OBJECTIVES: To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments. METHODS: ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells. RESULTS: PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). CONCLUSIONS PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.
Child ; Humans ; Animals ; Mice ; Mice, Inbred C57BL ; Becaplermin ; Imatinib Mesylate/therapeutic use* ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Thrombocytosis/etiology* ; RNA, Messenger

Humans ; Child ; Retrospective Studies ; Thrombocytosis/etiology*

BACKGROUND AND OBJECTIVES: Immunological variability in Kawasaki disease (KD) shows age-specific differences; however, specific differences in laboratory values have not been compared between infants and non-infants with KD. We compared age-adjusted Z-values (Z) of white and red blood cells in infants with KD with those in non-infants with KD. METHODS: This study retrospectively investigated 192 infants and 667 non-infants recruited between 2003 and 2015 at the Korea University Hospital. Laboratory values for infants with KD and non-infants with KD were analyzed and age-unadjusted raw values (R) and age-adjusted Z for blood cells counts were determined. RESULTS: Z in infants with KD during pre-intravenous immunoglobulin (IVIG), post-IVIG, and chronic phases showed increased lymphopenia and eosinophilia, low neutrophil:lymphocyte and neutrophil:eosinophil ratios, worse anemia, increased thrombocytosis, and reduced erythrocyte sedimentation rates compared with those in non-infants with KD. The optimal cut-off value for pre-IVIG Z-hemoglobin for prediction of KD in all patients was <−0.01 (area under the curve [AUC], 0.914; sensitivity/specificity, 0.999/0.886; p=0.04). The optimal cut-off value for pre-IVIG C-reactive protein (CRP) for prediction of KD in infants compared to that in febrile control infants was >40 mg/L (AUC, 0.811; sensitivity/specificity, 0.712/0.700; p=0.04). CONCLUSIONS: Laboratory characteristics enable differentiation between infants and non-infants with KD and contribute to a better understanding of changes in blood cell counts. Infants with incomplete KD can be more easily differentiated from infants with simple febrile illness using pre-IVIG Z-hemoglobin and pre-IVIG CRP values.
Anemia ; Blood Cell Count ; Blood Cells ; Blood Sedimentation ; C-Reactive Protein ; Eosinophilia ; Erythrocytes ; Humans ; Immunoglobulins ; Infant ; Korea ; Leukocyte Count ; Lymphopenia ; Mucocutaneous Lymph Node Syndrome ; Retrospective Studies ; Thrombocytosis

OBJECTIVE: To explore the effect of high volume platelet reduction therapy on the white blood cell (WBC) count and hemoglobin (Hb) level in patients with thrombocytosis. METHODS: Thirty-two plateletphoreses were performed for patients with thromocytosis by using ELP or MNC program of blood component isolator of COBE spectra continuous flow concentrifugation and the ACD-A preservation solution for blood as blood anticoagulant. In each treatment of patients, 2.5-3.0 tines total blood volume (TBV) were circulated, then the platelet suspension of 1/5-1/4 time TBV was prepared and collected. RESULTS: A single plateletpheresis took (212.53±41.54) minutes in which (8 812.63±2087.15) ml blood were treated, and (798.84±190.77) ml platelet suspension was collected. In the suspension, the platelet count was 4 486.50 (3 058.50-5 279.50)×10/L, containing 3 455.50 (2 288.68-4 226.71)×10. WBC count was 13.79 (10.21-20.72)×10/L, containing 11.90(7.81-14.40)×10. Hemoglobin concentration was (3.28±1.25) g/L，containing (2.62 ± 1.17) g. Before and after plateletpheresis, the patients' platelet count was 1 263.00 (1 052.50-1 807.50)×10/L and (778.83±247.25)×10/L（Z=4.94, P＜0.01), WBC count was 9.96(6.44-14.01)×10/L and 8.59(5.37, 13.12)×10/L (Z=13.31, P＜0.05), Hemoglobin concentration was (112.63 ± 24.56)g/L and (109.55 ± 24.46)g/L (t=1.68，P＞0.05). CONCLUSION Using continuous flow centrifugation and blood component separating in plateletpheresis for the patients with thrombocytosis can obviously decrease the high ratio of platelets, and improve the effect of plateletpheresis. The high volume platelet reduction therapy can lead to decrease of WBC count to some alent, degree but WBC count still in the normal range, moreover not affect the hemoglobin level significantly.
Hemoglobins ; Humans ; Leukocyte Count ; Platelet Count ; Plateletpheresis ; Thrombocytosis

