OBJECTIVE: This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity. METHODS: Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed. RESULTS: CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model. CONCLUSION These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.
Animals ; Blood Chemical Analysis ; Carbon Tetrachloride ; toxicity ; Hepcidins ; pharmacology ; Injections, Intraperitoneal ; Interleukin-6 ; pharmacology ; Iron ; blood ; metabolism ; Leukocytosis ; chemically induced ; therapy ; Liver Cirrhosis ; chemically induced ; therapy ; Male ; Rats ; Thioacetamide ; toxicity ; Thrombocytopenia ; chemically induced ; therapy ; Transferrin ; metabolism

OBJECTIVE: To investigate the incidence for heparin-induced thrombocytopenia (HIT) in patients undergoing cardiac surgery and to evaluate the risk factors for the generation of HIT-antibody.
 METHODS: A total of 315 patients undergoing cardiac surgery in the Department of Cardiothoracic Surgery, Xiangya Hospital between December, 2013 and July, 2014 were enrolled for this study. Among them, 120, 154 and 41 were for surgery of congenital heart defect, valve and coronary artery bypass graft, respectively. There were 170 male patients and 69 patients were under 18 years old. Platelet counts, HIT-antibody and concentration of platelet factor 4 (PF4) were tested before and after the surgery. Diagnosis of HIT was based on "4Ts" (Pretest Clinical Scoring System). 
 RESULTS: HIT was diagnosed in 11 patients (3.5%, 11/315). And thromboembolic events occurred in 2 of 11 patients with HIT. The positive ratio for HIT-antibody was 36.5% (115/315). The coronary artery disease patients had a higher incidence of HIT than that of either the valve disease or the congenital heart defect (17.1%, 7/41 versus 1.9%, 3/154 or 0.8%, 1/120; P<0.05). The congenital heart defect patients had a higher positive ratio for HIT-antibody than that of both the valve disease and the coronary artery disease. The valve disease patients had a higher positive ratio for HIT-antibody than that of the coronary artery disease (51.7%, 62/120 versus 30.5%, 47/154 versus 14.6%, 6/41; P<0.05). Major postoperative complications occurred more frequently in HIT patients (36.4%, 4/11 versus 10.5%, 32/304; P<0.05). Age was a risk factor for HIT (P=0.030, OR=1.083, 95% CI 1.008-1.163). Cardiopulmonary bypass (CPB) (P=0.037, OR=3.113, 95% CI 1.071-9.050) and age (P<0.001, OR=0.970, 95% CI 0.959-0.982) were risk factors for HIT-antibody.
 CONCLUSION The incidence of HIT is low during cardiac surgery, but HIT is a highly risk factor for the major postoperative complications. More attentions should be paid to these severe complications and the risk factors for HIT.
Antibodies ; blood ; Cardiac Surgical Procedures ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; Female ; Heparin ; adverse effects ; Humans ; Incidence ; Male ; Platelet Count ; Platelet Factor 4 ; blood ; Postoperative Complications ; Risk Factors ; Thrombocytopenia ; chemically induced

Aged ; Cross Reactions ; Female ; Heparin ; adverse effects ; immunology ; Heparin, Low-Molecular-Weight ; adverse effects ; immunology ; Humans ; Male ; Middle Aged ; Platelet Factor 4 ; immunology ; Thrombocytopenia ; blood ; chemically induced ; immunology

Acute amiodarone toxicity after a single dose of intravenous amiodarone is very rarely seen. We report the case of a 64-year-old Chinese man who presented with atrial fibrillation and fluid overload due to congestive cardiac failure. He was treated with a single bolus dose of intravenous amiodarone, after which he developed elevated serum transaminases, coagulopathy, thrombocytopenia and acute renal failure. His parameters returned to normal after 25 days and his recovery was uneventful.
Acute Kidney Injury ; chemically induced ; Amiodarone ; adverse effects ; Anti-Arrhythmia Agents ; adverse effects ; Atrial Fibrillation ; drug therapy ; Blood Coagulation Disorders ; chemically induced ; Heart Failure ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Thrombocytopenia ; chemically induced ; Transaminases ; blood ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients.

METHODS24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC).

RESULTSThe lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected.

CONCLUSIONProphylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.

