Hemostasis Disturbances Research Articles

Scandinavian guidelines for neuraxial block and disturbed haemostasis: replacing wishful thinking with evidence based caution

CENTRAL neuraxial blockades (CNBs) have gained widespread use, but may also be associated with serious complications. Spinal haematoma (SH) complicating CNB was initially believed to be an exceptional event. Indeed, based on published case reports, the first incidence of SH following CNB was reported as 1 : 1,000,000. However, several studies published in the last decades have found significantly higher incidences, particularly following non-obstetric epidural blockade (EB). Two large studies report the incidence of SH among non-obstetric perioperative EB as 1 : 10,000– 20,000. The probability for any single patient to develop SH following EB is very low, but the potentially disastrous consequences require attention for preventive measures, and timely diagnosis and management of SH is mandatory for full restitution of the patient. As all studies indicate that SH is extremely rare following spinal blockade (SB), it is remarkable that one study reported SH following SB in a patient subgroup of five females with fractured neck of femur, allowing an incidence of 1 : 22,000. The incidence of SH in the remaining perioperative SBs was 1 : 480,000. Female orthopaedic patients also appear to be at a particular high risk of developing SH following EB for prosthetic limb surgery, with an incidence of approximately 1 : 4000, reported from both sides of the Atlantic. Other risk factors seem to be vascular surgery, and renal and hepatic impairment. Disturbed coagulation, pharmacologically induced or otherwise caused, is also of major concern regarding the risk of developing SH. Removal of an epidural catheter is as critical a moment as its placement, and coagulation might have been impaired following surgery. Several studies have addressed the CNB’s potential of reducing morbidity and mortality, with conflicting results. Recent advances in patient care and optimal CNB techniques are not always applied. The individual risk–benefit analysis has to take this into account, integrating adequate CNB technique with all other aspects of optimised perioperative medical care. It is also possible that the patient with the largest potential benefit of perioperative EB is at a greatest risk of developing complications following the blockade. On the other hand, obstetric patients are at a significantly lower risk of developing SH following any kind of CNB. A metaanalysis reported the incidence of SH as 1 : 168,000 following obstetric EB, and this low incidence was recently confirmed by a large study that reported no case of obstetric SH among 186,900 EB (including 25,350 continuous spinal-EBs). Moreover, the majority of the rare obstetric SHs are caused by coagulation disorders related to specific obstetric conditions, such as preeclampsia, coagulopathy following large obstetric haemorrhage, or the syndrome of haemolysis, elevated liver enzymes and low platelets. In contrast, bloody taps, so frequently encountered when performing obstetric EB, apparently do not cause SH in obstetrics, but are often associated with cases of perioperative SH. Pregnancy itself induces a condition of increased coagulation, and NSAIDs are rarely used during pregnancy. Pharmacologically impaired coagulation is infrequent during pregnancy, and there are

Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice. The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus on recommendations for best clinical practice in providing effective and safe CNBs in patients with an increased risk of bleeding. We performed a literature search and expert evaluation of evidence for (1) the possible benefits of CNBs on the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from hereditary and acquired bleeding disorders and antihaemostatic drugs used in surgical patients for thromboprophylaxis, for (3) risk evaluation in published case reports, and for (4) recommendations in published national guidelines. Proposals from the taskforce were available for feedback on the SSAI web-page during the summer of 2008. Neuraxial blocks can improve comfort and reduce morbidity (strong evidence) and mortality (moderate evidence) after surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical abnormalities of the spine and spinal blood vessels, elderly patients, and renal and hepatic impairment are risk factors for spinal bleeding (strong evidence). Published national guidelines are mainly based on experts' opinions (weak evidence). The task force reached a consensus on Nordic guidelines, mainly based on our experts' opinions, but we acknowledge different practices in heparinization during vascular surgery and peri-operative administration of non-steroidal anti-inflammatory drugs during neuraxial blocks. Experts from the five Nordic countries offer consensus recommendations for safe clinical practice of neuraxial blocks and how to minimize the risks of serious complications from spinal bleeding. A brief version of the recommendations is available on http://www.ssai.info.