OBJECTIVE: Myeloproliferative neoplasm (MPN) is considered as one of the risk factors of ischemic stroke. Some MPN patients manifest stroke as their first symptom. Our purpose was to assess diagnostic rate of MPN in newly diagnosed acute ischemic stroke patients. METHODS: This study was performed using National Health Insurance Service Ilsan Hospital dataset. Data retrieving was performed by defining by defining the patient with coding of acute ischemic stroke from January 2013 to June 2017. We selected only the patients who had checked brain magnetic resonance imaging and complete blood cell count (CBC) in emergency room or on admission. Among the results of CBC finding, hemoglobin and platelet count were analyzed. Erythrocytosis was defined >16.5 g/dL (male), >16 g/dL (female) according to revised World Health Organization (WHO) classification of polycythemia vera (PV) criteria. Thrombocytosis was >450,000/µL according to revised WHO classification of essential thrombocythemia (ET). RESULTS: Total number of newly diagnosed acute ischemic stroke was 1,613 patients. Seven patients (0.43%) were diagnosed MPN (ET=2, PV=5) after ischemic stroke. Patients who had thrombocytosis and erythrocytosis were 18 and 105, respectively. Three patients who had thrombocytosis were diagnosed MPN (ET=2, PV=1). Two patients with erythrocytosis were diagnosed MPN (PV=2). Two patients had both thrombocytosis and erythrocytosis, and two of them were diagnosed PV. Seventy-one patients who had erythrocytosis were normalized in follow-up period. Six patients who had thrombocytosis and 30 patients who had erythrocytosis did not further evaluate. CONCLUSION: CBC has to be carefully read and MPN can be suspected. Diagnosis must be confirmed by hematologist to initiate appropriate treatment. It is important to recognized suspected MPN patients to prevent stroke.
Blood Cell Count ; Brain ; Classification ; Clinical Coding ; Dataset ; Diagnosis ; Emergency Service, Hospital ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; National Health Programs ; Platelet Count ; Polycythemia ; Polycythemia Vera ; Risk Factors ; Stroke ; Thrombocythemia, Essential ; Thrombocytosis ; World Health Organization

OBJECTIVE: To investigate the association between pre-treatment thrombocytosis and prognosis in patients with ovarian cancer (OC). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for articles regarding the prognosis of OC patients with pre-treatment thrombocytosis by the end of March 2018. Pooled estimates for overall survival (OS) and progression-free survival (PFS) events were calculated as hazard ratios (HRs) either on a fixed or random effect model by Stata 13.0 software. Funnel plot and Egger's test were applied to evaluate publication bias and sensitivity analyses were undertaken to estimate the strength of outcomes. RESULTS: Eleven studies that met the inclusion criteria were enrolled, including a total of 4,953 patients. Pooled results showed that pre-treatment thrombocytosis was significantly associated with OS (HR=1.722; 95% confidence interval [CI]=1.437–2.064) and PFS (HR=1.452; 95% CI=1.323–1.593) in the cohort. Significant correlation was found in OS and PFS between pre-treatment thrombocytosis and both epithelial OC (all stages and differentiation degrees of OC) and advanced epithelial OC (III or IV) by subgroup analyses, which were performed according to publication year, country, case numbers, OC category, International Federation of Gynecology and Obstetrics stage, and cut-off value. However, subgroup analyses indicated no significant correlation between pre-treatment thrombocytosis and OS for patients with high-grade serous (poorly differentiated or undifferentiated) OC (HR=1.220; 95% CI=0.946–1.573; p=0.125). Egger's test demonstrated no obvious publication bias in the articles enrolled in this study (OS: p=0.226; PFS: p=0.071). CONCLUSION: Pre-treatment thrombocytosis might be taken as an independent prognostic indicator for patients with OC.
Cohort Studies ; Disease-Free Survival ; Gynecology ; Humans ; Obstetrics ; Ovarian Neoplasms* ; Prognosis* ; Publication Bias ; Publications ; Thrombocytosis*

BACKGROUND: Non-conversion of sputum smear and culture prolongs the infectivity of the patient and has been associated with unfavorable outcomes. We aimed to evaluate factors associated with persistent sputum positivity at the end of two months of treatment of new case pulmonary tuberculosis (TB). METHODS: Data of 87 human immunodeficiency virus-negative patients with culture-positive drug-susceptible pulmonary TB admitted to local university hospital between September 2015 and September 2016 were reviewed. Factors associated with sputum smear and/or culture positivity at the end of the second month of treatment were analyzed. RESULTS: Twenty-two patients (25.3%) remained smear and/or culture-positive. Male sex, lower body mass index (BMI), unemployment, alcohol abuse, higher number of lobes involved and cavities on chest X-rays, shorter time to detection (TTD) on liquid cultures, higher respiratory sample smear grading and colony count in solid cultures, higher C-reactive protein, erythrocyte sedimentation rate, leukocytosis, thrombocytosis, and anemia were all significantly associated with persistent sputum positivity. However, in the logistic regression analysis only male sex, lower BMI, alcohol abuse, higher radiological involvement, cavitation, higher smear grading, higher colony count in solid cultures and shorter TTD were determined as independent factors associated with persistent sputum positivity at the end of 2 months of treatment. CONCLUSION: In conclusion, higher sputum smear and culture grading at diagnosis, shorter TTD, higher number of lobes involved, cavitation, male sex, alcohol abuse, and lower BMI were independently associated with persistent sputum positivity. These factors should be sought when distinguishing which patients will remain infectious longer and possibly have worse outcomes.
Alcoholism ; Anemia ; Blood Sedimentation ; Body Mass Index ; C-Reactive Protein ; Diagnosis ; Humans ; Leukocytosis ; Lithuania* ; Logistic Models ; Male ; Risk Factors ; Sputum* ; Thorax ; Thrombocytosis ; Treatment Outcome ; Tuberculosis* ; Tuberculosis, Pulmonary ; Unemployment

