Publications (51)152.02 Total impact
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Article: Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry.
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ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, complement-mediated hemolysis, frequently leading to debilitating clinical symptoms and life-threatening complications such as thromboembolism (TE). A retrospective analysis was performed on 301 patients from the South Korean National PNH Registry to describe disease burden and identify TE-associated risk factors. TE was identified in 18 % of patients and was associated with increased risk for mortality [odds ratio (OR), 6.85; P < 0.001]. A multivariate analysis showed that PNH patients with elevated hemolysis [lactate dehydrogenase (LDH) levels ≥1.5 times the upper limit of normal (ULN)] at diagnosis were at significantly higher risk for TE than patients with LDH <1.5 × ULN (OR 7.0; P = 0.013). The combination of LDH ≥1.5 × ULN with the clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria was associated with a greater increased risk for TE than elevated hemolysis or clinical symptoms alone. Continuous monitoring of these risk factors is critical for identifying PNH patients at risk for morbidities and mortality and allowing early intervention. (clinicaltrials.gov identifier: NCT01224483).International journal of hematology 05/2013; · 1.17 Impact Factor -
Article: Endogenous stromal cell-derived factor-1 (CXCL12) supports autonomous growth of acute myeloid leukemia cells.
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ABSTRACT: We investigated the role of endogenous stromal cell-derived factor-1 (SDF-1; CXCL12) in the survival and proliferation of acute myeloid leukemia (AML) cells in vitro. CD34+ cells from the peripheral blood of five patients with AML, as well as five AML cell lines, produced and secreted SDF-1. Knock-down of endogenous SDF-1 expression using siRNA technology downregulated the constitutive phosphorylation of SDF-1-related signaling molecules and significantly inhibited spontaneous proliferation of the AML cell lines during a 3-day incubation in serum-free conditions. These results indicate that endogenous SDF-1 expression by AML cells plays a role in the autonomous growth of the cells.Leukemia research 03/2013; · 2.36 Impact Factor -
Article: A multicenter retrospective analysis of the clinical features of pernicious anemia in a korean population.
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ABSTRACT: To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B(12) deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.Journal of Korean medical science 02/2013; 28(2):200-4. · 0.84 Impact Factor -
Article: Early Response to Bortezomib Combined Chemotherapy Can Help Predict Survival in Patients with Multiple Myeloma Who Are Ineligible for Stem Cell Transplantation.
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ABSTRACT: Novel agents to treat multiple myeloma (MM) have increased complete respone (CR) rates compared with conventional chemotherapy, and the quality of the response to treatment has been correlated with survival. The purpose of our study was to show how of early response to bortezomib combined chemotherapy influences survival in patients with newly diagnosed MM who are ineligible for stem cell transplantation. We assessed patient responses to at least four cycles of bortezomib using the International Myeloma Working Group response criteria. The endpoints were comparisons of progression free survival (PFS) and overall survival (OS) between early good response group (A group) and poor response group (B group). We retrospectively analyzed data from 129 patients registered by the Korean Multiple Myeloma Working Party, a nationwide registration of MM patients. The 3 yr PFS for the A and B groups was 55.6% and 18.4%, respectively (P < 0.001). The 3 yr OS for the A and B groups was 65.3% and 52.9%, respectively (P = 0.078). The early response to at least four cycle of bortezomib before next chemotherapy may help predict PFS in patients with MM who are ineligible stem cell transplantation.Journal of Korean medical science 01/2013; 28(1):80-86. · 0.84 Impact Factor -
Dataset: Acta Haem
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Article: Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α.
