BACKGROUND/AIMS: This study aimed to investigate the risk factors associated with provoked pulmonary embolism (PE). METHODS: This retrospective cohort study included 237 patients with PE. Patients that had transient risk factors at diagnosis were classified as having provoked PE, with the remaining patients being classified as having unprovoked PE. The baseline clinical characteristics and factors associated with coagulation were compared. We evaluated the risk factors associated with provoked PE. RESULTS: Of the 237 PE patients, 73 (30.8%) had provoked PE. The rate of respiratory failure and infection, as well as the disseminated intravascular coagulation score and ratio of right ventricular diameter to left ventricular diameter were significantly higher in patients with provoked PE than in those with unprovoked PE. The protein and activity levels associated with coagulation, including protein C antigen, protein S antigen, protein S activity, anti-thrombin III antigen, and factor VIII, were significantly lower in patients with provoked PE than in those with unprovoked PE. Multivariate analysis showed that infection (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 7.4) and protein S activity (OR, 0.97; 95% CI, 0.95 to 0.99) were significantly associated with provoked PE. CONCLUSIONS: Protein S activity and presence of infection were important factors associated with provoked PE. We should pay attention to the presence of infection in patients with provoked PE.
Cohort Studies ; Diagnosis ; Disseminated Intravascular Coagulation ; Factor VIII ; Humans ; Multivariate Analysis ; Protein C ; Protein S ; Pulmonary Embolism* ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors*

OBJECTIVETo assess the value of thrombotic biomarkers in estimation of venous thromboembolism (VTE) risk in cancer patients.

METHODSA total of 1473 cancer patients treated in the Tianjin Medical University General Hospital from 2009 to 201 were selected, including 845 males and 628 females in the age of 56 ± 17 years. The activities of von Willebrand factor antigen (vWF:Ag), factor VII (F VII:A), factor VIII (F VIII:A), antithrombin (AT:A), protein C (PC:A) and protein S (PS:A) were assayed using an ACL TOP 700 blood coagulation analyzer. The level of D-dimer (D-D) was assayed using the Biomerieux Mini Vidas Automated Immunoassay Analyzer. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic performance of the parameters. Cox regression analysis model was applied to evaluate the effect on prognosis, and Kaplan-Meier curve was used to implement the survival analysis.

RESULTSThe levels of vWF:Ag, D-D, and F VIII:A were significantly higher in all the specified tumor groups ( except the other tumor group ) than that of the control groups (P < 0.05). F VIII:A was significantly higher than that in the control group in all tumor groups except the renal carcinoma, prostatic cancer, lymphoma groups and the other tumor group (P < 0.05). The PC:A level was significantly lower in all tumor patients groups than in the control group, except glioma, breast cancer, gastric carcinoma, renal carcinoma and the other tumors groups (P < 0.05). The PS: A level was significantly lower in all tumor groups than in the control group, except the glioma, breast cancer, prostatic cancer, lymphoma and the other tumors groups (P<0.05). The AT: A level was significantly lower in all tumor groups than in the control group (P<0.05). When the optimum cut-off point of vWF:Ag for VTE diagnosis was 192% in the cancer group, the area under ROC curve = 0.828 (95% CI: 0.716 to 0.939). When the optimum cut-off point of D-dimer for VTE diagnosis was 1484 ng/ml in the cancer group, the area under ROC curve = 0.915 (95% confidence interval: 0. 840 to 0.988). When the optimum cut-off point of PC: A for VTE diagnosis was 75.2% in the cancer group, the area under ROC curve = 0.764 (95% confidence interval: 0.630 to 0.898). The Cox analysis showed that age, surgery, chemotherapy and D-dimer were independent risk factors for VTE event within three months in cancer patients. The cumulative probability of VTE was increased significantly in the cancer patients if whose plasma D-dimer level was over the cut-off value.

CONCLUSIONSThe plasma D-dimer level is obviously increased in cancer patients, and there is a relevance to thrombosis risk stratification and VTE cumulative probability. It is with good diagnostic performance, and may be used as an effective marker in estimation of VTE risk within 3 months in cancer patients.

