Correlation between protein C -1641A/-1654C haplotype and coagulation disorder in sepsis / 中华急诊医学杂志

Objective:To investigate the correlation between protein C -1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods:The genotypes of protein C gene -1641A>G (rs1799809) and -1654C>T (RS1799808) in septic patients were detected by direct sequencing, and their haplotypes were analyzed and divided into two groups according to the haplotype, -1641A/-1654C (AC) carriers and non-AC haplotype carriers. At the same time, unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters, including partial activated thrombin time, prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer levels, as well as APC levels between the two groups. Results:A total of 174 septic patients were included in this study, including 60 AC haplotype carriers and 114 non-AC haplotype carriers. Compared with non-AC haplotype carriers, AC haplotype carriers had significantly lower platelet counts, significantly longer partial activated thrombin time, and significantly decreased activated protein C levels. Other coagulation/fibrinolytic parameters including prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer were not significantly different between the two groups.Conclusions:In this study, the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts, and prolonged partial activated thrombin time in septic patients. These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.

The roles of activated protein C in experimental trauma models / 中华创伤杂志(英文版)

Trauma-induced coagulopathy is classified into primary and secondary coagulopathy, with the former elicited by trauma and traumatic shock itself and the latter being acquired coagulopathy induced by anemia, hypothermia, acidosis, and dilution. Primary coagulopathy consists of disseminated intravascular coagulation and acute coagulopathy of trauma shock (ACOTS). The pathophysiology of ACOTS is the suppression of thrombin generation and neutralization of plasminogen activator inhibitor-1 mediated by activated protein C that leads to hypocoagulation and hyperfibrinolysis in the circulation. This review tried to clarify the validity of activated protein C hypothesis that constitutes the main pathophysiology of the ACOTS in experimental trauma models.

Protective effects of activated protein C on neurovascular unit in a rat model of intrauterine infection-induced neonatal white matter injury / 华中科技大学学报（医学）（英德文版）

Activated protein C (APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 μg/kg lipopolysaccharide (LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection- induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin (H&E). Immunohistochemistry was used to evaluate myelin basic protein (MBP) expression in the periventricular white matter region. Blood-brain barrier (BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 (PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection- induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.

Activated protein C differentially regulates both viability and differentiation of osteoblasts mediated by bisphosphonates

Activated protein C (APC) is a cytoprotective anticoagulant that can promote cutaneous healing. We examined the effect of APC on viability and differentiation of the osteoblastic line, MG63, in the presence and absence of bisphosphonates (BPs). Osteoblasts were cultured and treated for 24 or 48 h with Alendronate (Aln), Zoledronate (Zol) or Pamidronate (Pam) at concentrations ranging from 10-4 to 10-6 M. Cell differentiation was measured using type 1 collagen production, Alizarin red staining and alkaline phosphatase activity, whereas cell viability was assessed using MTT and crystal violet assays. All three BPs induced MG63 cell death in a dose- and time-dependent manner. Pam- and Zol-related cell death was prevented by APC treatment; however, cell death induced by Aln was accelerated by APC. APC induced MG63 cell differentiation that was enhanced by Aln, but inhibited by Pam or Zol. Endothelial protein C receptor (EPCR) was expressed by MG63 cells and mediated the protective effect of APC on Zol-induced viability. In summary, we have demonstrated that (1) APC favorably regulates MG63 viability and differentiation toward bone growth, (2) APC differentially regulates the effects of specific BPs and (3) at least part of the effects of APC is mediated through EPCR. These findings highlight the potential importance of the PC pathway in bone physiology and provide strong evidence that APC may influence bone cells and has potential to be a therapeutic drug for bone regeneration, depending on concurrent BP treatment.

Activated Protein C Anticoagulant System Dysfunction and Thrombophilia in Asia

Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in Caucasians, thrombophilia that is common in the Japanese and Chinese involve dysfunction of the activated protein C (APC) anticoagulant system caused by abnormal protein S and protein C molecules. Approximately 50% of Japanese and Chinese individuals who develop venous thrombosis have reduced activities of protein S. The abnormal sites causing the protein S molecule abnormalities are distributed throughout the protein S gene, PROS1. One of the most common abnormalities is protein S Tokushima (K155E), which accounts for about 30% of the protein S molecule abnormalities in the Japanese. Whether APC dysfunction occurs in other Asian countries is an important aspect of mapping thrombophilia among Asians. International surveys using an accurate assay system are needed to determine this.

