No abstract available.
Dapsone* ; Purpura, Thrombocytopenic, Idiopathic*

BACKGROUND: In sepsis, large scale inflammatory responses can cause extensive collateral damage to the vasculature, because both coagulation and fibrinolysis are activated unevenly. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in modulating fibrinolysis. Since TAFI can be activated by both thrombin and plasmin, it is thought to be affected in sepsis. Hence, activated and inactivated TAFI (TAFIa/ai) may be used to monitor changes in sepsis. METHODS: TAFIa/ai-specific in-house ELISA can detect only the TAFIa/ai form, because the ELISA capture agent is potato tuber carboxypeptidase inhibitor (PTCI), which has selective affinity towards only the TAFIa and TAFIai isoforms. TAFIa/ai levels in plasma from 25 patients with sepsis and 19 healthy volunteers were quantitated with the in-house ELISA. RESULTS: We observed increased TAFIa/ai levels in samples from patients with sepsis (48.7+/-9.3 ng/mL) than in samples from healthy individuals (10.5+/-5.9 ng/mL). In contrast, no difference in total TAFI concentration was obtained between sepsis patients and healthy controls. The results suggest that TAFI zymogen was activated and that TAFIa/ai accumulated in sepsis. CONCLUSION: The detection of TAFIa/ai in plasma could provide a useful and simple diagnostic tool for sepsis. Uneven activation of both coagulation and fibrinolysis in sepsis could be caused by the activation of TAFI zymogen and elevation of TAFIa/ai. TAFIa/ai could be a novel marker to monitor sepsis and other blood-related disturbances.
Carboxypeptidase U ; Enzyme-Linked Immunosorbent Assay ; Fibrinolysin ; Fibrinolysis ; Humans ; Organothiophosphorus Compounds ; Plasma ; Protein Isoforms ; Sepsis ; Solanum tuberosum ; Thrombin

BACKGROUND: An early diagnosis of disseminated intravascular coagulation (DIC) before its progression to an overt stage is necessary for early treatment and positive outcomes. In 2001, the Scientific and Standardization Committee (SCC) of the International Society on Thrombosis and Hemostasis (ISTH) proposed new criteria for the preclinical diagnosis of overt and non-overt DICs. We investigated the clinical usefulness of the modified ISTH criteria for non-overt DIC diagnosis. METHODS: We enrolled 296 DIC patients (170 males and 126 females) admitted and evaluated at the Gangnam Severance Hospital, Seoul, Korea, between March 2006 and April 2007. Hemostatic tests, including platelet counts, prothrombin time (PT), D-dimer levels with antithrombin, and protein-C levels, were evaluated by excluding negative scores with clinical signs, in which more than 5 points of interest denoted non-overt DIC. Mortality rates were also evaluated. RESULTS: There were 289 patients with increased D-dimer levels and significant parametric changes suggesting DIC progression. Protein C and antithrombin levels were lower (99.2% each) and appeared earlier in patients with non-overt DIC than in patients with overt DIC. In all, 125 (43.3%) patients had non-overt DIC and, of which 27 died (mortality rate, 21.6%). The sensitivity and specificity for mortality were 73.0% and 55.9%, respectively, which were same as those for the original ISTH criteria. CONCLUSION: The modified ISTH criteria can be used for the early detection of non-overt DIC, and may be useful for the improvement of outcomes of non-overt DIC patients.
Dacarbazine ; Disseminated Intravascular Coagulation ; Early Diagnosis ; Fibrin Fibrinogen Degradation Products ; Hemostasis ; Humans ; Korea ; Male ; Platelet Count ; Protein C ; Prothrombin Time ; Sensitivity and Specificity ; Thrombosis

Technologies in laboratory diagnostics are changing fast with progress in understanding and therapy of diseases. Unfortunately, new analyzers are often needed to be installed in a clinical laboratory to implement such techniques. The demand for new hardware is a bottleneck in improving the diagnostic services for many facilities with limited resources. In this regard, hemostasis laboratories take a slightly different position.Because many in vitro diagnostic tests target the functional aspects of hemostasis, further meaningful information can be obtained from the same analyzers as in current use.Automated coagulometers are good candidates for such further utilization. Clot waveform analysis is a leading example. Behind the simple values reported as clotting time, clotting curves exist that represent the process of fibrin clot formation. Clot waveform analysis examines the clotting curves and derives new parameters other than clotting times. The clot waveform parameters are now in active use in assessing the hemostatic potential of hemorrhagic patients. Clinical application of coagulometers can also be widened by modifying the reagent formulation. For example, the chromogenic factor VIII assay with bovine source reagent compositions has recently been introduced for hemophilia A patients on emicizumab prophylaxis. Also, new immunoturbidimetric functional assays for von Willebrand factor have been developed recently. Thus, new clinically relevant information can be mined from the automated coagulometers that are based on old technology

