A prospective study of causes of haemolysis during venepuncture: tourniquet time should be kept to a minimum.

BACKGROUND: Haemolysis is defined as the release of cellular components of erythrocytes and other blood cells into the extracellular space of blood. These cellular components can cause interference in laboratory measurements, potassium being a commonly measured analyte to be affected. A number of factors have been implicated in the aetiology of haemolysis. We undertook this study to enable us to identify and hence rectify causes of haemolysis in samples from patients on acute medical and surgical wards. METHODS: We performed a prospective study of 353 blood sampling events during February and March 2007. A proforma was used to obtain detailed information of each blood-taking episode. Information from the proforma was linked to the incidence of haemolysis obtained from the hospital computer system. RESULTS: The incidence of haemolysis among the samples studied was 6.5%. While staff group, method of sampling, tourniquet time and number of attempts at venepuncture were each univariately associated with haemolysis, stepwise logistic regression resulted in a final model which only included tourniquet time (odds ratio for haemolysis if tourniquet time >1 min was 19.5 [95% confidence interval [CI] 5.6-67.4%]). CONCLUSION: Tourniquet time of more than a minute is associated with a significant increase in risk of haemolysis. Advice on tourniquet time is included in phlebotomy training within the hospital; hence a campaign of appropriately channelled continuing education on this issue may be successful in reducing the haemolysis rate.

Haemolysis in neonatal blood samples: a survey of practice.

OBJECTIVE: To survey how laboratories report, and neonatologists perceive them to report, the presence of haemolysis in neonatal blood samples. METHODS: A questionnaire was sent to clinical biochemists and neonatologists in 88 hospitals believed to be using Roche methodology. RESULTS: A 49% response rate was obtained. Seventeen hospitals were excluded from analysis owing to incomplete questionnaires or altered methodology. Of the remaining 71 hospitals, 30 (42%) laboratories and 18 (25%) neonatologists responded - where both responded, none gave identical replies. Eighteen laboratories admitted the use of serum indices to make decisions on haemolysed samples. Although recommended interference limits are available from Roche, there was little consensus between laboratories. CONCLUSIONS: Laboratories should have clear guidelines on the processing of haemolysed samples from neonates and these should be adequately communicated to those responsible for their direct care.

Increased urinary dopamine excretion in association with bilateral carotid body tumours-- clinical, biochemical and genetic findings.

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an (123)I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than non-familial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient.

Hepatic hemangioendothelioma associated with production of humoral thyrotropin-like factor.

We report on 7 patients referred for treatment of hepatic hemangioendothelioma with increased thyrotropin levels. The serum thyroxine level was decreased in 4 and increased in 2. Immunohistochemistry showed positive staining of tumor, but not of normal liver tissue, for thyrotropin. We propose secretion by the tumor of a thyrotropin-like factor.

Pitfalls in the interpretation of common biochemical tests.

This review considers some of the more common problems in the interpretation of the results of biochemical tests and, where possible, highlights ways in which errors can be identified or avoided.

New growth hormone receptor exon 9 mutation causes genetic short stature.

A novel form of congenital growth hormone insensitivity syndrome (GHIS), which lacks the classic phenotype associated with this condition, is described. Dominant inheritance is shown to result from a heterozygous 876-1 G to C transversion of the 3' splice acceptor site preceding exon 9 in the growth hormone receptor (GHR) gene. The result of this mutation is a severely truncated cytoplasmic domain of the GHR, which is incapable of transmitting a signal. The mutant receptor is shown to form a heterodimer with the wild-type GHR, the activity of which is inhibited in a dominant-negative manner.

Signal transduction defects in growth hormone insensitivity.

Growth hormone (GH) insensitivity is a heterogeneous condition that can result from mutations within the GH receptor (GHR) and that can be inherited as both an autosomal recessive and a dominant trait. However, evidence from a small number of growth hormone binding protein (GHBP)-positive families indicates that their GH insensitivity is independent of GHR mutations. Two of these families appear to have distinct abnormalities in GH signal transduction. Studies suggest that one family (classic Laron syndrome phenotype; designated family H) have a signalling defect close to the GHR, preventing activation of both the STAT and MAPK pathways, whereas the other family (less marked phenotype; family M) have a defect in activating MAPK but not the STAT pathway. The children studied here are specifically insensitive to GH and their defect must be exclusive to this signalling system. Thus, families with GHBP-positive GH insensitivity without GHR mutations are likely to be important models in which to study the specificity of GH signal transduction and the relationship between GH insensitive phenotype and signalling defect.

Human skin fibroblasts as a model of growth hormone (GH) action in GH receptor-positive Laron's syndrome.

Congenital GH insensitivity (Laron's syndrome, LS) is often associated with a dysfunctional GH receptor (GHR) causing complete insensitivity to GH and absent serum GH-binding protein (GHBP). However, a proportion of children with LS have normal GHBP levels. We have identified four girls from two families with this condition (height SD score, -3.4 to -6.8) and undertaken studies on 1) their GHR genes and 2) their GH responses in cultured skin fibroblasts to define the etiology of their GH insensitivities. No GHR gene mutations were identified in one family. In the other family, the affected siblings, an unaffected brother, and the father were heterozygous for a point mutation within exon 6 (D152H). In addition, use of intron 9 haplotypes to determine linkage to the GHR gene implied inheritance of different maternal GHR alleles in the two affected girls of the latter family. It is unlikely, therefore, that the D152H mutation alone could account for the LS phenotype. End points of GH action [DNA synthesis, insulin-like growth factor-binding protein-3 (IGFBP-3) messenger RNA (mRNA) and peptide production] in skin fibroblast cultures established from three of the LS subjects and four normal children were examined. Whereas normal fibroblasts incorporated [3H]thymidine dose dependently in response to 10-1000 ng/ml GH (increment at 1000 ng/ml, 77 +/- 19%), LS fibroblasts failed to respond significantly above basal levels (P < 0.01). In normal fibroblasts, IGFBP-3 mRNA and peptide increased maximally at 48 h in response to 200 ng/ml GH, as determined by ribonuclease protection assay, Western ligand blotting, and RIA. In comparison, LS fibroblasts produced significantly less IGFBP-3 peptide than normal fibroblasts in response to GH, whereas IGFBP-3 mRNA failed to increase above basal levels. These studies have shown that 1) cultured human skin fibroblasts can be used to define the end points of GH action; 2) fibroblast cultures from the LS children show absent or reduced responses to GH; and 3) GH insensitivity in these children does not appear to be caused exclusively by GHR mutations, but is probably due to dysfunctional GHR signalling. Such patients may prove particularly important to elucidation of the key events in GH signaling.

Giant cell tumor in a patient with osteopoikilosis.

A giant cell tumor developed in the distal femur of a 26-year-old man with preexisting osteopoikilosis. The authors are not aware of previous similar reports. Both conditions are rare, but a causal relationship between them remains unconfirmed.