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ABSTRACT: Given the important role of CXCR4 in cancer metastasis, microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion. Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior. CXCR4 is upregulated in several cancer cells under hypoxic conditions, suggesting a relationship between tumor hypoxia and CXCR4. However, the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood. KATO III gastric cancer cells were exposed to hypoxia or normoxia. CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry. Wound healing, migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12, a major CXCR4 ligand. CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATO III cells following exposure to hypoxia. This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses (migration and invasion) to CXCL12 treatment in vitro. The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA. Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner, and that upregulation of CXCR4 plays a role in cancer cell migration and invasion. Thus, disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer.Oncology Reports 09/2012; 28(6):2239-46. · 1.84 Impact Factor -
Article: Cutaneous plasmacytoma.
The Korean journal of hematology 09/2012; 47(3):162. -
Article: Chemokine (C-X-C motif) ligand 12 is associated with gallbladder carcinoma progression and is a novel independent poor prognostic factor.
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ABSTRACT: Although recent studies have suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) is important in the progression of various malignancies, its role in gallbladder carcinoma (GBC) remains unknown. We investigated CXCL12 expression in GBC and its biologic and prognostic role in GBC tumorigenesis. We examined CXCL12 expression in tumor specimens from 72 patients with GBC by immunohistochemistry and analyzed the correlation between CXCL12 expression and clinicopathologic factors or survival. The functional significance of CXCL12 expression was investigated by CXCL12 treatment and suppression of CXCR4, a major receptor of CXCL12, as well as by CXCL12 overexpression in in vitro and in vivo studies. CXCL12 was differentially expressed in GBC tissues. CXCL12 expression was significantly associated with a high histologic grade (P = 0.042) and nodal metastasis (P = 0.015). Multivariate analyses showed that CXCL12 expression (HR, 8.675; P = 0.014) was an independent risk factor for patient survival. CXCL12 significantly increased anchorage-dependent and -independent growth, migration, invasion, adhesiveness, and survival of GBC cells in vitro, and these effects were dependent on CXCR4. Consistent with these results, overexpression of CXCL12 significantly promoted GBC tumorigenicity in a xenograft model. Our results indicate that GBC cells express both CXCL12 and its receptor CXCR4, and CXCL12 may have a role in GBC progression through an autocrine mechanism. In addition, CXCL12 is a novel independent poor prognostic factor in patients with GBCs. Thus, targeting CXCL12 and CXCR4 may provide a novel therapeutic strategy for GBC treatment.Clinical Cancer Research 05/2012; 18(12):3270-80. · 7.74 Impact Factor -
Article: A Multicenter Retrospective Analysis of Adverse Events in Korean Patients Using Bortezomib for Multiple Myeloma
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ABSTRACT: The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0–10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of borte-zomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.International Journal of Hematology 04/2012; 83(4):309-313. · 1.27 Impact Factor -
Article: Multiple myeloma in Korea: past, present, and future perspectives. Experience of the Korean Multiple Myeloma Working Party
International Journal of Hematology 04/2012; 92(1):52-57. · 1.27 Impact Factor -
Article: Transitional cell carcinoma of the urinary bladder metastatic to the oral mucosa.
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ABSTRACT: Metastatic tumors in the oral cavity are rare and usually affect the jaws more often than the oral soft tissues. In particular, metastases confined to the oral mucosa are extremely rare and originate mainly from the lung and breast. Only one case restricted to the oral mucosa and originating from urinary bladder carcinoma has previously been described. We report on a painful polypoid mass located in the oral mucosa with no bone involvement that was confirmed to be a metastatic oral tumor that originated from transitional cell carcinoma of the urinary bladder and progressed rapidly.Oncology letters 02/2012; 3(2):343-345. · 0.11 Impact Factor -
Article: Comparable analysis of outcomes for allogeneic peripheral blood stem cell transplantation from matched related and matched unrelated donors in acute myeloid leukemia.
