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OBJECTIVE: To investigate the relation between the measured intravascular blood volume (BV) and current methods of indirectly assessing BV status in sick preterm infants on the first day of life. METHODS: Thirty eight preterm infants of gestation 24-32 weeks (median 30) and weight 480-2060 g (median 1220) were studied. Red cell volume was measured by the fetal haemoglobin dilution method in six infants and by the biotin labelled autologous red cell dilution method in the remaining 32. Total BV was calculated by dividing red cell volume by packed cell volume. Indirect assessments of BV status using heart rate (HR), core-peripheral temperature difference, mean arterial pressure, base excess, and packed cell volume were recorded. RESULTS: The mean (SD) initial measured BV was 71 (12) ml/kg (range 53-105). The mean HR was 148 beats/min (range 130-180), which correlated positively (r = 0.39, p = 0.02) with BV (higher HR was associated with higher BV). The mean base excess was -3.19 mmol/l (range -18 to +6.2). The negative base excess correlated significantly positively (r = 0.41, p < 0.01) with BV (more acidotic babies tended to have higher BV). There was no significant correlation between core-peripheral temperature difference, mean arterial pressure, or packed cell volume and BV. Regression analysis showed that base excess and HR were significantly related to BV; base excess alone can predict variability in BV only to 17%, and base excess with HR can predict variability in BV to 29%. CONCLUSION: The conventional clinical and laboratory indices are poor predictors of measured blood volume.

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BACKGROUND: Standard techniques for measuring blood volume (BV) entail administering radioactivity and human albumin. This is laborious, expensive, and impractical in acute settings. An alternative method suitable for widespread routine application was assessed. STUDY DESIGN AND METHODS: Seventy-nine ambulant outpatients and 18 intensive care unit (ICU) patients were prospectively recruited. Measurements of RBC volume (RCV) and plasma volume (PV) were performed with radiochromium-labeled RBCs (51Cr), radioiodinated albumin (125I), and fluorescein-labeled HES (FITC-HES). Small molecules overestimate PV because of vascular endothelial dysfunction (ED) and increased capillary permeability; a reference value for PV was therefore derived with the RCV and Hct. RESULTS: Mean PV with 125I dilution was 230 mL (SD, 185 mL) greater than that with FITC-HES in outpatients. This difference was more exaggerated, 345 mL (SD, 371 mL), in ICU patients likely to have ED. Both the PV measured with FITC-HES and the 125I dilution correlated closely with the PV derived with RCV and Hct (r = 0.950 and 0.925, respectively) in the ICU patients. CONCLUSION: FITC-HES estimates PV more accurately than 125I. FITC-HES should replace radioactive tracers for assessing BV. Comparing the estimates of PV with molecules of differing molecular weights may have clinical utility as an indicator of ED.

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The total circulating red cell volume (RCV) is a better guide to the oxygen-carrying capacity of the blood in the whole circulation than is the haemoglobin concentration (Hb) or haematocrit in a blood sample. Pre- and post-transfusion RCV (and blood volume (BV)) may be determined by flow cytometry by exploiting antigen differences between transfused donor red cells and the recipient's red cells. This paper describes the use of red cell antigen differences of Duffy, Kidd, MN and RhD between donor and recipient. In 20 infants, transfused on 21 occasions, pretransfusion RCV ranged from 12 to 39 mL kg(-1) body weight. Only at one transfusion could no usable donor-recipient antigen differences be exploited. Measurement of RCV, used routinely, may determine the transfusion requirements of sick infants more accurately, with the aim of normalizing RCV and BV--securing euvolaemia--at the end of the transfusion. This may allow a complete correction of the RCV deficiency at the first occasion of transfusion. This approach may reduce donor exposures and also optimize oxygen transport and organ perfusion of the infant undergoing intensive management, perhaps leading ultimately to improved survival rates and fewer long-term complications of neonatal intensive care.

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Clinical studies to assess the benefits of blood transfusion or haemodilution in critical illness should take account of measured CBV before, during and after intervention. As mentioned above, surrogate measures of CBV are inadequate and studies based on these must be considered incomplete, because they cannot distinguish between effects of changes in haemoglobin concentration and changes in blood volume. The choice of a suitable technique for measuring CBV depends on the facilities available locally. In general, methods based on labelled red cells are more reliable but are technically demanding and time consuming. Those based on albumin are likely to yield false high values and this is particularly true in all patients with impaired capillary integrity. The most promising plasma marker is hydroxyethyl starch which may be particularly useful when the polysaccharide is labelled with a fluorescent dye. Attaching fluorescein to hydroxyethyl starch is not difficult and, should demand be sufficient, it may well become available from manufacturers who are already capable of providing other fluorescent polysaccharides. The clinical benefits of such a development would include more rational schedules of i.v. fluid and blood transfusion management in surgical and intensive care patients.

