Increased serum concentrations of the carboxy-terminal cross-linked telopeptide of collagen type I in patients with Gram-negative septicaemia

The authors determined serum levels of the carboxy-terminal cross-linked telopeptide and the carboxy-terminal propeptide of type 1 collagen (ICTP and PICP) in 18 patients with Gramnegative septicaemia before (day 0) and 28 days after therapy and in 18 age- and sex-matched controls by radioimmunoassay. Elevated levels of ICTP were observed in septicaemic patients [median (range): 15 (7–49) μg L⁻¹ before therapy and 14 (6–45) μg L⁻¹ 28 days after therapy vs. 2.1 (1.4–4.3) μg L⁻¹ in normal subjects; P  < 0.01 for both], whereas PICP levels were not different between patients and controls [median (range): 119 (52–275) μg L⁻¹ (day 0) and 133 (79–288) μg L⁻¹ (day 28) vs. 91 (54–213) μg L⁻¹ in normal subjects, P  > 0.05 for all]. The findings suggest an increased production or release of ICTP in Gram-negative septicaemia, presumably owing to an alteration of extracellular matrix during septicaemia-related vascular inflammation.     

Factor XII-dependent increases in thrombin activity induce carboxypeptidase-mediated attenuation of pharmacological fibrinolysis

Summary.  Activation of the contact system in patients treated with fibrinolytic agents may be an important source of thrombin that activates thrombin-activated fibrinolysis inhibitor (TAFI) and attenuates fibrinolysis. Factor (F)XIIa in plasma increased 2-fold over 60 min in patients given either tissue plasminogen activator (t-PA) or streptokinase (SK). To determine whether FXIIa-mediated generation of thrombin and activated TAFI (TAFIa) attenuates fibrinolysis in vitro , plasma clots were incubated with SK (250 U mL⁻¹) or t-PA (2.5 g mL⁻¹) and the rate of lysis was measured. Plasma FXIIa impaired lysis judging from marked acceleration when 2.5 µ m corn trypsin inhibitor were added (lysis increased by 172 ± 144% for SK and 40 ± 31% for t-PA vs. no inhibitor, n  = 16, P  < 0.01). Moreover, inhibition of thrombin with hirudin and TAFIa with carboxypeptidase inhibitor accelerated lysis. We conclude that activation of FXII increases thrombin generation, which promotes TAFIa-mediated attenuation of fibrinolysis.     

SSC/ISTH classification of hemophilia A: can hemophilia center laboratories achieve the new criteria?

Summary.  To assess the practicality of the recent Scientific and Standardization committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) recommendations in respect of the classification of hemophilia we distributed samples from three untreated subjects with hemophilia A to 91 UK hemophilia centers (HCs), comprising 20 comprehensive care centers (CCCs) and 71 HCs. Laboratories were requested to perform their routine factor (F)VIII:C assays and to classify the severity of hemophilia. Median values of < 1 U dL⁻¹ were obtained on two samples. However, for each of the two, approximately 30% of laboratories obtained results in the range 1–29 U dL⁻¹ and 1–33 U dL⁻¹ respectively. For one of these samples 17 laboratories diagnosed severe hemophilia despite obtaining FVIII:C levels in the range 1–5 U dL⁻¹. The median FVIII:C for the third sample was 5.8 U dL⁻¹ with a range of 1.5–36 U dL⁻¹. For this sample eight centers diagnosed severe hemophilia. Fifty-four laboratories obtained a result > 5 U dL⁻¹; 21 of these diagnosed mild hemophilia, 31 moderate hemophilia and two severe hemophilia. Results from CCCs were more accurate and more precise than those from HCs. Our results indicate a need for improved standardization of FVIII assays. In the UK there remains a lack of consensus in respect of the laboratory diagnostic criteria for the classification of hemophilia A.     

