Prognostic Value of Uric Acid for Pulmonary Thromboembolism.

BACKGROUND: Pulmonary thromboembolism is a serious cardiovascular condition with considerable morbidity and mortality. Clinical studies have indicated that hyperuricemia is an independent risk factor for cardiovascular events. The aim of this study was to investigate possible value of the serum levels of uric acid (UA) in predicting 30-d pulmonary thromboembolism-related mortality. METHODS: Pulmonary thromboembolism was confirmed by computed tomography pulmonary angiography, demographic data, troponin, systolic pressure and pulse on admission, and simplified pulmonary embolism severity index assessment. UA levels were analyzed on admission. The primary end point was all-cause mortality during the first 30 d. RESULTS: A total of 337 acute pulmonary thromboembolism subjects, of whom 59% were females, were enrolled. The median (interquartile range) serum UA level was 5.35 (4.1-7.3) mg/dL. Serum UA levels of deceased subjects were higher than those of alive subjects during the study period (6.9 [4.6-10.0] mg/dL vs 5.2 [4.1-7.0] mg/dL, P = .038). In the receiver operating characteristic analysis, the area under the curve was 0.650 (CI 0.732-0.960) for UA levels for all-cause mortality. A level of serum UA ≥ 5 mg/dL showed 73% sensitivity and 88% negative predictive value for all-cause 30-d mortality. A weak correlation was determined between the UA levels and age (r = 0.25, P < .001) and any troponin (r = 0.267, P < .001). Serum UA level was an independent predictor of short-term mortality in pulmonary thromboembolism (odds ratio 1.2, P = .002). CONCLUSIONS: Serum UA levels may be a potential biomarker for predicting outcome in patients with acute pulmonary thromboembolism.

Can be galectin-3 a novel marker in determining mortality in hemodialysis patients?

BACKGROUND: Cardiovascular (CV) mortality is common in hemodialysis (HD) patients. There are some difficulties involved in determining CV risk. Galectin-3 is a molecule with a demonstrated correlation with CV mortality and which is approved in the stratification of heart failure (HF) risk. The purpose of this study was to assess the previously uninvestigated relationship between galectin-3 and cardiac mortality in HD patients. METHODS: Two hundred ninety clinically stable HD patients aged over 18 and on a thrice-weekly intermittent HD program lasting >3 months and 30 healthy individuals were enrolled in this multi-center, prospective, observational study and monitored over 24 months. Blood specimens were collected at the start of the study for the measurement of galectin-3 and other biochemical parameters. At the end of the study, the relations between galectin-3 and other biochemical and demographic parameters and mortality were analyzed. RESULTS: Galectin-3 levels were significantly higher in the HD group compared to the control group (p < 0.001). All-cause mortality was observed in 63 (21%) patients. At multivariate Cox regression analysis, age, low albumin, low DBP, high galectin-3 and high HsCRP were identified as prognostic determinants of all-cause mortality, while age, low albumin, high galectin-3 and high SBP were identified as prognostic determinants of cardiac mortality. CONCLUSION: This study shows, for the first time in the literature, that galectin-3 may be a novel biomarker of cardiac mortality in HD patients. We think that, when supported by further studies, galectin-3 can be a promising biomarker in predicting cardiac mortality in HD patients.

The effects of spinal, inhalation, and total intravenous anesthetic techniques on ischemia-reperfusion injury in arthroscopic knee surgery.

PURPOSE: To compare the effects of different anesthesia techniques on tourniquet-related ischemia-reperfusion by measuring the levels of malondialdehyde (MDA), ischemia-modified albumin (IMA) and neuromuscular side effects. METHODS: Sixty ASAI-II patients undergoing arthroscopic knee surgery were randomised to three groups. In Group S, intrathecal anesthesia was administered using levobupivacaine. Anesthesia was induced and maintained with sevoflurane in Group I and TIVA with propofol in Group T. Blood samples were obtained before the induction of anesthesia (t1), 30 min after tourniquet inflation (t2), immediately before (t3), and 5 min (t4), 15 min (t5), 30 min (t 6), 1 h (t7), 2 h (t8), and 6 h (t9) after tourniquet release. RESULTS: MDA and IMA levels increased significantly compared with baseline values in Group S at t2-t 9 and t2-t7. MDA levels in Group T and Group I were significantly lower than those in Group S at t2-t8 and t2-t9. IMA levels in Group T were significantly lower than those in Group S at t2-t7. Postoperatively, a temporary 1/5 loss of strength in dorsiflexion of the ankle was observed in 3 patients in Group S and 1 in Group I. CONCLUSIONS: TIVA with propofol can make a positive contribution in tourniquet-related ischemia-reperfusion.

