Normal MCV Research Articles

Protocolo diagnóstico de las anemias normocíticas

The term normocytic anemia is usually used to identify those arregenerative anemias with a MCV between 80 and 100 fl, generally related to a heterogeneous group of chronic disorders such as hepatopathy, renal insufficiency, autoimmune disorders, endocrinopathies, neoplasias, and chronic infections, in which several etiopatogenic mechanisms are involved, like an abnormal use of the organism iron or a deficient production of erythropoietin. The diferential diagnosis is frequently complicated as many of these patients often have an anemia of mixed etiology. Also, a number of anemias typically microcytic (like iron deficiency anemia) or macrocytic (like regenerative anemias) may appear with a normal MCV at the beginning. Treatment is based on the therapy of the underlying disease and frequently requires the administration of erythropoietin.

Unusual presentation of a patient with hemoglobin Constant Spring and immune hemolytic anemia

Abstract Introduction: Hemoglobin Constant Spring (Hb CS), a abnormal Hb characterized by elongated α-globin chain resulting from mutations of the termination codon in the α2 - globin gene , is the most common nondelitional α-thalassemic mutation and is an important cause of HbH like disease in Southeast Asia. Case Report: A 9- years-old female with immune hemolytic anemia and splenomegally and abnormal hemoglobin in Hb electrophoresis is reported. conclusion: The first presentation of our patient was weakness and dark urine. She had a hemolytic anemia with normal MCV and positive direct coombs. In Hb electrophoresis, she had abnormal hemoglobin near the A2 region and slow moving component. PCR testing showed homozygous mutation in codon 142. Hb CS-containing RBCs have membrane pathology and these pathology lead to destruction of her RBCs in reticuloendotelial system and she had a RBC sick syndrome resemble thalassemia intermedia.

Oral iron administration is benefical for anemia with smaller mean corpuscular volume (mcv) in hemodialysis patients with low hepcidin-25 levels

Oral iron administration (OIA) is little benefit, and I.V. iron injection (IVI) is recommended. IVI increases high serum ferritin (ferr) levels, increaseing serum hepcidin-25(hepc) levels, which inhibits intestinal iron absorption. In a state of low hepc levels, intestinal iron absorption can be well preserved. We examined whether smaller or normal MCV affects the therapeutic effect of OIA in HD patients with low hepc levels. Serum hepc were measured in 66 patients on HD. Of these, oral iron was immediately administered in 14 cases who had low serum hepc levels (<14ng/ml). Hb was measured before and 8 weeks after OIA. Serum levels of ferr, hepc, MCV and Hb were measured before starting HD. A correlation between the based MCV and improvement of Hb was analyzed. Mean hepc levels were 14.0± 22.6 ng/mL in 66 cases. Serum levels of hepc correlated with ferr (r=0.46, p<0.01). The values for MCV were less than 88fL in 6 cases (LMCV group, HD duration, 8.7±4.4 years, and the OIA dose, 50 mg/day). The remaining 8 cases showed normal MCV (96.6± 5.7fL) (NMCV group, 7.3±4.6 years, 62.5mg/day). In LMCV group, Hb increased from 9.4±0.4g/dL to 11.2±3.5g/dL. In NMCV group, they increased from 10.3±2.1g/dL to 11.1±2.2g/dL. An increment in Hb was significantly greater in LMCV group (3.1±1.2g/dL, p<0.05) than that in NMCV group (0.8±2.2g/dL). There was no difference between L and N MCV groups in Hb (9.4±0.4, vs. 10.3±2.1 g/dL), and serum levels of ferr (7.8±4.3, vs. 13.9±10.0ng/mL) and hepc (4.6±6.6, vs. 3.7 ± 4.0 ng/ mL). In conclusions, in a state of low hepcidin, OIA is more beneficial for anemia in HD patients with low MCV than in those with normal MCV.

