OBJECTIVESTo observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH).

METHODSA total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment.

RESULTSAfter 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05).

CONCLUSIONMQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Adiponectin ; metabolism ; Adult ; Blood Coagulation Factors ; metabolism ; Bone Density ; drug effects ; Bone Morphogenetic Protein 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Femur Head Necrosis ; blood ; drug therapy ; physiopathology ; Humans ; Male

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The finding that cellular microparticles (MPs) generated by injured cells profoundly impact on pathological courses of TBI has paved the way for new diagnostic and therapeutic strategies. MPs are subcellular fragments or organelles that serve as carriers of lipids, adhesive receptors, cytokines, nucleic acids, and tissue-degrading enzymes that are unique to the parental cells. Their sub-micron sizes allow MPs to travel to areas that parental cells are unable to reach to exercise diverse biological functions. In this review, we summarize recent developments in identifying a casual role of MPs in the pathologies of TBI and suggest that MPs serve as a new class of therapeutic targets for the prevention and treatment of TBI and associated systemic complications.
Animals ; Astrocytes ; metabolism ; pathology ; Biological Transport ; Blood Coagulation Factors ; genetics ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Injuries, Traumatic ; genetics ; metabolism ; pathology ; physiopathology ; Cell-Derived Microparticles ; chemistry ; metabolism ; pathology ; Cytokines ; blood ; genetics ; Disease Models, Animal ; Disseminated Intravascular Coagulation ; genetics ; metabolism ; pathology ; physiopathology ; Gene Expression Regulation ; Humans ; Microglia ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Signal Transduction

BACKGROUND: High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). METHODS: PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). RESULTS: The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (> or =200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (> or =240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. CONCLUSION: High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.
Adult ; Aged ; Blood Coagulation Factors/metabolism ; *Blood Coagulation Tests ; Cholesterol/blood ; Female ; Humans ; Linear Models ; Lipids/*blood ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Reproducibility of Results ; Thrombin/metabolism ; Triglycerides/blood

Hypercoagulable state and thrombosis are major lethal causes of ulcerate colitis (UC). The aim of the present study is to explore the change and role of protein C (PC) system in UC thrombosis. 4% dextran sulfate sodium (DSS) was used to induce the UC model, and the body weight, the length of colon, and the weight of spleen were measured after intake of DSS as drinking water for 1 week. The macroscore and microscore were examined. The quantity of macrophage in colon smooth muscle was observed by immunofluorescence, and TNF-α and IL-6 levels in plasma were evaluated by ELISA. Intravital microscopy was applied to observe colonic mucosal microvascular circulation, activities of PC and protein S (PS) were determined by immunoturbidimetry, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) expressions were detected by immunohistochemistry. In vitro, TNF-α and IL-6 levels were tested in supernatant of macrophage separated from colonic tissue. After stimulation of mouse colonic mucosa microvascular endothelial cells by TNF-α and IL-6 respectively, the activities of PC, PS, activated protein C (APC) were evaluated, and the expressions of EPCR and TM were detected by Western blotting. The results revealed that compared with control, the DSS mouse showed weight loss (P < 0.05), a shortened colon (P < 0.05), and swelled spleen (P < 0.05), accompanied by higher histological score (P < 0.05), as well as infiltration of macrophages, elevated TNF-α and IL-6 levels in plasma (P < 0.01). The intravital microscopy results revealed that compared with control, DSS mice showed significantly enhanced adhesion of leukocytes and colonic mucosal microvascular endothelial cells (P < 0.01), meanwhile, decreased activity of PC and PS in plasma (P < 0.01 or P < 0.05), and down-regulated expression of EPCR (P < 0.01). The degree of inflammation was negatively correlated with the PC activity. In vitro, TNF-α and IL-6 levels were increased in the supernatant of macrophages from DSS mice colonic tissue (P < 0.05), and after incubation of TNF-α or IL-6 with colonic mucosal microvascular endothelial cells, the APC activity was decreased (P < 0.05 or P < 0.01), and expression of EPCR was down regulated (P < 0.05). These results suggest that PC system is inhibited in UC mouse. Presumably, the mechanism may be due to the secretion of cytokines from macrophages and subsequential influence on the function of endothelia cells. Furthermore, enhancement of PC system activity may serve as a new strategy for the treatment of UC.
Animals ; Blood Coagulation Factors ; metabolism ; Colitis, Ulcerative ; chemically induced ; physiopathology ; Dextran Sulfate ; Immunohistochemistry ; Inflammation ; Interleukin-6 ; blood ; Intestinal Mucosa ; pathology ; Macrophages ; cytology ; Mice ; Protein C ; metabolism ; Receptors, Cell Surface ; metabolism ; Spleen ; pathology ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.
4-Hydroxycoumarins/*poisoning ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking/adverse effects/blood ; Anticoagulants/*poisoning ; Blood Coagulation/*drug effects ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Rodenticides/*poisoning ; Serum Albumin/metabolism ; Vitamin K/*blood ; Vitamin K Deficiency Bleeding/blood/*chemically induced/diagnosis/therapy ; Young Adult