BACKGROUND: We intended to find the mutations of von Willebrand factor (VWF) gene as the most important contributing factor of von Willebrand disease (VWD) in Korean patients. METHODS: In 40 known vWD patients mutations of vWF gene were sought by direct sequencing of PCR products targeting exons 18, 19, 20, 26, 28 and 52 frequently implicated as the locations of mutation. For factors other than VWF gene contributing to VWD phenotype, we tested ABO blood group and measured ADAMTS13 activity in VWD patients. RESULTS: Twenty-seven cases (67.5%) were type 1 vWD, 3 cases (7.5%) type 3, and 5 cases (12.5%) type 2A. Three cases were type 2A or 2B (7.5%) and 2 cases were suspected to be type 2N (5.0%). Among them six candidate missense mutations were found: V1279I, R1306W, R1308C, and V1316M were previously reported in type 2B and type 1 vWD, and C858W and T1477I were novel findings. All patients were heterozygotes. Blood group O was overly represented in VWD patients, while ADAMTS13 activity of the patients was not significantly different from that of normal control. CONCLUSIONS: Mutation of VWF gene detected by genetic studies can significantly improve the diagnostic accuracy, especially in subtype assignment of VWD. Two novel mutations, C858W and T1477I associated with VWD were found and expected to contribute to the elucidation of its pathophysiology.
ABO Blood-Group System ; ADAM Proteins/analysis ; Heterozygote ; Humans ; Korea ; *Mutation, Missense ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Analysis, DNA ; von Willebrand Disease/classification/diagnosis/*genetics ; von Willebrand Factor/analysis/*genetics

PURPOSE: Radical cystectomy has been the most widely used method in the treatment of bladder cancer, but it is limited by major problems. Therefore, we investigated the results of bladder-preserving treatment in patients with T3b, T4a, and T4b transitional carcinoma of the bladder who underwent transurethral resection of bladder cancer and subsequent administration of chemotherapy. MATERIALS AND METHODS: Of all patients who were diagnosed with bladder cancer and underwent bladder-preserving treatment between January 2001 and August 2008, 78 patients with at least 12 months of follow-up data were enrolled in this study. All patients received gemcitabine (1,000 mg/m2) and cisplatin (70 mg/m2) once per month postoperatively for a total of 6 months and completed a follow-up visit every 3 months. The patient survival rate and prognostic factors (age, tumor size, differentiation, number of lesions, stage, and presence of hydronephrosis) were assessed. The Kaplan-Meier method was used to analyze survival rate, and Cox multiple regression analysis was used for prognostic factors. RESULTS: The mean patient age was 68.32+/-8.6 years, the mean duration of follow-up was 54.70+/-32.8 months, and the median duration of follow-up was 49.0 months. The 5-year survival rate was 66.2%. Single lesions were found in 28 cases (35.9%), and multiple lesions were found in 50 cases (64.1%). Stage T3b lesions were identified in 56 cases (71.8%), stage T4a lesions were identified in 16 cases (20.5%), and stage T4b lesions were identified in 6 cases (7.7%). Tumor size was less than 4 cm in 4 cases (59.0%) and greater than 4 cm in 32 (41.0%). Hydronephrosis was present in 21 cases (26.9%). In the 5-year survival analysis, prognostic factors significantly influencing survival rate were T-stage of the tumor and absence of hydronephrosis and complete regression after treatment (p<0.05). Multivariate analysis revealed that tumor stage and the absence of hydronephrosis were statistically significant prognostic indicators. CONCLUSIONS: In patients with T3b, T4a, and T4b transitional carcinoma of the bladder, bladder preservation may prevent a decrease in quality of life. Also, our findings suggest that this approach could be considered a primary treatment option for patients with T3b stage tumors without evidence of hydronephrosis.
Carcinoma, Transitional Cell ; Cisplatin ; Cystectomy ; Deoxycytidine ; Follow-Up Studies ; Humans ; Hydronephrosis ; Multivariate Analysis ; Quality of Life ; Survival Rate ; Urinary Bladder ; Urinary Bladder Neoplasms

BACKGROUND: The Coapresta 2000 (Sekisui Medical CO., LTD, Japan) is a fully automated random-access multiparameter hemostasis coagulation analyzer, which is equipped with a photo-optical clot detection unit and a cap-piercing system. It is able to perform clotting time assays as well as colorimetric assays (synthetic substrate method and latex turbidimetric method). In this study, we evaluated the analytical performance of the Coapresta 2000 for coagulation test items and compared with that of the ACL-TOP (Instrumentation Laboratory, Lexingtion, MA, USA) analyzer, which is currently used for routine coagulation test items in our hospital. METHODS: The Coapresta 2000 was evaluated with respect to its technical characteristics in the determination of 8 routine coagulation test items: prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin-degradation product (FDP) antithrombin III, D-dimer, factors VIII and IX. Analyse-it (Analyse-it Software Ltd, UK) and SigmaStat (Systat Software, Inc., USA) were used for statistical analysis between items on the Coapresta 2000 and the ACL-TOP analyzer. RESULTS: The intra-assay and inter-assay coefficients of variation (CV) were below 5% for both groups of samples having values within the reference interval and outside the reference interval. Significant interference was observed with hemolytic and icteric samples. Carryover was not detected. The results obtained by Coapresta 2000 were well correlated with those obtained by the ACL-TOP analyzer (r2 in the range from 0.781 to 0.969). CONCLUSIONS: We concluded that Coapresta 2000 analyzer was well correlated with ACL-TOP analyzer for the routine coagulation test items tested.
Antithrombin III ; Fibrin Fibrinogen Degradation Products ; Fibrinogen ; Hemostasis ; Latex ; Partial Thromboplastin Time ; Prothrombin Time