Adenocarcinoma ; blood ; drug therapy ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Area Under Curve ; Carboplatin ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; blood ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy and safety of domestically manufactured recombinant human thrombopoietin (rhTPO) in the treatment for chemotherapy-induced thrombocytopenia in patients with solid tumors.

METHODSA non-randomized controlled study was conducted. Seventy-two patients with platelet count < 75 x 10(9)/L after chemotherapy were enrolled into this study according to the standard criteria of NCI-CTC toxicity stratification. Thirty-five patients in the treatment-group received subcutaneous injection of rhTPO at a dose of 15,000 U/d, another 37 patients in the control group received subcutaneous injection of rhIL-11a at a dose of 3 mg/d as the paralleled control.

RESULTSThe mean minimal platelet count after rhTPO treatment was (46.2 +/- 20.3) x 10(9)/L in the treatment-group versus (37.2 +/- 16.7) x 10(9)/L in the control-group (P < 0.05), while the mean maximal platelet count was (250.2 +/- 159.0) x 10(9)/L versus (160.5 +/- 96.4) x 10(9)/L (P < 0.05). The incidence rate of adverse effects and duration of grade III and IV thrombocytopenia in the treatment-group was also significantly lower than those in the control-group. Furthermore, the patients receiving platelet transfusion were 4/35 in the treatment-group versus 11/37 in the control-group (P > 0.05). The side-effect rate in the treatment-group was significantly lower than that in the control-group (11.4% versus 78.4%, P < 0.01).

CONCLUSIONCompared with rhIL-11, administration of rhTPO after chemotherapy is safe and effective with mild adverse effects in reducing the degree and duration of thrombocytopenia.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; blood ; drug therapy ; Female ; Fever ; chemically induced ; Headache ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment for chemotherapy-induced thrombocytopenia in patients with lung cancer.

METHODSFifty-one lung cancer patients with platelet count < 100 x 10(9)/L after chemotherapy were enrolled into this study. They were divided into three groups: mild, moderate and severe thrombocytopenia groups according to the platelet count. rhTPO was subcutaneously administered at a dosage of 300 microg kg(-1) d(-1) until the platelet count >or= 100 x 10(9)/L or absolute value of platelet count >or= 50 x 10(9)/L. Laboratory tests included routine blood count, serum biochemistry, and blood coagulation test.

RESULTSThe duration of the chemotherapy-induced thrombocytopenia was significantly shorter in the mild group than that in the moderate and severe groups (P < 0.01). After administration of rhTPO, the time of declined platelet count beginning to recover was also significantly shorter in the mild group than that in the moderate and severe groups (P < 0.01). There was a statistically significant difference in platelet transfusion needed among the three groups (P < 0.01). However, no significant difference was found among the three groups in the time of rhTPO treatment (P > 0.05) and platelet count improvement (P > 0.05).

CONCLUSIONRecombinant human thrombopoietin can be effectively and safely administered to deal with grade III/IV chemotherapy-induced thrombocytopenia in lung cancer patients with mild adverse effects.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Platelet Transfusion ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; therapy ; Thrombopoietin ; adverse effects ; therapeutic use

OBJECTIVETo investigate the relationship between peak concentration (Cmax) of gemcitabine at fixed-dose-rate and its hematological toxicity profile in patients with advanced non-small-cell lung cancer (NSCLC).

METHODSTwenty-one patients received gemcitabine at a fixed dose rate (1200 mg/m2 over 120 min) with carboplatin. Plasma concentrations of gemcitabine were measured by ion-pair reversed-phase high-performance liquid chromatography.

RESULTSThe mean value of Cmax in 21 eligible patients was(4.95+/-2.42) microg *ml(-1). The main hematological toxicity was grade III-IV thrombocytopenia and neutropenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 patients were (38.3+/-38.1)%, (31.3+/-73.6)%, (31.8+/-53.5)% and (12.0+/-12.2)%, respectively. The C(max)of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r2=0.4575, P<0.05). A significant correlation (r2=0.5671, P<0.05) was also observed between the percentage of reduction of PLTC and Cmaxof gemcitabine.

CONCLUSIONThe results of relationship between Cmax and toxicity profile suggest that gemcitabine administration should be individualized in order to decrease the occurrence of ADR.

