Recent evidence suggests that Ca supplements increase the risk of cardiovascular events, but the mechanism(s) by which this occurs is uncertain. In a study primarily assessing the effects of various Ca supplements on blood Ca levels, we also investigated the effects of Ca supplements on blood pressure and their acute effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of Ca or a placebo containing no Ca. Blood pressure was measured at baseline and every 2 h up to 8 h after their first dose and after 3 months of supplementation. Blood coagulation was measured by thromboelastography (TEG) in a subgroup of participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the groups, consistent with its normal diurnal rhythm. The reduction in systolic blood pressure was smaller in the Ca group compared with the control group by >5 mmHg between 2 and 6 h (P≤0·02), and the reduction in diastolic blood pressure was smaller at 2 h (between-groups difference 4·5 mmHg, P=0·004). Blood coagulability, assessed by TEG, increased from baseline over 8 h in the calcium citrate and control groups. At 4 h, the increase in the coagulation index was greater in the calcium citrate group compared with the control group (P=0·03), which appeared to be due to a greater reduction in the time to clot initiation. These data suggest that Ca supplements may acutely influence blood pressure and blood coagulation. Further investigation of this possibility is required.

This paper presents numerical results based on a macroscopic blood coagulation modelcoupled with a non-linear viscoelastic model for blood flow. The system of governingequations is solved using a central finite-volume scheme for space discretization and anexplicit Runge-Kutta time-integration. An artificial compressibility method is used toresolve pressure and a non-linear TVD filter is applied for stabilization. A simple testcase of flowing blood over a clotting surface in a straight 3D vessel is solved. This workpresents a significant extension of the previous studies [10] and [9].

Thrombus formation in flowing blood is a complex time- and space-dependent process ofcell adhesion and fibrin gel formation controlled by huge intricate networks ofbiochemical reactions. This combination of complex biochemistry, non-Newtonianhydrodynamics, and transport processes makes thrombosis difficult to understand. That iswhy numerous attempts to use mathematical modeling for this purpose were undertaken duringthe last decade. In particular, recent years witnessed something of a transition from the“systems biology” to the “systems pharmacology/systems medicine” stage: computationalmodeling is being increasingly applied to practical problems such as drug development,investigation of particular events underlying disease, analysis of the mechanism(s) ofdrug’s action, determining an optimal dosing protocols, etc. Here we review recentadvances and challenges in our understanding of thrombus formation.

Amla (Emblica officinalis Gaertn.) has been used for many centuries in traditional Indian Ayurvedic formulations for the prevention and treatment of many inflammatory diseases. The present study evaluated the anti-inflammatory and anticoagulant properties of amla fruit extract. The amla fruit extract potentially and significantly reduced lipopolysaccharide (LPS)-induced tissue factor expression and von Willebrand factor release in human umbilical vein endothelial cells (HUVEC) in vitro at clinically relevant concentrations (1–100 μg/ml). In a leucocyte adhesion model of inflammation, it also significantly decreased LPS-induced adhesion of human monocytic cells (THP-1) to the HUVEC, as well as reduced the expression of endothelial-leucocyte adhesion molecule-1 (E-selectin) in the target cells. In addition, the in vivo anti-inflammatory effects were evaluated in a LPS-induced endotoxaemia rat model. Oral administration of the amla fruit extract (50 mg/kg body weight) significantly decreased the concentrations of pro-inflammatory cytokines, TNF-α and IL-6 in serum. These results suggest that amla fruit extract may be an effective anticoagulant and anti-inflammatory agent.

The wide use of anticlotting drugs by patients scheduled for surgery is a challenge for the anaesthesiologist when considering a regional anaesthesia technique. This practice seems safe if there is an appropriate management based on safety intervals established according to the pharmacology of the drug and the regional technique. Some anaesthesiology societies have published recommendations for the safe practice of regional anaesthesia with the simultaneous use of anticoagulants (heparin, low molecular weight heparins, oral anticoagulants (OA), fondaparinux and others) and antiplatelet agents (aspirin, clopidogrel, ticlopidine, argatroban and others). One of the most recent guidelines has been published by the Spanish Society of Anaesthesia and Critical Care. This article reviews these recommendations and compares them with others published in the last years. The recommendations are similar, but some interesting differences can be observed and need to be considered. A European consensus in this setting would probably be necessary.

Regular moderate intensity physical activity and habitual diet providing no more than one third of energy from fats have been recommended for the prevention of atherosclerotic diseases. The background for these guidelines is the key role of plasma lipids. However, the importance of thrombogenesis in acute myocardial infarction has become obvious during the last decade. Hyperlipidaemia and excess of adipose tissue increase platelet aggregability and blood coagulation, and decrease fibrinolysis. Both regular physical activity and dietary fat reduction decrease blood lipids and body fat thereby diminishing the risk of thrombosis. Currently, data on interactions between physical activity and diet on haemostasis are scarce, and the few studies available have not demonstrated additional effects when these two lifestyle modifications have been combined. This paper is restricted only to studies using controlled randomized design. Regular moderate intensity physical activity as well as diet rich in omega-3 fatty acids decrease platelet aggregability. The effects of regular physical activity on plasma fibrinogen remain contradictory, while the impact of diet is even less clear. Plasminogen activator inhibitor-1, a possible link between insulin resistance syndrome and coronary heart disease, may decrease due to physical training or low fat diet. It can be hypothesized that moderation in physical activity and diet carries a more powerful impact on blood coagulation and fibrinolysis than either lifestyle modification alone. Studies focusing on the interactions of regular moderate physical activity and fat-modified diet are needed in efforts to optimize the preventive actions by lifestyle changes.

