Hemostatic Markers Research Articles

COMPLEX APPROACH TO TREATMENT OF SUBCHORIONIC HEMATOMA IN EARLY THREATENED ABORTION

<p>Background. Currently, miscarriage is considered to be a multietiological disorder with trombofilic violations<br />and hormone deficiency as the leading factors. Despite the achievements in treatment of miscarriage, the<br />frequency of preterm termination of the wanted pregnancies is still high and the number of perinatal losses is<br />significant. Therefore, pathogenetically based therapy, safe for the foetus, is very important in management of<br />pregnancy interruption in the first trimester. A proper drugs administration provides optimal concentration of<br />active ingredients and fast action. The aim is to improve effectiveness of the early threatened abortion treatment<br />in cases of subchorionic hematoma (SCH) by combination of sublingual natural micronized progesterone and<br />tranexamic acid<br />Objective. We examined 50 pregnant women with early threatened abortion with SCH. We studied system<br />of haemostasis, basic hormonal markers and ultrasound criteria of threatened abortion. We compared efficacy<br />of treatment between traditional (supportive) therapy (sedation, spasmolytic, haemostatic drug) and combination<br />of supportive therapy in combination with tranexamic acid and natural micronized progesterone.<br />Results. The result of lab tests showed minimal signs of hypercoagulation, hyperfibrinogenemia and platelet<br />hyperactivity, a significant β-hCG level decrease and approximate decrease in progesterone and free estriol<br />production.<br />Sonographic examination showed presents of local myometrial hypertonus, deformation of fertilized egg,<br />hypoplasia of chorion, low location of fertilized ovum, retarded growth of CRL.<br />The research proved that combined administration of sublingual micronized progesterone and tranexamic<br />acid for the treatment of threatened abortion with SCH has more significant positive effect for pregnancy<br />maintenance due to clinical, biochemical, hormonal and ultrasound results if compared with the group which<br />underwent supportive therapy.<br />Conclusions. Complex application of natural micronized progesterone 100 mg three times a day sublingually<br />and 500 mg of Tranexamic acid dissolved in 200 ml normal saline solution improves the dynamics of the<br />main hormonal, haemostatic and ultrasound markers of abortion and significantly reduces reproductive losses.<br />Tranexamic acid treatment proved a rapid and effective action on hematoma and absence of embryotoxical and<br />сoagulopathyc influence. Tranexamic acid does not cause any significant disorders of hemostatic system. This is<br />very important at the early gestation because of intravascular coagulation, physiological hypercoagulable condition<br />during pregnancy that can cause microthrombosis and disrupt placentation. On the other hand, it is<br />dangerous for the mother’s health because of the increased risk of thrombosis.<br />KEY WORDS: threatened miscarriage, subhorial hematoma, micronized progesterone, tranexamic<br />acid.</p>

Hemostatic Markers and Long-Term Risk of Intracerebral Hemorrhage in Postmenopausal Women

Known risk factors for intracerebral hemorrhage (ICH) include age, hypertension, smoking, alcohol intake, and anticoagulant use. Some previous reports have indicated that hemostatic factors measured many years before the onset of ICH might predict the later occurrence of ICH. The objective of this analysis was to test whether selected hemostatic factors measured years before the onset of ICH could identify patients at higher risk for future ICH. We performed a nested case-control study within the Women's Health Initiative (WHI) cohort. Postmenopausal women aged 50-79 years (mean 68) at baseline (1993-1998) were enrolled at 40 Clinical Centers in the United States and followed for adjudicated ICH for a mean of 11.4 years. ICH cases (N = 75) and controls (N = 75) were matched on age, ethnicity, blood pressure, anticoagulant use, and treated hypertension. Stored blood samples from the baseline WHI examination were tested for von Willebrand factor (vWF), a disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13 (ADAMTS13), tissue plasminogen activator (t-PA), and urokinase plasminogen activator (u-PA). Platelet count, white blood cell count, and hemoglobin concentration were also measured. Mean baseline levels of vWF (1.03 and .95 U/mL), ADAMTS13 (1.0 and 1.1 µg/mL), vWF:ADAMTS13 ratio (.99 and .92), t-PA (14.75 and 14.80 IU/mL), and u-PA (.09 and .10 IU/mL) were not significantly different by case-control status. Significant differences were also not identified for platelet count, hemoglobin, white blood count, or reported alcohol use. None of the 4 baseline hemostatic factors nor the platelet count was predictive of future ICH risk in this long-term study of older postmenopausal women.

