OBJECTIVE: To detect the serum levels of soluble endothelial glycoprotein endoglin (s-Eng) in patients with antiphospholipid syndrome (APS) and to evaluate the correlation between s-Eng levels and clinical features and laboratory parameters. METHODS: The levels of serum s-Eng were measured by enzyme linked immunosorbent assay (ELISA) in 139 patients with APS, 44 patients with SLE but no APS, 37 patients with primary Sjögren's syndrome (pSS), 23 patients with Bechet's disease (BD), 22 patients with systemic sclerosis (SSc) and 22 persistent anticardiolipin antibody (aCL) positive individuals without SLE or APS (simply aCL positive group) and 87 health controls (HC) without any auto-immune diseases. These APS patients included 64 primary APS patients and 75 APS patients secondary to SLE.The correlation between the clinical data, laboratory parameters, and serum s-Eng levels were analyzed.Independent samples t test, paired t test, Chi-square Test, Mann-Whitney U test, Pearson's χ² test were used for statistical analyses. RESULTS: (1) The serum levels of s-Eng were significantly higher in the patients with APS whether primary or secondary to SLE than in the health controls and simply aCL positive group and the patients with other autoimmune diseases, including SLE, pSS, BD and SSc (P<0.001). There was no significant difference in the serum s-Eng levels between simply aCL positive group and health controls [(5.17±2.00) mg/L vs. (5.04±1.11) mg/L, P>0.05]. (2) The best cut-off value for the diagnosis of APS was no less than 8.37 mg/L as mean ± 3SD value, with the sensitivity at 0.772 and the specificity at 0.928. The Youden index was 0.700. These results indicated good validity of s-Eng as a diagnostic marker for APS. (3) The proportions of artery thrombosis and pathological pregnancy were higher in the group of s-Eng-positive APS patients than that in s-Eng-negative group (46/81 vs. 19/58, 29/65 vs. 10/44, respectively, all P<0.05). The levels of PLT were lower in the group of s-Eng-positive APS patients (72.00×10⁹/L vs. 119.00×10⁹/L, P<0.001). (4) The proportions of the presence (93.83% vs. 37.93%, P<0.001) and titer (61.70 U/mL vs. 15.45 U/mL, P<0.001) of aCL were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group. The proportions of the presence (61.73% vs. 43.10%, P<0.05) and titer (33.48 U/mL vs.17.40 U/mL, P<0.05) of anti-β2-glycoprotein I antibody were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group too. CONCLUSION s-Eng serum levels were significantly increased in the patients with APS, and it may play a role as acomplementary serological marker for the diagnosis and risk prediction of APS.
Antibodies, Anticardiolipin ; Antiphospholipid Syndrome/diagnosis* ; Autoantibodies ; Endoglin/blood* ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Pregnancy

OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.
Abortion, Spontaneous ; Antibodies, Anticardiolipin ; Antibodies, Antinuclear ; Antibodies, Antiphospholipid ; Antithrombin III ; Blood Glucose ; Chromosome Aberrations ; Factor V ; Female ; Homocysteine ; Humans ; Killer Cells, Natural ; Live Birth ; Lupus Coagulation Inhibitor ; Plasminogen Activators ; Pregnancy ; Pregnancy Outcome* ; Pregnancy* ; Prolactin ; Protein C ; Protein S ; Thrombophilia ; Thyrotropin

OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.
Abortion, Spontaneous ; Antibodies, Anticardiolipin ; Antibodies, Antinuclear ; Antibodies, Antiphospholipid ; Antithrombin III ; Blood Glucose ; Chromosome Aberrations ; Factor V ; Female ; Homocysteine ; Humans ; Killer Cells, Natural ; Live Birth ; Lupus Coagulation Inhibitor ; Plasminogen Activators ; Pregnancy ; Pregnancy Outcome* ; Pregnancy* ; Prolactin ; Protein C ; Protein S ; Thrombophilia ; Thyrotropin