Vasoactive substances in early dumping syndrome: effects of dumping provocation with and without octreotide

In patients after gastric surgery, early dumping symptoms can be provoked by oral glucose challenge. Octreotide effectively prevents the occurrence of dumping symptoms. We have studied plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP) concentrations in nine patients with early dumping, 10 surgical control subjects and nine healthy control subjects after an oral glucose challenge preceded by either placebo or 25 μg of octreotide subcutaneously (s.c.). In the dumping group, basal PRA was signifi-cantly ( P  < 0.01) higher (3.9 ± 0.6 μg L⁻¹ h⁻¹) than in either surgical or healthy control subjects (1.1 ± 0.3 μg L⁻¹ h⁻¹ and 1.1 ± 0.2 μg L⁻¹ h⁻¹ respectively) and showed a significant rise after glucose ingestion to 5.4 ± 0.9 μg L⁻¹ h⁻¹ that did not occur in control subjects. Aldosterone concentration showed a concomitant rise. In dumping patients, plasma ANP decreased after glucose ingestion from 31 ± 6 ng L⁻¹ to 21 ± 5 ng L⁻¹ ( P  < 0.05). This decrease did not occur in control subjects. Early dumping is associated with an activation of the renin–aldosterone axis and a decrease in plasma ANP, reflecting a hypovolaemic state. Octreotide prevents the occurrence of these changes.     

Cardiac involvement in acute thrombotic thrombocytopenic purpura: association with troponin T and IgG antibodies to ADAMTS 13

Summary.  Introduction: Evidence for cardiac involvement in thrombotic thrombocytopenic purpura (TTP) is uncommonly described. Methodology: We retrospectively reviewed 41 patients assessing troponin T as a marker for cardiac involvement in acute TTP with clinical symptoms, electrocardiograms (ECG) and echocardiograms. A histopathological review of five patients who died of acute TTP was also undertaken. Results: In 54% (22/41) of patients, troponin T was ≥ 0.05μg L⁻¹ (normal range 0–0.01 μg L⁻¹). Half (12/22) had cardiac symptoms and 8/22 with a raised troponin T reported chest pain. ECG changes were present in 62% of patients with a raised troponin T. Median anti-ADAMTS 13 IgG antibody was significantly higher ( P  = 0.018) in patients with troponin T ≥ 0.05 μg L⁻¹ (58.5% (range 17–162%), compared with patients with troponin T < 0.05 μg L⁻¹ (35%, range 9–134%). Patients who died had higher troponin T levels (median 0.305 μg L⁻¹) and raised anti-ADAMTS 13 IgG (median 66.5%). On admission, there were no deaths in those with troponin T ≤ 0.04μg L⁻¹. Histology confirmed widespread myocardial microvascular thrombi. Conclusion: Clinical symptoms, ECG changes and echocardiograms are poor predictors of cardiac disease in acute TTP. Troponin T is specific for cardiac muscle and a sensitive marker of myocardial damage. In TTP patients, raised levels (≥ 0.05 μg L⁻¹) signify myocardial necrosis associated with microvascular thrombi. Mortality and acute morbidity was associated with higher admission troponin T and raised IgG antibody (> 67%) to ADAMTS 13.     

Inhibition of paracrine angiotensin-converting enzyme in vivo: effects on interstitial glucose and lactate concentrations in human skeletal muscle

Microdialysis was used to selectively assess the effect of the paracrine renin–angiotensin system (RAS) on interstitial glucose and lactate concentration profiles in skeletal muscle of healthy volunteers ( n  = 8) during basal and insulin-stimulated conditions. Paracrine RAS was selectively inhibited by local retrodialysis with enalaprilate. Under basal conditions, local administration of enalaprilate (2 μg mL⁻¹) increased interstitial dialysate glucose concentration from 0.71 ± 0.14 mmol L⁻¹ to 0.84 ± 0.14 mmol L⁻¹ and decreased the serum interstitial gradient (SIG_glu) compared with baseline ( P  < 0.02). Under clamp conditions, enalaprilate, even at the lowest concentration (0.02 μg mL⁻¹), increased interstitial dialysate glucose concentration from 0.77 ± 0.11 mmol L⁻¹ to 1.02 ± 0.09 mmol L⁻¹ and decreased SIG_glu compared with baseline ( P  < 0.01). Interstitial lactate concentrations slightly increased during basal as well as during clamp conditions ( P  < 0.05 vs. baseline). Selective inhibition of paracrine muscle angiotensin-converting enzyme (ACE) increases interstitial glucose and lactate concentrations and decreases SIG_glu in muscle by facilitating transcapillary glucose transport. This effect is more pronounced during hyperinsulinaemia and may be of clinical relevance in diabetic patients treated with therapeutic doses of enalapril.     

