PURPOSE: To evaluate the significance of thrombophilic factors in retinal vein occlusive diseases. METHODS: Thirty-two patients with retinal vein occlusion (19 patients at the age of 55 or less, 13 patients at the age of 56 or more) underwent laboratory evaluation for CBC, lipid profile, VDRL/TPHA, homocysteine, protein C activity, protein S activity, lipoprotein (a), platelet aggregation test, Factor V Leiden, lupus anticoagulant, anticardiolipin antibody, fibrinogen, and antithrombin III. RESULTS: The abnormal laboratory findings (high homocysteine, hyperlipidemia, thrombocytosis, lipoprotein (a), high ESR, and decreased protein S activity) were found more often in patients of 55 years or less than those of 56 or more. CONCLUSIONS: The thrombophilic factors were more common positive findings at or less than 55 years. Thrombophilic factor tests are recommended in young patients with retinal vein occlusion.
Antibodies, Anticardiolipin ; Antithrombin III ; Factor V ; Fibrinogen ; Homocysteine ; Humans ; Hyperlipidemias ; Lipoprotein(a) ; Lupus Coagulation Inhibitor ; Platelet Aggregation ; Protein C ; Protein S ; Retinal Vein Occlusion ; Retinal Vein* ; Retinaldehyde* ; Thrombocytosis

PURPOSE: To determine the prevalence of hematologic abnormalities in patients with retinal vein occlusion (RVO) less than 55 years of age. METHODS: Medical records of twenty-three patients with RVO less than 55 years old were reviewed to evaluate the results of CBC, ESR, homocysteine, Protein C, Protein S, antithrombin III, anticardiolipin antibody, lupus anticoagulant and lipid profile. Patients were considered to have a positive test if the results were outside the laboratory's established range. RESULTS: Four patients had ischemic central retinal vein occlusion (CRVO), 8 non-ischemic CRVO, and 11 branch retinal vein occlusion (BRVO). The prevalence of AT III and protein S deficiency were 4.3% and 13.0% respectively. The prevalence of homocystinemia, lupus anticoagulant, hyperlipidemia were 8.7%, 4.3% and 26.1% respectively. There was no positive finding in anticardiolipin antibody or protein C deficiency. CONCLUSIONS: Hypercoagulability may play a role in the pathogenesis of RVO in patients less than 55 years old, especially in those who had no systemic risk factors. The authors recommend examining systemic risk factor evaluation and hematologic evaluation to rule out thrombophilia. Those who show positive findings should be given a consultation with a hematologist for the proper management.
Antibodies, Anticardiolipin ; Antithrombin III ; Homocysteine ; Humans ; Hyperlipidemias ; Lupus Coagulation Inhibitor ; Medical Records ; Middle Aged ; Prevalence ; Protein C ; Protein C Deficiency ; Protein S ; Protein S Deficiency ; Retinal Vein Occlusion* ; Retinal Vein* ; Retinaldehyde* ; Risk Factors* ; Thrombophilia

BACKGROUND/AIMS: Idiopathic portal hypertension (IPH) is defined as portal hypertension with splenomegaly and hypersplenism in the absence of cirrhosis or obstruction of portal vein or hepatic vein. It has been recently suggested that hypercoagulable state and thromboembolic event of small portal veins have an important role in the pathogenesis of IPH. In this study, we evaluated the clinical and pathological characteristics of IPH. METHODS: We reviewed clinical, endoscopic, radiologic and liver biopsy findings of 10 cases of IPH retrospectively. RESULTS: The tests for antithrombin III deficiency, protein C deficiency, protein S deficiency, resistance to activated protein C, lupus anticoagulant, antiphospholipid antibodies, anticardiolipin antibodies were normal. Pathologic findings revealed portal vein dilatation (10/10), loss of portal vein (6/10), portal vein sclerosis (1/10), dilated megasinusoids (9/10), dilation of terminal hepatic vein (8/10), narrowing of terminal hepatic vein (2/10), hairline fibrous septa (1/10), and regenerative nodule (1/10). CONCLUSIONS: The pathologic finding of IPH showed various manifestations of obliterative portal venopathy although there was no hypercoagulable state.
Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid ; Antithrombin III Deficiency ; Biopsy ; Dilatation ; Fibrosis ; Hepatic Veins ; Hypersplenism ; Hypertension, Portal* ; Liver ; Lupus Coagulation Inhibitor ; Portal Vein ; Protein C ; Protein C Deficiency ; Protein S Deficiency ; Retrospective Studies ; Sclerosis ; Splenomegaly

