Myelopoietic cell proliferation in granulocytopenia of refractory anaemia and preleukaemic states with hyper-plastic bone marrow

Summary Myelopoiesis in healthy subjects and in 8 cases of refractory anaemia or preleukaemic states was studied by the combined cytophotometric-autoradiographic method. Granulocytopenia was present in 7 of 8 cases. The results can be summarized as follows: 1. Mature myelocytes of healthy persons are a mainly differentiating cell population with a low labelling index (3–10%) and a high incidence in G₁-Phase. 2. The proliferating immature granulopoietic cells of the patients with neutropenia showed a reduced labelling index with³H-thymidine as a result of an arrest of these cells in G₁ (6 of 8 cases). 3. A similar result was obtained in the study of the hyperplastic myelopoiesis of an other patient with preleukaemia and normal granulocyte count in peripheral blood, with the disturbance of cell proliferation preceding the symptom neutropenia. 4. Finally in only one case an increased frequency of myelopoietic cells in G₂-phase was found suggesting an arrest of cell proliferation in the premitotic phase.We wish to thank Miss Broszies for her excellent technical assistance.     

Prediction of Survival in Adults with Acquired Bi- or Pancytopenia

In a retrospective study of 44 adults with acquired bi- or pancytopenia without evidence of any causal disorder, the survival curve suggested the existence of a subgroup of short survivors, mainly with aplastic anaemia, with death within 4 months. The initial values of 14 single clinical, blood and bone marrow variables were significantly associated with survival < 4 months. Stepwise multiple logistic regression analyses identified 2 combinations of variables displaying significant simultaneous associations with short survival: (i) increased % of non-myeloid bone marrow cells and haemorrhagic manifestations initially; (ii) increased % of non-myeloid marrow cells, circulating erythroblasts and no history of any drug exposure. The predictive capacities of a resulting estimate of the probability of short survival and of previously introduced prognostic indices were approximately equal. The frequency of a correct prediction of a survival shorter than 4 months was in the range of 0.71–0.78 and that of longer survival in the range of 0.74–0.94.     

Deoxyuridine Metabolism in Human Megaloblastic Marrow Cells

Despite the clinical use of the ‘deoxyuridine suppression test’ to document vitamin B₁₂ or folate deficiency its biochomical basis is unclear and currently disputed. Because of this the metabolism of deoxyuridine in marrow cells has been examined. In normoblastic marrow cells the ratio of radio-labelled deoxyuridine to thymidine incorporation into DNA approximates one and preincubation of cells with unlabelled deoxyuridine results in progressive reduction of uptake of both radio-labelled deoxynucleosides. In the same cells methotrexate significantly reduces the DNA incorporation of deoxyuridine but not that of thymidine. In megaloblastic marrow the ratio of radio-labelled deoxyuridine to thymidine uptake is less than one and the reduced deoxyuridine uptake is not significantly altered by either cyanocobalamin or folk acid. With megaloblastic samples the reduction by deoxyuridine of radio-labelled deoxyuridine uptake is less marked than that observed with normoblastic cells and to achieve similar results requires folic acid. These findings suggest that reduced deoxyuridylate conversion to deoxythymidylate by thymidylate synthetase is appropriate to explain the ‘deoxyuridine suppression test’ in megaloblastic marrow cells and that altered substrate requirements for this activity may occur in megaloblastic cells.     

Pulpal necrosis with sickle cell anaemia

Aim To investigate radiographic manifestations of sickle cell anaemia (SCA) and whether or not a pulpal necrosis may develop without a pathological history. Methodology Thirty‐six patients with homozygous SCA were evaluated, and a further 36 individuals without SCA were included in the study as a control group. All 72 patients participating in the study ranged between the ages of 16 and 40 years. General and dental histories of the individuals were recorded. Electrical pulp test, percussion and thermal tests were applied to all the teeth having no restorations. Orthopantomograms of all the subjects were taken. Data obtained from questionnaires, sensitivity tests and radiographic examinations were evaluated by chi‐square and Fischer's exact test. Results Fifty‐one (6%) of the teeth having no restorations or history of trauma were determined as being nonvital in the SCA group. In 30 (83%) of these patients orofacial and dental pain with no obvious cause was detected and in 24 (67%) of the patients the quality of the bone tissue as examined radiologically had deteriorated. In eight (22%) of the patients cortical thinning and irregularity in the mandible was noted. A statistically significant difference between the SCA and control groups (P < 0.05) was found in terms of pulpal sensitivity and radiological findings. Conclusion SCA is a genetic and systemic disease which may cause pulp necrosis without necessarily having an identifiable aetiology. SCA causes radiographically observable differences in jaw structure especially in the mandible.     