Coagulation inhibitors and activated protein C resistance in recurrent pregnancy losses in Indian women.

Background: Thrombophilias, both acquired and inherited, have been investigated in the etiopathogenesis of unexplained recurrent pregnancy loss. Aim: To study coagulation inhibitors and activated protein C resistance (APCR) in recurrent pregnancy losses (RPL) occurring in second and third trimesters. Materials and Methods: A total of 30 pregnant women (group A) with two or more recurrent unexplained fetal loses were evaluated for APCR, protein C deficiency, protein S deficiency, antithrombin deficiency, and antiphospholipid antibodies (APLA). Thirty age-matched controls were taken (group B) comprising of pregnant women with at least one live issue. Statistical Analysis: Comparisons between two group frequencies and group means were made using Chi square test and Student's t test, respectively. Results: Protein C and protein S levels were reduced in group A compared with group B and the difference was statistically significant (P=0.005 and P=0.032, respectively). The mean value of antithrombin was slightly reduced in group A compared with group B. APCR was observed in 16.6% cases and 3.3% controls. However, the difference was not statistically significant. APLA was observed in 20% cases and none of the controls. Of these, lupus anticoagulant was positive in 16.6% cases and anticardiolipin antibodies in 10% cases. Combined defects were seen in seven patients. Conclusion: There is a significant risk of RPL in pregnant women with thrombophilias. Therefore, screening for thrombophilias may be justified in pregnant women with unexplained recurrent fetal wastage, especially in second and third trimester.

The clinical value of activated protein C in pediatric leukemia patients with acute lung injury / 中国小儿急救医学

Objective To investigate the changes of plasma activated protein C(APC)in the pediatric leukemia patients with acute lung injury(ALI),and the relationship with the outcome.Methods During the study period(from Jan to Dec 2009),17 pediatric leukemia patients with ALI were selected.They were divided into neutropenic(n =10)and non-neutropenic(n =7)group.We collected the basic data including the age,gender,stage of chemotherapy,pediatric critical illness score,mechanical ventilation time,ICU time.The blood gas and plasma APC levels were detected on day 1 and day 4 of ALI onset.Results Compared with the non-neutropenic group,the neutropenic group had a significantly longer mechanical ventilation time [(16.60 ± 1 0.83)d vs(3.79 ± 4.08)d,P =0.009 6],lower PaO2 level on day l[(54.90 ± 17.05)mm Hg vs (92.70 ± 27.53)mm Hg,P =0.009 7],and lower APC level on day 4[(193.06 ± 63.19)pg/mlvs(286.28 ±25.12)pg/ml,P =0.007 7].Conclusion The APC generation is severely impaired in the neutropenic group,especially in those who died.The lower APC level is,the longer is the mechanical ventilation time,the worse is oxygenation,the poorer is the prognosis.APC replacement therapy may be promising in these patients.

Study of the role of activated protein C in the apoptosis of endothelial cell / 中华急诊医学杂志

Objective To study the protective effects of activated protein C (AFC) on the apoptosis of endothelial cells induced by lipopolysaccharide (LPS) in order to clarify the mechanisms associated with the expression of some genes related to apoptosis. Method The human umbilical vein endothelial cells were incubated with LPS (1.0 μg/mL) for one hour to make the models of cell apoptosis, and then the different concentrations of AFC (10 ng/mL and 50 ng/mL) were added to the models of cell apoptosis as treatment group. Therefore, there were two groups, model group and APC treated group. The factors related with apoptosis such as P53, Bax, Bcl-2, and caspase-3 mRNA or protein level were measured by using RT-PCR and Western blotting. Results Compared with LPS stimulated cells, the expressions of P53, Bax and caspase-3 mRNA and levels of protein were decreased and the expression of Bcl-2 mRNA and protein level were increased in APC treated cells particularly in APC 50 ng/mL treated cells (P <0.05). Conclusions The APC inhibits the apoptosis of HUVECs induced by LPS via regulating the mitochondrial-dependent apoptosis pathway, and it may become a novel therapeutic agent for infection disease.

