The prevalences of deficiencies in antithrombin III (AT III), protein C (PC), protein S (PS) and in the activated protein C (APC) resistance in the thrombotic population of the Trakya region, Turkey were investigated. 37 patients with venous thrombosis (VT) and 17 patients with arterial thrombosis (ArT) were included in this study. The mean ages of the patients with VT and ArT were 46 years (range 20-70) and 38 years (range 32-40), respectively. The activity of AT III was measured by commercially available immuno-turbidimetric assay. The activities of PC and PS were determined by coagulometric assay. The APC resistance was measured using a modified APTT-based clotting assay. Among the VT patients, there were 2 cases (5.4%) with AT III, 5 (13.51%) with PC deficiency, 5 (13.51%) with PS deficiency and 2 (5.4%) with APC resistance. In the ArT patient group, there was 1 patient (5.88%) with AT III, 3 (17.64%) with PC deficiency, 1 (5.88%) with PS deficiency and no APC resistant patients, while there was one (2.08%) with PC deficiency and one (2.08%) with APC resistance in the control group (49 persons, mean age 41 years). The relative risk of thrombosis (odds ratio) was 1.7 in the deficiency of PC and 5.6 in the deficiency of PS. The data presented suggests that the prevalences of AT III, PC and PS deficiencies causing thrombophilia in the Trakya region of Turkey are higher than in other reported studies while the APC resistance is lower than in others. Further studies including more patients would be required to clarify these discrepancies.
Activated Protein C Resistance/complications ; Adult ; Antithrombin III Deficiency/complications ; Human ; Middle Age ; Prevalence ; Protein C Deficiency/complications ; Protein S Deficiency/complications ; Risk Factors ; Thrombophilia/epidemiology* ; Thrombosis/etiology ; Turkey/epidemiology

PURPOSE: The risk factors and clinical characteristics in young patients with deep venous thrombosis (DVT) were analyzed. METHOD: The clinical characteristics of the 118 patients registered at our DVT clinic, from September 2000 to August 2002, were retrospectively reviewed. Information reviewed included sex ratio, site and extent of DVT, frequency of pulmonary embolism (PE), recurrence rate, and thrombophilic states. The patients were dichotomized into two groups according to their age, less than 40 years vs. older than 40 years. Their risk factors were also analyzed according to "Reporting Standards in Venous Disease". RESULT: Among 118 patients, 48 (40.7%) were younger than 40 years. Right leg DVT was more common (37.5% vs. 18.2%) in the younger group although the more common site for DVT was in the left leg. Also, PE (14.6% vs. 10.0%) and mesenteric venous thrombosis (14.6% vs. 4.3%) were more common, with higher recurrence rates (35.4% vs. 21.4%), in the younger group. However, there was no significant difference. Except for age or pregnancy and postpartum state, mean total scores of risk factors were higher in the older group (1.06 vs. 1.77). On the contrary, positive family history of DVT (10.4%) was found only in the younger group. Thrombophilic states, including antithrombin III, protein C, and protein S deficiencies, and Behcet's disease were more prevalent in the younger group whereas activated protein C resistance was found more often in the older group. In patients who had thrombophilic states, recurrence rate of DVT was much higher. CONCLUSION: For proper diagnosis and management of young DVT patients, especially to prevent a disastrous PE and recurrence, we must make efforts to identify risk factors including thrombophilic states.
Activated Protein C Resistance ; Antithrombin III ; Diagnosis ; Humans ; Leg ; Postpartum Period ; Pregnancy ; Protein C ; Protein S Deficiency ; Pulmonary Embolism ; Recurrence ; Retrospective Studies ; Risk Factors ; Sex Ratio ; Thrombophilia ; Venous Thrombosis*

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

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*

Deep vein thrombosis (DVT) is a common condition that is often under-diagnosed. Acquired or hereditary defects of coagulation or a combination of these defects may facilitate the development of DVT. Recurrent DVT, a positive family history or unusual presentation may warrant investigation for hereditary thrombophilia. Investigations are best when conducted at least one month after completion of a course of anticoagulant therapy. Most patients are managed with heparin in the acute stage overlapped by warfarin. The case presented here describes a 40-year old man undergoing three episodes of DVT. Investigations revealed protein C and protein S deficiency. Protein C, protein S and antithrombin deficiency either singly or in combination, are relatively common causes of hereditary thrombophilia. The case presented here serves as a reminder of the need to look into the underlying cause of venous thromboembolism.
Heparin ; Humans ; Protein C ; Protein S ; Protein S Deficiency ; Thrombophilia ; Venous Thromboembolism ; Venous Thrombosis ; Warfarin

Acute renal infarction is an uncommon disease that is often misdiagnosed initially because of its nonspecific presentation. Cardiovascular disease is the major cause of thromboembolic event, but renal infarction can also occur in patient with special conditions such as hypercoagulable states. Protein S deficiency is a rare cause of the hypercoagulable states and induces both venous and arterial thrombosis. Protein S are a vitamin K dependent plasma protein that serves as a cofactor for the anticoagulant effects of activated protein C. Patients deficient in protein S is prone to recurrent thromboembolic disease. We reported a case of acute renal infarction that was associated with type II protein S deficiency in a 38-year old patient without underlying cardiovascular disease.
Cardiovascular Diseases ; Humans ; Infarction ; Plasma ; Protein C ; Protein S ; Protein S Deficiency ; Thrombophilia ; Thrombosis ; Vitamin K