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ABSTRACT: This study compared the results of allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated and related donors in 142 consecutive patients with acute myeloid leukemia (AML). The cumulative incidence of acute graft-versus-host disease (GVHD) was 37.6% in the related PBSCT group and 53.7% in the unrelated PBSCT group. The cumulative incidence of extensive chronic GVHD was also higher in the unrelated PBSCT group (19.5%) than in the related PBSCT group (8.9%). The overall survival rate at 4 years was 62.4 ± 5.4 and 53.8 ± 1.2% (p = 0.535) in the related and unrelated PBSCT group, respectively. In a multivariate analysis, unrelated PBSCT was identified as a risk factor for the development of extensive chronic GVHD (hazard ratio = 3.019, p = 0.027). Unfavorable cytogenetics and the disease status at the time of transplantation were found to be related to overall survival. In the case of high-risk AML, the survival rate and relapse incidence were significantly better in the matched unrelated PBSCT group (p = 0.047 and 0.039, respectively). In conclusion, the allogeneic PBSCT outcomes for AML were comparable in the matched related and matched unrelated groups. Nonetheless, for high-risk AML patients, matched unrelated PBSCT was found to be preferable to matched related PBSCT.Acta Haematologica 12/2011; 127(2):81-9. · 1.35 Impact Factor -
Article: Clinical implications of elevated antiphospholipid antibodies in adult patients with primary immune thrombocytopenia.
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ABSTRACT: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/µL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.The Korean Journal of Internal Medicine 12/2011; 26(4):449-54. -
Article: Differential effects of CXCR4 antagonists on the survival and proliferation of myeloid leukemia cells in vitro.
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ABSTRACT: Antagonists of CXC chemokine receptor 4 (CXCR4), including AMD3100, induce peripheral mobilization of hematopoietic stem cells and have been approved for clinical use. We explored whether the CXCR4 antagonists affected the survival and proliferation of myeloid leukemia cells in vitro. The effects of CXCR4 antagonists AMD3100 and T140 on the survival and proliferation of myeloid leukemia cell lines (U937, HL-60, MO7e, KG1a, and K562) as well as CD34(+) cells obtained from patients with AML and CML were analyzed by flow cytometry by using annexin V and a colorimetric cell proliferation assay. AMD3100, but not T140, stimulated the proliferation of leukemia cells in vitro in a dose-dependent manner for up to 5 days (~2-fold increase at a concentration of 10(-5) M), which was not abrogated by pretreatment of the cells with pertussis toxin, but was attenuated by RNAi knockdown of CXCR7 transcripts. In contrast, AMD3100 induced a marked decrease in the cell numbers after 5-7 days. AMD3100, but not T140, induced phosphorylation of MAPK p44/p42. AMD3100 increased the number and size of leukemia cell colonies and reduced cell apoptosis during the first 5-7 days of incubation, but the phenomena were reversed during the later period of incubation. The effects of CXCR4 antagonists on the proliferation of myeloid leukemia cells are not uniform. AMD3100, but not T140, exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of the cells in vitro.The Korean journal of hematology 12/2011; 46(4):244-52. -
Article: Expression of stromal cell-derived factor-1α is an independent risk factor for lymph node metastasis in early gastric cancer.
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ABSTRACT: Lymph node metastasis is considered to be a significant prognostic factor for early gastric cancer (EGC). However, no real consensus exists on which patient and/or tumor characteristics are associated with lymph node metastasis. We investigated whether stromal cell-derived factor (SDF)-1α expression correlates with lymph node metastasis in patients with EGC by immunohistochemically examining the expression of SDF-1α in 138 archival tissue specimens of EGC. Of these specimens, 59 (42.8%) and 79 (57.2%) were grouped into SDF-1α-positive and SDF-1α-negative groups, respectively. No significant differences existed with respect to age, gender, tumor location, proportion of tumors >20 mm in size, macroscopic type, depth of invasion or histology between the SDF-1α-positive and -negative groups. However, the SDF-1α-positive group was significantly correlated with lymphovascular invasion and lymph node metastasis. Results of the univariate analyses indicated that lymphovascular invasion, undifferentiated histology and SDF-1α positivity were statistically significant risk factors affecting lymph node metastasis in patients with EGC. Multivariate analyses showed that lymphovascular invasion [hazard ratio (HR), 8.595; 95% confidence interval (CI), 1.694-43.595; P=0.009], undifferentiated histology (HR, 2.965; 95% CI, 1.037-8.471; P=0.043) and SDF-1α positivity (HR, 2.108; 95% CI, 1.316-10.135; P=0.013) were independent risk factors predicting lymph node metastasis in EGC. In conclusion, these results suggest that SDF-1α expression in tumor cells is a predictive marker of lymph node metastasis in EGC.Oncology letters 11/2011; 2(6):1197-1202. · 0.11 Impact Factor -
Article: Excision repair cross-complementation group 1 expression predicts response and survival in locally advanced cervical carcinoma patients treated with concurrent chemoradiotherapy.