Summary

Background and objective: Crystalloid haemodilution has been widely found to enhance coagulation onset, but the duration of this effect has never been documented. Methods: Twelve healthy, consenting volunteers had a rapid infusion of 14 mL kg−1 of normal (0.9%) saline. Blood samples were taken, prior to (control), and immediately after (30 min) the rapid saline infusion was completed (30 min). They were then repeated at regular intervals up to 120 min. Haematocrit/platelet counts were taken to determine the degree of dilution and thrombelastograms, with and without platelet antagonists (ReoPro, Abciximab), were measured in all samples. Antithrombin levels were selectively measured. Results: The haematocrit and platelet count showed a rapid dilutional decrease at 30 min (mean of −12.2% and −14.4%, respectively), with values returning towards baseline within 15 min after finishing the infusion. There was a significantly faster onset of coagulation (decrease in r-time) in the post-infusion sample (30 min) compared to control (P < 0.05), again returning towards normal as the dilution effect was reversed. Similar thrombelastograms findings were evident in the plasma factor only group (platelets inhibited by ReoPro). Antithrombin levels changed in keeping with the haemodilution effect (P < 0.0001). There was a linear relationship between antithrombin and thrombelastograms r-time (P = 0.012). Conclusion: The faster onset of coagulation brought on by haemodilution return towards normal as the dilutional effect is reversed. This effect is mediated through plasma clotting factors. Of interest is the significant inverse correlation of the onset of coagulation increasing as the antithrombin levels decreased with dilution.

Spatial dynamics of fibrin clot formation in non-stirred system activated by glasssurface was studied as a function of FIX activity. Haemophilia B plasma was obtained fromuntreated patients with different levels of FIX deficiency and from severe haemophilia B patienttreated with FIX concentrate (Ahemphil B) during its clearance with half-life t1/2=12 hours. Asreported previously (Ataullakhanov et al. Biochim Biophys Acta 1998; 1425: 453-468), clotgrowth in space showed two distinct phases: activation and propagation. The activation phase ischaracterized by the time required to start clot growth from the activator, while the characteristicparameter of the propagation phase is the clot elongation rate. This rate reaches steady state inapproximately ten minutes after the beginning of growth. In haemophilia B plasma, clotformation is substantially impaired: clot starts to grow from the activating surface later than inhealthy donor plasma, and its propagation rate is considerably lower. The most significantabnormalities in clot growth kinetics are observed at FIX activity below 10% of normal.Simulation of these experiments was performed theoretically using a detailed biochemical model(Panteleev et al. Biophys J 2006; 90: 1489-1500) adapted for experimental conditions used.Suitability of the assumptions used to describe triggering contact activation was verified.

The aetiopathogenesis of acute unilateral peripheral vestibular dysfunction (APV), also known as vestibular neuritis, is still debated: the principal cause is viral infection with vascular factors second in importance.

Plasmatic D-dimer, considered a plasmatic index of hypercoagulation, was measured in a group of 45 APV patients and in a group of 25 patients suffering from Ménière’s disease. Measurements were taken both during the acute stage and after a four to six week period of pharmacological washout. The mean D-dimer levels were significantly higher than those measured in the controls both during the acute phase (301 SD161 vs 202 SD113 ng/mL) and after follow up (304 SD211 vs 192 SD111 ng/mL) (p = 0.008). Moreover, during the acute stage 23 of the APV patients (51.1 per cent) had plasmatic D-dimer levels above the upper normal limit (i.e.: <300 ng/mL), compared to four of those with Ménière’s disease (16 per cent).

Our results lead us to postulate an involvement of the haemostatic system in APV.

Profound and complex coagulation disorders are encountered during liver transplantation. They include preoperative coagulation disorders related to the liver disease and haemostatic changes related to the procedure itself. They commonly lead to increased intraoperative bleeding, especially due to increased fibrinolysis, the contribution of which can be demonstrated by the relative efficacy of antifibri-nolytics. Given the multifactorial nature of bleeding in liver transplantation, preoperative coagulation tests cannot predict blood loss even if some statistical relationship is occasionally found.Preoperative correction of coagulation defects has not been shown to be effective in reducing intraoperative bleeding. Throughout the procedure, a rapid and sensitive method for monitoring coagulation is necessary in order to guide the rational use of blood components and pharmacological agents. The usefulness of such a method to assist management of blood loss or blood component requirements is poorly documented and controversial.

Based on amino acid sequence similarities that exist between the fibrinogen γ-chain and κ-casein, and also functional similarities between milk and blood coagulation, considerable effort has been made to investigate the effects of milk proteins and peptides on platelet function and thrombosis. In particular, a number of peptides derived from the glycomacropeptide segment of κ-casein, have been shown to inhibit platelet aggregation and thrombosis. KRDS, a peptide from lactoferrin has also been shown to inhibit platelet aggregation but to a lesser extent than its fibrinogen analogue RGDS. Despite their functional and structural similarities they do not act in the same way on platelet function and are thought to affect thrombus formation differently. Further investigation is needed to determine if these milk-derived bioactive peptides are released naturally following ingestion and might therefore be useful as the basis for milk-based products with anti-thrombotic properties.

A retrospective survey was undertaken of 142 adults who had undergone cardiac surgery with cardiopulmonary bypass. According to the manufacturer's instructions for thromboelastography, patients were identified as showing evidence of fibrinolysis if after coming off bypass the Ly30 index was ≥7.5%. In the 20 fibrinolytic patients, fibrinolysis was readily corrected by tranexamic acid but these patients needed more colloid and more vasopressor support than the non-fibrinolytic patients. There were three deaths, all in the fibrinolytic patients. It is possible that fibrinolysis is a marker for onset of systemic inflammation syndrome. It is recommended that, until the association between fibrinolysis and worse outcome is investigated further, patients showing fibrinolysis early after cardiopulmonary bypass should not be discharged too soon from intensive care.