Activated Protein C Protects Myocardium Via Activation of Anti-apoptotic Pathways of Survival in Ischemia-reperfused Rat Heart

Activated protein C (APC) is known to be beneficial on ischemia reperfusion injury in myocardium. However, the protection mechanism of APC is not fully understood. The purpose of this study was to investigate the effects and possible mechanisms of APC on myocardial ischemic damage. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 hr of reperfusion. Rats were randomly divided into four groups; Sham, I/R, APC preconditioning and postconditioning group. Myocardial infarct size, apoptosis index, the phosphorylation of ERK1/2, Bcl-2, Bax and cytochrome c genes and proteins were assessed. In APC-administrated rat hearts, regardless of the timing of administration, infarct size was consistently reduced compared to ischemia/reperfusion (I/R) rats. APC improved the expression of ERK1/2 and anti-apoptotic protein Bcl-2 which were significantly reduced in the I/R rats. APC reduced the expression of pro-apoptotic genes, Bax and cytochrome c. These findings suggest that APC produces cardioprotective effect by preserving the expression of proteins and genes involved in anti-apoptotic pathways, regardless of the timing of administration.

Trombose venosa em criança / Venous thrombosis in children

A incidência de trombose venosa profunda (TVP) em crianças (0 a 18 anos) é baixa. O objetivo desse trabalho é estudar uma criança de 12 anos que, após um trauma, apresentou TVP. Atividades de proteína C, proteína S, antitrombina e resistência à proteína C ativada (RPCA) foram analisadas em coagulômetro. O fator V de Leiden (FVL) foi pesquisado. O paciente e seu pai (assintomático até o momento) foram heterozigotos para FVL e sua mãe foi homozigota normal. Concluímos que o FVL associado a outras condições clínicas tende a ser multiplicativo para a ocorrência de trombose, que é multifatorial.

The incidence of deep venous thrombosis (DVT) in children (0-18 years old) is low. The aim of this study was to investigate the case of a 12 year-old child that had DVT after a trauma. Protein C and protein S activities, antithrombin and resistance to activated protein C were analyzed in coagulometer. Factor V Leiden (FVL) was studied. The patient and his father were heterozygotes for FVL. His mother was normal homozygote. We concluded that the presence of FVL associated with other medical conditions tends to multiply the occurrence of thrombosis, which is a multifactorial disease.

O uso da drotrecogina alfa ativada na prática clínica e as atuais evidências / Drotrecogin alfa activated in clinical practice and the current evidences

JUSTIFICATIVA E OBJETIVOS: O debate sobre a segurança e eficácia da drotrecogina alfa (DrotAA) encontra-se na ordem do dia, principalmente, em função dos resultados negativos observados em ensaios clínicos subseqüentes ao PROWESS e do impacto econômico no sistema de saúde relacionado ao custo elevado do fármaco. O objetivo deste estudo foi rever os principais estudos sobre a utilização da DrotAA em pacientes com sepse grave, com ênfase nas questões ligadas a sua eficácia e segurança. CONTEÚDO: Foram selecionados artigos sobre a utilização da DrotAA em pacientes com sepse publicados nos últimos dez anos no MedLine. Os seguintes unitermos foram utilizados: activated protein C; drotrecogin alfa; sepsis; septic shock; Xigris®. Estudos referenciados nos artigos selecionados na busca também foram utilizados. CONCLUSÕES: As taxas de letalidades e as complicações hemorrágicas associadas com o uso do fármaco foram maiores em grandes estudos observacionais do que aquelas descritas previamente nos ensaios clínicos. A luz dos resultados atualmente disponíveis, o uso da DrotAA deve ser reconsiderado até que novos ensaios clínicos possam subsidiar com informações adicionais sobre eficácia, segurança e na identificação dos subgrupos de pacientes com sepse grave que porventura possam ter benefício com o uso deste medicamento. A DrotAA deve servir de exemplo para que haja maior cautela com a rápida transposição de evidências ainda em construção para recomendações e diretrizes de tratamento de pacientes com sepse grave.