Adult ; Aged ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; pharmacokinetics ; therapeutic use ; Carboplatin ; adverse effects ; blood ; pharmacokinetics ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; Chromatography, High Pressure Liquid ; Deoxycytidine ; adverse effects ; analogs & derivatives ; blood ; pharmacokinetics ; Female ; Humans ; Infusions, Intravenous ; Lung Neoplasms ; drug therapy ; metabolism ; Male ; Metabolic Clearance Rate ; Middle Aged ; Neutropenia ; chemically induced ; Thrombocytopenia ; chemically induced

The study was aimed to investigate the value of activated plasma clotting time (APCT) for estimating the efficacy of platelet transfusion therapy. There were twenty patients with hematological diseases, who received transfusion of platelet, involved in the test. APCT was determined before and after transfusion of these patients, then APCT was contrasted with corresponding CCI and PPR. The results showed that 1 hour and 24 hour APCTs were shortened obviously. APCT before transfusion was (103.7 +/- 11.3) seconds, but the 1 hour and 24 hour APCTs were shortened to (60.0 +/- 9.7) seconds and (68.5 +/- 9.8) seconds respectively (P < 0.01). According to the judging criteria of CCI and PPR (CCI and PPR values at 1 and 24 hours after transfusion are < 7500, < 5000 and < 30%, < 20% respectively, the transfusion is invalid), two patients received invalid transfusion. Their 1 and 24 hour CCIs were 7415, 2966 and 6913, 4988 respectively. Their 1 and 24 hour PPRs were 28.0%, 11.2% and 25.2%, 14.1% respectively. One patient's PPR reached the standard of invalid transfusion, but his CCI showed a valid transfusion he received. Two patients' PPR reached the standard of invalid transfusion, but their 1 hour CCI reached the standard of valid transfusion, and their 24 hour CCI reached the standard of invalid transfusion. It is concluded that APCT reflects the variations of quantity and quality of platelet simultaneously, and can evaluate precisely the efficacy of platelet transfusion.
Adolescent ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Bleeding Time ; Blood Platelets ; physiology ; Female ; Humans ; Leukemia ; drug therapy ; therapy ; Male ; Middle Aged ; Myelodysplastic Syndromes ; therapy ; Partial Thromboplastin Time ; Platelet Count ; Platelet Transfusion ; adverse effects ; Thrombocytopenia ; chemically induced ; therapy ; Whole Blood Coagulation Time ; methods

OBJECTIVETo investigate the effectiveness, safety and possible mechanism of recombinate human interleukin 11 (rhIL-11) in the treatment of chemotherapy-induced thrombocytopenia.

METHODSThirty-four patients (totally 76 cycles) with chemotherapy-induced thrombocytopenia received subcutaneous injection of rhIL-11 at the dose of 25 microg.kg(-1).d(-1) for 4 to 16 days. Serum IL-11 level was measured by ELISA, and IL-11 R alpha expression was detected by RT-PCR.

RESULTSThe mean baseline platelet count before chemotherapy was (135.0 +/- 54.3) x 10(9)/L for the 1st cycle and (259.4 +/- 64.5) x 10(9)/L for the 2nd cycle. The time to administer rhIL-11 was 7 to 16 days (median 12 days) in the 1st cycle and 4 to 10 days (median 6 days) in the 2nd, respectively (P < 0.05). The duration of post-chemotherapy platelet count below 50 x 10(9)/L was 7 to 13 days (median 10 days) for the 1st cycle and 3 to 8 days (median 5 days) for the 2nd, respectively (P < 0.05). Platelet count reached 300 x 10(9)/L or above in 30 chemotherapy cycles. The maximum platelet count was found to appear at D10 to D 17 (median D14), and negatively correlated with the pre-chemotherapy serum IL-11 level after administration of rhIL-11. Major adverse reactions included edema, headache, muscle and joint pain.

CONCLUSIONrhIL-11 is effective and safe for the treatment of chemotherapy-induced thrombocytopenia, with a relatively slow but sustained effect on the recovery of platelet count. Pre-chemotherpy serum IL-11 level might predict the efficacy of rhIL-11.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Female ; Humans ; Injections, Subcutaneous ; Interleukin-11 ; administration & dosage ; adverse effects ; blood ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; drug therapy ; Treatment Outcome