Assessing Circulating Factor VIIa-Antithrombin Complexes in Acute Ischemic Stroke: A Pilot Study.

The goal of this study was to determine the levels of factor VII (FVII), factor VIIa-antithrombin complexes (FVIIa-AT), total tissue factor (TF), and tissue factor-bearing microparticles (MPs-TF) in patients with acute ischemic stroke. Further, we sought evidence of an association between hemostatic markers, time of blood sampling, type of treatment, and patient outcomes. Venous blood samples were collected from 33 patients on the first day and on the seventh day after stroke diagnosis. Age-matched controls were also included (n = 20). Plasma levels of FVII, FVIIa-AT, total TF, and MPs-TF were measured by enzyme-linked immunosorbent assay. We divided patients into 2 groups: thrombolysis group (n = 13) and nonthrombolysis group (n = 20). Furthermore, evaluation of the National Institutes of Health Stroke Scale and the Barthel Index was performed on the first day and the seventh day. Patients with ischemic stroke showed significantly lower plasma FVII, FVIIa-AT, and total TF levels than controls (median, 112.25% vs 132.05%, P = .004; 107.97 pmol/L vs 154.94 pmol/L, P < .001; 81.74 pg/mL vs 105.71 pg/mL, P < .001, respectively). In contrast, levels of plasma MPs-TF were significantly higher in patients with stroke compared to healthy controls (1.60 pg/mL vs 0.74 pg/mL, P < .001). Additionally, the thrombolysis group had lower FVII levels on the seventh day compared to the first day (median, 109.80% vs 115.74%, P = .04). Factor VII, FVIIa-AT, and total TF are decreased, while MPs-TF are elevated in patients with ischemic stroke. We observed a slight but significant effect of alteplase on FVII plasma levels.

Longitudinal changes in hemostatic parameters and reduced pulsatility contribute to non-surgical bleeding in patients with centrifugal continuous-flow left ventricular assist devices

Bleeding and thromboembolic events are identified complications in patients supported with newer centrifugal continuous-flow left ventricular assist devices (cfLVADs). Bleeding events have been associated with acquired von Willebrand syndrome (vWS) in these patients, though longitudinal changes and the effect of pulsatility remain unquantified. We evaluated longitudinal effects of third-generation cfLVADs on hemostatic biomarkers, non-surgical bleeding, and thromboembolic events. We investigated the association between pulsatility (as defined by aortic valve opening) on von Willebrand Factor (VWF) profile and bleeding. We prospectively studied 28 patients implanted with the HeartWare (HeartWare International, Framingham, MA) cfLVAD for up to 360 days. We performed bleeding and coagulation assays 8 times from pre-implant to Day 360 (D360) post-implant, including platelet aggregometry, VWF collagen binding activity-to-antigen (CBA/Ag) ratio, thromboelastography, soluble P-selectin, platelet-specific marker soluble glycoprotein VI (sGPVI), and platelet microparticles. Aortic valve opening was assessed by echocardiography at each assessment. Bleeding and thromboembolic events were documented. Bleeding events occurred in 14 patients (50%). Maximal platelet inhibition occurred by D30. VWF profile impairment (VWF CBA/Ag < 0.8) was demonstrated in 89% of patients at D30, with subsequent recovery but further deterioration after D180. Bleeding was associated with elevated pre-implant sGPVI (p = 0.008). Pulsatility was associated with higher VWF CBA/Ag (p = 0.02) and a trend to less bleeding. Third-generation cfLVADs were associated with longitudinal changes in hemostatic markers, and bleeding was associated with elevated pre-implant plasma sGPVI. Further, pulsatility may contribute to recovery of the VWF profile and potentially lower bleeding risk.

Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study

BackgroundTo compare the effects of nateglinide and rosiglitazone on inflammatory markers, GLP-1 levels and metabolic profile in patients with type 2 diabetes (DM2).MethodsA prospective study was performed in 20 patients with DM2, mean age 51.82 ± 8.05 years, previously treated with dietary intervention. Participants were randomized into rosiglitazone (4–8 mg/day) or nateglinide (120 mg 3 times a day) therapy. After 4 months, the patients were crossed-over with 8 weeks washout period to the alternative treatment for an additional 4-month period on similar dosage schedule. The following variables were assessed before and after 4 months of each treatment period: (1) a test with a standardized 500 calories meal for 5 h including frequent measurements of glucose, insulin, glucagon, proinsulin, GLP-1, free fat acids (FFA), and triglycerides levels was obtained. The lipid profile and HbA1 levels were measured at fasting. (2) Haemostatic and inflammatory markers: platelet aggregation, fibrinogen, PAI-1 activity, C reactive protein (CRP), IL-6, TNF-α, leptin, sICAM and TGFβ levels.ResultsBoth therapy decreased blood glucose levels under the postprandial curve but neither affected glucagon and GLP-1 levels. Nateglinide was associated with higher insulin and pro-insulin secretion, but similar pro-insulin/insulin ratio when compared with rosiglitazone. Only rosiglitazone decreased Homa β, PAI-1 activity, CRP, fibrinogen, TGFβ, FFA and triglyceride levels.ConclusionsNateglinide and rosiglitazone were effective in improving glucose and lipid profile and β cell function, but rosiglitazone afforded a better anti-inflammatory effect. No drug restored alpha cell sensitivity or changed GLP-1 levels. Maintenance of haemostatic factors, inflammatory factors and glucagon levels can be related to the continuously worsening of cardiovascular function and glucose control observed in DM2.

Intrarenal Vascular Resistance is Associated With a Prothrombotic State in Hypertensive Patients

Background/Aims: Hypertensive nephroangiosclerosis is associated with progressive increase of intrarenal vascular resistance. In addition to blood pressure, other factors can contribute to hypertensive renal damage including a prothrombotic state. We investigated the relationship between hemostatic markers and intrarenal vascular resistance in hypertension. Methods: In 115 untreated, nondiabetic, hypertensive subjects free of cardiovascular complications and advanced renal function impairment, we measured 24-hour creatinine clearance (GFR) and urinary albumin excretion (UAE), fasting plasma glucose, HOMA-index, and plasma levels of fibrinogen, D-dimer, prothrombin fragment 1+2, plasminogen activator inhibitor-1, homocysteine, and lipoprotein(a). In all patients, measurement of intrarenal resistance was obtained by renal Doppler ultrasound with calculation of the renal resistance index (RI). Results: Patients in the highest tertile of RI were older and had greater body mass index, pulse pressure, fibrinogen, and D-dimer levels and lower GFR than patients in the lowest RI tertile. RI was directly correlated with age, pulse pressure, HOMA-index, UAE, D-dimer, and inversely with GFR. On multivariate analysis, RRI was independently associated with age, GFR, and plasma D-dimer. Conclusions: A prothrombotic state is associated with increased intrarenal vascular resistance in nondiabetic hypertensive patients and might contribute to the early stages of hypertensive renal disease.

Thrombin generation and endothelial dysfunctional markers in different stages of nephrotic syndrome

Objectives: Venous thromboembolism is an important and potentially life-threatening complication of nephrotic syndrome (NS). This study aims to evaluate the functional test of thrombin generation (TG) in different stages of NS; determine its relation with the coagulation screening tests (prothrombin time [PT] and activated partial thromboplastin time), hemostatic activation markers (thrombin–antithrombin complex [TAT] and prothrombin fragment 1+2 [PF1+2]), and von Willebrand factor (vWF) and its proteolytic enzyme ADAMTS-13; and determine the correlation between TG and NS severity, as reflected by the levels of proteinuria and albumin. Materials and Methods: This case–control cross-sectional study included 125 patients (n = 40, nephrotic range proteinuria; n = 45, NS; n = 40, remission) and 80 controls. Calibrated automated thrombogram assay (endogenous thrombin potential [ETP]) was performed to determine TG. TAT, PF1+2, vWF, and ADAMTS-13 were measured using enzyme-linked immunosorbent assay. Results: TG (ETP), TAT, PF1+2, and vWF levels were significantly higher in all of the patient groups (P Conclusion: Our findings confirm activation of the coagulation pathway in nephrotic patients. However, the degree of hypercoagulopathy (especially TG [ETP]) is positively correlated with proteinuria. Proteinuria could be considered an indirect indicator of the highest risk of thrombotic disease in patients with NS.

Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology

Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology

Prothrombotic state in patients with severe and prednisolone-dependent asthma

Epidemiologic studies have shown that asthmatic patients, in particular those with severe disease, have increased risk of pulmonary embolism. It is unknown whether these patients have a prothrombotic state under stable conditions. We sought to compare coagulation and fibrinolysis parameters between healthy subjects and patients with mild, severe, and prednisolone-dependent asthma under stable conditions and to investigate whether hemostatic markers correlate with airway inflammation. In 126 adults (33 healthy control subjects, 31 patients with mild asthma, 32 patients with severe asthma, and 30 patients with prednisolone-dependent asthma) parameters of inflammation (peripheral blood eosinophils and neutrophils) and markers of hemostasis (endogenous thrombin potential [ETP], thrombin-antithrombin complex, plasmin-α2-antiplasmin complex, plasminogen activator inhibitor type 1 [PAI-1], D-dimer, and von Willebrand factor [vWF]) were measured in plasma. One-way ANOVA with the post hoc Bonferroni test was used for group comparison, and linear regression analysis was used for correlations. We observed increased ETP (121% vs 99%, overall P<.01), plasmin-α2-antiplasmin complex (520 vs 409μg/L, overall P=.04), PAI-1 (10 vs 7ng/mL, overall P=.02), and vWF (142% vs 87%, overall P<.01) levels in asthmatic patients compared with healthy control subjects. ETP, PAI-1, and vWF levels increased with increasing asthma severity. In addition, we found a correlation between ETP and vWF with neutrophil but not eosinophil counts. Asthmatic patients have a prothrombotic state that increases with asthma severity. This might explain why patients with asthma, in particular those with severe disease, have an increased risk of venous thromboembolism.

Hemostatic, inflammatory, and oxidative markers in pesticide user farmers

The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.

Retinal vessel calibres and haemostasis in black and white South Africans: the SABPA study.

Retinal arteriolar narrowing associates with hypertension development and indicates increased cardiovascular risk. Evidence on whether the retinal vessel calibres are related to the haemostatic system is limited, especially in the black hypertension-prone population with a high stroke incidence. We therefore investigated the relationships between haemostatic markers and retinal vessel calibres. We performed a cross-sectional study involving 170 black (mean age, 58 years; 44% women) and 189 white (mean age, 49 years; 52% women) teachers, and determined ambulatory blood pressure, haemostatic factors (fibrinogen, von Willebrand factor, D-dimer, plasminogen activator inhibitor-1 and clot lysis time) and retinal vessel calibres (central retinal artery and vein equivalent). The black and white groups were stratified by median split of the retinal arteriolar calibre. Both ethnic groups with a smaller arteriolar calibre had higher SBP and narrower venular calibres. In the black population, the central retinal vein equivalent was positively (β = 0.293; P = 0.024) associated with fibrinogen, whereas in the white population, the central retinal artery equivalent (β = -0.256; P = 0.016) was negatively and central retinal vein equivalent (β = 0.234; P = 0.021) positively associated with von Willebrand factor. Furthermore, clot lysis time was negatively associated with the central retinal artery equivalent (β = -0.390; P = 0.014) in the black group and positively associated with the central retinal vein equivalent (β = 0.275; P = 0.008) in the white group. Relationships between markers of haemostasis and the retinal vessel calibres exist, and vary between ethnicities. Haemostatic alterations are linked to early retinal microvascular changes, and future studies should investigate whether it translates into an elevated stroke risk.

ABO blood group and neurodegenerative disorders: more than a casual association.