Detection of Complex Hemoglobinopathies: Recommendations on Screening and DNA Testing

The following recommendations should be taken into account during the evaluation and elucidation of the complex hemoglobinopathies: (a) in complex hemoglobinopathies performing DNA studies on all family members might be essential; (b) complex gene-gene interactions offer major diagnostic challenges both at the technical and clinical level; (c) hematological &amp; DNA analyses must be run in parallel. Some cases may be straight forward but others may require indepth DNA work-up; (d) co-inheritance of α-thalassemia offers added challenge as it may affect phenotype significantly; (e) sickle cell anemia (SS), co-inherited with a-thal, can be a phenocopy of Sβ0-thal. The HbA2 increase can be mistaken for Sβ-thal. DNA Sequencing is imperative; (f) only a selected number of normal MCV, MCH, borderline HbA2 cases must be referred for DNA analysis. However, in certain cases, following hematological and family evaluation, the β and δ genes may need to be sequenced; (g) DNA Sequencing will increasingly become the method of choice for screening and DNA mutation analysis. However, new methods like MLPA-which analyzes gene dosage- must be used more commonly to rule out deletion mutants to avoid false negative sequencing results; (h) these recommendations should be reviewed every 2–3 years reflecting new methods, new findings and new findings from ethnic groups.

Analysis of the molecular characterization of a Chinese pedigree with rare β thalassemia genotype

Objective To investigate the molecular characterization of a Chinese pedigree with rare β thalassemia genotype.Methods Phenotypic analysis was performed using standard hematological tests to measure red blood cell parameters, including RBC,Hb,MCV,MCH,MCHC and RDW.SPIFE automatic Hb agarose gel electrophoresis instrument was used to measure hemoglobin fraction Hb A,Hb A2 and Hb F.The alleles of β thalassemia mutation were determined by RDB assay, and then cloning and sequencing were performed to define the mutation sites.Results The proband and his father had typical microcytic hypochromic anemia with low MCV and MCH(79.8, 63.1 fl and 19.9, 20.9 pg, respectively) and high level of Hb A2 (5.66% and 5.60%, respectively).The proband′s mother had normal MCV and MCH. β thalassemia mutation analysis with RDB assay showed that the proband had thalassemia minor resulting from double mutations on one globin gene.One showed codons 41/42 (-TTCT) mutation and the other was CAP mutation from positions +40 to +43 in the promoter region.These two mutations were inherited from his father.The genotype of the proband and his father was β41/42、CAP/βA ,and the genotype of his mother was βA/βA.Conclusions It′s rare that double mutations occur on single β globin gene, with one mutation on CD41/42(-TTCT) and the other mutation from positions +40 to +43 relative to the mRNA cap site in the promoter region.The findings enrich knowledge of the mutation spectrum of β thalassemia. Key words: beta-Thalassemia; Pedigree; Globins; Mutation; Two-hybrid system techniques

A Reassessment of the Red Blood Cell Folate Assay

AbstractAbstract 3209 Background:The red blood cell folate (RCF) assay has historically been recommended as a more reliable indicator of tissue folate stores compared to the serum folate (SF) assay, as it is not affected by recent ingestion of food. However, the RCF assay suffers from inherent problems with imprecision and accuracy, which are not encountered with SF measurements. Furthermore, following the advent of required folic acid supplementation of many foods by the Food and Drug Administration (FDA) in 1992, folate deficiency is increasingly rare. Very few studies have looked at the value of the RCF versus the SF. We undertook a 10 year retrospective analysis of RCF and SF results to determine the clinical utility of RCF beyond that of SF. Methods:We retrieved all RCF and SF results from the laboratory information system at Mayo Clinic (Rochester, MN) ordered on inpatients and outpatients between 1999–2009. Data for patients who had concurrent orders for SF and RCF were analyzed and chart reviews were conducted on those patients with normal SF but low RCF. Abnormal values were defined by the National Health and Nutrition Examination Surveys (NHANES)/Center for Disease Control (CDC) criteria for folate deficiency (SF< 3.0 ng/ml, RCF < 140 ng/ml). Results:A total of 152,166 SF and 15,708 RCF were performed over the decade of the study. The prevalence of folate deficiency using only SF values was 0.39% and 0.27% using only RCF values. There were 1082 patients in which SFA and RCFA were ordered concurrently (Table 1).Table 1Analysis of patients with paired SF and RCF using NHANES/CDC definition of folate deficiencySerum FolateAbnormal (<3.0 ng/ml)Normal (>3.0 ng/ml)RECAbnormal (<140 ng/ml)1 (0.09%)4 (0.4%)Normal (>140 ng/ml)8 (0.7%)1069 (98.8%)Only 1 patient (0.09%) had both abnormal SF and RCF. Chart reviews of the 4 patients with a normal SF but low RCF were as follows: 1) a 6 year old (yo). male with known folic acid transporter deficiency treated with Leucovorin. 2) a 58 yo male with history of gout, hypertension, psoriasis, and hyperlipidemia with normal hemoglobin (Hb) and MCV. 3) a 65 yo male with chronic diarrhea and suspected alcohol abuse; slight macrocytosis (MCV=100.3 fL) but normal Hb. 4) a 51 yo male with multifactorial gait disorder and alcohol abuse. There was a previous history of vitamin B12 deficiency but B12 levels were normal at this time. The CBC was notable for macrocytosis (MCV=115.1 fL) without anemia. Only in patient 4 did the RCF value result in the institution of folic acid supplementation. Conclusions:The RCF provides no additional information beyond that provided by the SF in virtually all situations. Thus SF alone is sufficient for assessment of folate stores. However, there is no evidence to support routine ordering of either SF or RCF, as true folate deficiency in the current era of FDA mandated folic acid supplementation is exceedingly rare. Disclosures:No relevant conflicts of interest to declare.