BACKGROUND/AIMS: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. METHODS: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. RESULTS: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/microL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. CONCLUSIONS: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.
Adolescent ; Adult ; Aged ; Antibodies, Anticardiolipin/*blood ; Antibodies, Antiphospholipid/blood ; Chi-Square Distribution ; Female ; Glucocorticoids/therapeutic use ; Humans ; Lupus Coagulation Inhibitor/*blood ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Prospective Studies ; Purpura, Thrombocytopenic, Idiopathic/*blood/drug therapy ; Thrombocythemia, Essential/*blood/drug therapy ; Thrombosis ; Young Adult

Antiphospholipid antibody syndrome (APS) is defined as the presence of lupus anticoagulant antibody or anticardiolipin antibody with vascular thrombosis or pregnancy complications. APS can be associated with autoimmune disease or infectious disease. APS has also been reported in conjunction with variety of solid and hematologic malignancies. There were some reports on APS which were accompanied by hematologic malignancy, but there was no report with solid malignancy in Korea. We experienced one case of secondary APS, which was diagnosed during pre-operative evaluation of thyroid cancer. This patient had prolonged aPTT (activate partial thromboplastin time) and decreased coagulation factors which were regarded as hemophilia at first. Although the precise mechanism of the relationship between APS and cancer has not been proven thoroughly, APS can be accompanied by various malignancies. So proper screening and early detection of malignancies in APS patients are recommended.
Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Autoimmune Diseases ; Blood Coagulation Factors ; Communicable Diseases ; Hematologic Neoplasms ; Hemophilia A ; Humans ; Korea ; Lupus Coagulation Inhibitor ; Mass Screening ; Pregnancy Complications ; Thromboplastin ; Thrombosis ; Thyroid Gland ; Thyroid Neoplasms

Abortion, Habitual ; drug therapy ; immunology ; Antibodies, Anticardiolipin ; blood ; Aspirin ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heparin ; administration & dosage ; Humans ; Integrative Medicine ; methods ; Prednisone ; therapeutic use ; Pregnancy

BACKGROUND: The presence of antiphospholipid antibodies (aPLs) is associated with the clinical features of antiphospholipid syndrome (APS), which comprises venous and arterial thrombosis and pregnancy loss, and systemic lupus erythematosus (SLE). The prevalence of aPLs has been reported to be different in patient populations affected by either of these conditions. We performed a retrospective study to evaluate the prevalence and clinical associations of aPLs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in a cohort of Korean patients with SLE. METHODS: This study included samples from 88 SLE patients for whom aPL testing had been advised between June 2006 and July 2009 at the Dong-A University Hospital. Serum and plasma samples were tested for LAC, aCL (IgG, IgM), and anti-beta2-GPI (IgG, IgM) antibodies. Clinical data from patients were obtained from a review of medical records. RESULTS: LAC was the most common (34.1% of total patients, 30/88) antibody, followed by IgM aCL (31.8%, 28/88), IgG aCL (18.2%, 16/88), and IgM and IgG anti-beta2-GPI (both 5.7%, 5/88 each). Positivity for LAC was strongly associated with venous/arterial thrombosis (P=0.002). CONCLUSIONS: LAC was the most common antibody detected in Korean SLE patients and is shown to have a significant association with the presence of venous/arterial thrombosis. The measurement of LAC may be clinically useful in identifying patients with SLE who are at a high risk for venous/arterial thrombosis.
Adolescent ; Adult ; Antibodies, Anticardiolipin/*blood ; Antibodies, Antiphospholipid/*blood ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Lupus Coagulation Inhibitor/*blood ; Lupus Erythematosus, Systemic/epidemiology/*immunology ; Male ; Middle Aged ; Pregnancy ; Prevalence ; Retrospective Studies ; Risk Factors ; Venous Thrombosis/epidemiology/immunology