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

PURPOSE: This study was performed to determine whether abnormalities of thrombosis and fibrinolysis are associated with nontraumatic osteonecrosis of the femoral head. MATERIALS AND METHODS: A case-control study was conducted in 24 patients with nontraumatic osteonecrosis of the femoral head. These patients were matched with 24 controls for gender, age (1-year range), and time of presentation (1-year range). The study included 19 men and 5 women, and the mean age of patients and controls was 46 years (range, 16-68 years). Eight patients had idiopathic osteonecrosis and the remaining 16 patients had secondary osteonecrosis. Protein C activity, protein C antigenicity, protein S activity, protein S antigenicity, antithrombin III, anticardiolipin antibody-Ig G, anticardiolipin antibody-Ig M, lupus anticoagulant, plasminogen, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were investigated. RESULTS: Protein C antigenecity and protein S antigenecity, which have been known to decrease in osteonecrosis patients, were increased in patients compared with those of controls (P<0.05). No significant differences were found in the levels of other thrombotic or fibrinolytic factors. In a subgroup of 16 patients with secondary osteonecrosis, the level of anticardiolipin antibody immunoglobulin M was greater than in the respective controls (P<0.05). CONCLUSION: The results of the current study suggest that abnormalities in the coagulation and fibrinolytic system are not associated with the pathogenesis of osteonecrosis of the femoral head.
Antibodies, Anticardiolipin ; Antithrombin III ; Case-Control Studies ; Female ; Fibrinolysis ; Head* ; Humans ; Immunoglobulin M ; Lipoprotein(a) ; Lupus Coagulation Inhibitor ; Male ; Osteonecrosis* ; Plasminogen ; Plasminogen Activators ; Protein C ; Protein S ; Thrombophilia ; Thrombosis ; Tissue Plasminogen Activator

The etiology of ischemic stroke remains undetermined in nearly 40% of patients despite extensive evaluations. Coagulopathies associated with cerebrovascular ischemia may be familial or acquired and account for 4% of all strokes. The four important naturally occurring circulation proteins that inhibit coagulation are protein C, protein S, antithrombin III, and heparin cofactor II. A carefully balanced interaction between these proteins and normal vascular endothelial cells comprise a major barrier inhibiting thrombosis. The true deficiencies of these proteins are usually inherited although many conditions such as DIC, malignancy, malnutrition, infection, and neutropenia can be associated with acquired deficiencies. Although some data suggest an association between arterial strokes and the deficiency of these proteins in young adults, cerebral venous thrombosis and venous infarcts gave been reported far more commonly with deficiencies of any of these proteins. The understanding of the molecular events underlying coagulation has improved in recent years. This has led to development of specific assays that can identify genetic abnormalities which can cause coagulopathies. Although the technology has improved the fundamental approach to the patient has not changed. A primary care physician requires a basic knowledge of the principles of blood coagulation so as to treat patients with simple problems and refer patients with more unusual or complex disorders on to the specialist. The recognition that hypercoagulable states are sometimes found in ischemic stroke patients has led to testing for these rare conditions. Coagulopathies related to protein C, protein S, or antithrombin III deficiencies, activated protein C resistance, prothrombin gene mutation, anticardiolipin antibodies, or lupus anticoagulant can be evaluated with various coagulation testing strategies.
Activated Protein C Resistance ; Antibodies, Anticardiolipin ; Antithrombin III ; Antithrombin III Deficiency ; Blood Coagulation ; Dacarbazine ; Endothelial Cells ; Heparin Cofactor II ; Humans ; Ischemia ; Lupus Coagulation Inhibitor ; Malnutrition ; Neutropenia ; Physicians, Primary Care ; Protein C ; Protein S ; Prothrombin ; Specialization ; Stroke* ; Thrombosis ; Venous Thrombosis ; Young Adult