A Prospective Study of Platelets Function During the Process of Stem Cells Mobilisation in Healthy, Allogeneic Blood Stem Cell Donors Using the Method of Impedance Aggregometry.

Abstract 5079Potential haemostasis disturbances accompanying the process of peripheral stem cells harvest are still underestimated. Although the last two decades have witnessed an important increase in the use of peripheral blood stem cells (PBSC) for allogeneic transplantations, we are still lacking a satisfactory analysis of mobilization related risk of thrombosis or an unexpected bleeding. It was previously proved, that G-CSF administration may induce a hypercoagulable state by increasing levels of FVIII;C. On the other hand, platelet aggregation is reduced after cytokine application. Numerous, remaining unsolved questions in this matter prompted us to study prospectively 26 PBSC healthy donors. All donors were medically evaluated initially to eliminate any identifiable pathology in their medical history, especially concerning cardiovascular system. Any concomitant medication was excluded. All donors studied were excluded if they had an abnormal platelet count, activated partial thromboplastin time (APTT) or prothrombin time(PT) prior to cytokine administration.All donors received G-CSF (Neupogen, Amgen) at 5ug/kg of body weight subcutaneously twice daily for nine consecutive doses. We were analyzing the group of donors in the context of hemostasis alteration using the method of impedance aggregometry. The basic device used was “MULTIPLATE' aggregometer produced by DYNABYTE (Munich). We analyzed the primary hemostasis measuring the reaction of platelets to collagen (COL-TEST), ADP (ADP-test) and TRAP –test.We performed platelets aggregation analysis before G-CSF administration, and subsequently on the first day of stem cells mobilization, three times. The first sample was obtained just before the beginning of separation, the second in the half time point of the procedure and the last sample was drawn immediately after the cessation of stem cell collection procedure. We found reduced platelet aggregation after G-CSF administration, comparing the data before cytokine stimulation and preceding the leukapheresis (p<0,05).In contrast to this finding, there was a considerable increase in platelet activation parameters in the course of apheresis procedure, concerning both COL-test (p<0,04) nad TRAP-test (p<0,05).The clinical implications of these findings confirm important and significant coagulation system stimulation during separation procedure. DisclosuresNo relevant conflicts of interest to declare.

Intérêt de la surveillance biologique d'un patient présentant un coup de chaleur d'exercice

We present a 27-year-old soldier exertional heat stroke case report. Clinical examination has been reassuring during hospitalization. However biological disorders, especially liver and haemostasis disturbances, show off exertional heat stroke is a serious pathology on which clinician and biologist attention must be focalized, even if evolution is the more often favourable when an adapted and rapid treatment is used.

Is needle electromyography safe in patients on anticoagulation or antiplatelet therapy?

Needle electromyography (EMG) is a valuable diagnostic tool in the evaluation of the PNS and yet the risk of complications with this procedure in patients on anticoagulant or antiplatelet medications is unknown. Guidelines recommend caution when performing needle EMG in patients with disturbances of hemostasis because of the risks of intramuscular hemorrhage or other bleeding. This commentary reviews a study by Lynch et al. that investigated the risk of hematoma formation following needle EMG of the tibialis anterior muscle in 158 patients on antiplatelet or anticoagulant medications. The authors used a standardized approach to the needle examination, followed by application of direct pressure to the insertion site after removal of the needle. Three hematomas were detected--two in patients on warfarin, and one in a patient taking clopidogrel. None of the patients had symptomatic bleeding. These results indicate that the risk of hematoma formation is low following needle EMG when direct pressure is applied after removal of the needle.