Unsuccessful Treatment with Lenalidomide in a Diamond-Blackfan Anemia Patient.

Abstract 4219 BackgroundDiamond-Blackfan Anemia (DBA) is an autosomal dominant inherited bone marrow failure syndrome due to a defect in the ribosomal protein (RP) synthesis. Diagnostic criteria consist of presentation of anemia before birth with near normal or slightly decreased neutrophil counts, variable platelet counts, reticulocytopenia, macrocytosis, and normal marrow cellularity with a paucity of red cell precursors (Diamond et al 1976). Patient characteristicsIn 2002 a 34 year old man was presented with a hemoglobin (Hb) level of 2.4 mmol/l, a MCV of 117 fl, no reticulocytes and a normal leukocyte and platelet count. Except shortness of breath he had no other complaints. He did not use any medication. On physical examination there was only a short stature. Marrow cytology showed 20% erythropoesis with some dyserythropoesis. Marrow histology and cytogenetic were normal. A recent parvovirus infection was excluded. His medical history started in 1968 at the age of five weeks. A DBA was diagnosed and treated successfully with corticosteroids. There was a relapse at the age of 3 with again a good response on corticosteroids.In 2002 he was initially treated with 6 units of red blood cells, resulting in a rise of the Hb to 6.4 mmol/l. After five months he had a Hb of 3.8 mmol/l, a normal MCV and 50.109/l reticulocytes. Kidney and adrenal function were normal, there was no hypogonadism and no splenomegaly. Hb electrophoresis showed an elevated HbF of 6.4%. By exclusion of other causes of anemia, it was concluded that the anemia had to be considered as a relapse DBA. Corticosteroids (1 mg/kg) for 6 months did not show any improvement. Cyclosporine 100 mg two times a day raised the Hb above 8 mmol/l from November 2003 till May 2004. While on cyclosporine he relapsed again and became red blood cell transfusion dependent from February 2006. A search for a HLA identical donor at that time was unsuccessful. ATG, cyclosporine and corticosteroids did not diminish the need for red blood cell transfusion. In 2007 the RPS19 (ribosomal protein S19) mutation was demonstrated in this patient, which definitively confirmed the diagnosis made 35 years ago. In 2008, still red blood cell transfusion dependent, treatment with lenalidomide 10 mg/day for 21 days during each 28 days was initiated. Treatment considerationsAll mutated genes in DBA cause a decreased synthesis of ribosomal proteins. As a consequence erythroid progenitors and precursors are highly sensitive to apoptosis (Perdahl et al 1994). One of the mechanisms is activation of p53 (Danilova et al 2008). Both the 5q- syndrome and DBA show haploinsufficiency for closely related ribosomal proteins RPS-19 and RPS-14. It is assumed that the pathophysiology of the 5q- syndrome and DBA are the same (Ebert et al 2007). Because lenalidomide is effective in patients with the 5q- syndrome, lenalidomide was considered as treatment option in DBA at the Annual DBA International Consensus Conferences in 2008 and 2009. ResultsDue to severe pancytopenia, lenalidomide was stopped after 5 weeks. During the next 6 months a slow recovery of white blood cells and platelets was observed. Before and 3 months after the start of the lenalidomide treatment marrow cytology, histology and cytogenetics were done. Both times there was a red cell aplasia, no signs of myelodysplasia and no cytogenetic abnormalities. Rechallenge with lenalidomide in a dose of 10 mg each fourth day resulted again in a pancytopenia in 6 weeks time. Each 3 weeks 3 units of red blood cells are necessary ever since. Discussion and ConclusionTreatment of DBA with lenalidomide in this patient was unsuccessful and resulted in a temporarily and severe neutropenia and thrombocytopenia. These adverse effects are also documented in 62% of the 5q- syndrome patients treated with 10 mg Lenalidomide. Moreover, in retrospect, we doubt if lenalidomide can be effective when red cell aplasia is already present as a late complication of DBA. Disclosures:No relevant conflicts of interest to declare.