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The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO 'non-responders', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for < or = 28 weeks), low initial haematocrit or low initial reticulocyte count (61% for haematocrit < or = 0.48 and reticulocytes < or = 9%, respectively). Considerable differences among centres were found for sampling blood loss, iron supply, and transfusion rate, which ranged from 13% to 73% and was related to the volume of diagnostic blood loss (19% vs 80% for blood loss < 1 vs > or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants.

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A 16-year-old girl with multiple cerebral infarcts was reported to have a normal transthoracic echocardiogram, but transesophageal echocardiography revealed vegetations on the atrial surfaces of both mitral leaflets at their line of closure. Blood cultures were negative, and prolonged treatment with intravenous antibiotics produced no echocardiographic improvement in the appearance of the vegetations. A diagnosis of primary antiphospholipid syndrome was made subsequently, although test results for this condition had initially been normal. Serial transesophageal echocardiograms showed complete resolution of the vegetations but some persistent thickening of the mitral leaflets, after warfarin therapy for 9 months. We suggest that in patients with culture-negative endocardial vegetations, specific tests should be performed for the primary antiphospholipid syndrome and a therapeutic trial of warfarin should be undertaken before contemplating heart surgery.

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We report a case of feto-maternal haemorrhage and describe a new flow-cytometric method of determining a fetus's or infant's pre-transfusion red cell volume (RCV). We validate this method against an established technique, employing fetal haemoglobin (HbF) dilution, for determining the RCV in fetuses and neonates requiring intravascular transfusion. We discuss advantages and other potential applications of this new method.

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At 30 weeks' gestation, half of the approximately 110 ml/kg total blood volume (BV) of the feto-placental circulation is in the fetus, rising, by term, to about 90 ml/kg. In preterm infants at birth, subnormal blood volume is the rule, because of immediate cord clamping. Blood volume, typically 50-60 ml/kg during critical care, limits systemic oxygen (O2) transport and, because of shunting, causes hepato-splanchnic ischaemia and impaired lung function. Haemoconcentration results from plasma extravasation because of vascular endothelial damage. This elevates the haematocrit, masking the red cell lack. By allowing placental transfusion at birth, delaying cord clamping by 30-60 seconds, initial oligovolaemia is obviated, and post-natal lung adaptation greatly facilitated. The complications and costs of care can thereby be much reduced. Losses of haemopoietic stem cells are reduced, vital for haematologic and immunologic constitution and for response to haemopoietic growth factors. Further work is urgently needed to determine how to optimize this vital opportunity in preventive medicine in perinatology, with the objective of preventing complications, and reducing costs of all kinds, in management of the infant born preterm.

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In vivo, realisation of the physiological reserve capacity of haemopoiesis depends on stimulation by cytokines, growth factors produced by autologous blood mononuclear cells. These cytokines include erythropoietin, granulocyte/macrophage colony stimulating factors, and thrombopoietin. In preterm infants, inadequate haemopoietic growth factor production limits haemopoiesis in its response to demands for extra blood cell production in stress situations. Haemopoiesis may also be inhibited by inflammatory disease and by nutritional deficiencies. In infants in intensive care, losses of blood, which contain haemopoietic stem cells and other progenitors, may also impair blood cell production. Recombinant haemopoietic growth factors promise to prevent or correct in part, this haemopoietic inadequacy. Verification of their therapeutic roles depends on further improvements in management of the preterm infant. These improvements include the optimisation of nutritional support and, especially, in terms of the endowment of blood from the placenta at birth, which strongly influences clinical outcome.

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We describe a case of reactive haemophagocytic syndrome (RHS) in a patient with previous polyarticular juvenile chronic arthritis (JCA). This is the first reported association of these conditions and may be indicative of defective immunological responses to viral infections in this form of JCA.

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OBJECTIVE: To investigate the clinical effects of regulating umbilical cord clamping in preterm infants. DESIGN: A prospective randomised study. SETTING: The Queen Mother's Hospital, Glasgow. SUBJECTS: 36 vaginally delivered infants over 27 and under 33 weeks' gestation. INTERVENTION: Holding the infant 20 cm below the introitus for 30 seconds before clamping the umbilical cord ("regulated" group, 17 patients), or conventional management ("random" group, 19 patients). MAIN OUTCOME MEASURES: Initial packed cell volume, peak serum bilirubin concentrations, red cell transfusion requirements, and respiratory impairment (assessed by ventilatory requirements, arterial-alveolar oxygen tension ratio over the first day in ventilated infants, and duration of dependence on supplemental oxygen). RESULTS: There were statistically significant differences between the two groups in mean initial packed cell volume (regulated group 0.564, random group 0.509) and median red cell transfusion requirements (regulated group zero, random group 23 ml/kg). 13 infants from each group underwent mechanical ventilation and showed significant differences in mean minimum arterial-alveolar oxygen tension ratio on the first day (regulated group 0.42, random group 0.22) and in median duration of dependence on supplemental oxygen (regulated group three days, random group 10 days). Differences in final outcome measures such as duration of supplemental oxygen dependence and red cell transfusion requirements were mediated primarily through arterial-alveolar oxygen tension ratio and also packed cell volume. CONCLUSIONS: This intervention at preterm deliveries produces clinical and economic benefits.