The effect of dexmedetomidine on oxidative stress during pneumoperitoneum.

PURPOSE: This study was intended to investigate the effect of dexmedetomidine on oxidative stress response in pneumoperitoneum established in rats. METHODS: Animals were randomized into three groups, group S: with no pneumoperitoneum, group P: with pneumoperitoneum established, and group D: given 100 mcg intraperitoneal dexmedetomidine 30 min before establishment of pneumoperitoneum. Plasma total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) activity were measured 30 min after conclusion of pneumoperitoneum. RESULTS: The mean TOS level was significantly higher in group P than in the other two groups, and the TOS level was significantly higher in group D than in group S (P < 0.05). Plasma TAS level was found to be lower in group P than in the other two groups, and the TAS level was lower in group D than in group S (P < 0.05). Consequently, the OSI was significantly higher in group P than in groups D and S (P < 0.05). CONCLUSIONS: Ischemia-reperfusion phenomenon that occurs during pneumoperitoneum causes oxidative stress and consumption of plasma antioxidants. Dexmedetomidine decreases oxidative stress caused by pneumoperitoneum and strengthens the antioxidant defense system.

The Diagnostic Value of ß-Human Chorionic Gonadotropin, Progesterone, and Ischemia-Modified Albumin and Their Combined Use in the Prediction of First Trimester Abortions.

Objective. To investigate serum levels of free ß-HCG, progesterone, and ischemia-modified albumin (IMA) and their combined use in the prediction of first trimester abortions. Methods. A total of 156 pregnant women between 5 and 13 weeks of gestational age were included in this study. At admission, serum levels of free ß-HCG, progesterone, and IMA were noted and all cases were divided into two groups; Group I (n = 77) resulted in abortion including missed abortion, incomplete/complete abortion, and inevitable abortion whereas Group II (n = 79) included normal pregnancies. Results. Compared to Group II, the significantly decreased value of free ß-HCG progesterone and significantly increased value of IMA were found in Group I (P < 0.01, P < 0.01, P < 0.01, resp.). When combining all three parameters, sensitivity 75%, specificity 99%, PPV 98%, and NPV 76% were obtained. The multivariate logistic regression analysis revealed the free ß-HCG, progesterone, and IMA independent factors in the prediction of abortions. Conclusions. The combined use of free ß-HCG, progesterone, and IMA levels can be useful in the prediction of first trimester spontaneous abortions.

Diagnostic and prognostic value of Ischemia-modified albumin in patients with Crimean-Congo hemorrhagic fever.

The aim of this study was to determine the diagnostic and prognostic significance of ischemia modified albumin (IMA) levels in patients with Crimean-Congo hemorrhagic fever (CCHF). This retrospective study was conducted with patients with CCHF. IMA levels in patients with CCHF were determined using the rapid colorimetric method. IMA levels of CCHF patients were significantly higher compared with the control group (P = 0.0001). At an IMA cut-off point of 0.555 ABSU (absorbance units), sensitivity was 65.1%, specificity 82.5%, positive predictive values (PPV) 82.5%, and negative predictive values (NPV) 65.1%. IMA levels of patients with hemorrhage were significantly higher compared with patients without hemorrhage (P = 0.005). IMA has been validated as both a new and sensitive ischemia and oxidative stress biomarker. In addition to its diagnostic significance, IMA investigated in CCHF patients at time of arrival may be an important marker with its prognostic role in determining in the early stage whether the disease will follow a hemorrhagic course.

New marker of platelet activation, SCUBE1, is elevated in hypertensive patients.

