杉原 尚. 先天性溶血性貧血. In：金澤一郎, 他編. 内科学. 1版. 東京：医学書院；2006, p.1948-53.
Renée L Crisp, Liliana Solari, Daiana Vota, Eliana García, Gabriela Miguez, Maria E Chamorro, Gabriel A Schvartzman, Graciela Alfonso, Daniel Gammella, Sergio Caldarola, Cecilia Riccheri, Daniela Vittori, Belen Venegas, Alcira Nesse, Hugo Donato
A prospective study to assess the predictive value for hereditary spherocytosis using five laboratory tests (cryohemolysis test, eosin-5'-maleimide flow cytometry, osmotic fragility test, autohemolysis test, and SDS-PAGE) on 50 hereditary spherocytosis families in Argentina.
Ann Hematol. 2011 Jun;90(6):625-34. doi: 10.1007/s00277-010-1112-0. Epub 2010 Nov 16.
Abstract/Text
This prospective study was carried out to assess the usefulness of five laboratory tests in the diagnosis of hereditary spherocytosis (HS), based on the correlation of erythrocyte membrane protein defects with clinical and laboratory features, and also to determine the membrane protein deficiencies detected in Argentina. Of 116 patients and their family members tested, 62 of them were diagnosed to have HS. The specificity of cryohemolysis (CH) test was 95.2%, and its cut-off value to distinguish HS from normal was 2.8%. For flow cytometry, cut-off points of 17% for mean channel fluorescence (MCF) decrease and 14% coefficient of variation (CV) increase showed 95.9% and 92.2% specificity, respectively. Both tests showed the highest percentages of positive results for diagnosis. Either CH or flow cytometry was positive in 93.5% of patients. In eight patients, flow cytometry was positive only through CV increase. Protein defects were detected in 72.3% of patients; ankyrin and spectrin were the most frequently found deficiencies. The CV of the fluorescence showed significantly higher increases in moderate and severe anemia than in mild anemia (p = 0.003). Severity of anemia showed no other correlation with tests results, type of deficient protein, inheritance pattern, or neonatal jaundice. CH and flow cytometry are easy methods with the highest diagnostic accuracy. Simultaneous reading of mean channel fluorescence (MCF) decrease and CV increase improve diagnostic usefulness of flow cytometry. This test seems to be a reliable predictor of severity. The type of detected protein deficiency has no predictive value for outcome. Predominant ankyrin and spectrin deficiencies agree with reports from other Latin American countries.
Paula H B Bolton-Maggs, Jacob C Langer, Achille Iolascon, Paul Tittensor, May-Jean King, General Haematology Task Force of the British Committee for Standards in Haematology
Guidelines for the diagnosis and management of hereditary spherocytosis--2011 update.
Br J Haematol. 2012 Jan;156(1):37-49. doi: 10.1111/j.1365-2141.2011.08921.x. Epub 2011 Nov 5.
Abstract/Text
Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton-Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with splenectomy in those with asymptomatic gallstones). Further potential long term hazards of splenectomy are now recognised. Advances have been made in our understanding of the biochemistry of the red cell membrane which underpins the choice of tests. Biochemical assays of membranes proteins and genetic analysis may be indicated (rarely) to diagnose atypical cases. The diagnostic value of the eosin-5-maleimide (EMA) binding test has been validated in a number of studies with understanding of its limitations.
© 2011 Blackwell Publishing Ltd.
P H B Bolton-Maggs, R F Stevens, N J Dodd, G Lamont, P Tittensor, M-J King, General Haematology Task Force of the British Committee for Standards in Haematology
Guidelines for the diagnosis and management of hereditary spherocytosis.
Br J Haematol. 2004 Aug;126(4):455-74. doi: 10.1111/j.1365-2141.2004.05052.x.
Abstract/Text
Hereditary spherocytosis (HS) is a heterogeneous group of disorders with regard to clinical severity, protein defects and mode of inheritance. It is relatively common in Caucasian populations; most affected individuals have mild or only moderate haemolysis. There is usually a family history, and a typical clinical and laboratory picture so that the diagnosis is often easily made without additional laboratory tests. Atypical cases may require measurement of erythrocyte membrane proteins to clarify the nature of the membrane disorder and in the absence of a family history, occasionally molecular genetic analysis will help to determine whether inheritance is recessive or non-dominant. It is particularly important to rule out stomatocytosis where splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 years and with appropriate counselling about the infection risk. In all cases careful dialogue between doctor, patient and the family is essential. Laparoscopic surgery, when performed by experienced surgeons, can result in a shorter hospital stay and less pain.
François Mullier, Elodie Lainey, Odile Fenneteau, Lydie Da Costa, Françoise Schillinger, Nicolas Bailly, Yvan Cornet, Christian Chatelain, Jean-Michel Dogne, Bernard Chatelain
Additional erythrocytic and reticulocytic parameters helpful for diagnosis of hereditary spherocytosis: results of a multicentre study.
Ann Hematol. 2011 Jul;90(7):759-68. doi: 10.1007/s00277-010-1138-3. Epub 2010 Dec 22.