Aged ; Antithrombins ; blood ; Biomarkers ; blood ; Factor VII ; analysis ; Factor VIII ; analysis ; Female ; Fibrin Fibrinogen Degradation Products ; Humans ; Male ; Middle Aged ; Neoplasms ; blood ; Prognosis ; Protein C ; analysis ; Protein S ; analysis ; ROC Curve ; Regression Analysis ; Risk Assessment ; Risk Factors ; Venous Thromboembolism ; etiology ; von Willebrand Factor ; analysis

Protein S (PS), a vitamin K-dependent glycoprotein, performs an important role in the anticoagulation cascade as a cofactor of protein C. Because of the presence of a pseudogene and two different forms of PS in the plasma, protein S deficiency (PSD) is one of the most difficult thrombophilias to study and a rare blood disorder associated with an increased risk of thrombosis. We describe a unusual case of previously healthy 37-year-old man diagnosed with portal-splenic-mesenteric vein thrombosis secondary to PSD. The patient was admitted to the hospital due to continuous nonspecific abdominal pain and nausea. Abdominal computed tomography revealed acute venous thrombosis from inferior mesenteric vein to left portal vein via splenic vein, and laboratory test revealed decreased PS antigen level and PS functional activity. Conventional polymerase chain reaction and direct DNA sequencing analysis of the PROS1 gene demonstrated duplication of the 166th base in exon 2 resulting in frame-shift mutation (p.Arg56Lysfs*10) which is the first description of the new PROS1 gene mutation to our knowledge. Results from other studies suggest that the inherited PSD due to a PROS1 gene mutation may cause venous thrombosis in a healthy young man without any known predisposing factor.
Adult ; Anticoagulants/therapeutic use ; Base Sequence ; Blood Proteins/*genetics ; Codon, Terminator ; Exons ; Humans ; Male ; Mesenteric Veins/radiography ; Polymorphism, Restriction Fragment Length ; Portal Vein/radiography ; Protein S Deficiency/complications/*diagnosis ; Sequence Analysis, DNA ; Splenic Vein/radiography ; Tomography, X-Ray Computed ; Venous Thrombosis/*diagnosis/drug therapy/etiology

BACKGROUND: Dysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population. METHODS: Part 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome. RESULTS: Antithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high. CONCLUSIONS: Decreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.
Adult ; Aged ; Anticoagulants/*blood ; Antithrombins/*blood ; Blood Platelets/cytology ; Blood Proteins/analysis ; Disseminated Intravascular Coagulation/complications/*diagnosis/mortality ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Humans ; Male ; Middle Aged ; Platelet Count ; Prognosis ; Protein C/*analysis ; Protein S/analysis ; Prothrombin Time ; Regression Analysis ; Sepsis/complications/*diagnosis ; Severity of Illness Index

Vascular access thrombosis is one of the major causes of morbidity in patients maintained on chronic hemodialysis. Thrombophilia has been recognized as a risk factor of vascular access thrombosis. The authors report a case of inherited protein S deficiency associated with vascular access thrombotic events. DNA sequence analysis of the PROS1 gene identified a novel heterozygous nonsense mutation in exon 10 by transition of AAG (lysine) to TAG (stop codon) at codon 473 (c.1417A>T, p.K473X). Results from the study suggest that the inherited protein S deficiency due to a PROS1 gene mutation may cause vascular access thrombosis in hemodialysis patients.
Codon ; Codon, Nonsense ; Exons ; Humans ; Protein S ; Protein S Deficiency ; Renal Dialysis ; Risk Factors ; Sequence Analysis, DNA ; Thrombophilia ; Thrombosis