BACKGROUND: Reactive thrombocytosis (RT) is a common condition among children, although no studies have examined the etiology or clinical characteristics of RT among Korean children. METHODS: This retrospective study evaluated children with RT at a single Korean tertiary center during a 10-year period. RESULTS: RT accounted for 13.5% of children who were admitted to the pediatric ward (4,113/30,355): mild RT, 82.7%; moderate RT, 14.1%; severe RT, 1.1%; and extreme RT, 2.1%. There was a negative correlation between platelet count and Hb level (P=0.008). There were positive correlations between platelet count and WBC (P=0.001), erythrocyte sedimentation rate (ESR) (P=0.007), and admission duration (P=0.006). The most common cause of RT was infection and the second most common was Kawasaki disease (KD). The highest proportion of lower respiratory tract infection was observed in extreme RT (P < 0.001). The proportion of KD was highest in extreme RT (P < 0.001) and in children aged 1–7.9 years (P < 0.001). The proportion of refractory KD was highest in extreme RT (P=0.005). In cases of KD, there was a positive correlation between platelet count and fever duration (P=0.006). Non-KD autoimmune inflammation was only observed in mild/moderate RT, and its proportion was highest in children aged 8–18 years (P < 0.001). CONCLUSION: In children, more severe RT was associated with lower Hb, increased WBC, ESR, and prolonged admission. With respiratory infection or KD, extreme RT was associated with more severe disease course.
Blood Sedimentation ; Child* ; Fever ; Humans ; Inflammation ; Mucocutaneous Lymph Node Syndrome ; Platelet Count ; Respiratory Tract Infections ; Retrospective Studies* ; Thrombocytosis*

Drug reaction with eosinophilia and systemic symptoms(DRESS), which occurs 2–8 weeks after taking a medication is a rare and potentially life-threatening drug-induced hypersensitivity reaction, which includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ such as liver, lung, kidney involvement. Antiepileptic agents (e.g., carbamazepine, lamotrigine, phenytoin, and phenobarbital) and allopurinol are the most commonly reported causes. However, new antiepileptic agents, such as oxcarbazepine, rarely cause drug reaction with eosinophilia and systemic symptoms. A 11-year-old boy who was administered oxcarbazepine for 34 days developed widespread rashes, facial edema, fever, cough, nasal stuffiness, tonsillitis, and cervical lymphadenopathy. Laboratory test results showed leukocytosis, eosinophilia, thrombocytosis, elevated c-reactive protein, and elevated liver transaminase levels. As we suspected drug reaction with eosinophilia and systemic symptoms, we immediately withdrew oxcarbazepine and commenced corticosteroid therapy. The patient's skin lesions and abnormal laboratory results slowly improved. Before change the antiepileptic agents, we performed human leukocyte antigen (HLA) typing to assess the genetic risk factors of the drug reaction and the result was positive for HLA DRB1*04:03 known to cause severe acute drug hypersensitivity, such as Stevens-Johnson syndrome by oxcarbazepine in Koreans. We have presented the first report of drug reaction with eosinophilia and systemic symptoms associated with oxcarbazepine in a patient with HLA DRB1*04:03. Although DRESS by oxcarazepine is extremely rare and unpredictable, when suspected clinical symptoms occur, it is necessary to interrupt the causative drug rapidly and confirming the patient's HLA typing may help to select a safer alternative drug.
Allopurinol ; Anticonvulsants ; C-Reactive Protein ; Carbamazepine ; Child ; Cough ; Drug Eruptions ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome* ; Edema ; Eosinophilia ; Exanthema ; Fever ; Histocompatibility Testing ; Humans ; Hypersensitivity ; Kidney ; Leukocytes ; Leukocytosis ; Liver ; Lung ; Lymphatic Diseases ; Male ; Palatine Tonsil ; Phenytoin ; Risk Factors ; Skin ; Stevens-Johnson Syndrome ; Thrombocytosis ; Tonsillitis

A 30-year-old woman in her first pregnancy was admitted with headache and horizontal diplopia indicating left abducens nerve palsy. Brain magnetic resonance imaging revealed a cerebral venous thrombosis. She had thrombocytosis in the peripheral blood, and a genetic test for thrombocytosis revealed the presence of the valine-to-phenylalanine (V617F) mutation of the Janus kinase 2 (JAK2) gene. Treatment with low-molecular-weight heparin resolved her symptoms of headache and diplopia. The presence of genetic disorders such as the JAK2-V617F gene mutation should be assessed in patients with cerebral venous thrombosis and coexisting thrombocytosis.
Abducens Nerve Diseases ; Adult ; Brain ; Diplopia ; Female ; Headache ; Heparin, Low-Molecular-Weight ; Humans ; Janus Kinase 2 ; Magnetic Resonance Imaging ; Pregnancy ; Thrombocytosis ; Venous Thrombosis