The value of the erythrocyte indices as a screening procedure in predicting nutritional deficiencies

The results of a large number of nutritional screen requests (n = 871) were compared with corresponding values of erythrocyte indices considered predictive of nutritional deficiencies to determine if such indices could be used in a prospective screening procedure to restrict the number of serum vitamin B12, folate, and ferritin assays. Low mean cell haemoglobins (MCH less than 27 pg) were found to be superior to low mean cell volumes (MCV less than 77 fl), in predicting low serum ferritin values. The occurrence of deficient ferritin values was 90% when the MCH was very low (MCH less than 23 pg). Vitamin B12 or folate deficiency could not be predicted from the MCV. A normal MCV was found in more than 55% of vitamin B12 deficient samples and some 30% of serum B12 deficients (less than 150 micrograms/l) showed no evidence of anaemia (Hb greater than 12 gm/dl) or macrocytosis (MCV less than 100 fl). It would not seem appropriate to use erythrocyte indices alone as a method of selecting samples for further investigation of folate or vitamin B12 status.

Presence of JAK2 Mutations in MDS/MPD-u WHO Classified Patients and Not Other Forms of MDS Suggests Their Derivation from Classical Myeloproliferative Syndrome.

The WHO classification of myeloid neoplasms recognizes a category of myeloid disorders that overlaps traditional myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) as the entity MDS/MPD disease. This disease category includes CMML, JMML, atypical CML and MDS/MPD unclassifiable (MDS/MPD-u). The provisional entity termed RARS associated with marked thrombocytosis (RARS-t) is currently best classified as MDS/MPD-u until further information is available regarding its pathogenesis. Recently a JAK2 mutation V617F (G→T) was identified as a pathogenetic lesion in typical myeloproliferative disorders (Kralovics et al, NEJM , 2005). Subsequent studies of the JAK2 mutation concentrated on more proliferative forms of MDS or MDS/MPD such as CMML and CNL (Steensma et al, Blood , 2005). These studies demonstrated that homo- and heterozygous JAK2 mutants are present in a rather small proportion of these patients. Based on similar clinical features, we theorized that JAK2 mutants might be also found in patients with MDS/MPD-u. We have collected a cohort of these patients (N=202) and analyzed them for the presence of JAK2 mutation using a molecular allele-specific PCR assay. Positive cases were confirmed by sequencing with a sensitivity of about 20% of mutated cells. A group of patients with PV, MF and ET served as positive controls (N=66). In agreement with previous reports, the detection rate of JAK2 mutants for PV, MF and ET was 92%, 55% and 55%, respectively. Our experimental group included 104 patients with MDS or MDS/MPD (53 RA/RS, 14 RAEB, 22 RAEB-t/sAML, and 15 CMML). Most significantly, the RA/RS group contained 13 patients with WHO-defined MDS/MPD overlap and 3 with RARS-t (among these patients, 3 were JAK2 mutants; all of them were heterozygous - 18.8%). Within 16 patients with CMML1 or 2 we found only 2 heterozygous for JAK2 mutation (12.5%). The remaining cohort of 73 patients in MDS categories revealed only 1 patient to be heterozygous for JAK2 mutation (RARS, 1.4%). As expected MDS/MPD patients with JAK2 mutation showed various degrees of BM fibrosis, splenomegaly and less pronounced cytopenias. Except for one patient, JAK2 mutants had normal cytogenetics. All had normal MCV and ANC. In 4/5 increased megakaryocytes with/or without atypia was seen. One CMML patient with abnormal cytogenetics showed an unusual translocation t(8;9)(q22;p24). JAK2 is located at 9p24 so it is possible that the JAK2 gene was involved in the translocation generating a novel fusion protein in addition to an activating JAK2 mutant. Our results showed that JAK2 mutations are rarely found in typical cases of MDS or CMML. However, further analysis of JAK2 mutational status in patients with MDS/MPD-u is warranted. The reported detection rate may suggest that the pathogenesis of these entities is more akin to myeloproliferative than myelodysplastic syndromes.