Endothelial Function and Novel Adhesion Molecule CD44 in Kidney Allograft Recipients

Background Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these 2 processes and inflammation is closely related to endothelial dysfunction. Patients and Methods This cross-sectional study on serum concentrations of markers of endothelial damage and inflammation in relation to adhesion molecules was performed in 90 kidney allograft recipients and 30 healthy volunteers. We measured markers of endothelial damage—von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), CD146, CD44, and CD40L; markers of inflammation—high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFα), and interleukin-6 (IL-6); and other hemostatic parameters—thrombin-antithrombin complexes (TAT), plasmin-antiplasmin complexes, and thrombin activatable fibrinolysis inhibitor (TAFI) using commercially available kits. Results Markers of endothelial dysfunction and inflammation were significantly elevated in kidney allograft recipients compared with control subjects. CD44 was independently related to hsCRP ( r = .37; P < .01), ICAM ( r = .23; P < .05), eGFR ( r = −.37; P < .01), thrombomodulin ( r = .43; P < .001), VCAM ( r = −.44; P < .001), hemoglobin ( r = −.26; P < .01), red blood cell count ( r = −.25; P < .05), creatinine ( r = .37; P < .01), CD146 ( r = .34; P < .01), and CD40L ( r = .23; P < .05). Upon multiple regression analysis the predictors of elevated CD44 were hsCRP concentration (beta = .25; P < .05), CD146 (beta = .39; P < .05), creatinine (beta = .55; P < .01), and thrombomodulin (beta = .39; P < .05) with an adjusted R 2 = .40 ( F = 4.12; P < .00028; SE of estimate = 151.19). Conclusions As demonstrated in multiple regression analysis, kidney function was strictly linked to the degree of inflammation and endothelial injury. Endothelial cell injury and the presence of an inflammatory state, as reflected by elevated marker concentrations, and endothelial activation/injury may play roles in the pathogenesis of atherosclerosis and cardiovascular complications among kidney allograft recipients.

The clinic implication of markers detected in hemostasis and coagulation disturbance in children

正常的止凝血功能有赖于血管壁的完整性、血小板数量及功能的稳定以及凝血、纤溶系统的平衡.各种急重症如严重感染、急性创伤、恶性肿瘤等可因炎症因子的增多(如IL-6、肿瘤坏死因子等)、血管内皮损伤、组织因子的释放等激活体内凝血系统,导致毛细血管内广泛的微血栓形成,消耗血浆内各种凝血及抗凝成分,造成小儿止凝血功能异常,如果不能及时发现并给予纠正,患儿很快会发展成DIC并出现多种组织器官内缺血或出血,导致多器官功能衰竭,甚至死亡。

Relationship between oxidized fibrinogen and hemostasis disturbances and endothelial dysfunction in myocardial infarction

Oxidative modification of fibrinogen in acute myocardial infarction increased 1.3-fold compared to that in CHD and 1.5-fold surpassed that in the control without CHD. Elevated content of oxidized fibrinogen correlated with increased levels of LPO products, von Willebrand factor, and fibrin degradation products, with accelerated leukocyte and platelet aggregation, and reduced content of NO metabolites in the plasma. Independent associations of oxidized fibrinogen with myocardial infarction and typical thrombogenic and hypercoagulation hemostasis disorders and endothelial dysfunctions were revealed.

The value of rotation thromboelastometry to monitor disturbed perioperative haemostasis and bleeding risk in patients with cardiopulmonary bypass

Rotation thromboelastometry (ROTEM) performed on whole-blood samples provides information on the contribution of fibrinogen and platelets to clot formation. Such measurements are believed superior to classical plasma coagulation measurements as a means of monitoring disturbed haemostasis. On-pump cardiac surgery is associated with high bleeding risk. The study objective was to obtain information on the frequency of abnormal values of ROTEM variables and to assess their value in estimating bleeding risk in such patients. We studied 150 patients undergoing elective on-pump cardiac surgery. We found a significant surgery-induced decrease in haemostatic potential, with more abnormal ROTEM values in intrinsically activated coagulation (up to 50%) than in extrinsically activated coagulation (up to 27%) or the maximum clot firmness in FIBTEM (10%), a test measuring the contribution of fibrinogen. All ROTEM variables tend to normalize within 14-18 h postoperatively. Best positive predictive values and specificity for a postoperative blood loss above 600 ml were found for the clot formation time in extrinsically activated coagulation (71%/94%) and the maximum clot firmness in FIBTEM (73%/95%); these values were superior to the activated partial thromboplastin time or prothrombin time (56%/72% and 43%/5%, respectively). There was no relation between preoperative or early postoperative ROTEM values and intraoperative bleeding. ROTEM recorded a benefit of administration of platelet concentrates or fresh-frozen plasma, particularly when given postoperatively, on haemostasis. In contrast, intraoperative administration of red blood cells impaired haemostasis. ROTEM can provide a more detailed diagnostic basis enabling a focused therapy to cardiac surgery patients with high bleeding risk.