Histopathology 09/2011; 59(3):564-7. · 3.08 Impact Factor -
Article: Clinical features and outcomes of autoimmune hemolytic anemia: a retrospective analysis of 32 cases.
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ABSTRACT: There has been no report on the clinical features or natural history of autoimmune hemolytic anemia (AIHA) in the Korean adult population. This study retrospectively analyzed the clinical characteristics and long-term outcomes of AIHA in the Korean adults. Patients newly diagnosed with AIHA between January 1994 and December 2010 at Chungnam National University Hospital were enrolled. Patient characteristics at diagnosis, response to treatment, and the natural course of the disease were documented. Thirty-two patients (31 females and 1 male) with a median age of 48 years (range, 17-86) were enrolled. Of these, 21.9% were initially diagnosed with secondary AIHA. Thirteen patients (40.6%) were initially diagnosed with Evans' syndrome. Of the 29 patients who were placed on therapy, 27 (93.1%) showed a partial response or better. Nevertheless, 1 year after initiating treatment, 80% of the patients were still treatment-dependent. During follow-up (median length 14 months; range, 0.5-238), 14 of 25 patients (56.0%) who were initially diagnosed with primary warm antibody AIHA were found to have systemic lupus erythematosus (SLE). Median time to conversion to SLE was 8.0 months (95% CI, 4.3-11.7), and the probabilities of conversion at 12 and 24 months were 63% and 91%, respectively. Younger age (<60 years) and a positive fluorescent anti-nuclear antibody test were associated with a higher probability of SLE conversion (P=0.01 and P<0.001, respectively). Primary AIHA is rare. Regular, vigilant testing for SLE is required in patients initially diagnosed with AIHA.The Korean journal of hematology 06/2011; 46(2):111-7. -
Article: Long-term outcome of isolated thrombocytopenia accompanied by hypocellular marrow.
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ABSTRACT: Hypocellularity of bone marrow (BM), not associated with significant dyshematopoiesis, is often found in patients with isolated thrombocytopenia, but its clinical implications have not been studied. We prospectively studied the clinical features and natural history of these patients. Adults with isolated thrombocytopenia (platelet counts <100×10(9)/L) in the absence of dyshematopoiesis, cytogenetic abnormalities, or megakaryocytic hyperplasia and who had BM hypocellularity (below 30% in patients aged less than 60 years; below 20% in patients aged 60 years or more) were enrolled at Chungnam National University Hospital between January 2002 and December 2006. They were monitored regularly for changes in platelet counts or development of additional cytopenia. Twenty patients (17 men and 3 women) were enrolled in the study. The median age was 29 years (range, 18-70 years). At initial presentation, the platelet counts ranged from 12×10(9)/L to 99×10(9)/L (median, 63×10(9)/L) and were >50×10(9)/L in 16 patients (80%). BM cellularity ranged from 5% to 25% (median, 15%) and was ≤10% in 6 patients (30%). During the median 48-month follow-up (range, 12-90 months), platelet counts of 3 of the 20 patients recovered to normal levels (>150×10(9)/L) after 12, 56 and 66 months. Three patients developed pancytopenia after 11, 70 and 90 months. Two patients were consistent with moderate aplastic anemia, and 1 was confirmed as having refractory cytopenia with multilineage dysplasia. In the remainder of the patients, platelet counts remained unchanged. Isolated thrombocytopenia accompanied by hypocellular marrow encompasses a group of heterogeneous conditions.The Korean journal of hematology 06/2011; 46(2):128-34. -
Article: Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia.