BACKGROUND: Hypertension is associated with an increase in platelet activation and endothelial dysfunction and leads to a tendency to cardiovascular events (CVEs). Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) is a novel platelet activation marker. There are currently no studies showing the level of SCUBE1 in hypertensive patients. The purpose of this study was to determine the level of SCUBE1 in this patient group and to investigate the parameters affecting that level. METHODS: Forty-five newly diagnosed, untreated, stage 1 hypertensive patients and 21 healthy individuals were included. Blood specimens were collected to determine SCUBE1, soluble CD40 ligand, prothrombin time, partial thromboplastin time, fibrinogen, D dimer, hemogram, lipid parameters, blood urea nitrogen, creatinine, and uric acid levels. The relation between SCUBE1 level and demographic data and biochemical parameters was then investigated. RESULTS: SCUBE1 and sCD40L levels obtained from plasma specimens from the hypertensive group were significantly higher than those of the control group (P < 0.001; P < 0.05, respectively). Hypertensive group blood pressure (BP) values and uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels were also statistically higher than those of the control group. Parameters affecting SCUBE1 levels were systolic and diastolic BP, sCD40L, lipid parameters, and uric acid levels. CONCLUSIONS: We show elevated levels of SCUBE1, a novel platelet activation marker, in primary hypertensive patients. We think that, when supported by further clinical studies, this newly described marker may be useful in the monitoring of CVEs in this patient group, in which platelet activation is known to be associated with such events.

Do hemodialysis adequacy data reflect reality?

Hemodialysis (HD) adequacy requires monitoring in line with standards and at appropriate intervals. However, the use of inappropriate or incorrectly applied techniques in the determination of HD adequacy can lead to highly unfortunate results. This study was intended to identify the path to a solution by determining how far HD adequacy in HD centers in our region reflects reality. Three hundred and thirty HD patients from eight centers were included. On the first visit, predialysis and postdialysis blood collection with the centers' own methods being used were observed and errors were recorded. Kt/V1 was calculated from pre- and postdialysis blood specimens taken by the units themselves. On the second visit, one session later, pre- and postdialysis blood samples were collected in line with guidelines by ourselves, the authors, and Kt/V2 was calculated from these samples. The eight units' total Kt/V2 value was significantly lower compared with Kt/V1 (<0.0001). The level of patients in all centers with Kt/V1 <1.2 was 13.5%, and that of patients with Kt/V2 <1.2 was 22.1%. No center, apart from one unit, managed to complete the collection of blood specimens as recommended by the guidelines. With one exception, blood collection for HD adequacy was not performed using proper technique in any center. This simple but easily overlooked situation, HD being regarded as adequate though in fact it is not, may lead to patients not being treated effectively and accurately and to a rise in mortality and morbidity in the long term.

Thrombin activatable fibrinolysis inhibitor (TAFI) levels in hypertensive patients and a comparison of the effects of amlodipine and ramipril on TAFI levels.

Hypertension is associated with fibrinolysis abnormality. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a novel molecule-linking coagulation and fibrinolysis. The aim of this study was to investigate the levels of TAFI in primary hypertensive patients and to compare the effects of amlodipine and ramipril on TAFI levels. The study was performed with 58 hypertensive subjects and 27 healthy volunteers. Biochemical and hematological parameters and TAFI levels were measured at baseline and after 1-month follow-up. TAFI concentrations increased in hypertensive patients compared with the controls (P = .030). Additionally, TAFI levels decreased with blood pressure control at 1-month follow-up (P = .026). There was no significant difference between TAFI levels in the amlodipine and ramipril groups at baseline. However, after 1-month follow-up, TAFI levels were decreased in the amlodipine group (P = .037) but not in the ramipril group. Our study is the first in the literature to determine increased TAFI levels in primary hypertension patients. In addition, we determined a decrease in TAFI levels in the amlodipine group after 1 month, but none in the ramipril group.

Ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury in a rat ovarian-torsion model.

BACKGROUND/AIMS: To evaluate the ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury in a rat ovarian-torsion model. METHODS: 32 Sprague-Dawley rats were randomly divided into four groups: (1) ischemia group (n = 8) in which only left adnexal torsion was performed for 2 h, but no treatment was given; (2) vehicle group (n = 8) in which left adnexal torsion was performed for 2 h and at the end of 2 h ischemia polyethylene glycol (3% PEG, 1 ml, i.p.) was administered and a 24-hour reperfusion was continued; (3) clotrimazole group (n = 8) in which left adnexal torsion was performed for 2 h and at the end of 2 h ischemia clotrimazole (30 mg/kg, i.p.) was administered and a 24-hour reperfusion was continued, and (4) control group (sham-operated, n = 6) in which no adnexal torsion and no treatment were given. The criteria for ovarian ischemia were follicular cell degeneration, vascular congestion, hemorrhage and infiltration by inflammatory cells. Each specimen was scored for each criterion (0, none; 1, mild; 2, moderate; 3, severe). RESULTS: Clotrimazole significantly decreased plasma levels of serum malondialdehyde, ischemia-modified albumin, and total oxidant status. CONCLUSION: This study showed the ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury.

Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) level in hemodialysis patients and parameters affecting that level.

BACKGROUND: Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-domain-containing protein 1 (SCUBE1) is a cell surface protein belonging to the SCUBE gene family. SCUBE1 has been shown to rise in parallel with platelet activation in acute ischemic events. However, there are no studies showing levels in the hemodialysis patient group, in which there is known to be an increase in platelet function impairment and activation. The purpose of this study was to investigate SCUBE1 levels in a hemodialysis patient group and the factors affecting those levels. MATERIALS AND METHODS: One hundred three hemodialysis patients and 21 age-matched healthy controls were included. SCUBE1 and sCD40L levels were investigated from blood specimens collected on pre- and post-hemodialysis sessions. We investigated the correlation between SCUBE1 levels and sCD40L, patients' demographic data, parameters with hemodialysis treatment and routine biochemical tests. RESULT: SCUBE1 levels were significantly higher in the hemodialysis patient group compared with the controls (p=0.000). There was a significant rise in SCUBE1 levels in the post-hemodialysis session (p=0.000). We determined a positive correlation between SCUBE1 and sCD40L (p=0.016, r=0.215). Gender, blood pressure, BUN, creatinine, hematocrit and high-sensitivity C-reactive protein (hsCRP) levels, hemodialysis membrane surface area, amount of ultrafiltration, blood flow rate, dialysis flow rate and carnitine use significantly affected SCUBE1 levels. CONCLUSION: We have shown, for the first time in the literature, that SCUBE1 level, a potential acute ischemia marker, is elevated in hemodialysis patients with no clinical ischemic event, and that various factors affect this elevation.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome.

OBJECTIVES: This study was intended to investigate the value of suPAR, C-reactive protein (CRP) and procalcitonin (PCT) in the determination and prognosis of systemic inflammatory response syndrome (SIRS) patients. METHODS: The study was performed among patients with at least two SIRS criteria. PCT, CRP and suPAR were analyzed from the blood specimens taken. RESULTS: Eighty-five patients were enrolled in the SIRS group (44 bacteremia, 20 urinary tract infection, 12 pneumonia and 9 non-infection), and 53 individuals in the control group. A significant correlation was determined between suPAR, PCT and CRP values in both groups (P<0.0001). A suPAR cutoff value of 2.8ng/mL was associated with an NPV of 87% and PPV of 91%, with 92% sensitivity and 85% specificity. A relatively high suPAR level that might predict fatality was also determined in fatal cases (P=0.001). CONCLUSION: suPAR possesses high sensitivity and specificity levels in terms of differential diagnosis, and high suPAR levels can predict fatality.

Relation between serum ischemia-modified albumin levels and rectus abdominis muscle flap viability.

Ischemia is a major cause of flap failure in reconstructive surgery. To detect circulatory compromise, many flap monitoring methods are used; however, there is no any optimal standard method. Ischemia-modified albumin (IMA) is an ischemia marker, which has recently been investigated in many studies and largely validated for early detection of ischemia. In this study, we investigated possible relationship between muscle flap viability and serum IMA levels in experimental flap model. The rectus abdominis muscle flap model was used in 18 New Zealand white rabbits. The study was planned using 3 groups. In group 1, the rectus abdominis muscle flap was harvested as a superior pedicle-based flap in which the inferior pedicle was sacrificed. In group 2, the flap was harvested by severing the superior pedicle. Both pedicles were harvested in group 3. Serum IMA levels were measured before the procedure and 1 hour, 6 hours, and 7 days postoperatively and then compared. In group 3, in which the ischemia was evident, and in group 1, IMA levels were significantly high 1 hour postoperatively (P < 0.05). There was no other significant difference in any of the other studied parameters between the groups. In conclusion, IMA can be used as a biochemical parameter for monitoring muscle flap viability.

Acute increase in plasma D-dimer level in ovarian torsion: an experimental study.