Along with their expression on red blood cells, ABO blood group antigens (namely, A, B, AB and O) are also highly expressed by a large number of human cells and tissues including epithelia, platelets, vascular endothelia and neurons1,2. Over the last 50 years, various investigators have assessed whether this biological characteristic of the ABO blood system has a clinical significance beyond that played in transfusion and transplantation medicine. Indeed, there is now a large body of evidence on the role of ABO antigens in the pathogenesis of various systemic diseases, including cancer, infectious disorders and cardiovascular diseases3–6. Considering the role played by the ABO system in neurogenesis7, some investigators have studied the system’s relationship with ageing-related neurodegenerative disorders, but with conflicting results. While no significant differences was found in ABO blood group distribution in Parkinson’s disease patients compared with controls in two studies conducted by Strang8 and by Chia and Liu9, in another study published by Kak and Gordon there was an excess of blood group B among patients with Parkinson’s disease10. No significant association between ABO blood groups and Alzheimer’s disease was found by Renvoize11 or, more recently, by Vasan and collegues12. The interest in the link between ABO antigens and neurological disorders has been recently renewed thanks to two further published studies13,14. The first case-control study (495 cases with cognitive impairment and 587 controls) was conducted by Alexander and colleagues and tested the possibility that non-O blood type adults might show poorer cognitive trajectories13. The authors found that AB blood type and increased coagulation factor VIII levels were associated with a higher incidence (odd’s ratio for AB blood type vs O blood type: 1.82, 95% confidence interval: 1.15–2.90; odds ratio for each 40 IU/dL higher factor VIII: 1.24, 95% confidence interval: 1.10–1.38) of cognitive decline. In the second, more recent study, De Marco and Venneri investigated volumetric differences in grey matter between O (76 cases) and non-O (113 cases) healthy individuals14. Surprisingly, the authors observed that O blood type, compared with non-O blood type, was associated with larger volumes of grey matter in the cerebellum and temporal-mediotemporal/limbic regions, suggesting that O blood group might play a protective role against those ageing-related neurodegenerative conditions, particularly Alzheimer’s disease, associated with volumetric loss in these cerebral areas. The most reasonable explanation for the protection exerted by O blood type against the cognitive decline typical of ageing-related neurodegenerative disorders lies in the lower levels of circulating von Willebrand factor and factor VIII levels observed in O blood type individuals than in non-O blood type individuals, which could reduce the risk of thrombotic adverse events, including those in the brain, in the former group15–17. This hypothesis is compatible with the results of a recently published systematic review and meta-analysis documenting a positive association between increased levels of some haemostatic markers, including von Willebrand factor, in vascular dementia and cognitive impairment18. The increased prevalence of O blood type found in centenarians in two recent studies by our group19,20 is also in agreement with these findings, suggesting that individuals with group O might be less vulnerable to age-related illnesses with a resulting longer life-expectancy. However, another possible intriguing mechanism could involve the anti-angiogenic properties of von Willebrand factor, resulting in a positive modulation of brain vascular endothelium in O blood type individuals21, who have lower von Willebrand factor and factor VIII plasma levels than non-O subjects. Further experimental and clinical studies on large cohorts of patients are needed to elucidate the association between ABO blood type and degenerative neurological disorders and the underlying pathogenic mechanisms.

Associations between venous thromboembolism onset, D-dimer, and soluble fibrin monomer complex after total knee arthroplasty.

BackgroundPrevention and early detection of venous thromboembolism (VTE) is important after arthroplasty of the lower limb. The purpose of this study was to investigate the associations between VTE and hemostatic markers after minimally invasive total knee arthroplasty (MIS-TKA).MethodsWe performed a retrospective study of 50 patients (55 knees) who underwent primary unilateral MIS-TKA with periodic determination of D-dimer and soluble fibrin monomer complex (SFMC) concentrations and with ultrasonography. The development of symptomatic and asymptomatic VTE, location of deep venous thrombosis (DVT; proximal or distal), changes in SFMC and D-dimer concentrations, and correlations between hemostatic markers and VTE onset were evaluated.ResultsTwenty-six patients (47 %) had an asymptomatic distal DVT, but none had proximal DVT, pulmonary embolism, or symptomatic DVT. DVT was detected at postoperative day 1 (POD1) in 16 patients, POD3 in six, and POD5 in three (excluding detections of the same DVT in the same position on different days). DVT onset correlated significantly with SFMC concentration on POD1 and with D-dimer concentration on POD3. The D-dimer concentration did not differ significantly between patients who developed DVT (DVT+) and those who did not (DVT−) at each postoperative time. SFMC concentration differed between DVT+ and DVT− patients only on POD1. Analysis of each hemostatic marker classified as either within or outside the normal concentration range showed no significant correlations between D-dimer concentration and DVT onset at each period. There were significant correlations between SFMC concentrations and DVT onset on POD1 and POD3. There were also significant correlations between D-dimer positive (+) findings and/or SFMC+ findings and DVT onset on POD1 and POD3. D-dimer+ and/or SFMC+ findings had better specificity on POD1 and a positive predictive value on POD1 and POD3 compared with SFMC+ alone.ConclusionsSFMC concentration is an effective hemostatic marker for early detection of DVT. D-dimer concentration alone has limited value as a hemostatic marker for early detection of DVT. Measurement of both D-dimer and SFMC concentrations might be a more sensitive diagnostic tool than measuring SFMC concentration alone.