Vitamin B12 deficiency in dementia and cognitive impairment: the effects of treatment on neuropsychological function.

Vitamin B12 assay is part of the routine investigation of dementia, although few studies have investigated the effects of treatment on cognition. We examined the effects of B12 treatment on neuropsychological function and disease progression in patients presenting with dementia or cognitive impairment. From 1432 patients who were assessed at the Bristol Memory Disorders Clinic, 125 patients with low serum B12 were identified. Sixty-six patients presenting with dementia, and 22 with cognitive impairment were seen for a second assessment after treatment. Changes in neuropsychological test scores were compared with those of patients with normal serum B12, matched by age and diagnosis. The majority of patients with low serum B12 had normal Hb and MCV values. We found no cases of reversible B12 deficiency dementia. The B12 treatment patients who presented with dementia showed no significant improvement, and no less deterioration, in their neuropsychological function than their matched group. However, a treatment effect was demonstrated among the patients presenting with cognitive impairment. These improved significantly compared to matched patients on the verbal fluency test (p<0.01). All patients with cognitive impairment should be investigated for B12 deficiency. Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia.

Elevation of zinc protoporphyrin levels in lead workers with iron-sufficient microcytosis.

Zinc protoporphyrin (ZPP) measurement is a required test under the Occupational Safety and Health Administration's lead standard. However, there is no mention of the influence of hemoglobinopathy on the ZPP test value. We undertook a retrospective laboratory review of 382 employees at the Argonne National Laboratory who had been subjects in a lead surveillance program since 1982. A total of 321 samples were analyzed, after female subjects and samples with abnormally high bilirubin levels were excluded. A group with low mean red blood cell volume (MCV; less than 80.0 fL) was compared with a group with normal MCV (greater or equal to 80.0 fL). A statistically significant difference was noted in ZPP (P < 0.007) and total bilirubin (P < 0.0003) values of two groups. There was no statistically significant difference noted in age, lead levels, or iron levels between the two groups. Abnormally high ZPP levels may occur in individuals with hemoglobinopathies. Only a minor part of this elevation could be explained by the higher bilirubin levels.

77 ANEMTA OF ACUTE INFECTION IN INFAFNCY AND CHILDHOOD

Aim : Acute infections could play an important role among the causes of mild anemia. The purpose of this study is to determine the prevalence of anemia of acute infection (AAI) and related diseases. Desing and methods : Randomly selected 200 children whose venous Hb levels were under 11 gr/dl were included in this study. They were between 4 months-16 years of age. Children having a definite infection, normal MCV, MCH and MCHC and increased ESR were classified as AAI. The test performed : Hb, Hct, WBC, MCV, MCH, MCHC, ESR, Serum iron concentration (SIC), iron-binding capacity (TIBC), Fe: TIBC were carried out at the begining and after 30 days. Serum ferritin concentration (SFC) and enytrocyte protoporphyrin (EP) values could not performed. Results : 1- 29,5 % ot 200 children had AAI. 2- The infections related to AAI were pneumonia ( 22/59 ), acute gastroenteritis ( 9/59 ), upper respiratory tract infections ( 13/59 ), acute viral hepatitis ( 5/59 ), urinary tract infections ( 6/59 ) and the others ( 4/59 ). 3- After 30 days of infection Hb values had returned to normal and the increase was significant ( p < 0.01 ). 4- A depression in Fe: TIBC was not observed in AAI. Conclusion : Acute infection is an important cause of anemia in children. If SFC and EP couldn't be performed, the normal value of Fe: TIBC is a helpfull parameter for AAI.