BACKGROUND AND OBJECTIVES: The debate on efficacy and patient safety related to the use of drotrecogin alfa (DrotAA) is timely, principally due to the negative results observed in clinical studies performed after the PROWESS study, and the economic cost-related impact of the drug on the healthcare system. The aim of this study was to review the main studies on the use of DrotAA in patients with severe sepsis. The focus was on drug efficacy-and patient safety-related issues. CONTENTS: Articles were selected by a MedLine search for studies on the use of DrotAA in patients with sepsis using the following key words: activated protein C; drotrecogin alfa; sepsis; septic shock; Xigris®. Additional references were retrieved from the studies initially selected. CONCLUSIONS: Mortality and bleeding complications associated with the use of DrotAA were more frequent in large observational studies than those reported in randomized trials. In the light of the current knowledge, routine use of DrotAA should be reevaluated until well-designed confirmatory clinical trials can clarify the true efficacy and safety of the drug and help identify the subgroup of patients that can benefit from use of DrotAA. Physicians should be cautious with the rapid transfer of evidences not well-documented, to the guidelines and recommendations practiced in the care and treatment of patients with severe sepsis.

Research Progress of Activated Protein C / 实用儿科临床杂志

Activated protein C(APC)is generated through hydrolysis of protein C by thrombin-thrombomodulin complex.APC has been proved to play different roles in many human diseases,such as anticoagulant,antiinflammatory,profibr-inolysis,antiapoptotic and endothelial cytoprotective activities.In this review,the research progress of the functions of APC and related diseases,especially the neural protective roles of APC in central nervous system were summarized.

Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-β2-glycoprotein-I antibodies / Resistencia a la proteína C activada y actividad de anticoagulante lúpico inducidas por plasma y por anticuerpos purificados humanos del IgG anti β2-glicoproteína I

ABSTRACT Introduction. We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-β2-glycoprotein-I (anti-β2GP-I) antibodies. Patients and methods. We studied plasma and sera samples from 29 patients with persistently positive anti-β2GP-I: 22 with thrombosis (12 with primary APS, 10 with APS secondary to SLE) and seven without thrombosis (all with SLE); 25 healthy subjects were studied as controls. We detected anticardiolipin antibodies (ACA); IgG (and its subclasses) and IgM anti-β2GP-I, on irradiated and non-irradiated plates by ELISA. APCR was assessed by the activated partial thromboplastin time (APTT)-based assay and by the modified test. The FV Leiden mutation was studied by PCR. LA determination included screening and confirmatory dRVVT. Serum anti-β2GP-I were affinity purified on sepharose columns and their isotype, subclass, and reactivity against various antigens were studied by ELISA. Results. We found that titers of IgG anti-β2GP-I on irradiated plates were higher than on non-irradiated plates (p = 0.002), IgG2 was the predominant subclass. Fifteen patients (13 with thrombosis) had LA and 15 (also 13 with thrombosis) induced the APCR phenotype. Eleven (all with thrombosis) had both. Two patients were heterozygous for the Leiden mutation. Two purified antibodies, monospecific for β2GP-I, induced an in vitro APCR phenotype and LA activity. Conclusions. Our results seem to indicate that the inhibition of the APC anticoagulant function by IgG2 anti-β2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS.

Introducción. Investigamos la resistencia a la proteína C activada (RPCA) y la actividad de anticoagulante lápico (AL), inducidas por anticuerpos anti-β2-glicoproteína-I (anti-β2GP-I). Pacientes y métodos. Estudiamos los plasmas y sueros persistentemente positivos para anti-β2GP-I de 29 pacientes: 22 tuvieron trombosis (12 con síndrome de antifosfolípidos (SAF) primario y 10 con SAF secundario a lupus erítematoso generalizado (LEG)) y siete sin trombosis (todos con LEG). Como controles estudiamos 25 sueros de personas clínicamente sanas. Detectamos anticuerpos anticardiolipina, anti-β2GP-I IgG (y sus subclases) e IgM por ELISA en placas irradiadas y no irradiadas. Evaluamos la RPCA por medio del tiempo parcial de tromboplastina activada y por la prueba modificada. Estudiamos la mutación FV de Leiden por PCR y el anticoagulante lápico con el método de dRVVT screening y confirmatorio. Después de purificar los anti-β2GP-I séricos con una columna de antígeno unido a sefarosa, analizamos por ELISA sus isotipos, subclases y reactividad contra β2GP-I y algunos fosfolípidos. Resultados. Los títulos de anti-β2GP-I IgG fueron más altos en placas irradiadas que en no irradiadas (p = 0.002), predominó la subclase IgG2. Quince plasmas (13 de pacientes con trombosis) tuvieron AL y 15 (13 también de pacientes con trombosis) indujeron el fenotipo de RPCA. Once plasmas (todos de pacientes con trombosis) indujeron ambas actividades. Dos pacientes fueron heterocigotos para la mutación de Leiden. Dos anticuerpos purificados monoespecíficos para β2GP-I indujeron el fenotipo de la RPCA y la actividad de AL in vitro. Conclusiones. Nuestros resultados sugieren que la RPCA, inducida por los anti-β2GP-I que concomitantemente tienen actividad de AL, puede tener implicaciones patogénicas en la trombofílía del SAF.