Emerging Vascular Risk Factors in Women: Any Differences from Men?

Gender differences have been reported for traditional vascular risk factors such as smoking, obesity, diabetes, hypertension, dyslipidemia, age and family history of premature coronary heart disease. The prevalence, severity, associations and response to treatment of several emerging cardiovascular disease (CVD) risk factors may also differ between men and women. Such CVD risk factors include certain inflammatory and hemostatic markers, endothelial dysfunction, homocysteine, lipid disorders, microalbuminuria/proteinuria, coronary artery calcium score, arterial stiffness, periodontitis, inflammatory bowel syndrome, obstructive sleep apnea, impaired glucose metabolism, metabolic syndrome and non-alcoholic fatty liver disease. Further larger prospective studies are needed to establish these relationships. Hormone replacement therapy may also affect vascular risk. These data should be taken into consideration when assessing and treating CVD risk in women.

22. Joint effect of acute myocardial infarction on lipoprotein(a), C- reactive protein and markers of haemostasis

Objectives An issue of considerable interest is the relative contribution of each component of atherogenesis to CAD risk. An integrated approach encompassing the relationship between non traditional risk factors and coagulation assembly needs further studies.This study aimed at an integrated approach to study the joint changes in lipoprotein(a) [Lp(a)], high sensitivity C-reactive-protein (hsCRP) and haemostatic parameters in patients with acute myocardial infarction(AMI) and their correlation with clinical characteristics in these patients. Methods This study was conducted at the departments of physiology, emergency medicine and cardiology. Serial blood samples were collected from 50 patients with AMI on admission to the hospital (1st sample), after 3–4days (post revascularization, 2nd sample) and at 2–3months of follow up (3rd sample) and control group of 22 healthy subjects. The relationship of these markers were also studied with the presence and severity of CAD assessed by vessel and Gensini scoring. Blood samples were analyzed for lipids, Lp(a), hsCRP, fibrinogen, total(TFPI-T) & free(TFPI-F) tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1), and tissue-plasminogen-activator (t-PA). Results Lp(a), hsCRP, fibrinogen, PAI-1, TFPI-T and TFPI-F were significantly higher in AMI compared to control subjects. Lp(a) significantly increased in 2nd sample by 19.5% ( P P Conclusions Acute myocardial infarction affects Lp(a), hsCRP and hemostatic markers significantly. Lp(a), hsCRP and TFPI-T related significantly to CAD severity. While fibrinogen, PAI-1 and TFPI-F were related to the presence of CAD but there was no relationship with its severity.

First In Vivo Results of a Novel Pediatric Oxygenator with an Integrated Pulsatile Pump.

Extracorporeal membrane oxygenation (ECMO) is a pivotal bridge to recovery for cardiopulmonary failure in children. Besides its life-saving quality, it is often associated with severe system-related complications, such as hemolysis, inflammation, and thromboembolism. Novel oxygenator and pump systems may reduce such ECMO-related complications. The ExMeTrA oxygenator is a newly designed pediatric oxygenator with an integrated pulsatile pump minimizing the priming volume and reducing the surface area of blood contact. The aim of our study was to investigate the feasibility and safety of this new ExMeTrA (expansion mediated transport and accumulation) oxygenator in an animal model. During 6 h of extracorporeal circulation (ECC) in pigs, parameters of the hemostatic system including coagulation, platelets and complement activation, and flow rates were investigated. A nonsignificant trend in C3 consumption, thrombin-antithrombin-III (TAT) complex formation and a slight trend in hemolysis were detected. During the ECC, the blood flow was constantly at 500 ml/min using only flexible silicone tubes inside the oxygenator as pulsatile pump. Our data clearly indicate that the hemostatic markers were only slightly influenced by the ExMeTrA oxygenator. Additionally, the oxygenator showed a constant quality of blood flow. Therefore, this novel pediatric oxygenator shows the potential to be used in pediatric and neonatal support with ECMO.