Metabolic syndrome, haemostasis and thrombosis

The metabolic syndrome (metS), a concurrence of abdominal fat, disturbed glucose and insulin metabolism, dyslipidemia, and hypertension has been strongly associated not only with subsequent development of type 2 diabetes but also with atherothrombosis. The physiopathology of this association is complex. The metS affects the thrombogenicity of circulating blood. Apart from its effect on platelets, a procoagulant and hypofibrinolytic state has been identified; mainly the result of the inflammatory state, dyslipidemia, and liver fat accumulation that accompany the MetS. Among haemostasis disturbances, the strong rise in the inhibitor of plasminogen activator type 1 plasma level is the most documented abnormality implicating the participation of the oxidative stress and inflammatory state developed during the metS. Endothelial dysfunction is also a central feature. Moreover, secretion products of fat tissues (adipokines) are now thought to have direct modulating effects on the vascular and the circulating cells. In support of these data, the metS, may predispose not only to atherosclerosis but also to venous thrombosis.

EFFECT OF THE HEME OXYGENASE INDUCER HEMIN ON BLOOD HAEMOSTASIS MEASURED BY HIGH-FREQUENCY ULTRASOUND

1. Heme compounds, like hemin, a heme oxygenase-1 inducer, are used in the treatment of acute porphyria treatment. The side-effects of hemin on haemostasis have been reported. To address those effects, in the present study we used a sensitive, high-frequency ultrasound technique to record acoustic velocity and to investigate whole blood clotting in Wistar rats treated chronically with hemin (50 mg/kg per day). 2. The hemin-induced disturbances in haemostasis measured were comparable to the heparin reference treatment, with a significant decrease in clotting velocity in both groups compared with controls (e.g. the time to clot was 40 +/- 5, 53 +/- 13 and 10 +/- 2 min, respectively; P < 0.05). Precautions must be taken when using high doses of hemin or in the treatment of bleeding diseases. 3. Further investigations are required to explore the effects of hemin in thrombosis models, because it could be a promising 'old drug' for the treatment of venous thrombosis in patients.

Activation and Disturbance of Blood Haemostasis Following Strenuous Physical Exercise

Activation and Disturbance of Blood Haemostasis Following Strenuous Physical Exercise

Is the activated partial thromboplastin time suitable to screen for von Willebrand factor deficiencies?

The diagnostic approach to von Willebrand factor deficiencies is challenging and requires discretionary use of laboratory resources. Although extensive preoperative testing is not recommended, the activated partial thromboplastin time may be useful, especially in selected categories of patients. To establish the diagnostic sensitivity of this test to identify isolate von Willebrand factor deficiencies, 204 consecutive patients underwent a routine preoperative screening consisting of activated partial thromboplastin time, von Willebrand factor antigen, intrinsic pathway clotting factors activity, lupus anticoagulants and thrombin time. Thirty-seven patients were diagnosed with haemostasis disturbances other than von Willebrand factor deficiencies and were excluded from the evaluation. Isolated von Willebrand factor deficiency was diagnosed in 11 of the remaining 167 patients. A significant correlation was observed between von Willebrand factor antigen and activated partial thromboplastin time. Receiver operating characteristic curve analysis showed an area under the curve of 0.982 (95% confidence interval: 0.972-0.992; P < 0.001). At the 1.17 upper limit of the activated partial thromboplastin time, sensitivity and specificity were 100 and 85%, respectively, with negative and positive predictive values of 100 and 31%, respectively. These results demonstrate that activated partial thromboplastin time has an excellent diagnostic sensitivity and a satisfactory specificity for identifying isolated von Willebrand factor deficiencies.

Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury

University of Louisville, Louisville, Kentucky. ozan.akca@louisville.eduI read with interest the excellent article by Choi et al. 1about the preventive role of mechanical ventilation, with lower tidal volumes plus positive end-expiratory pressure (PEEP), on alveolar coagulation. They demonstrated that mechanical ventilation with lower tidal volumes and PEEP (10 cm H2O) decreases the procoagulant activity in the lungs of even otherwise healthy surgical patients. The observed procoagulant activity change was explained by mechanical ventilation with high tidal volume and no PEEP. In previous studies, the same researchers and others showed that there were similar pulmonary hemostasis disturbances in patients with adult respiratory distress syndrome and pneumonia. Although much is unknown about the topic, the authors gave a detailed discussion as to whether this procoagulant activity is a possible sign of repair or a further trigger of proinflammatory process in the lung.If we exclude this important work by Choi et al. , the recent literature provides conflicting evidence on the role of high-tidal volume with no PEEP in causing ventilator-associated lung injury in healthy human lungs.2–4Possibly because of the short amount of time that mechanical ventilation is provided during general anesthesia, it was hard to see any clinical effects of potential lung stretch in relatively healthy human lungs. Another explanation would be that high-tidal-volume ventilation alone is not a sufficient trigger to cause lung injury in healthy human lungs. Two recent articles from Wrigge et al. 4,5support the latter explanation. Accepting this, one can hypothesize that mechanical ventilation with high tidal volumes without PEEP does not initiate any tissue injury that can be monitored by proinflammatory cytokine response.However, when we take the article by Choi et al. into account and further consider the bidirectional relation between coagulation and inflammation in pathogenesis of vascular disease as well summarized previously by Levi et al. ,6we realize that there are different questions to be asked and various hypotheses to be made to fully understand the mechanism of ventilator-associated lung injury in previously healthy subjects. For example, what might be the absolute first trigger to initiate stretch injury in the lungs? As in the vascular pathophysiology, is it the direct stretch of mononuclear cells (in this case alveolar macrophages) that triggers the proinflammatory or procoagulant pathways? Is it a set of proinflammatory cytokines originating from the alveolar macrophages (or even epithelial cells) triggering the procoagulant process in the lungs? Can such processes be triggered by lung cellular stretch through the activation of integrin–mitogen-activated protein kinase–interleukin-8 pathway, which would lead to further chemokine responses?7,8Or do any of the toll-like receptors play a triggering role in initiating transcriptional processes through nuclear factor κB to deliver proinflammatory pathways including tumor necrosis factor α or interleukin 1β? Can it be that high-tidal-volume, no-PEEP ventilation cancels the alveolar integrity and stability of alveolar macrophages maintained by transforming growth factor β?9The sequence of triggers would bring the real mechanisms behind the ventilator-associated lung injury and associated lung injury. Therefore, it is extremely important to understand the sequence of triggers and potential pathways. At this point, if Choi et al. performed any other tests in the bronchoalveolar lavage samples, such as proinflammatory cytokines, chemokines, or any transcriptional pathway agents, simultaneously with their procoagulant tests, it would be valuable to share such data for further development of new hypotheses to test the bidirectional relation between coagulation and inflammation.University of Louisville, Louisville, Kentucky. ozan.akca@louisville.eduThe author thanks Nancy Alsip, Ph.D. (University of Louisville, Louisville, Kentucky), for editorial assistance.