Heparin-induced thrombocytopenia (HIT) is usually caused by anti-platelet factor 4 (PF4)/heparin antibodies, leading to intravascular platelet activation. Circulating anti-PF4/heaprin antibody (IgG, IgA and IgM) was detected by ELISA (Asserachrom HPIA, Diagnostia Stago, Asnieres, France) in a 61-yearold man with coronary artery disease and dyspnea on exercise. He had undergone a coronoary angiography using 2,000 unit of heparin before a procedure. On admission, laboratory testing revealed a platelet count of 296x10(9)/L and aPTT (activated partial thromboplastin time) of 38.1 sec. The fall in the platelet count was progressive, resulting in 42% and 53% of platelet counts on the 6th and 12th days after intravenous heparin administration, respectively. He was discharged after coronary artery bypass graft. On discharge, platelet count was normalized to be 212x10(9)/L. On the 7th day after dischage, anti-PF4/heaprin antibody was detected by ELISA (Asserachrom HPIA, Diagnostia Stago, Asnieres, France).
Angiography ; Antibodies ; Coronary Artery Bypass ; Coronary Artery Disease ; Dyspnea ; Enzyme-Linked Immunosorbent Assay ; Heparin* ; Immunoglobulin A ; Platelet Activation ; Platelet Count ; Thrombocytopenia* ; Thromboplastin ; Transplants

BACKGROUND: Exon deletions of Duchenne muscular dystrophy (DMD) gene account for most of the alterations found in DMD and Becker muscular dystrophy (BMD). This study was to evaluate the usefulness of dual priming oligonucleotide multiplex PCR (DPO PCR) in detection of exon deletions of DMD gene. METHODS: Thirty-seven DMD or BMD patients who had known exon deletions detected by conventional multiplex PCR (conventional PCR) and nine control subjects were enrolled in this study. When a discrepancy was shown between the results of conventional PCR and DPO PCR, the multiplex ligation-dependent probe amplification (MLPA) technique was performed as a confirmation test. RESULTS: The same deletions previously identified by conventional PCR in 32 out of 37 subjects were also detected by DPO PCR. For the five subjects (13.5%) showing discrepant results between the conventional PCR and DPO PCR, MLPA was performed and its results were found to correlate better with those of DPO PCR. The discrepancies were due to false positive or false negative results of the conventional PCR. CONCLUSIONS: DPO PCR shows a high agreement of results with the conventional PCR and is considered an adequate method to be used as a primary genetic test for the diagnosis of DMD. Because of an improved accuracy, especially for determining the boundaries of DMD gene deletions, DPO PCR can be very useful as a supplement to the conventional PCR.
*DNA Mutational Analysis ; DNA Primers ; Dystrophin/*genetics ; Female ; Gene Deletion ; Genetic Screening ; Humans ; Male ; Muscular Dystrophy, Duchenne/*diagnosis/genetics ; Nucleic Acid Amplification Techniques ; Oligonucleotide Probes ; Polymerase Chain Reaction/*methods ; Reagent Kits, Diagnostic ; Reproducibility of Results

BACKGROUND: Although the pericentric inversion of chromosome 9, inv(9)(p11q13), is generally considered a normal variation, it is also associated with solid tumors and several hematologic malignancies such as biphenotypic acute leukemia, ALL, AML, and myeloproliferative neoplasms. However, to the best of our knowledge, there have been no reports that suggest an association between CML and constitutional pericentric inversion of chromosome 9. The purpose of this retrospective study was to investigate the frequency and clinical features of CML patients with concomitant inv(9) and t(9;22)(q34;q11.2) variation at our institution. METHODS: We reviewed the bone marrow chromosome database entries between October 2006 and December 2008 to identify patients with concomitant inv(9) and t(9;22) variations. Laboratory and clinical data of the patients were obtained from the electronic medical record system. RESULTS: Among the 51 CML patients, 4 (7.8%) had concomitant inv(9) and t(9;22) variations. CONCLUSIONS: Although the association between inv(9) variation and CML is still controversial, we believe that hematologists should consider the role of constitutional inv(9) variation in CML patients to avoid overlooking the impaired engraftment potential of hematopoietic stem cells harboring inv(9). Therefore, we suggest that more effort should be invested to develop cytogenetic tests for detecting constitutional inv(9) variation in CML patients.
Adult ; Asian Continental Ancestry Group/*genetics ; Centrosome ; *Chromosome Inversion ; *Chromosomes, Human, Pair 9 ; Female ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/diagnosis/*genetics ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Translocation, Genetic