A Study of Prevalence of Activated Protein C Resistance and Leiden Mutation among Korean Patients with Venous Ulcers / 대한피부과학회지

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.

The relationship between anti-phospholipid antibodies and activated protein C resistance / 中华风湿病学杂志

Objective To investigate the relationship between the anti-phospholipid antibodies (APLs)and activated protein C resistance (APCR). Methods The response to activated protein C (APC) was studied by an APTT-based (clotting) assay with a Stago autoanalyzer and expressed as the ratio between the APTT obtained in the presence and absence of exogenous APC. APC sensitive ratio higher than 2 was regarded as APCR. Anti-?2-glycoprotein Ⅰ (?2GP-Ⅰ) antibody and anti-cardiolipin antibodies (ACL) were measured by an enzyme-linked immunosorbent assay (ELISA). Lupus anticoagulant (LA) was tested by activated partial thromboplastin time (APTT). Results The existence of LA and acquired APCR showed significant correlation (?2=16.332, P=0.008). Acquired APCR was significantly associated with the presence of anti-?2GP-Ⅰ antibody (?2=6.179, P=0.012), but not ACL. The presence of APCR was associated with an increased frequency of history of thromboembolic events and/or recurrent abortions (?2=7.347, P=0.01). Conclusion This study suggests that APCR is linked to the presence of LA and anti-?2GP-Ⅰ antibody. APLs may interfere with the activation of protein C. APCR phenotype may be a major risk factor for thrombophilia in patients with APLs. Combined detection of APLs has the potential value for predicting thrombosis.

The prevalence of hereditary thrombophilia in the Trakya region of Turkey

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 and Factor V Leiden Mutation in Patients with Arterial Ischemic Stroke

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.

Antiphospholipid Antibodies and Activated Protein C Resistance in Patients with Leg Ulcers / 대한피부과학회지

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.

The Effects of Anticoagulant Proteins Defect in Maternal Plasma on Spontaneous Abortion / 中华围产医学杂志

Objective To investigate the mechanism of anticoagulant proteins defect in patients with unexplained miscarriage. Methods Fifty-seven patients with a history of unexplained abortion in Peking union hospital during may. 1999 to April 2000. were tested for protein S, protein C, and antithrombin(AT)Ⅲ, activated protein C resistance(APC-R).The control group consisted of 50 healthy women with a history of normal pregnancy and delivery. Blood samples were taken for measuring protein S, protein C, AT-Ⅲ and APC-R. Patients with APC-R positive were measured for FV Leiden gene mutation by PCR-RFLP method. Results Of the 57 patients, there were 21.1%?1.8% and 8.8% with protein S?protein C and AT-Ⅲ deficiency respectively. For APC-R 22.8% of the 57 patients were positive .In control group, 4.0% were protein S deficiency; None was protein C and AT-Ⅲ deficiency ; 6.0% were positive for APC-R .No FV Leiden gene mutation was found in all the patients with APC-R positive .The incidence of anticoagulant proteins defect is higher in late spontaneous abortion group than that in early abortion group. Conclusions This study demonstrate that anticoagulant protein defects may be associated with pregnancy loss, especially the late spontaneous abortion.

Study on Activated Protein C in Patients with Neuropsychiatric Lupus Erythematosus / 中华皮肤科杂志

Objective To explore the significance of activated protein C resistance (APCR) and antiphospholipid antibody(APA) in patients with neuropsychiatric lupus erythematosus(NPLE). Methods APCR, anticardiolipid antibody (ACA)(IgG, M, A), lupus anticoagulant (LA) were measured with APTT? APC, ELISA, PTT－ LA methods, respectively, in 21 NPLE patients and 88 SLE patients without NPLE(NNPLE). Results The positive rates of APCR and ACA(IgG) in NPLE group were 78.9％ (15/19) and 52.4％ (11/21), respectively, which were significantly higher than those in NNPLE group: 44.3％ (39/88) and 22.7％ (20/88), respectively (P