Clinical impact of HLA-DR15, a minor population of paroxysmal nocturnal haemoglobinuria-type cells, and an aplastic anaemia-associated autoantibody in children with acquired aplastic anaemia

Aplastic anaemia (AA) is defined as a pancytopenia caused by bone marrow failure, and its pathogenesis is thought to involve autoimmune processes. Several predictive markers of the response to immunosuppressive therapy (IST) have been proposed, which appear to reflect the immune pathophysiology. We prospectively investigated the presence of human leucocyte antigen (HLA)-DR15, a minor population of paroxysmal nocturnal haemoglobinuria (PNH)-type cells, and antibodies to the recently identified autoantigen postmeiotic segregation increased 1 (PMS1) in 103 children with AA enrolled in a multicentre study. In contrast to adults, children with AA did not show an increased frequency of HLA-DR15. In addition, a sensitive flow cytometric assay revealed that children with AA have a much lower prevalence of PNH-type cells (21·4%) than reported for adults with this disease. An immunoblotting assay detected anti-PMS1 antibody in 15 of 103 (14·6%) of the children. Finally, the response rate to IST was not significantly different between patients with and without DR15 (45·5% vs. 54·0%), PNH-type cells (68·2% vs. 53·1%) or anti-PMS1 antibody (40·0% vs. 59·1%). The current study did not confirm a correlation between these markers and the response to IST, suggesting that there is a difference in the pathophysiologies of adult and paediatric AA.     

Peri-operative administration of tranexamic acid in lower limb arthroplasty: a multicentre,prospective cohort study

In the UK, tranexamic acid is recommended for all surgical procedures where expected blood loss exceeds 500 ml. However, the optimal dose, route and timing of administration are not known. This study aimed to evaluate current practice of peri-operative tranexamic acid administration. Patients undergoing primary total hip arthroplasty, total knee arthroplasty or unicompartmental knee arthroplasty during a 2-week period were eligible for inclusion in this prospective study. The primary outcome was the proportion of patients receiving tranexamic acid in the peri-operative period. Secondary outcomes included: dose, route and timing of tranexamic acid administration; prevalence of pre- and postoperative anaemia; estimated blood loss; and red blood cell transfusion rates. In total, we recruited 1701 patients from 56 NHS hospitals. Out of these, 1523 (89.5%) patients received tranexamic acid and of those, 1052 (69.1%) received a single dose of 1000 mg intravenously either pre- or intra-operatively. Out of the 1701 patients, 571 (33.6%) and 1386 (81.5%) patients were anaemic (haemoglobin < 130 g.l⁻¹) in the pre- and postoperative period, respectively. Mean (SD) estimated blood loss for all included patients was 792 (453) ml and 54 patients (3.1%) received a red blood cell transfusion postoperatively. The transfusion rate for patients with pre-operative anaemia was 6.5%, compared with 1.5% in patients without anaemia. Current standard of care in the UK is to administer 1000 mg of tranexamic intravenously either pre- or intra-operatively. Approximately one-third of patients present for surgery with anaemia, although the overall red blood cell transfusion rate is low. These data provide useful comparators when assessing the efficacy of tranexamic acid and other patient blood management interventions in future studies.     

Observations on the Effect of CO2 and Temperature on the Sickling Phenomenon

Abstract. The explanation of the effect of CO₂ on the sickling phenomenon has, in the past, been based solely on the alteration of the oxygen affinity of haemoglobin induced by the CO2, and hence solely on the oxygen saturation of the haemoglobin. A re-investigation of this phenomenon, reported here, shows that this explanation is inadequate; rather, a full explanation requires the use of Perutz's hypothesis that the haemoglobin molecule can exist in various conformationally distinct states, the relative concentrations of which are dependent not only on the oxygen saturation of the molecules but also on other factors such as pH and 2, 3-diphosphoglycerate (DPG) concentration. The effect of temperature on the sickling phenomenon is explained in a similar fashion. Low temperature is found to have no effect on the morphology of irreversibly sickled cells.