Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation

Background. Development of hydroxyethyl starches (HES) with a low impact on blood coagulation but a long intravascular persistence is of clinical interest. A previous in vitro study showed that low substituted high molecular weight HES does not compromise blood coagulation more than medium molecular weight HES. In the present study we assessed the individual effects on blood coagulation of molar substitution and C2/C6 ratio of a high molecular weight HES. Methods. Blood was obtained from 30 healthy patients undergoing elective surgery and mixed with six high molecular weight (700 kDa) HES solutions differing in their molar substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40 and 60% dilution. Blood coagulation was assessed by Thrombelastograph® analysis (TEG) and plasma coagulation tests.Data were compared using a three-way analysis of variance model with repeated measures on the three factors. Results. Higher molar substitution compromised blood coagulation most (for all TEG parameters, P0.50). The higher molar substitution was associated with a lesser increase in PT (P=0.007) and a greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von Willebrand factors were not significantly influenced by molar substitution (P for all >0.20). No significant differences between solutions with the same molar substitution but different C2/C6 ratios were found in plasma coagulation parameters (P for all >0.05). Conclusions. TEG analysis indicates that high molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the lowest effect on in vitro human blood coagulatio

Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors

A gene-centric analysis of activated partial thromboplastin time and activated protein C resistance using the HumanCVD focused genotyping array.

Activated partial thromboplastin time (aPTT) is an important routine measure of intrinsic blood coagulation. Addition of activated protein C (APC) to the aPTT test to produce a ratio, provides one measure of APC resistance. The associations of some genetic mutations (eg, factor V Leiden) with these measures are established, but associations of other genetic variations remain to be established. The objective of this work was to test for association between genetic variants and blood coagulation using a high-density genotyping array. Genetic association with aPTT and APC resistance was analysed using a focused genotyping array that tests approximately 50 000 single-nucleotide polymorphisms (SNPs) in nearly 2000 cardiovascular candidate genes, including coagulation pathway genes. Analyses were conducted on 2544 European origin women from the British Women's Heart and Health Study. We confirm associations with aPTT at the coagulation factor XII (F12)/G protein-coupled receptor kinase 6 (GRK6) and kininogen 1 (KNG1)/histidine-rich glycoprotein (HRG) loci, and identify novel SNPs at the ABO locus and novel locus kallikrein B (KLKB1)/F11. In addition, we confirm association between APC resistance and factor V Leiden mutation, and identify novel SNP associations with APC resistance in the HRG and F5/solute carrier family 19 member 2 (SLC19A2) regions. In conclusion, variation at several genetic loci influences intrinsic blood coagulation as measured by both aPTT and APC resistance

The use of viscoelastic haemostatic assays in non-cardiac surgical settings. a systematic review and meta-analysis

Background: Thrombelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic haemostatic assays (VHA) which exploit the elastic properties of clotting blood. The aim of this systematic review and meta-analysis was to evaluate the usefulness of these tests in bleeding patients outside the cardiac surgical setting. Materials and methods: We searched the Cochrane Library, MEDLINE, EMBASE and SCOPUS. We also searched clinical trial registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. Results: We found 4 randomised controlled trials (RCTs) that met our inclusion criteria with a total of 229 participants. The sample size was small (from 28 to 111 patients) and the follow-up periods very heterogenous (from 4 weeks to 3 years). Pooled data from the 3 trials reporting on mortality (199 participants) do not show any effect of the use of TEG on mortality as compared to standard monitoring (based on the average treatment effect from a fixed-effects model): Risk Ratio (RR) 0.71; 95% Confidence Interval (CI): 0.43 to 1.16. Likewise, the use of VHA does not reduce the need for red blood cells (mean difference -0.64; 95% CI: -1.51 to 0.23), platelet concentrates (mean difference -1.12; 95% CI: -3.25 to 1.02), and fresh frozen plasma (mean difference -0.91; 95% CI: -2.02 to 0.19) transfusion. The evidence on mortality and other outcomes was uncertain (very low-certainty evidence, down-graded due to risk of biases, imprecision, and inconsistency). Conclusions: Overall, the certainty of the evidence provided by the trials was too low for us to be certain of the benefits and harms of viscoelastic haemostatic assay in non-cardiac surgical settings. More, larger, and better-designed RCTs should be carried out in this area

Haematalogical investigations in children

The haematology laboratory is able to perform a number of tests to help establish the cause of illness in children. The full blood count (FBC, also known as a complete blood count, CBC) is one of the most basic blood tests performed on children attending hospital or a primary care clinic. All doctors should therefore have an understanding of how the test is performed, possible pitfalls, be able to interpret results and know when more specialised testing or advice is required. Other haematological investigations in routine use include coagulation screens, blood film examination, reticulocyte counts and methods for estimation of iron stores and detection of abnormal haemoglobins. This section will focus on these basic tests and simple algorithms for the subsequent investigation and differential diagnosis of the commonest haemato-logical abnormalities encountered in general paediatric practice. The reader is referred to Chapter 15 for an account of the clinical presentation and management of primary haematological disorders in children

Effects of moderate weight loss on anginal symptoms and indices of coagulation and fibrinolysis in overweight patients with angina pectoris