Effects of hemicolectomy on bile acid metabolism in relation to colon carcinogenesis in man

Bile acids are probably important in colon carcinogenesis. Regional differences in bile acid metabolism within the colon were studied to illuminate the preferential distal occurrence of colon cancer in Western countries. Faeces (24 h) were collected for bile acid measurement from 25 patients with hemicolectomy (nine left and 16 right) and 17 adenoma patients with an intact colon (control subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of faecal water were also studied. The median percentage of deoxycholic acid (DCA) was lower in the hemicolectomy groups [left 48% (range 38–57%), right 45% (2–62%) vs. control subjects 59% (38–70%), P  < 0.05]. In duodenal bile, the proportion of DCA in left [4% (1–25%)] was lower than in the patients with right hemicolectomy [19% (0–69%)] and control subjects [24% (7–50%)], P  < 0.05. Faecal concentration of protonated DCA was higher in those with right hemicolectomy (0.101 μmol g⁻¹) than in those with left hemicolectomy (0.048 μmol g⁻¹), which coincided with a higher cytolytic [right 49% (3–93%), left 2% (1–37%)] and alkaline phosphatase activity [right 6.7 U mL⁻¹ (1.2–40.1 U mL⁻¹), left (2.0 U mL⁻¹ (1–25.7 U mL⁻¹), both P  < 0.02]. These findings suggest differences in bile acid metabolism between the proximal and distal colon that may contribute to the disparity in cancer risk.     

P38An Acute Hemolytic Transfusion Reaction Due to Anti-Wra Antibodies.

The Wr^a antigen is found on the red blood cells of approximately 1 : 1000 caucasians. Anti-Wr^a antibodies have been reported to be present in 1 : 25 to 1 : 100 healthy blood donors and an even higher proportion of hospital patients. Wr^a incompatibilty might therefore be expected to occur in approximately one in 50,000 blood transfusions. Reports of hemolytic transfusion reactions (HTR) and hemolytic disease of the newborn (HDN) due to anti-Wr^a are however rare. We report an acute HTR due to anti- Wr^a in a 58 year old male with MDS associated with rigors, shortness of breath and a significant rise in serum bilirubin from 16 μmol L⁻¹ pre-transfusion to 110 μmol L⁻¹ immediately afterwards. This was accompanied by the appearance of bilirubin and urobilinogen in his urine and a fall in haemoglobin of nearly 2 g dL⁻¹ following the transfusion. Anti- Wr^a was the only antibody implicated. Wr^a antigen expressing reference panel cells and the unit being transfused during the gave 2–3+ reactions by IAT against the recipient's plasma. The donation typed as positive with Wr^a antisera. The recipient typed as Wr^a antigen negative. The reaction resulted in the patient being admitted to hospital for 2 days. The increasing use of electronic issue may result in more frequent reports of reactions due to anti-Wr^a as commonly used screening cells do not express this antigen.     

Relationship between lipoprotein(a) phenotypes and albumin excretion rate in non-insulin-dependent diabetes mellitus: protective effect of ‘null’ phenotype?

The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that generates conflicting views. In addition, Lp(a) phenotypes have not previously been considered as factors influencing AER. In order to clarify this issue, we studied 70 non-insulin-dependent diabetes mellitus (NIDDM) patients without clinically detectable macroangiopathy, 27 with microalbuminuria and 43 without it. Both groups were matched for the known variables that could influence AER and serum Lp(a) levels. Lp(a) was determined by enzyme-linked immunosorbent assay (ELISA), and Lp(a) phenotypes were assessed by electrophoresis followed by immunoblotting. Lp(a) phenotypes were grouped as follows: 'small' (F, S1 and S2), 'big' (S3 and S4) and 'null'. The NIDDM patients with microalbuminuria presented higher serum Lp(a) concentrations than the patients without it [15.7 mg dL⁻¹ (95% CI 0.5–36.5) vs. 4.5 mg dL⁻¹ (95% CI 0.1–18.5); P  < 0.001] and a direct correlation between Lp(a) and AER was observed ( r  = 0.34; P  < 0.01). AER was significantly different when Lp(a) phenotypes were considered ['small': median 19 μg min⁻¹ (range 1–195); 'big': median 9.5 μg min⁻¹ (range 1–186); 'null': 4 μg min⁻¹ (range 1–9); P  = 0.04]. None of the NIDDM patients with a 'null' phenotype showed an AER of > 10 μg min⁻¹. In conclusion, this case–control study provides evidence that microalbuminuria is associated with high serum Lp(a) in NIDDM without clinically detectable macroangiopathy. Furthermore, NIDDM patients with a 'null' phenotype could be considered at low risk for the development of microalbuminuria.     