PURPOSE: Antiphospholipid syndrome is a disorder of recurrent vascular thrombosis, recurrent abortion, thrombocytopenia, neurologic disorders associated with the elevation of antiphospholipid antibodies. The aim of our study was to characterize the patient profile and frequency of antiphospholipid syndrome in patients with deep vein thrombosis of the lower legs. METHOD: From January 1998 to December 1999, 25 patients with the lower leg swelling were classified according to their risk factors. Deep vein thrombosis was confirmed by radiologic diagnosis such as duplex ultrasonography or venography. The items for the identification of hypercoagulability were antithrombin III, protein-C, protein-S, lupus anticoagulant, anticardiolipin antibody (IgG). For the differential diagnosis of systemic lupus erythematosus, we tested antinuclear antibody and anti-dsDNA for the patients with positive results of antiphospholipid antibodies. Antiphospholipid syndrome was diagnosed according to its criteria. RESULT: Of the 25 patients with the lower leg swelling, 17 patents (68%) were revealed to have deep vein thrombosis. In that 17 patients, 8 patients showed hypercoagulabilities including 4 patients (24%) with positive test for lupus anticoagulant, 1 patient (6%) with combined multiple abnormalities of protein C and protein S deficiencies and lupus anticoagulant positivity, 2 patients (12%) with antithrombin III deficiencies, 1 patient (6%) with protein C deficiency, and there was no patient with IgG type anticardiolipin antibody positivity. According to the American Rheumatism Association criteria (ARA), there was no patient with systemic lupus erythematosus, but we could find out 1 patient (6%) who met the dagnostic criteria of antiphospholipid syndrome. CONCLLUSION: In our study, 6% (1of 17) of patient with the lower leg deep vein thrombosis revealed antiphospholipid syndrome. We described the clinical profile and diagnostic process of antiphospholipid syndrome in this study.
Abnormalities, Multiple ; Abortion, Habitual ; Antibodies, Anticardiolipin ; Antibodies, Antinuclear ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome* ; Antithrombin III ; Antithrombin III Deficiency ; Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin G ; Leg ; Lupus Coagulation Inhibitor ; Lupus Erythematosus, Systemic ; Nervous System Diseases ; Phlebography ; Pregnancy ; Protein C ; Protein C Deficiency ; Protein S Deficiency ; Rheumatic Diseases ; Risk Factors ; Thrombocytopenia ; Thrombophilia ; Thrombosis ; Ultrasonography ; Venous Thrombosis*

BACKGROUND: Venous thromboembolism is a serious medical problem causing considerable morbidity and mortality. Risk factors of thrombosis are surgery, trauma, pregnancy, tumor, oral contraceptive as well as genetic risk factors (deficiencies of protein C, protein S, antithrombin III) though genetic risk factors were found in about 5 to 10% of cases. Recently, it is known that point mutations in the factor V gene and the prothrombin gene are common risk factors of idiopathic deep vein thrombosis (DVT) in Caucasian. But the frequency of these mutations in Asian population are reported lower than Caucasian's. We investigated the incidence of hereditary risk factors of venous thrombosis at single institution. METHOD: From April 1998 to June 1999, patients who were diagnosed as venous thromboembolism and under 50 years old were enrolled. All patients were requested for protein C, protein S (total, free), antithrombin III, APC resistance test, factor VIII activity, anticardiolipin antibody, lupus anticoagulant (LA), anti-beta2-glycoprotein-I (anti-beta2-GPI). Point mutations of factor V (Arg506->Gln, Arg306->Thr, Arg306->Gly, A4070G) and prothrombin G20210A allele mutation were checked by allele specific PCR amplification. RESULTS: Thirty-four patients (M:F=19:15, median age 38, 22-49) were diagnosed as DVT (7), pulmonary embolism with/without other site venous thrombosis (5/7), retinal vein occlusion (10), venous thrombosis of unusual site (5). Nine patients had past thrombosis history. One patient had familial DVT history. Thirteen patients had acquired risk factors of thrombosis. All the results of APC resistance test were within normal range. There was no single case of factor V mutations or prothrombin G20210A allele mutation. Three patients had positive anti-beta2-GPI and one patient had positive LA. We also found free protein S deficiency : 5/31, combined deficiency of free protein S and antithrombin III: 3/31. Twenty-five patients (73.5%) had elevated factor VIII (>150%). CONCLUSION: In this study, we couldn't detect factor V point mutations, prothrombin G20210A allele mutation in thromboembolic patients. But we found high prevalence of elevated factor VIII. Follow-up test for factor VIII and clinical observation for recurrent thrombosis are in progress.
Activated Protein C Resistance ; Alleles ; Antibodies, Anticardiolipin ; Antithrombin III ; Asian Continental Ancestry Group ; Factor V ; Factor VIII ; Follow-Up Studies ; Humans ; Incidence ; Lupus Coagulation Inhibitor ; Middle Aged ; Mortality ; Point Mutation ; Polymerase Chain Reaction ; Pregnancy ; Prevalence ; Protein C ; Protein S ; Protein S Deficiency ; Prothrombin ; Pulmonary Embolism ; Reference Values ; Retinal Vein Occlusion ; Risk Factors* ; Thromboembolism ; Thrombosis ; Venous Thromboembolism ; Venous Thrombosis*