Objective: To evaluate the effects of moderate weight loss, in overweight patients with angina, on plasma coagulation, fibrinolytic indicies and pain frequency. Design: Single- stranded 12-week dietary intervention, an individualised eating plan with quantitative advice delivered by a dietitian. Target weight loss of 0.5 kg per week. Setting: Outpatient research clinic. Subjects: Fifty-four volunteers with angina pectoris were recruited. Five subjects withdrew, so 27 males, 22 females, mean body mass index (BMI) 29.3 (s.d. 4.3) kg/m(2) and age 60.3 (s.d. 6.5) y completed the intervention. Measurements: Body weight and frequency of anginal pain. Plasma fibrinogen, red cell aggregation (RCA), viscosity, factor VII activity, plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator antigen (t-PA), plasma cholesterol, triglyceride and insulin. Results: After the 12-week dietary intervention period, mean body weight fell by 3.5 (s.d. 2.6) kg or 4.3% (P = 0.0001), range -11.7 to +1.7 kg. Mean angina frequency fell by 1.8 (s.d. 3.6) from 3.2 to 1.4 episodes/week (P = 0.009) and plasma cholesterol by 0.4 (s.d. 0.7) from 6.3 to 5.9 mmol/1 (P = 0.0001). HDL cholesterol and triglyceride were unchanged. Of the coagulation and fibrinolytic factors, factor VII activity and RCA were significantly reduced by 5 (s.d. 20), IU/dl (P = 0.04) and 1.3 (s.d. 1.3) arbitrary units (P = 0.014), respectively. Conclusions: A conventional dietetic intervention, resulting in 4% weight loss, offers the potential to reduce atherosclerotic and thrombotic risk, and to reduce pain frequency, in angina patients. Given the importance of this result in a public health context, these results indicate that this may be a fruitful area for future nutrition research

C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent cardiovascular disease

C-reactive protein (CRP) has been proposed as a risk factor for cardiovascular disease; however, this association is confounded by mutual relationships with both classical and haematological cardiovascular risk factors. We, therefore, measured CRP with a high-sensitivity assay in stored plasma samples from 414 men and 515 women in the north Glasgow MONICA (MONItoring trends in CArdiovascular diseases) survey, to study its correlation with haematological variables, classical risk factors and prevalent cardiovascular disease. CRP correlated with age, oral contraceptive use, menopause and most classical cardiovascular risk factors (except blood pressure). CRP also correlated with plasma levels of the pro-inflammatory cytokine interleukin 6, and haematocrit, viscosity, red cell aggregation, white cell count, and coagulation factors [fibrinogen, factor (F) VII in women, FVIII, FIX] and inhibitors (antithrombin and protein C in women; protein S) but not coagulation activation markers. CRP was significantly associated with prevalent cardiovascular disease in both men (P = 0.03) and women (P = 0.009), however, the association became non-significant after adjustment for firstly classical risk factors, then fibrinogen. We conclude that correlations with classical and haematological risk factors account for a substantial component of the association of CRP with prevalent cardiovascular disease, but there is evidence of a residual, independent effect among women

Platelet Biochemistry and Morphology after Cryopreservation

Platelet cryopreservation has been investigated for several decades as an alternative to room temperature storage of platelet concentrates. The use of dimethylsulfoxide as a cryoprotectant has improved platelet storage and cryopreserved concentrates can be kept at −80 °C for two years. Cryopreserved platelets can serve as emergency backup to support stock crises or to disburden difficult logistic areas like rural or military regions. Cryopreservation significantly influences platelet morphology, decreases platelet activation and severely abrogates platelet aggregation. Recent data indicate that cryopreserved platelets have a procoagulant phenotype because thrombin and fibrin formation kicks in earlier compared to room temperature stored platelets. This happens both in static and hydrodynamic conditions. In a clinical setting, low 1-h post transfusion recoveries of cryopreserved platelets represent fast clearance from circulation which may be explained by changes to the platelet GPIbα receptor. Cryopreservation splits the concentrate in two platelet subpopulations depending on GPIbα expression levels. Further research is needed to unravel its physiological importance. Proving clinical efficacy of cryopreserved platelets is difficult because of the heterogeneity of indications and the ambiguity of outcome measures. The procoagulant character of cryopreserved platelets has increased interest for use in trauma stressing the need for double-blinded randomized clinical trials in actively bleeding patients

Beating heart coronary surgery and renal function: a prospective randomised study (Presented at 18th Spring Meeting of the Association of Cardiothoracic Anaesthetists: Selected abstracts, Cambridge, UK. 22 June 2001)

Introduction Cardiopulmonary bypass (CPB) is widely regarded as an important contributor to renal failure, a well recognised complication, following coronary artery surgery (CABG). Off-pump coronary surgery (OPCAB) is intuitively considered renoprotective. We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass (ONCAB).Methods Forty patients awaiting elective CABG were prospectively randomized into those undergoing OPCAB (n = 20) and ONCAB (n = 20). Table 1 illustrates the exclusion criteria. Glomerular and tubular injury were assessed, respectively, by urinary excretion of microalbumin and retinol binding protein (RBP) indexed to urinary creatinine [1]. Daily measurements were made from admission to postoperative day 5. Fluid balance, serum creati-nine and blood urea were also monitored. Results No mortality or renal complication was observed. Both groups had similar demographic make-up. The OPCAB group received fewer coronary grafts than their counterparts (1.8 versus 2.8; P = 0.002). Serum creatinine and blood urea remained normal in both groups throughout the study. A dramatic and similar rise in mean ± 2SD urinary RBP:creatinine ratio occurred in both groups peaking on day 1 (3183 ± 2534 versus 4035 ± 4078; P = 0.43) before returning to baseline levels. These trends were also observed with the urinary microalbumin:creatinine ratio (5.05 ± 2.66 versus 6.77 ± 5.76; P = 0.22). ONCAB patients had a significantly more negative fluid balance on postoperative day 2 (-183 ± 1118 versus 637 ± 847 ml; P < 0.05). Conclusions Although renal dysfunction did not clinically occur in any patient, sensitive indicators revealed significant and similar injury to both renal tubules and glomeruli following either OPCAB or ONCAB. These suggest that avoidance of CPB per se does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life