Unprovoked deep vein thrombosis (DVT) is uncommon in pediatric patients and, among those, combined hereditary thrombophilia is particularly rare. We present a 9-year-old Korean boy who developed lower extremity pain with swelling, and was diagnosed with unprovoked DVT due to hereditary (combined hereditary thrombophilia). Coagulation test revealed antithrombin III and protein S deficiency. The genetic work up confirmed the first case of combined antithrombin III deficiency and protein S deficiency by SERPINC1 heterozygous termination mutation [c.685C>T (p.Arg229*)] and PROS1 heterozygous missense mutation [c.1597G>A (p.Val533Met)]. He was treated with continuous heparin and catheter intervention but those were ineffective or transiently effective. His DVT gradually improved only after prolonged anticoagulation.
Antithrombin III Deficiency ; Antithrombin III* ; Catheters ; Child ; Heparin ; Humans ; Lower Extremity ; Male ; Mutation, Missense ; Protein S Deficiency* ; Protein S* ; Thrombophilia* ; Venous Thrombosis*

OBJECTIVETo investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage.

METHODSFifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombin III (AT-III), as well as activated protein C resistance (APC-R). The control group consisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for, measuring serum activity of protein C, protein S, AT-III, and APC-R. Patients with positive APC-R were tested for factor V (FV) Leiden gene mutation by PCR-RFLP method.

RESULTSOf the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-III deficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-III deficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FV Leiden gene mutation was identified in all the patients with positive APC-R results. Late spontaneous abortion cases had higher incidence of anticoagulation protein defect than the early cases.

CONCLUSIONAnticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurring in late stage of pregnancy.

Abortion, Habitual ; blood ; etiology ; Activated Protein C Resistance ; blood ; complications ; genetics ; Adult ; Antithrombin III ; metabolism ; Antithrombin III Deficiency ; blood ; complications ; Factor V ; genetics ; Female ; Humans ; Point Mutation ; Protein C ; metabolism ; Protein C Deficiency ; blood ; complications ; Protein S ; metabolism ; Protein S Deficiency ; blood ; complications

PURPOSE: We report two young patients who developed central retinal vein occlusion (CRVO) without any systemic disease, and various thrombophilia tests were performed to determine the etiology. CASE SUMMARY: Two young patients, a 22-year-old female and a 23-year-old male, who had acute vision loss were diagnosed with nonischemic CRVO via fluorescein angiography. They had no other disease and no common risk factors for CRVO. We performed various tests to determine the thrombophilic risk factors and discovered a transient decrease in protein S antigen and protein C antigen in the female and male patients, respectively. CONCLUSIONS: CRVO in young patients without systemic disorders may have different mechanisms in the pathology and thus additional laboratory tests to determine thrombophilic disorders are necessary.
Female ; Fluorescein Angiography ; Humans ; Male ; Pathology ; Protein C ; Protein C Deficiency ; Protein S ; Protein S Deficiency ; Retinal Vein* ; Risk Factors ; Thrombophilia* ; Young Adult

PURPOSE: To determine the prevalence of thrombophilia in Korean patients with an arterial thromboembolism (ATE) or a venous thromboembolism (VTE), and to evaluate the characteristic of VTE in patients with thrombophilia. METHODS: Hospital records of 294 patients (228 with VTE, 66 with ATE) including two foreign ones (mean age, 51.4 years) who underwent thrombophilia testing between August 2006 and March 2015 were reviewed retrospectively. In general, such screening was performed according to the guidelines of the international consensus statement for VTE. Thrombophilia testing included evaluations of the factor V Leiden and prothrombin G20210A mutations, levels of proteins C and S and antithrombin, and antiphospholipid antibody syndrome (APLS). RESULTS: A factor V Leiden mutation was not found in the 292 Korean patients. A prothrombin G21210A mutation was investigated in 33 patients but none was found. Among 226 Korean patients with VTE, 130 demonstrated no thrombophilia and 55 patients did after exclusion of 41 patients without confirmatory test. The most common form was protein S deficiency (31 of 55, 56%) followed by protein C deficiency, antithrombin deficiency, and APLS. When comparing patients with a VTE or deep vein thrombosis (DVT) according to the presence of thrombophilia, thrombophilia was associated with younger age (P = 0.001 for VTE; P < 0.001 for DVT) and a family history (P < 0.001 for VTE and DVT). CONCLUSION: We did not find any factor V Leiden mutation in Korean subjects at high risk for thrombophilia. Therefore, this testing is not warranted. Thrombophilia was associated with VTE in younger age and a family history.
Antiphospholipid Syndrome ; Consensus ; Factor V ; Hospital Records ; Humans ; Korea ; Mass Screening ; Prevalence ; Protein C Deficiency ; Protein S Deficiency ; Prothrombin ; Retrospective Studies ; Thromboembolism* ; Thrombophilia* ; Venous Thromboembolism ; Venous Thrombosis