BACKGROUND: The presence of lupus anticoagulants (LA) is a strong risk factor for thrombosis in antiphospholipid syndrome. We investigated the usefulness of addition of silica clotting time (SCT) to the pre-existing dilute Russell's viper venom test (dRVVT) for detection of LA. Also, we analyzed differences in the thrombotic features and the characteristics of antiphospholipid antibodies between dRVVT and SCT. METHODS: A total of 167 patients positive for LA or anti-cardiolipin (anti-CL) antibody and 76 healthy controls were enrolled. The dRVVT and SCT were used for detection of LA. Anti-CL, anti-beta2-glycoprotein I (anti-beta2 GPI) and anti-prothrombin (anti-PT) antibodies were measured using commercial ELISA kits. RESULTS: In detection of thrombosis, the sensitivity of the combined test of SCT and dRVVT was 56.4%, which was higher than that of dRVVT alone (46.2%) or SCT alone (23.1%). The specificity of the combined test (80.9%) was comparable to that of dRVVT (81.9%). Also, odds ratio for predicting thrombosis was higher in the combined test than in dRVVT or SCT alone. When normalized LA ratio of the two tests was compared, the group of patients with higher ratio of SCT showed significantly higher prevalence of recurrent abortion and higher positivity of IgG types of anti-CL, anti-beta2 GPI and anti-PT than the group with higher ratio of dRVVT. CONCLUSIONS: Addition of SCT to dRVVT can improve the detection sensitivity of thrombosis in LA test. And the high normalized LA ratio of SCT may be a useful parameter for detection of recurrent abortion.
Adult ; Aged ; Antibodies, Anticardiolipin/analysis ; Antibodies, Antiphospholipid/analysis ; Blood Coagulation Tests/*methods ; Female ; Humans ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Lupus Coagulation Inhibitor/*blood ; Male ; Middle Aged ; Prothrombin/immunology ; Prothrombin Time/methods ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Silicon Dioxide/*chemistry ; Thrombosis/diagnosis ; beta 2-Glycoprotein I/immunology

PURPOSE: To report a case of central retinal artery obstruction (CRAO) caused by protein S deficiency. CASE SUMMARY: A 36-year-old man presented with acutely reduced visual acuity in the right eye. The patient had no other diseases such as diabetes mellitus or hypertension. The visual acuity was 20/20 in the right eye and light perception in the left eye. Afferent pupillary defect was observed in theleft eye. Fundus examination showed diffuse retinal opacification and a cherry-red spot at the macula. Thus the patient was diagnosed with CRAO in the left eye. There were no abnormal findings on routine hematologic tests including blood coagulation test. Protein C activity, antithrombin III activation, anticardiolipin antibody were within normal limits but protein S activity was decreased. Thus, the patient was diagnosed with CRAO with protein S deficiency. CONCLUSIONS: Coagulation factors such as protein S need to be measuredin cases of CRAO in young patients without medical problems.
Adult ; Antibodies, Anticardiolipin ; Antithrombin III ; Blood Coagulation Factors ; Blood Coagulation Tests ; Diabetes Mellitus ; Eye ; Hematologic Tests ; Humans ; Hypertension ; Light ; Protein C ; Protein S ; Protein S Deficiency ; Pupil Disorders ; Retinal Artery ; Retinaldehyde ; Visual Acuity

PURPOSE: To report a case of central retinal artery obstruction (CRAO) caused by protein S deficiency. CASE SUMMARY: A 36-year-old man presented with acutely reduced visual acuity in the right eye. The patient had no other diseases such as diabetes mellitus or hypertension. The visual acuity was 20/20 in the right eye and light perception in the left eye. Afferent pupillary defect was observed in theleft eye. Fundus examination showed diffuse retinal opacification and a cherry-red spot at the macula. Thus the patient was diagnosed with CRAO in the left eye. There were no abnormal findings on routine hematologic tests including blood coagulation test. Protein C activity, antithrombin III activation, anticardiolipin antibody were within normal limits but protein S activity was decreased. Thus, the patient was diagnosed with CRAO with protein S deficiency. CONCLUSIONS: Coagulation factors such as protein S need to be measuredin cases of CRAO in young patients without medical problems.
Adult ; Antibodies, Anticardiolipin ; Antithrombin III ; Blood Coagulation Factors ; Blood Coagulation Tests ; Diabetes Mellitus ; Eye ; Hematologic Tests ; Humans ; Hypertension ; Light ; Protein C ; Protein S ; Protein S Deficiency ; Pupil Disorders ; Retinal Artery ; Retinaldehyde ; Visual Acuity