Selected endothelial hemostatic markers in patients with peripheral arterial disease after endovascular revascularization and restenosis formation

Surgical and endovascular revascularization of ischemic legs in patients with peripheral arterial disease (PAD) can damage the arterial wall (endothelial and smooth muscle cells). Hemostatic factors released during endothelial dysfunction can lead to restenosis. 1. Determination of selected endothelial hemostatic factors in PAD patients and a reference group. 2. Prospective observation of new restenosis appearance in PAD patients after endovascular revascularization. 3. Comparison of selected endothelial hemostatic factors between non-restenotic and restenotic PAD patients. 150 PAD patients after endovascular revascularization - 90 men and 60 women, aged 44-88 (mean 65.5) years - were examined. During one-year observation after the revascularization procedures in 38 PAD patients restenosis occurred, when blood samples were also collected. The reference group consisted of 53 healthy persons - 44 men and 9 women, aged 20-56 years. Blood was drawn in the morning into 3.2% sodium citrate at a ratio of 9:1. Tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) were measured in plasma with commercial tests using the enzyme immunoassay. In the plasma of PAD patients after revascularization, the concentrations of TF and vWF were significantly higher, TM lower, TFPI and t-PA similar compared to the reference group. Six months after revascularization the level of TF had increased and vWF had significantly decreased. The endothelial hemostatic factors before and after restenosis did not significantly differ except TF, which after restenosis was higher. Increased TF and vWF levels in PAD patients indicate arterial endothelial cell damage, by atherosclerotic and revascularization processes. In PAD patients with restenosis compared to these patients before restenosis the determined endothelial hemostatic factors, except TF level, did not significantly differ. Perhaps TF participates in restenosis formation.

Associations Between Inflammatory Markers, Hemostatic Markers, and Microvascular Complications in 182 Chinese Patients With Type 2 Diabetes Mellitus.

To examine the associations between inflammatory markers, coagulation and fibrinolysis parameters, and microvascular complications in 182 Chinese patients with type 2 diabetes mellitus (T2DM) who sought treatment at a large hospital in Zhejiang province, China. We investigated the relationships of blood inflammatory markers with hemostatic markers in 87 patients with T2DM who did not have complications and 95 patients with T2DM who had microvascular complications. C-reactive protein (CRP) and interleukin-6 (IL-6) were significantly correlated with fibrinogen, thrombin-antithrombin III complex (TAT III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and coagulation factors (F) VII in patients with T2DM who had microvascular complications (P <.05). Based on logistic regression analysis, the highest-tertile groups of fibrinogen, FVII, and FVIII, corresponded to a greater risk of high CRP, whereas risk of high IL-6 was significantly greater in the groups with highest-tertile values for fibrinogen, FVII, TAT III, PAI-1, and activated protein C (APC). Elevated levels of CRP and IL-6 might be associated with increased coagulability and a tendency towards thrombus formation in patients with T2DM who have microvascular complications.

Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women.

Design and Evaluation of New Unified Criteria for Disseminated Intravascular Coagulation Based on the Japanese Association for Acute Medicine Criteria

Current disseminated intravascular coagulation (DIC) criteria are insufficient for predicting mortality. Hemostatic endothelial molecular markers are useful for DIC diagnoses. We aimed to design new DIC criteria involving these markers based on the recently published Japanese Association for Acute Medicine (JAAM) DIC criteria, which exhibit higher sensitivity for mortality. Patients with severe sepsis or septic shock admitted to a tertiary referral hospital in Japan between September 2009 and November 2011 were included. Clinical data, including hemostatic endothelial molecular markers, were measured within 12 hours after admission. Receiver operating characteristic analyses were conducted for 8 candidate variables to identify the mortality-related markers. Then, we designed new unified criteria based on the JAAM DIC criteria and involving the identified optimal markers. Of the 79 patients, 66 (83.5%) survived and 13 (16.5%) died. Protein C activity correlated best with mortality with a very high prognostic value (area under the curves [AUCs] = 0.850; P < .001), followed by plasminogen activator inhibitor 1 (AUC = 0.828; P < .001). The unified criteria, consisting of the JAAM DIC criteria plus these 2 markers, exhibited greater prognostic value for mortality (sensitivity, 84.6%; specificity, 80.3%). Moreover, DIC-positive patients using the unified criteria had significantly higher disease severity, as indicated by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Our unified criteria involving hemostatic endothelial molecular markers reflected not only mortality but also the severity of illness in patients with severe sepsis.