OBJECTIVE: The predominant histopathologic lesion in Behcet's disease is vasculitis. Thrombotic complications have been reported in approximately 10-40% of patients with Behcet's disease, but the precise mechanisms are not known. To investigate the coagualtion abnormalities in patients with Behcet's disease, coagulation and fibrinolytic activities were examined. METHODS: Thirty-two patients with Behcet's disease and thirty-two healthy individuals as a control group were included in the study. The presence of thrombosis and risk factors for hypercoagulability, and blood components concerning coagulation and fibrinolytic activites were evaluated. RESULTS: Of thirty-two patients with Behcet's disease, thrombosis was found in four patients(13%). No patient had risk factors for hypercoagulability except one with lymphoma. Levels of white blood cell count(mean+/-SD 8,362+/-2,893 vs 5,934+/-1,755/mm2, p<0.001), erythrocyte sedimentation rate(40.5+/-37.6 vs 3.3+/-2.73mm/hr, p<0.001), C reactive protein(2.26+/-3.99 vs 1.20+/-0.26mg/dl, p=0.008), fibrinogen(387.7+/-128.5 vs 240.6+/-49.5mg/dl, p<0.001) and von Willebrand factor antigen(131.9+/-46.6 vs 105.2+/-1.75%, p=0.008) were significantly higher in patients with Behcet's disease compared with controls. The level of fibrinogen correlated with erythrocyte sedimentation rate(r=0.721, p<0.001) and C reactive protein(r=0.454, p=0.018). High density lipoprotein(HDL) cholesterol(46.6+/-12.7 vs 65.5+/-16.1mg/dl, p<0.001), apolipoprotein A-1(118.8+/-24.7 vs 134.6+/-18.5mg/dl, p=0.018) and antithrombin III(92.8+/-16.7 vs 106.3+/-14.7%, p=0.004) were significantly lower in patients with Behcet's disease. No differences were observed in lipoprotein(a), plasminogen, protein C, and protein S activities. Activated protein C(APC) resistance was not observed in any patients with Behcet's disease. Lupus anticoagulant was positive in four patients(13%), one of whom had deep vein thrombosis. Antiphospholipid antibody was found in one patient(3%), but thrombosis was not found. CONCLUSIONS: Significantly higher level of von Willebrand factor antigen was observed in Behcet's disease, which suggested injury of vascular endothelium. Levels of HDL cholesterol, apolipoprotein A-1 and antithrombin III were decreased in Behcet's disease. APC resistance was not found.
Activated Protein C Resistance ; Antibodies, Antiphospholipid ; Antithrombin III ; Apolipoprotein A-I ; Apolipoproteins ; Blood Sedimentation ; Cholesterol, HDL ; Endothelium, Vascular ; Fibrinogen ; Fibrinolysis ; Humans ; Leukocytes ; Lipoprotein(a) ; Lupus Coagulation Inhibitor ; Lymphoma ; Plasminogen ; Protein C ; Protein S ; Risk Factors ; Thrombophilia ; Thrombosis ; Vasculitis ; Venous Thrombosis ; von Willebrand Factor