BACKGROUND: Torsion of the ovary is a rare but serious cause of gynecologic surgical emergency. Specific laboratory markers that support the preoperative diagnosis of ovarian torsion are not currently available in the clinical routine. The aim of this study was to investigate the diagnostic value of plasma D-dimer level as an early indicator of ovarian torsion in an experimental rat ovarian torsion model. METHODS: Sixteen female adult Sprague-Dawley rats were used for this controlled experimental study. Eight rats in the sham operation group (Group I) underwent a surgical procedure similar to Group II but the ovary was not occluded. In Group II (eight rats), a torsion model was created by using atraumatic vascular clips just above and below the right ovary for a 2-h period of ischemia. Right ovaries were surgically removed at the end of the procedure in each group. Blood was sampled before and after operation to assess plasma D-dimer levels. The main outcome measure was ovarian histopathologic findings scores and plasma D-dimer levels. RESULTS: There was no significant difference in pre-operative plasma D-dimer levels (0.5963 ± 0.2047 mg/l in Group I, 0.6344 ± 0.1348 mg/l in Group II, P = 0.815, Mann-Whitney U-test). However, mean plasma D-dimer value for Group II was significantly higher than that in the control group (1.2267 ± 0.3099 versus 0.6213 ± 0.2346 mg/l, respectively, Mann-Whitney U-test, P < 0.001), following 2 h of ovarian torsion. Ovarian tissue damage scores were also statistically significantly different among groups. CONCLUSIONS: If the observations made in a rat model are extended to humans, plasma D-dimer measurement may be a valuable parameter in the early diagnosis of ovarian torsion.

The role of fibrinolytic and antifibrinolytic activities in the pathophysiology of HELLP syndrome.

OBJECTIVE: To determine the role of the fibrinolytic and antifibrinolytic systems in HELLP syndrome. METHODS: This study consisted of patients with HELLP Syndrome (study group, n = 17), women who were admitted for routine prenatal care (pregnant control group, n = 21) and those presenting for routine gynecologic examination (non-pregnant control group, n = 21). Plasma tissue-type plasminogen activator (tPA), thrombin-activatable fibrinolysis inhibitor (TAFI), plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT) and thrombomodulin (TM) were measured at admission for all groups. They were again measured after 7 days of biochemical improvement in HELLP Syndrome group. RESULTS: The mean ages of women in the study, pregnant, and non-pregnant control groups were 29.82 ± 4.98, 29.71 ± 5.64, and 27.60 ± 4.21, respectively. Demographically, the patients in all three groups were similar with regard to maternal age, race, and body mass index. Compared to the control groups, the mean tPA, PAI-1, TAFI, TAT, and TM levels were significantly increased in HELLP Syndrome. The mean plasma TAFI antigen concentration 7 days after delivery was significantly lower compared to the baseline (5.84 ± 7.14 % change, p < 0.01). Significant decreases in the mean plasma concentrations were also found in tPA (21.78 ± 20.93 ng/mL mean difference, p < 0.01), PAI-1 (14.22 ± 10.38 ng/mL mean difference, p < 0.001), TAT (0.93 ± 1.19 ng/mL mean difference, p < 0.01), and TM (0.54 ± 0.94 ng/mL mean difference, p < 0.05). CONCLUSION: It is likely that the impaired fibrinolytic and antifibrinolytic systems, in response to thrombus formation, affect the pathophysiology of HELLP syndrome.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. It has recently been reported that soluble urokinase-type plasminogen activator receptor (suPAR), secreted from endothelial cells and the mononuclear phagocyte system, one of the main targets of the CCHF virus, is a potential biomarker for several bacterial and viral infection diseases. OBJECTIVES: This study was intended to determine the diagnostic and prognostic significance of suPAR levels in CCHF. STUDY DESIGN: This retrospective study was conducted between June 2006 and August 2009 using plasma from patients monitored with a diagnosis of CCHF and from healthy blood donors. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. RESULTS: One hundred CCHF patients were enrolled in the study. The control group was made up of 53 healthy blood donors. suPAR values of 6.2 ± 4.2 were determined in the CCHF patients and of 2.3 ± 0.6 in the control group (p<0.0001). A suPAR level optimum diagnostic cut-off point of 3.06 ng/mL was determined, with an area underneath the ROC (AUROC) curve of 0.94 (95% CI: 0.89-0.97), sensitivity of 87% (95% CI: 79-93%), specificity of 92% (95% CI: 82-98%), PPV of 95% and NPV of 79%. Five of the patients died. suPAR was 18.4 ± 9.1 in the patients that died and 5.6 ± 2.6 in the survivors (p=0.034). In terms of mortality, suPAR level had an optimum diagnostic cut-off point of 10.6 ng/mL, AUROC of 0.97 (95% CI: 0.94-0.99), sensitivity of 100% (95% CI: 48-100%), specificity of 96% (95% CI: 90-99%), PPV of 50% and NPV of 100%. CONCLUSIONS: Plasma suPAR level, a new biomarker, is a test that can be used in the differential diagnosis and monitoring of CCHF in patients admitted to hospital with suspected infection. The test is at the same time important in being a possible predictor of mortality.

