody might be closely associated with lupuslike clinical manifestations in a subset of progressive systemic sclerosis or definite progressive systemic sclerosis with thrombocytopenia, rheumatoid factor, or anti-nRNP antibodies.