Complement activation during plasma production depends on the apheresis technique

Elevated anaphylatoxin concentrations have been found in fresh frozen plasma packs produced by apheresis. The aim of this study was to investigate anaphylatoxin generation during apheresis production in relation to two frequently used techniques: employing either centrifugation alone or centrifugation with simultaneous filtration. The concentrations of C3a, C5a and sC5b-9 were measured in 50 plasmas after apheresis and before freezing generated by combined centrifugation and filtration and in 50 plasmas generated solely by centrifugation and in the corresponding 100 donors before apheresis. The median C3a concentration increased during apheresis by centrifugation alone from 62 (donor) to 380 μg L⁻¹ (FFP pack) and during apheresis by combined centrifugation and filtration from 70 to 992 μg L⁻¹. The median C5a concentration increased during apheresis by centrifugation alone from 0.38 to 0.83 μg L⁻¹ and during apheresis by combined centrifugation and filtration from 0.29 to 4.9 μg L⁻¹. The soluble terminal complement complex increased only by combined centrifugation and filtration apheresis from 162 to 426 μg L⁻¹. Complement activation during apheresis by combined centrifugation and filtration is more pronounced than that obtained by the centrifugation method alone. Changes in the construction or the materials used in the membrane-type separation units may reveal possibilities of prevention.     

A new approach to treatment of bleeding episodes in young hemophilia patients: a single bolus megadose of recombinant activated factor VII (NovoSeven®)

Summary.  Recombinant activated factor VII (rFVIIa, NovoSeven^®) represents an effective treatment for hemophilia patients with inhibitors, but no consensus as to the best dosing regimen exists. We assessed the efficacy and safety of a rFVIIa 'megadose' (300 µg kg⁻¹ bolus) as treatment for bleeds in three young inhibitor patients. Of 114 bleeds, 95 responded to a single dose. Pain relief was faster and therapy duration significantly shorter than with continuous infusion (CI) regimens or standard boluses (90 µg kg⁻¹ every 3 h). Rebleeding occurred in 9.6% of cases and 19/114 episodes required a second bolus injection. Although rFVIIa consumption per bleed (median: 300 µg kg⁻¹) was higher than with standard boluses (180–270 µg kg⁻¹), patients found single bolus administration more convenient than recurrent injections or CI. With two exceptions, no complications occurred within 3 h of treatment, despite high FVII:C levels (median: 27.4 U mL⁻¹; range: 19.8–54 U mL⁻¹). Treatment of bleeds with a rFVIIa megadose in young inhibitor patients is effective and well tolerated.     

Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C → T variant, and the risk of myocardial infarction in young women: effect of female hormones on homocysteine levels