Diagnostic value of pleural effusion ischaemia-modified albumin in patients with cardiac failure.

BACKGROUND: Ischaemia-modified albumin (IMA) is a relatively new marker of ischaemia. IMA has not been studied previously in pleural effusions due to congestive heart failure (CHF). The aim of our study was to assess the diagnostic value of IMA in the pleural fluid (PF) and serum for the identification of pleural effusion due to CHF. METHODS: The concentrations of pleural fluid and serum IMA were measured in a total of 40 patients: 10 with CHF and 30 with non-cardiac failure (10 with acute pulmonary embolism, 10 with parapneumonic effusion and 10 with malignancy). The area under the curve (AUC) quantified the overall diagnostic accuracy of the tests. RESULTS: The study demonstrated that IMA concentration was higher in both pleural fluid and serum of CHF patients compared with non-cardiac patients. PF and serum IMA demonstrated AUCs of 0.927 (95% CI: 0.844-1.00, P < 0.001), and 0.792 (95% CI: 0.653-0.930, P = 0.006), respectively, for diagnosing effusions due to CHF. The sensitivity and specificity of PF-IMA for CHF at the cut-off concentration of ≥1.0 absorbance units was 90% and 80%, respectively. Its negative predictive value (NPV) was quite high (96%). Positive correlation was found between PF-IMA concentrations and serum-IMA (r = 0.540, P < 0.001). CONCLUSIONS: Measuring IMA concentrations in serum and pleural fluid may be helpful in distinguishing pleural effusion due to a cardiac or non-cardiac aetiology.

Treatment related changes in antifibrinolytic activity in patients with polycythemia vera.

Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.

Combined risk stratification with computerized tomography /echocardiography and biomarkers in patients with normotensive pulmonary embolism.

BACKGROUND: Right ventricular dysfunction (RVD) detected by computerized tomography (CT)/echocardiography or elevated biomarkers is associated with a poor prognosis for pulmonary embolism (PE). However, these prognostic factors have not previously been concomitantly elucidated in the same patient group. METHODS: This prospective study included 108 consecutive patients with normotensive PE confirmed by CT pulmonary angiography (CTPA). On admission, patient serum NT-proBNP and troponin T (Tn-T) levels were measured, and echocardiography was performed within 24 hours after diagnosis of PE. Receiver operating characteristic (ROC) analysis was performed to determine the optimal echocardiographic end-diastolic diameters of the right ventricle, the ratio of the right ventricle to left ventricle (RV/LV ratio) on CTPA, and NT-proBNP and Tn-T cut-off levels with regard to prognosis. RESULTS: All-cause 30-day mortality was 13% and PE-related mortality was 5.6%. RVD was defined as a right/left ventricular dimension ratio≥1.1 on CTPA and RV>30 mm on echocardiography by ROC analysis. A cut-off level of NT-proBNP≤90 pmol/ml had a high positive predictive value of 98% for survival, whereas NT-proBNP>300 and Tn-T≥0.027 had a negative predictive value, for all-cause deaths, of 95% and 96%, respectively. PE mortality in patients with NT-proBNP>300 and Tn-T≥0.027 reached 64%. In univariable analysis, the combination of Tn-T≥0.027 ng/ml with a echocardiographic RVD were the most significant predictors of overall mortality and PE-related death [HR: 14 (95% CI: 4.6-42,) and HR: 37.6 (95% CI: 4.4-324)], respectively. In multivariable Cox's regression analysis, NT-proBNP>300 and Tn-T≥0.027 HR: 26.5 (95% CI: 4.1-169.9, p<0.001) were the best combination to predict all-cause of mortality. CONCLUSIONS: The combination of NT-proBNP and Tn-T clearly appears to be a better risk stratification predictor than biomarkers plus RVD on CT/ echocardiography in patients with normotensive PE.