PURPOSE: Hyperhomocysteinemia is accepted as an independent risk factor for peripheral arterial disease (PAD). The purpose of this study is to evaluate the correlation between the preoperative plasma homocysteine concentration and restenosis after therapeutic revascularization. METHODS: We retrospectively analyzed the clinical records of 58 consecutive patients (they were confined to Trans Atlantic Inter-Society Consensus [TASC] type C & D) among 103 patients who were diagnosed as having infrainguinal PAD and who were treated with bypass surgery or endovascular surgery from July 2003 to July 2009. We analyzed the effect of several factors such as gender, age, the plasma lipid profile and the protein C, protein S, fibrinogen, C-reactive protein, diabetes mellitus, hypertension, ankle-brachial index (ABI), and homocysteine levels, which are all considered to be risk factors for restenosis. Multivariate and univariate analyses were performed to assess the effect of possible confounders. RESULTS: The subjects were 50 men and 8 women (mean age: 63.8+/-10.9). There were 33 (56.9%) cases of bypass surgery and 25 (43.1%) cases of endovascular surgery. Of them, 19 cases (32.8%) showed restenosis after revascularization. In the patients with restenosis, 18 cases (94.7%) showed a preoperative high plasma homocysteine level and 1 case (5.2%) showed a normal level. A lower ABI and hyperhomocysteinemia were significantly more common in the patients with restenosis (P=0.025, P<0.001). There were no significant differences of the other factors, except for the plasma homocysteine level on multivariate analysis (P=0.001). CONCLUSION: We can regard the preoperative hyperhomocysteinemia level as a predictive marker of restenosis after revascularization. Special attention may need to be given to the patients who have a lower preoperative ABI and hyperhomocysteinemia after revascularization.
Ankle Brachial Index ; C-Reactive Protein ; Consensus ; Diabetes Mellitus ; Female ; Fibrinogen ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Hypertension ; Male ; Multivariate Analysis ; Peripheral Arterial Disease ; Plasma ; Protein C ; Protein S ; Retrospective Studies ; Risk Factors

A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531x10(9)/L. The patient was anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day, oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and LMWH was discontinued at third hospital day. On the third day of oral anticoagulation therapy, he complained of left leg swelling and prolonged painful penile erection of 24 hr-duration. His platelet count reached a nadir 164x10(9)/L at that time, and the patient had a deficiency of protein C and S, with an activity level of 16% and 20% of normal value. Warfarin was stopped and he underwent penile aspiration. The next day, left leg edema and penile erection was disappeared, but penile and glans penis necrosis was started. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis.
Adenocarcinoma/complications/diagnosis ; Anticoagulants/*adverse effects ; Heparin/*adverse effects ; Humans ; Lung Neoplasms/complications/diagnosis ; Male ; Middle Aged ; Necrosis ; Penile Erection/drug effects ; Penis/*pathology ; Platelet Count ; Protein C/analysis ; Protein S/analysis ; Pulmonary Artery ; Thrombocytopenia/*chemically induced ; Thrombosis/complications/diagnosis/drug therapy ; Warfarin/*adverse effects

BACKGROUND: Pulmonary embolism (PE) is a common clinical problem in the West that is associated with substantial morbidity and mortality. The diagnostic modality has been changed since 2001. This study retrospectively reviewed the PE mortality with the aim of identifying the risk factors associated with mortality since the multidetector computed tomography (MDCT) was introduced. METHODS: We analyzed 105 patients with acute PE proven by multidetector CT or ventilation perfusion scan. The primary outcome measure was the all-cause mortality at 3 months. The prognostic effect of the baseline factors on survival was assessed by multivariate analysis. RESULTS: The main risk factors were prolonged immobilization, stroke, cancer and obesity. Forty nine percent of patients had 3 or more risk factors. The overall mortality at 3 months was 18.1%. Multivariate analysis revealed low diastolic blood pressure and the existence of cancer to be independent factors significantly associated with mortality. Forty two PE patients were examined for the coagulation inhibitors. Four of these patients had a protein C deficiency (9.5%), and 11 had a protein S deficiency (26%). CONCLUSION: PE is an important clinical problem with a high mortality rate. Close monitoring may be necessary in patients with the risk factors.
Blood Pressure ; Hospitals, Teaching ; Humans ; Immobilization ; Multidetector Computed Tomography ; Multivariate Analysis ; Obesity ; Outcome Assessment (Health Care) ; Perfusion ; Prognosis ; Protein C Deficiency ; Protein S Deficiency ; Pulmonary Embolism ; Retrospective Studies ; Risk Factors ; Stroke ; Thrombophilia ; Venous Thrombosis ; Ventilation