Summary.  In young women data are limited about the association between myocardial infarction (MI) and hyperhomocysteinemia, low folate or methylenetetrahydrofolate reductase ( MTHFR ) genotypes. The effect of oral contraceptive (OC) use on plasma homocysteine levels is not clear. We assessed the association between hyperhomocysteinemia, low folate, MTHFR 677TT mutation and risk of MI, and we investigated the effect of OC use on homocysteine levels in controls. In 181 patients with a first MI and 601 controls 18–49 years of age from a population-based case–control study, non-fasting blood samples were available. The homozygote mutant allele (TT) was detected in 12% of the patients and in 10% of controls. The odds ratio (OR) for MI in TT patients compared with the wild-type (CC) controls was 1.3 [95% confidence interval (CI) 0.8, 2.3]. For all MTHFR genotypes combined, the OR for MI in the lowest quartile of folate (<5.4 nmol L⁻¹) compared with the highest quartile (>10.4 nmol L⁻¹) was 3.0 (95% CI 1.7, 5.1). A 2-fold increased risk of MI was found in women with the TT genotype who had folate levels below the median of 7.4 nmol L⁻¹ compared with CC genotype and folate levels above the median (OR = 2.0; 95% CI 1.0, 3.7). Mean homocysteine levels were 12.2 µmol L⁻¹ in OC users and 12.3 µmol L⁻¹ in non-users. Only at the 97.5 percentile (cut-off 21.0 µmol L⁻¹) was the adjusted OR for higher vs. lower homocysteine levels increased by 2.8-fold (95% CI 1.2, 6.8). Low folate is a risk factor for MI, particularly in women with the MTHFR 677TT genotype. Homocysteine levels were not influenced by OC use.     

Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor

Summary.  Background:  Oral contraceptives (OC) containing different types of progestogens induce different sensitivities to activated protein C (APC) measured with the thrombin generation-based APC-resistance test. These differences in APC resistance may be the biological explanation for the differences in thrombotic risk of the various pills. The mechanistic basis of APC resistance observed in OC users is unknown. Our objective was to study the effect of OC on the two main determinants of the APC-resistance test, free protein S and free tissue factor pathway inhibitor (TFPI). Patients/methods:  We measured free protein S and free TFPI in 156 users of various types of OC. Results:  Users of desogestrel-containing OC, known to double the risk of thrombosis compared with levonorgestrel-containing OC, had lower free protein S (24 vs. 33 U dL⁻¹) and TFPI free antigen (2.9 vs. 3.6 ng mL⁻¹) levels than users of OC containing levonorgestrel. Women using cyproterone acetate-containing OC, known to confer a high thrombotic risk, had the lowest free protein S (19 U dL⁻¹) and free TPFI antigen (2.5 ng mL⁻¹) levels. Users of OC containing drospirenone had lower free protein S (23 U dL⁻¹) and TFPI antigen levels (3.2 ng mL⁻¹) than users of levonorgestrel-containing OC. Low free protein S and low free TFPI antigen levels were associated with an increased resistance to APC, an established risk factor for thrombosis. Conclusions:  This study observed that the differences in APC resistance induced by OC containing different progestogens can at least in part be explained by different effects of OC on free protein S and TFPI.     

Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects

Summary.  Background:  NN1731 is a recombinant activated factor VII (rFVIIa) analog with enhanced activity. Objectives:  This clinical trial aimed to assess the safety and pharmacokinetics of single doses of NN1731 in healthy male subjects. Methods : This was a randomized, placebo-controlled dose - escalation trial with four dose tiers (NN1731 5 – 30 μg kg⁻¹). Eight subjects were randomized to either NN1731 ( n  =   6) or placebo ( n  =   2) in each tier. Results:  No thromboembolic or serious adverse events were reported and no antibody formation towards NN1731 was detected. NN1731 was demonstrated to be pharmacologically active based on coagulation-related parameters (prothrombin fragment 1+2, activated partial thromboplastin time and prothrombin time). There were five mild/moderate adverse events in three subjects. The FVIIa activity of NN1731 after ascending single-dose administration of NN1731 fits well with a two-compartment model, indicating a bi-exponential decline with a rapid initial distribution of approximately 73% FVIIa activity (half-life   =   20 min), followed by a less rapid terminal elimination phase eliminating the remaining 27% (half-life   =   3 h). Dose proportionality in healthy male subjects at the dose levels investigated (5 – 30 μg kg⁻¹) was supported by the FVIIa activity data. Conclusions:  Based on the results of this trial, NN1731 appears safe and well tolerated in healthy subjects at doses up to 30 μg kg⁻¹. No immunogenic or thromboembolic events were reported. The pharmacokinetic profile of NN1731 as measured by FVIIa activity appears to follow two-compartment pharmacokinetics characterized by an initial rapid distribution phase followed by a less rapid elimination phase.     