BACKGROUND: Gestational diabetes mellitus (GDM) is a hyperglycemic condition caused by increased insulin resistance and impaired insulin secretion during pregnancy. It is known to be temporary, but it can cause perinatal complications in the mother and baby. Additionally, it may progress to type 2 diabetes mellitus (T2DM). In the present study, we evaluated the risk factors for complications and progression to T2DM in patients with GDM. METHODS: The study included 130 pregnant women who were diagnosed with GDM at gestational weeks 24-28 in 2011. Body mass index and the levels of glucose, total cholesterol, lipoproteins, and coagulation factors (von Willebrand factor and plasminogen activator inhibitor-1) were assessed in all patients. RESULTS: The level of high-density lipoprotein (HDL) was significantly lower and the triglyceride/HDL ratio and coagulation factor levels were significantly higher in the group of patients with perinatal complications compared to those in the group of patients without complications. After delivery, the level of HDL was lower and the value of homeostasis model assessment of insulin resistance (HOMA-IR) was higher in women with impaired glucose metabolism compared to those in women with normal glucose metabolism. In logistic regression analysis, perinatal complications were independently associated with HDL and PAI-1 levels (OR = 0.929 and 1.101, respectively). CONCLUSION: The findings of our study show that the levels of HDL and coagulation factors are notable risk factors of perinatal complications. Additionally, we showed that lower HDL level may influence the progression to T2DM. Large-scale population studies are needed to verify our findings.
Blood Coagulation Factors ; Body Mass Index ; Cholesterol ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Diabetes, Gestational* ; Female ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Lipoproteins ; Lipoproteins, HDL ; Logistic Models ; Metabolism ; Mothers ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Postpartum Period* ; Pregnancy ; Pregnant Women ; Risk Factors* ; von Willebrand Factor

OBJECTIVETo investigate the correlation between pro coagulation factors and anti-coagulation factors synthesized by the liver, and the correlation between fibrin degradation products (FDP) and D-dimer (D-D) concentration and coagulation proteins synthesized by extra-hepatic tissues, in different liver diseases; to explore the relationship between coagulation and bleeding in hepatic diseases.

METHODSChronic hepatitis B (CHB) patients, CHB-related liver cirrhosis patients, CHB-related liver failure patients and healthy (normal) controls were selected for study and provided blood samples for analysis. The activity of coagulation factors (F) II, V, VII, VIII, IX, X, XI, and XII was detected using the one-stage clotting method. Coagulogram analysis, including activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT), was conducted by the solidification method. Antithrombin III (AT-III) and protein C (PC) activities were measured by chromogenic substrate assay. FDP concentration was detected using immunoturbidimetry. Tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), von Willebrand factor (vWF), and tissue factor (TF) concentrations were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTSWith the exception of FVIII, coagulation factors and anticoagulant proteins synthesized by the liver were decreased and the coagulogram was extended for all patients. Likewise, the FDP and D-D concentrations were increased in blood. CHB patients, however, presented with increased levels of FVIII, TFPI, TM, vWF, and TF. Pairwise comparison indicated statistical differences existed among CHB, CHB-related liver cirrhosis, and liver failure patients: TFPI: 239.3+/-206.4, 315.0+/-258.6, and 319.5+/-298.1 -- higher than normal control: 104.0+/-87.1, F = 5.453, P less than 0.05; vWF: 70.3+/-29.5, 105.5+/-58.0, and 179.3+/-61.7 -- higher than normal control: 21.9+/-7.2, F = 20.104, P less than 0.05; TF: 85.9+/-85.7, 234.2+/-202.9, and 344.7+/-214.6 -- higher than normal control: 12.8+/-8.1, F = 8.619, P less than 0.05; FVIII: 157.2+/-53.4, 206.9+/-86.9, and 335.7+/-117.7 -- higher than normal control: 105.5+/-46.2, F = 13.418, P less than 0.05.

CONCLUSIONIn parallel to the progression of liver diseases, pro coagulation and anti-coagulation elements synthesized by the liver were reduced. In contrast, fibrinolysis activity was enhanced, which is expected to lead to an imbalance between blood clotting and anti-clotting factors. This may be an important cause for the bleeding that occurs in end-stage liver disease. Expressions of TFPI, TM, vWF, and TF significantly change in the early stage of liver diseases, as compared to normal (healthy) levels, and may represent a sensitive indicator of vascular injury.

Adult ; Aged ; Antithrombin III ; metabolism ; Blood Coagulation Factors ; metabolism ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Hepatic Insufficiency ; blood ; physiopathology ; Hepatitis B, Chronic ; blood ; physiopathology ; Humans ; Hydrocarbons, Chlorinated ; metabolism ; Lipoproteins ; metabolism ; Male ; Middle Aged ; Young Adult ; von Willebrand Factor ; metabolism

OBJECTIVETo study the hemostatic effect of chemical constituents from Callicarpa nudiflora.