Krwotok okołoporodowy z ciężkimi zaburzeniami hemostazy - możliwości leczenia z zastosowaniem ludzkiego rekombinowanego czynnika krzepnięcia rFVIIa NovoSeven - własne doświadczenia kliniczne

Krwotok okołoporodowy z ciężkimi zaburzeniami hemostazy - możliwości leczenia z zastosowaniem ludzkiego rekombinowanego czynnika krzepnięcia rFVIIa NovoSeven - własne doświadczenia kliniczne

Thyroid Function, Endothelium, and Inflammation in Hemodialyzed Patients: Possible Relations?

Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and inflammation are common complications of kidney diseases. Endothelial dysfunction may link these two processes. A cross-sectional study on thyroid hormones in relation to markers of endothelial damage and inflammation in 96 hemodialyzed (HD) patients and 39 healthy volunteers was performed. The study took place in the dialysis unit at a university hospital. Thyroid hormones, markers of endothelial damage (von Willebrand factor, thrombomodulin, intracellular adhesion molecule, and CD146), markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor alpha), other hemostatic parameters (thrombin-antithrombin complexes, prothrombin fragments 1 + 2 - F1 + 2, plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, tissue factor pathway inhibitor, and platelet glycoprotein V) were measured using commercially available kits. Free T3 and total T3 were lower in HD patients compared with controls. Markers of endothelial dysfunction and inflammation were significantly elevated in HD patients compared with controls. In multiple regression analysis T3 was independently related to time on dialyses, albumin, iron, ferritin, C-reactive protein (CRP), and F1 + 2 in HD patients. Free T3 was also independently related to total protein, total calcium, and triglycerides. In patients with CRP less than 6 mg/L in multiple regression analysis the only correlates of T3 were albumin and ferritin, whereas the only correlates of free T3 were albumin and time on dialyses. Multiple regression analysis showed that in HD patients with CRP greater than equal to 6 mg/L predictors of free T3 were CRP, F1 + 2, and dose of erythropoietin. In healthy volunteers T3 was related to tissue factor pathway inhibitor and platelet glycoprotein V was related to thyroid-stimulating hormone. We described novel relations between thyroid hormones and markers of endothelial dysfunction and inflammation in HD patients. Thyroid dysfunction is related to time on dialyses, endothelial damage, and inflammatory state, frequently encountered in uremia. Therefore, the relations between thyroid axis and endothelium in HD subjects merit additional studies.

Tissue factor and urokinase-type plasminogen activator system are related to the presence of cardiovascular disease in hemodialysis patients

Introduction The disturbances of haemostasis and enhanced oxidative stress (SOX) appear to contribute to the cardiovascular disease (CVD) in hemodialysis (HD) patients. The aim of the present study was to investigate if the disorders of coagulation/fibrinolysis system are associated with the presence of CVD in these patients. Materials and methods We compared pre-dialysis levels of uPA, suPAR, tissue factor (TF) and its inhibitor (TFPI), prothrombin fragment F1 + 2 (F1 + 2); a marker of SOX-Cu/Zn superoxide dismutase (Cu/Zn SOD) and a surrogate of inflammation-high sensitivity C-reactive protein (hs CRP) in HD patients with and without CVD. Results The uPA/suPAR system and hs CRP values were significantly greater in patients with CVD than in those without CVD; whereas TF, TFPI, F1 + 2 and Cu/Zn SOD levels were comparable in both patient groups. TF was positively correlated with both uPA ( p < 0.001) and suPAR levels ( p < 0.05). Logistic regression analysis showed that elevated levels of suPAR, TF and uPA were independently associated with the presence of CVD in HD patients. Conclusions The association between TF and uPA/suPAR system is significantly related to the presence of CVD in HD patients.