Low-density lipoprotein-induced formation of nitric oxide by cultured vascular smooth muscle cells of the rat

There is evidence that low-density lipoprotein (LDL) plays a crucial role in atherogenesis. On the cellular level, LDL has been shown to activate a number of mechanisms involved in atherogenesis and vasoconstriction. Local immoderate vasoconstriction is physiologically antagonized by nitric oxide, which is released from the endothelium. To find out whether LDL also influences the synthesis of nitric oxide in vascular smooth muscle cells, both the conversion of arginine to citrulline and the production of nitrite were determined as a measure of nitric oxide formation. After incubation of rat vascular smooth muscle cells with native LDL (25 μg mL⁻¹) for 24 h, the production of both l -[¹⁴C]-citrulline [39 600 (3600) cpm mg⁻¹ cell protein] and nitric oxide [2.95 (0.56) μmol L⁻¹] were about twice and 1.5-fold the amount of the corresonding values in untreated cells (mean ± SD, P  < 0.05, n  = 4). Oxidized LDL was less effective than the native form. The presence of the arginine analogue N ^G-methyl- l -arginine reduced citrulline production dose-dependently but augmented DNA synthesis, both induced by LDL. In addition, the lipoprotein caused a 1.6-fold increase in cyclic GMP production following a 24-h incubation [control = 10.9 (3.8) pmol mg⁻¹ cell protein, P  = 0.016]. The results suggest that native LDL might partly impair its atherogenic potential on the vasculature by stimulating the production by smooth muscle cells of both nitric oxide and cyclic GMP.     

Effects on complement activation of a new continuous autotransfusion system

Allogeneic blood transfusions may subject patients to risks of infection and allergic reactions. Various techniques for transfusion of shed blood have been developed. The aim of this study was to evaluate a new continuous autotransfusion system (Fresenius CATS^®) as regards its impact on the complement system, and on erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin, leucocytes, platelets, albumin and protein were determined in the patient's blood preoperatively, 1 min before the start of transfusion, 15 and 60 min after transfusion; and in the reservoir, in the waste bag and in the retransfusion blood. Increased concentrations of C3a and SC5b-9 were found in the collected reservoir blood ( P  < 0.05). The washing and centrifugation procedure reduced these concentrations (< 0.001). High levels of free haemoglobin were found in the collected blood as well as in the processed product. The median haemoglobin level in the processed blood was 260 g L⁻¹ (range 104–289 g L⁻¹). Inflammatory mediators from the complement cascade are removed by continuous autotransfusion technique. The processed blood contains high levels of free haemoglobin.     

ATP-sensitive potassium channels mediate vasodilatation produced by calcitonin gene-related peptide in human internal mammary but not gastroepiploic arteries

The purpose of this study was to elucidate the mechanism of action of calcitonin gene-related peptide-induced vasodilatation of human gastroepiploic and internal mammary arteries. Calcitonin gene-related peptide (0.1–100 nmol L⁻¹) elicited relaxations of preconstricted vessels, with a significantly greater effect in the gastroepiploic artery ( P  < 0.05). This effect was independent of endothelium-derived vasodilating substances. The response of the internal mammary artery but not the gastroepiploic artery to calcitonin gene-related peptide was attenuated by glybenclamide (1.0 μmol L⁻¹) ( P  < 0.05). In vitro autoradiography indicated that [¹²⁵I]-calcitonin gene-related peptide bound to the tunica media but not the endothelial cells in both types of artery, with a significantly higher degree of binding in the gastroepiploic artery. It is concluded that calcitonin gene-related peptide acts directly on vascular smooth muscle via specific binding sites to induce vasodilatation. In addition, K_ATP channels are involved in the action of calcitonin gene-related peptide in the internal mammary artery but not in the gastroepiploic artery.     