Molecular Analysis of Atypical β‐Thalassemia Heterozygotesa

This paper reviews the molecular pathology of a heterogeneous group of beta-thalassemia heterozygotes which may be referred to as atypical beta-thalassemia. This group includes four different categories of heterozygous beta-thalassemia, which are characterized, respectively, by (1) normal MCV and MCH; (2) normal Hb A2; (3) normal MCV, MCH, and Hb A2 and imbalanced globin chain synthesis only or, (4) the presence of clinical manifestations. The first group is represented by a limited proportion of double heterozygotes for alpha- and beta-thalassemia. The second group includes two categories. One category is double heterozygotes for delta- and beta-thalassemia with the delta-thalassemia mutation in cis or in trans to beta-thalassemia. A number of delta-thalassemia mutations which produce this phenotype by interacting with beta-thalassemia have been described. The other category within the second group is heterozygotes for some mild beta(+)-thalassemia mutations. Within the third group, conclusive evidence for a mutation within the beta-globin gene cluster producing the silent beta-thalassemia phenotype has been obtained solely for a C----T substitution at -101 within the CACCC box of the beta-globin gene. Possible candidates are the complex rearrangements (-T, +ATA; -T, +ATATA) found at position -530 from the cap site. In the group of thalassemic hemoglobinopathies, a series of mutations mostly located in the third exon and producing elongated or truncated molecules have been recently reported. Most of the mutations are silent at the protein level, produce inclusion bodies in peripheral erythrocytes, and show a dominant transmission pattern or occur sporadically.

DRINKWATCHERS — DESCRIPTION OF SUBJECTS AND EVALUATION OF LABORATORY MARKERS OF HEAVY DRINKING

Clinical examination and measurement of MCV and GGT were carried out on 124 self-referred 'healthy' Drinkwatchers, all of whom had consumed at least 80 g alcohol/day for more than 2 years. The majority (66.1%) were in social classes II and III. Sixty-three subjects (54.1%) had a raised MCV, GGT or hepatomegaly. A raised MCV was significantly more likely to occur in men. Forty-five subjects (36.3%) had an enlarged liver of whom 17 had a normal MCV and GGT. This study shows that MCV and GGT are poor screening tests for excessive alcohol consumption in 'healthy' subjects but, if used at all, MCV appears to be more sensitive in women and GGT in men. Neither test is an adequate substitute for a careful history and full clinical examination.

Iron depletion and anaemia: prevalence, consequences, diagnostic and therapeutic implications in a developing Pakistani population.

The prevalence of iron deficiency anaemia in Karachi, Pakistan, was examined in a group of 100 children, aged 2 to 6 years, and 200 adult females, aged 17 to 35 years. Anaemia, defined as a haemoglobin level less than 11.5 g/dl, was present in 47% of the children and 30% of the adult females. The majority of subjects had normal red cell counts and MCV, but haematocrit and MCH were below normal in one-quarter of the children and one-third of the adult females. More than half of both children and adult females had serum ferritin levels below normal. Many also had elevated iron binding capacity and reduced serum iron levels. Iron deficiency may be superimposed on folate deficiency in this population. The potentially serious consequences and higher prevalence of iron deficiency anaemia in children and women of childbearing age demand greater efforts toward diagnosis and eradication in developing countries.

Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis.

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.

Interaction of alpha- and delta beta o- thalassaemia: haematological features and globin chain synthesis analysis.

An observation of suspected interaction of δβ0- and α-thalassaemia, identified through careful examination of the family, is reported. The δβ0-thalassaemia was of the usual type found in Sardinia, characterised by high Hb F levels and very low levels of glycine in the isolated γCB3 peptide. The haematological findings in the double δβ0-/α-thalassaemia heterozygotes were: normal MCV and Hb A2 levels, increased Hb F (11·3 to 16·8%) heterogeneously distributed in red cells, and almost balanced α/β globin chain synthesis ratios.

Restoration of normal red cell size after treatment in megaloblastic anaemia.

The return of the MCV to normal after treatment in megaloblastic anaemia follows a biphasic pattern. The initial more rapid decline in MCV is due to disappearance of pretreatment macrocytes from the circulation and the rate of fall is determined by their mean cell life. The second slower component is probably due to a mixture of pretreatment macrocytes and new macrocytes, the result of a young red cell population. The MCV often returned to normal most rapidly in the most severely megaloblastic patients due to a very short mean red cell life span. However, there was no significant correlation between either initial MCV or red cell count and the time after treatment for a return of a normal MCV.