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Anaemia has been shown to be associated with an increased apnoeic pause frequency and with cyanotic breath-holding spells. In this study, the relationship between anaemia and apparent life-threatening events was retrospectively investigated in 72 term infants referred for assessment and home monitoring following an apparent life-threatening event. For 41 infants (25 male, 16 female; 38 Caucasian, three Asian) a venous red blood cell count was available. Their median age at the time of the apparent life-threatening event was 2.0 (0.6-6.7) months. The Hb levels in these 41 infants were plotted against normal data from the literature. Thirty-four infants had Hb levels below the mean, whilst six infants had values above the corresponding normal mean; the one remaining infant had a Hb value identical to the normal mean. Significantly more infants than expected had Hb levels below the mean (p less than 0.001, binomial test). Anaemia may have played a role in the pathophysiology leading to life-threatening events in some of the infants investigated in this study.

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In present practice, patients in intensive care are managed with subnormal haematocrit values and oligovolaemia. Optimization of the blood for oxygen transport in preterm infants in intensive care yields major benefits in their prognosis. A rational basis is described for this optimization in terms of the circulating blood volume and haematocrit, represented by circulating red cell volume (mass). Extrapolation of these lessons in haematological management is proposed for adult patients in critical care, so as to reduce dependence on respiratory support and minimize clinical complications and costs.

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Peripheral haematocrit (PCV) is the traditional target and monitor in many transfusion regimens. Without negating the importance of PCV as a determinant of whole blood viscosity, the present article outlines two important reasons why the red cell volume (RCV) should replace PCV in the central target role during blood transfusion in intensive care and other emergency situations: 1. PCV reflects both RCV and plasma volume (PV) and is therefore not directly proportional to the total blood oxygen carrying capacity. At best, the relationship between PCV and RCV is hyperbolic and this is often overlooked when relating the two parameters in practice. At worst, the hyperbolic relationship is unreliable because PV and RCV can vary independently and the PCV is a fluctuating ratio of variable numbers. 2. PCV is not a good indicator of blood volume (BV), which is another important determinant of oxygen delivery to tissues and a crucial parameter in intensively managed patients. BV is directly proportional to RCV and this relationship also is often overlooked in clinical practice. The recommended values for RCV are 30 ml/kg in men. 25 ml/kg in women and between 30 ml/kg and 45 ml/kg in neonates within the first week of life.

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Determination of circulating red cell volume (RCV) in anemic preterm infants is, in theory, a better indicator of transfusion needs than Hb concentration. Our study reports the results of RCV measurement using biotin labeling of red cells on 40 occasions in preterm infants of 25-34 wk gestation. In 20 infants, who had estimations made within 24 h of birth, the RCV varied between 17.7 and 66 mL/kg. Twenty measurements were made at a later age at the time of a blood transfusion. RCV values were between 13.1 and 41.5 mL/kg before transfusion. In 13 infants, RCV was determined simultaneously using two methods, biotin and dilution of autologous HbF with donor HbA at transfusion. There was no significant difference between the results of RCV estimations using these two methods. Our study demonstrates that biotin labeling is an effective method for determining RCV in preterm infants.

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To test the hypothesis that haemoglobin concentration is a poor predictor of benefit from transfusion in preterm infants, and that red cell volume is the most important indicator of anaemia, 24 preterm infants receiving red cell transfusions had red cell volume, haemoglobin concentration, and cardiac output measured before and after transfusion. Red cell volume was measured either using dilution of autologous fetal haemoglobin with donor adult haemoglobin, or with a new technique using biotin as a red cell label. The two techniques give similar results. Mean (SD) values before transfusion were 27.4 (13.3), and after transfusion 45.0 (13.7) ml/kg. Cardiac output was measured using imaging and Doppler ultrasonography, and fell with transfusion from mean 286 (121) to 251 (95.6) ml/kg/min. The red cell volume before transfusion correlated well with changes in cardiac output following transfusion, infants with a red cell volume before transfusion of less than 25 ml/kg showing a fall in cardiac output, and those with a red cell volume of greater than 25 ml/kg not showing a significant fall. There was no correlation between haemoglobin concentration, packed cell volume, or change in packed cell volume with changes in cardiac output after transfusion. A red cell volume of 25 ml/kg seems to be critical in preterm infants with anaemia, and infants with values below this are those most likely to benefit from transfusion.

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