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ABSTRACT: To investigate the correlation of trough imatinib mesylate (IM) levels with cytogenetic or molecular responses, we measured trough IM levels in patients with chronic myeloid leukemia, chronic phase (CML-CP), at 6 months of treatment with a standard dose of IM. Eighty-seven newly diagnosed patients with CML-CP were prospectively enrolled. Seventy-eight patients (89.7%) showed an optimal response (complete or partial cytogenetic response) at 6 months. Trough IM levels were 1378 ± 725 ng/mL. When categorized into two groups, there was a statistically significant difference in numbers of patients with optimal and suboptimal responses at 6 months (group with <1000: 80.6% vs. 19.4%; ≥ 1000: 94.6% vs. 5.4%; p = 0.032), and in numbers of patients with early major molecular response (early-MMR) and without MMR at 6 months (group with <1000: 3.2% vs. 96.8%; ≥ 1000: 21.4% vs. 78.6%; p = 0.047). In conclusion, the incidence of optimal cytogenetic response or early-MMR in patients with CML-CP treated with IM for 6 months was significantly higher in those with a trough level of ≥ 1000 compared with those with a level of <1000. Dose escalation of IM can be one option in patients with CML showing suboptimal response or resistance to the standard dose of IM, especially with low trough plasma IM levels (<1000 ng/mL).Leukemia & lymphoma 04/2011; 52(6):1024-9. · 2.40 Impact Factor -
Article: Clinical features of severe acquired ADAMTS13 deficiency in thrombotic thrombocytopenic purpura: the Korean TTP registry experience.
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ABSTRACT: The clinical significance of ADAMTS13 activity for response to treatment, mortality rate, recurrence, and prognosis is unclear. Therefore, we investigated the characteristics of severe ADAMTS13 deficiency and evaluated its prognostic features in Thrombotic thrombocytopenic purpura (TTP). The Korean TTP Registry includes 66 patients from 13 teaching hospitals in Korea who received the diagnosis of TTP from January 2005 to December 2008. Blood samples obtained upon admission were sent for ADAMTS13 analysis (multimer analysis by sodium dodecyl sulfate electrophoresis) to a central laboratory along with patient clinical information. Patients with severe ADAMTS13 deficiency had lower serum creatinine levels (P = 0.001) than patients with non-severe ADAMTS13 deficiency. Although severe ADAMTS13 deficiency was associated with better response rate (75 vs. 53%, P = 0.145), remission rate (81 vs. 61%, P = 0.209), and mortality rate (19 vs. 31%, P = 0.508) than non-severe ADAMTS13 deficiency, treatment outcomes did not differ significantly between groups. After adjusting for clinical and laboratory features, multivariate analysis did not reveal any independent risk factors for TTP-associated mortality. Patients with severe ADAMTS13 deficiency had lower serum creatinine levels at presentation, but severe ADAMTS13 activity deficiency at TTP diagnosis does not appear to have prognostic significance.International journal of hematology 02/2011; 93(2):163-9. · 1.17 Impact Factor
Top co-authors
Top Journals
Institutions
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2003–2013
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Chungnam National University
- • Department of Internal Medicine
- • Department of Laboratory Medicine
Seongnam, Gyeonggi, South Korea
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2011
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Catholic University of Korea
- Department of Internal Medicine
Seoul, Seoul, South Korea
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2010–2011
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Kyungpook National University Hospital
Seoul, Seoul, South Korea
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