Possible Relations Between Thyroid Function, Endothelium, and Kidney and Liver Function in Kidney Allograft Recipients

Background Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes. Aim and methods This cross-sectional study examined thyroid hormones in relation to markers of endothelial damage and inflammation among 80 kidney allograft recipients and 29 healthy volunteers. Thyroid hormones, markers of endothelial damage ( vWF, thrombomodulin, intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146), markers of inflammation (hsCRP), other hemostatic parameters (thrombin-antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet glycoprotein [V-GPV]) as well as P-selectin were measured using commercially available kits. Results Total T3 was significantly lower among kidney allograft recipients, whereas markers of endothelial dysfunction and inflammation were significantly elevated over controls. In kidney allograft recipients total T3 was independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin, urea, eGFR, dose of cyclosporine and treatment with mycophenolate mofetil/azathioprine. Total T4 was related to aspartate and alanine aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and cyclosporine dose. In healthy volunteers GPV was related only to TSH. Conclusions We described novel relations between thyroid hormones and markers of endothelial dysfunction in kidney transplant recipients. In kidney transplant recipients thyroid function metrics were associated with endothelial damage, immunosuppressive treatment, liver and kidney function. Therefore, the relations between thyroid axis and endothelium in kidney allograft recipients merit additional studies.

Evidence of hypercoagulability and inflammation in young patients long after acute cerebral ischaemia

Introduction Young subjects with acute cerebral ischaemia – stroke or transient ischaemic attack – form an etiologically heterogeneous and often not clearly explained group of patients. The aim was to investigate possible disturbances in haemostasis and inflammation long after an acute cerebral ischaemic event. Materials and methods Forty-four consecutive patients referred after having suffered from acute cerebral ischaemia before the age of 45 participated 1 to 9 years (median value 5 years) after the event. At the time of blood sampling 33 (75%) patients were receiving antithrombotic treatment. Forty-six apparently healthy subjects of the same age group served as controls. In all subjects global haemostasis parameters (overall haemostasis, coagulation and fibrinolytic potential), thrombophilia, several markers of haemostasis activation and inflammation were determined. Results Patients did not differ from controls in most of the conventional risk factors and the presence of most forms of thrombophilia, although in seven (17.5%) patients the weak presence of lupus anticoagulants was observed. Patients had significantly increased overall haemostasis and coagulation potential, increased soluble P-selectin and D-dimer, decreased overall fibrinolysis potential and increased fibrinogen and C-reactive protein compared to controls. The subgroups of patients receiving antiplatelet treatment, with thrombophilia and recurrent acute cerebral ischaemia, did not differ significantly from the other patients. Conclusions In young patients long after acute cerebral ischaemia an imbalance in the haemostatic system and a minor, but significant degree of inflammation was detected. The mechanisms behind haemostatic imbalance seem to be enhanced thrombin generation, platelet activation and depressed fibrinolysis.

Hemostasis and fibrinolysis in non-diabetic overweight and obese men and women. Is there still a role for leptin?

Leptin has been associated with disturbances in hemostasis and fibrinolysis, with inconsistent results on the influence of fat mass. However, the influence of the amount of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) has not yet been studied. In this study, we investigated the relationship between leptin and fibrinogen, von Willebrand factor antigen (vWF:Ag), and plasminogen-activator inhibitor-1 (PAI-1) activity and determined the influence of associated metabolic variables and VAT versus SAT. Fibrinogen, vWF:Ag, PAI-1,VAT and SAT (CT-scan), and insulin resistance (homeostasis model assessment; HOMA-IR) were measured in 199 women and 81 men with overweight or obesity visiting the weight management clinic of a university hospital. Leptin did not relate to fibrinogen (r = 0.11 and 0.13 in women and men respectively; P > 0.05), a relationship with vWF:Ag was only found in men (r = 0.31; P = 0.005), while leptin related to PAI-1 activity in both men (r = 0.36; P < 0.001) and women (r = 0.23; P < 0.001). Further analysis showed leptin to have an effect on the variation of PAI-1 independent of VAT and HOMA-IR in women, but not in men. Multiple regression showed HOMA-IR to be the most important determinant of PAI-1, both in men and women, but leptin also showed an independent effect. As for vWF:Ag, leptin was an independent determinant in men only. PAI-1 related to leptin levels independent of fat mass percentage, HOMA-IR, and the amount of VAT and SAT. For vWF:Ag this relationship was found only in men, and not in women, while a relationship with fibrinogen could not be demonstrated.