METHODThe chemical constituents were isolated and purified via silica gel and Sephadex LH-20 column chromatography. Their structures were determined on the basis of spectral analysis. prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB) of the constituents rabbit blood samples were tested with rabbit blood in vitro.

RESULTEleven compounds were isolated and identified as two diterpenens: 7alpha-hydroxy sandaracopimaric acid (1), 16, 17-dihydroxy-3-oxophyllocladane (2). Two phenoic glycosides: acteoside (3), samioside(4). Three triterpenes: 2alpha, 3alpha, 24-trihydroxy-ursa-12-en-28-oic acid (5), 2alpha, 3alpha, 19alpha-trihydroxyursa-12-en-28-oic acid-28-0-beta-D-glucopyranosyl ester (6), and 2alpha, 3alpha, 19alpha, 23-tetrahydroxy-ursa-12-en-28-oic acid-28-0-beta-D-glucopyranosyl ester (7). Four flavones: rhamnazin (8), 5-Hydroxy-3, 7, 4'-trimethoxy-flavone (9) , 5-Hydroxy-3, 7, 3', 4'-tetramethoxyflavone (10), and luteoloside (11). All Compounds cannot significantly shorten the PT (P < 0.01), compounds 3, 4, 7, 10 can remarkedly increase APTT (P < 0.01), compound 5 can prolong the T( P < 0.01) obviously, and compound 8 can significantly increase the contents of FIB (P < 0.01).

CONCLUSIONCompounds 2, 4 and 10 were isolated from this genus for the first time, and compounds 1, 3, 5, 6, 7 and 9 had been isolated from this plant for the first time. The hemostatic effect of C. nudiflora may be related to the activation of the intrinsic blood coagulation system.

Animals ; Blood Coagulation Factors ; metabolism ; Callicarpa ; chemistry ; Hemostasis ; drug effects ; Male ; Organic Chemicals ; analysis ; pharmacology ; Rabbits

OBJECTIVETo explore the expression of CD34 in patients with acute promyelocytic leukemia (APL) and investigate the clinical and laboratory features of CD34(+) APL patients.

METHODS262 APL patients diagnosed by chromosome analysis and/or fusion gene examination in the last five years were retrospectively analyzed in this study. To survey the expression of CD34 in those patients, all the cases were divided into two groups (CD34(+) APL vs. CD34(-) APL). The clinical features including age, gender, abnormal values of the peripheral hemogram before treatment, the complete remission (CR) rate and the incidence of DIC and laboratory data such as the results of morphology, immunology, cytogenetics and molecular biology (MICM) between those two groups were compared.

RESULTSOf the 262 APL patients, 38 (14.5%) cases were positive for CD34 expression. There were no statistically significant differences between CD34(+) APL and CD34(-) APL groups in gender and age (P > 0.05). Before treatment, the median level of WBC in CD34(+) APL was 25.92 x 10(9)/L, which was significantly higher than that of CD34(-) APL (5.3 x 10(9)/L, P < 0.05). CD34(+) APL by morphology classification were mostly of the subtypes M3b and M3v (65.8%), while these subtypes in CD34(-) APL (40.3%) were significantly less (P < 0.01). There were no statistically significant differences between the two groups compared in respect of complete remission (CR) rate and the incidence of DIC (P > 0.05). The expression level of CD34 in APL had correlation to the expression level of CD2, CD7 and CD117; the latter three phenotypes in CD34(+) APL were significantly higher than those in CD34(-) APL (P < 0.01). No significant difference was found between those two groups by chromosome analysis, but there was more PML-RAR-alpha transcript short form in CD34(+) APL than that in CD34(-) APL (P < 0.05).

CONCLUSIONCD34(+) acute promyelocytic leukemia is a unique subtype of APL with different biological characteristics.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; blood ; Antigens, CD7 ; blood ; Antineoplastic Agents ; therapeutic use ; CD2 Antigens ; blood ; Child ; Disseminated Intravascular Coagulation ; etiology ; Female ; Humans ; Immunophenotyping ; Leukemia, Promyelocytic, Acute ; complications ; drug therapy ; genetics ; immunology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Phenotype ; Promyelocytic Leukemia Protein ; Proto-Oncogene Proteins c-kit ; blood ; Receptors, Retinoic Acid ; metabolism ; Remission Induction ; Retinoic Acid Receptor alpha ; Retrospective Studies ; Transcription Factors ; metabolism ; Translocation, Genetic ; Tretinoin ; therapeutic use ; Tumor Suppressor Proteins ; metabolism ; Young Adult

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection.
Acute Disease ; Blood Coagulation Factors/metabolism ; Child, Preschool ; Hepatitis A/blood/diagnosis/*etiology ; Humans ; Male ; Mycoplasma pneumoniae/pathogenicity ; Partial Thromboplastin Time ; Pneumonia, Mycoplasma/blood/*complications