Stimulation of arginine vasopressin secretion by a small increase in blood ionized calcium in normal men

Evidence has been provided for an increase in baseline serum corticotrophin (ACTH) levels in response to a rise in circulating ionized calcium (Ca_i) levels within the physiological range. In order to establish whether small Ca_i increments are also able to modify the basal secretion of arginine vasopressin (AVP), we infused calcium gluconate through an intravenous infusion pump in eight healthy male subjects (25–31 years old). Serum Ca_i, ACTH and AVP concentrations were measured every 10 min over an infusion period lasting 90 min. A significant progressive rise in serum Ca_i (baseline: 42 ± 0.9 mg dL⁻¹; 90 min: 47.2 ± 0.9 mg dL⁻¹, P  < 0.001), ACTH (baseline: 30.7 ± 1.3 pg mL⁻¹; mean peak at 80 min: 37.4 ± 2.4 pg mL⁻¹, P  < 0.01) and AVP levels (baseline: 2.1 ± 0.6 pg mL⁻¹; mean peak at 80 min: 3.2 ± 0.5 pg mL⁻¹, P  < 0.01) was observed during calcium infusion. Furthermore, a significant positive correlation ( r  = 0.71; P  < 0.001) was observed between ACTH and AVP responses to calcium infusion at 60, 70, 80 and 90 min. These data demonstrate that AVP secretion is stimulated by a slight rapid increase in serum Ca_i levels even though absolute serum Ca_i levels remain within the normal range. In addition, the positive correlation between Ca_i-induced ACTH and AVP increments suggests that AVP plays a releasing role on ACTH secretion during calcium infusion.     

An individualized pre-operative blood saving protocol can increase pre-operative haemoglobin levels and reduce the need for transfusion in elective total hip or knee arthroplasty

summary .  We have prospectively evaluated the efficacy of an individualized pre-operative blood saving protocol in elective total hip arthroplasty (THA) or total knee arthroplasty (TKA). The primary aim was to obtain a pre-operative haemoglobin (Hb) level of ≥14 g dL⁻¹. A reduction in requirements for allogeneic transfusion was considered the second aim. Several strategies are available for increasing pre-operative Hb levels and reducing red blood cell (RBC) transfusions following THA or TKA, but the success of these programmes depends on selecting the most appropriate treatment for each patient. Three hundred and five patients with an indication of elective THA or TKA were individually assigned to the following strategies according to Hb and ferritin levels and medical conditions: (a) no pre-operative intervention, (b) oral iron therapy, (c) intravenous (i.v.) iron therapy, (d) recombinant human erythropoietin alpha with i.v. iron and (e) pre-operative autologous donation (PAD) plus oral iron. Eighty-two percent of the patients reached a pre-operative Hb level of ≥14 g dL⁻¹ compared with 62% of patients with Hb levels of ≥14 g dL⁻¹ at the baseline visit. Treatment with PAD showed a significant reduction in the pre-operative Hb levels. The rate of RBC transfusion was 18·8% compared with 31·5% of matched historic group ( P  < 0·001). In conclusion, all patients scheduled to undergo THA or TKA should be candidates for an individualized pre-operative blood salvage programme.     

Transfusion trigger – how precise are we? Intraoperative blood transfusion practices in a tertiary centre in Nigeria

summary .  To determine how well anaesthetists in Nigeria determine the need for transfusion based solely on physiological variables and estimated blood loss. To determine the incidence of inappropriate blood transfusion. Anaesthetists in our hospital determine when to transfuse patients based solely on clinical acumen. This may result in inappropriate transfusion especially in this subregion where blood donors are scarce and risk of transmission of infection high. All surgical patients requiring blood transfusion were prospectively studied over 3 months. Transfusion was based solely on the discretion of the attending anaesthetist. Haemoglobin (Hb) concentration was measured prior to transfusion and 24 h postoperatively. Appropriate transfusion was defined as blood transfusion at Hb < 8 g dL⁻¹ or 10 g dL⁻¹ in the elderly and those with medical comorbidities. The trigger for transfusion was documented as well as estimated blood loss. Thirty-four patients were studied. The mean pretransfusion Hb was 8·09 ± 2·45 g dL⁻¹ (range 4·6–14·2). Twenty-one patients (61·8%) had appropriate blood transfusion. The commonest transfusion triggers were clinical pallor (82·4%), excessive blood loss (76·4%), delayed capillary refill (55·9%) and severe hypotension (50%). The use of near patient monitoring devices might further improve blood transfusion practice in this setting where donor blood is scarce.