BACKGROUND: The multidrug resistance (mdr1), multidrug resistance associated protein (mrp1), and glutathione-s-transferase (gst) pi genes have been associated with treatment failure in acute myeloid leukemia (AML). c-jun N-terminal kinase (JNK) activity is increased in response to chemotherapeutic agent. METHODS: To investigate the significance of multidrug resistance (mdr) parameters and JNK activity, bone marrow or peripheral blood cells from 52 patients with AML were analyzed. RT-PCR was performed for mdr1, mrp1, and gst pi gene expression. JNK expression and activity were measured using an immunoe- nzymatic kinase assay and a western blot method. RESULTS: High level expression of mdr1, mrp1, and gst pi mRNA was observed in 38.5%, 48.1% and 54.3% of AML cases, respectively. The remission rate was significantly low in cases with an older age (>55 yr), a high WBC count, poor chromosomal abnormalities, a high level expression of mdr1 and mrp1. The WBC count and mdr1 mRNA expression were independent predictors for the outcome to induction chemotherapy. There was a shorter duration of overall survival in the patients with an older age, a high WBC count, chromosome aberrations, high level expressions of mdr1 and mrp1 mRNA, and JNK activation. The patient's age, WBC count and chromosomal abnormalities were independent predictors for overall survivals. The majority (28/30) of AML cases did not show any levels of JNK activation except for two cases, which were associated with an extremely high WBC count, chromosomal aberration, high level expressions of mdr1, mrp1 and gst pi mRNA, and treatment resistance. CONCLUSIONS: These data indicate the influences of mdr1 and mrp1 mRNA expression on the clinical outcome of AML to induction chemotherapy. But it will be necessary to investigate further whether blast cells of AML resistant to chemotherapy retain the capacity to activate JNK, and relate to MDR parameters.
Adolescent ; Adult ; Aged ; *Drug Resistance, Multiple/genetics ; *Drug Resistance, Neoplasm/genetics ; Female ; Glutathione S-Transferase pi/genetics ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Leukemia, Myeloid, Acute/*drug therapy/genetics/metabolism ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins/genetics ; P-Glycoprotein/genetics ; RNA, Messenger/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Analysis ; Treatment Outcome

OBJECTIVETo study the relation between histopathologic grading and some of the cytogenetic and molecular biology characteristics of breast cancer.

METHODSOn the basis of estrogen receptor (ER) expression, DNA content, S-phase fraction (SPF), bcl-2 and mutant p53 protein (mtp53) expression were examined by FCM in 121 breast cancer patients. In 66 patients with invasive ductal breast cancer, histopathologic grading was also examined.

RESULTSThe aneuploidy rate and DNA index (DI) were significantly different in grade I, II and III breast cancer. SPF and mtp53 expression significantly increased with increase in histopathologic grading (P < 0.05), but bcl-2 did not show this trend. SPF and mtp53 expression were significantly more in breast cancer with negative ER than in those with positive ER (P < 0.05). Again, no such differences in bcl-2 regardless of ER expression. Correlations existed between DI vs SPF, DI vs mtp53, and SPF vs mtp53 expressions (P < 0.01) but bcl-2 did not correlate with any one of them.

CONCLUSIONCytogenetic and molecular biology studies on the basis of histopathologic grading may provide more information in prognostic prediction of breast cancer.

Adolescent ; Adult ; Aneuploidy ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; DNA, Neoplasm ; analysis ; Female ; Flow Cytometry ; Humans ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Receptors, Estrogen ; biosynthesis ; genetics ; S Phase ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics