BACKGROUND: Recently, resistance to activated protein C(APC) is known to be an important risk factor for venous leg ulcers. Leiden mutation in clotting factor V is the most common genetic defect leading to APC resistance in western countries. Until now, the prevalence of APC resistance and Leiden mutation in Korean patients with venous ulcers has been ill defined. OBJECTIVE: We performed this study in order to investigate the prevalence of APC resistance and Leiden mutation in Korean patients with venous ulcers. METHODS: The functional analysis for APC resistance(APC resistance ratio) and genetic study for Leiden mutation were conducted in 40 patients with venous ulcers. RESULTS: 1. Of the 40 patients with venous ulcers, resistance to APC was documented in 11 individuals (27.5%). 2. We could not find factor V Leiden mutation in 40 patients. 3. Patients with APC resistance more frequently represented recurrence of venous ulcers and venous thrombosis than in their non-APC resistant counterparts. CONCLUSION: APC resistance may be one of the thrombophilic defects in relation with venous ulcers in Korea. However, Leiden mutation may be rare in Korean patients with venous ulcers than in Caucasians. These findings suggested that the other genetic or non-genetic factors may be involved in the pathogenesis of APC resistance in Korea.
Activated Protein C Resistance* ; Factor V ; Humans ; Korea ; Leg Ulcer ; Prevalence* ; Recurrence ; Risk Factors ; Varicose Ulcer* ; Venous Thrombosis

PURPOSE: The purpose of the present study was to evaluate the potential association of the G1691A mutation of factor V (factor V Leiden), which is a main causative factor of activated protein C resistance leading to intravascular coagulation, with osteonecrosis (ON) of the femoral head. MATERIALS AND METHODS: Genomic DNA was extracted from peripheral blood leukocytes of 116 consecutively identified patients with nontraumatic ON of the femoral head and 59 healthy controls. The region in exon 10, that encodes an APC cleavage site in factor V gene, was amplified by polymerase chain reaction (PCR) with use of the 2 primers (Korea Biotech Inc., Daejeon): 5'-GGA ACA ACA CCA TGA TCA GAG CA-3' (forward primer) and 5'-TAG CCA GGA GAC CTA ACA TGT TC-3'(reverse primer). Amplified product was subjected to MnlI restriction enzyme digestion and resulting fragments were separated by electrophoresis on 3% agarose gel. The homozygous and heterozygous patterns of DNA fragments of 1691G-A mutation in the factor V gene was investigated. RESULTS: The prevalence of factor V Leiden was 0% in the patients group and in the control group. CONCLUSIONS: The data suggested that thrombophilia by the G1691A mutation of factor V (factor V Leiden) was less likely to be associated with the development of ON of the femoral head in Koreans.
Activated Protein C Resistance ; Digestion ; DNA ; Electrophoresis ; Exons ; Factor V* ; Head* ; Humans ; Leukocytes ; Osteonecrosis* ; Polymerase Chain Reaction ; Prevalence ; Sepharose ; Thrombophilia

OBJECTIVE: A study showed that resistance to activated protein C may develope some cases of severe preeclampsia. A common missense mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C. Our objective was to determine whether this mutation is more prevalent in patients with severe preeclampsia than in normotensive controls. METHOD: Deoxyribonucleic acid was extracted from whole blood of 158 gravid women of severe preeclampsia and 403 normotensive gravid women. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by allele-specific restriction with Mnl 1 for mutation detection. RESULTS: No patients were homozygous for the Leiden mutation. We could not find any positive case with FV:Q506 in the normal or patient group. CONCLUSION: We could not find that carriers of the factor V Leiden mutation are increased risk for severe preeclampsia. In contrast to the reports in Caucasian, the prevalence of APC resistance and FV:Q506 might be very low or absent in the Korean population. But, carriers of this common thrombophilic mutation may be identified so that other causes and risk factors for inherited thrombophilia should be investigated in the Korean population.
Activated Protein C Resistance ; DNA ; Exons ; Factor V* ; Female ; Humans ; Mutation, Missense ; Polymerase Chain Reaction ; Pre-Eclampsia* ; Pregnant Women* ; Prevalence ; Protein C ; Risk Factors ; Thrombophilia

BACKGROUND: In the western hemisphere, resistance to activated protein C (APCR) is the most common risk factor for venous thromboembolic disease. A one-point mutation in the coagulation factor V that renders it APCR is found in more than 90% of patients with APC-resistant venous thrombosis. In Hispanic and Caucasian patients with arterial ischemic stroke, the prevalence of APC-R is approximately 10%. To determine the prevalence of APC resistance and its causative factor V mutation (Arg 506 Gln) in Koreans, we screened a group of Korean ischemic stroke patients. METHODS: We evaluated 60 Korean patients with arterial ischemic stroke diagnosed by either magnetic resonance neu-roimaging, conventional angiogram, or both, after 2 weeks of symptom onset. The mean age of the subjects was 59.2 years (13-82 years). APC resistance was expressed as a ratio of the activated partial thromboplastin time (aPTT) with and without adding APC to the subject's plasma. The presence of the factor V Leiden (Arg 506 Gln) mutation was determined by a direct polymerase chain reaction-based assay on peripheral blood leukocytes. RESULTS: Only one patient (n=1/60, 1.6%) had APC resistance and none were found to have the factor V Leiden (Arg 506 Gln) mutation. CONCLUSIONS: APCR and the factor V Leiden mutation do not seem to be a significant genetic risk factor for arterial ischemic stroke in Koreans.
Activated Protein C Resistance* ; Factor V* ; Hispanic Americans ; Humans ; Leukocytes ; Partial Thromboplastin Time ; Plasma ; Prevalence ; Protein C ; Risk Factors ; Stroke* ; Venous Thrombosis

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*

BACKGROUND: Hemostatic function is regarded to be preserved after an off-pump coronary artery bypass grafting (CABG), compared to conventional CABG, and the preserved hemostatic function may increase thrombotic occlusion of the graft. We studied the changes of hemostatic variables in patients undergoing off-pump CABG, and compared to those of on-pump CABG. MATERIAL AND METHOD: We studied the changes of coagulation function in 11 patients who underwent off-pump CABG (group I), and compared them with those of 11 patients who underwent on-pump CABG and Dor procedure (group II). Coagulation status was evaluated by thromboelastography and blood coagulation test preoperatively, postoperative 1st day, 2nd day, 3rd day, and 5th day, respectively. RESULT: Among the variables measured by thromboelastography (such as r time, k time, alpha angle, and MA value) and blood coagulation test (such as factor VII, protein S, protein C, antithrombin III, activated protein C resistance test, plasminogen, D-dimer, prothrombin time, activated partial thromboplastin time, platelet count, hemoglobin, and fibrinogen), there were significant differences in the MA value, alpha angle, and platelet counts between the two groups. MA values were 140+/-72% and 153+/-98% in group I, and 87+/-27% and 78+/-28% in group II, at postoperative 3rd and 5th days, respectively (p<0.05). alpha angle was 122+/-92% in group I and 69+/-23% in group II at postoperative 3rd day (p=0.09). Platelet count was 63+/-55% in group I and 33+/-13% in group II at postoperative 3rd day (p<0.05). CONCLUSION: Patients who underwent off-pump CABG showed increased coagulability during postoperative periods, compared to those who underwent on-pump CABG. Our data suggest that aggressive perioperative anticoagulation therapy is warranted in patients undergoing off-pump CABG.
Activated Protein C Resistance ; Antithrombin III ; Blood Coagulation Tests ; Coronary Artery Bypass ; Coronary Artery Bypass, Off-Pump ; Factor VII ; Humans ; Partial Thromboplastin Time ; Plasminogen ; Platelet Count ; Postoperative Period ; Protein C ; Protein S ; Prothrombin Time ; Thrombelastography ; Transplants

BACKGROUND: Antiphospholipid antibodies(APA) including anticardiolipin antibodies(ACA) are significantly associated with ulcerations of the leg. Moreover, resistance to activated protein C(aPC) may be an important risk factor in leg ulcerations. Until now, there has been no clinical investigation about the positivity of APA or resistance to aPC in patients with leg ulcers in Korea. OBJECTIVE: We investigated the positivity to APA and the presence of resistance to aPC in patients with leg ulcers in Korea. METHODS: Venous or arterial ultrasonic Doppler, semiquantitative assay for serum APA and functional analysis for aPC resistance were conducted in 32 patients with leg ulcers. RESULTS: 1. Of the 32 patients with leg ulcers, 34,3% had a positive APA. APA were more frequently associated with venous ulcerations of the leg than in subjects with leg ulcers of arterial or mixed origin. 2. aPC resistance based upon the functional analysis, occurred in 43.7% to 46.8% of leg ulcer patients. 3. Livedo reticularis (38.1%) and superficial thrombophlebitis (19.0%) were the most common cutaneous manifestations accompanied by leg ulcers in 21 APA-positive and/or aPC resistant patients. Deep vein thrombosis of extremities was the most common complication (47.6%) among the systemic thrombotic sequelaes in APA-positive and/or aPC resistant patients. CONCLUSION: APA positivity and aPC resistance may be relatively common anticoagulant defects among patients with leg ulcerations in Korea. APA positivity and aPC resistance should be considered important risk factors for the development of not only leg ulcers but also systemic thrornbotic complications.
Activated Protein C Resistance* ; Antibodies, Antiphospholipid* ; Extremities ; Humans ; Korea ; Leg Ulcer* ; Leg* ; Livedo Reticularis ; Risk Factors ; Thrombophlebitis ; Ulcer ; Ultrasonics ; Varicose Ulcer ; Venous Thrombosis

Thrombophilia refers to inherited or acquired hemostatic disorders that result in a predisposition to blood clot formation. When combined with the hypercoagulable state that is characteristic of pregnancy, there is an increased risk of severe and recurrent pregnancy complications. Activated protein C resistance caused by factor V Leiden (FVL) mutation is known to be the most common cause of inherited thrombophilia in Caucasian population. FVL mutation has been related to pregnancy complications associated with hypercoagulation, e.g. miscarriage, intrauterine fetal demise, placental abruption, and intrauterine growth retardation. Although the FVL mutation is easily detected using molecular DNA techniques, patients who are heterozygous for this disorder often remain asymptomatic until they develop a concurrent prothrombotic condition. Because there are potentially serious effects of FVL mutation for pregnancy, and because effective treatment strategies exist, early detection and treatment of this condition might be considered.
Abortion, Spontaneous ; Abruptio Placentae ; Activated Protein C Resistance ; DNA ; Factor V ; Female ; Fetal Death ; Fetal Growth Retardation ; Hemostatic Disorders ; Humans ; Pregnancy Complications ; Pregnancy ; Pregnant Women ; Thrombophilia

The study was aimed to investigate the factor V coagulation activity (FV:C), and to evaluate FVgene polymorphisms and activated protein C resistance (APCR) in the patients with venous thromboembolism (VTE). 95 patients with VTE and 95 normal controls were investigated for FV gene polymorphisms. FV Leiden, FVCambridge, and FVHong Kong were detected by PCR, MnlI and BstNI digestion respectively. FVAsp79His and FVI359T were detected by MassARRAY. FV:C and APCR in 65 patients with VTE and 60 normal controls were determined by a one-stage clotting method and the APTT-based assays respectively. The results showed that the mean levels of plasma FV:C were significantly higher in VTE group than that in controls (108.03% +/- 28.29% vs 95.17% +/- 29.75%) (P = 0.008), the incidence of APCR were 20.0% (13 of 65 cases) in patients with VTE and 5.0% (3 of 60 cases) in normal controls (P = 0.012). FV Leiden, FVCambridge, FVHong Kong, FVAsp79His and FVI359T mutations were not found in two groups. It is concluded that the increased plasma level of FV:C is a risk factor for VTE. There is APCR in both groups, APCR is also a risk factor to VTE. APCR may not be associated with mutations of FV Leiden, FVCambridge, FVHong Kong, FVAsp79His and FV I359T polymorphisms, other factors need to study further in APCR.
Activated Protein C Resistance ; complications ; genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Factor V ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Protein C ; metabolism ; Venous Thromboembolism ; blood ; complications ; genetics ; Young Adult