Abstract/Text
Hereditary spherocytosis (HS) is characterised by weakened vertical linkages between the membrane skeleton and the red blood cell's lipid bilayer, leading to the release of microparticles. All the reference tests suffer from specific limitations. The aim of this study was to develop easy to use diagnostic tool for screening of hereditary spherocytosis based on routinely acquired haematological parameters like percentage of microcytes, percentage of hypochromic cells, reticulocyte counts, and percentage of immature reticulocytes. The levels of haemoglobin, mean cell volume, mean corpuscular haemoglobin concentration, reticulocytes (Ret), immature reticulocytes fraction (IRF), hypochromic erythrocytes (Hypo-He) and microcytic erythrocytes (MicroR) were determined on EDTA samples on Sysmex instruments from a cohort of 45 confirmed SH. The HS group was then compared with haemolytical disorders, microcytic anaemia, healthy individuals and routine samples (n = 1,488). HS is characterised by a high Ret count without an equally elevated IRF. All 45 HS have Ret >80,000/μl and Ret(10(9)/L)/IRF (%) greater than 7.7 (rule 1). Trait and mild HS had a Ret/IRF ratio greater than 19. Moderate and severe HS had increased MicroR and MicroR/Hypo-He (rule 2). Combination of both rules gave predictive positive value and negative predictive value of respectively 75% and 100% (n=1,488), which is much greater than single parameters or existing rules. This simple and fast diagnostic method could be used as an excellent screening tool for HS. It is also valid for mild HS, neonates and ABO incompatibilities and overcomes the lack of sensitivity of electrophoresis in ankyrin deficiencies.
L A Michaels, A R Cohen, H Zhao, R I Raphael, C S Manno
Screening for hereditary spherocytosis by use of automated erythrocyte indexes.
J Pediatr. 1997 Jun;130(6):957-60.
Abstract/Text
OBJECTIVE: To determine whether the mean corpuscular hemoglobin concentration (MCHC) or other erythrocyte indexes, as determined by automated cell counters, remains a useful screening test for identifying patients with hereditary spherocytosis (HS).
METHODS: Erythrocyte indexes from 112 children with HS who had not undergone splenectomy were compared with those measured in an equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance.
RESULTS: Mean corpuscular hemoglobin concentration in the HS group was 35.9 gm/dl, significantly higher than in normal control subjects (34.3 gm/dl; p < 0.001). Mean erythrocyte distribution width also was significantly higher in patients with HS (19.3 vs 12.6; p < 0.001). The MCHC distinguishes individuals with HS, with an area under the receiver operating characteristic curve of 0.86. Although not disease specific, an erythrocyte distribution width > 14 has 85% sensitivity and 97% specificity and an area under the receiver operating characteristic curve of 0.92. An MCHC > 35 gm/dl has a sensitivity of 70% and a specificity of 86%. Combining the MCHC and erythrocyte distribution width increases the area under the receiver operating characteristic curve to 0.97. Specificity is 100% and likelihood ratio is infinite when both the MCHC and erythrocyte distribution width are elevated.
CONCLUSIONS: The automated MCHC is an effective screening test to identify children with HS. An elevated erythrocyte distribution width adds additional specificity and is itself a powerful screening tool. The combination of the two tests is an excellent predictor for the diagnosis of HS.
小峰光博：自己免疫性溶血性貧血. 臨床血液. 1992：33：897-901.
A Salama, H Berghöfer, C Mueller-Eckhardt
Red blood cell transfusion in warm-type autoimmune haemolytic anaemia.
Lancet. 1992 Dec 19-26;340(8834-8835):1515-7.
Abstract/Text
Blood transfusions are regarded as hazardous in patients with warm-type autoimmune haemolytic anaemia (AIHA) because of potential intensification of haemolysis and a presumed high incidence of alloimmunisation. We have retrospectively analysed data of 79 multitransfused patients (74 adults, 5 children) with detectable warm autoantibodies and transitory or persisting haemolytic anaemia. All patients had received blood transfusions on at least two occasions. Patients were reexamined at least twice within the first 6 months of transfusion (duration of follow-up 6 months-12 years). 53 patients had received blood transfusions because of decompensated AIHA, all of whom presented with detectable autoantibodies against red blood cells. None of these patients had transfusion-related alloimmunisation or a definite increase in haemolysis, even when the transfused red cells were serologically incompatible because of free serum autoantibodies. The other 26 patients had no signs of AIHA at presentation (negative direct and indirect antiglobulin test), but received blood transfusions for anaemia due to various other causes. 23 of these 26 patients went on to develop alloantibodies as well as autoantibodies upon transfusion, and 3 patients developed autoantibodies alone. Our findings do not support the generally accepted notion that transfusion therapy should be avoided in AIHA patients. Rather, they indicate that the incidence of alloimmunisation as well as adverse haemolytic transfusion reactions are less common in AIHA patients than in other multitransfused patients.
Toyomi Kamesaki, Takashi Oyamada, Mitsuhiro Omine, Keiya Ozawa, Eiji Kajii
Cut-off value of red-blood-cell-bound IgG for the diagnosis of Coombs-negative autoimmune hemolytic anemia.
Am J Hematol. 2009 Feb;84(2):98-101. doi: 10.1002/ajh.21336.
Abstract/Text
Direct antiglobulin test (DAT)-negative autoimmune hemolytic anemia (Coombs-negative AIHA) is characterized by laboratory evidence of in vivo hemolysis, together with a negative DAT performed by conventional tube technique (CTT) in clinically suspected AIHA patients. The immunoradiometric assay (IRMA) for red-blood-cell-bound immunoglobulin G (RBC-IgG) can be used to diagnose patients in whom CTT does not detect low levels of red cell autoantibodies. We investigated the diagnostic cutoff value of the IRMA for RBC-IgG in Coombs-negative AIHA and calculated its sensitivity and specificity. Of the 140 patients with negative DAT by CTT referred to our laboratory with undiagnosed hemolytic anemia, AIHA was clinically diagnosed in 64 patients (Coombs-negative AIHA). The numbers of Coombs-negative AIHA and non-AIHA patients changed with age and gender. The cutoff values were determined from receiver operating characteristic (ROC) curve according to age and gender. The IRMA for RBC-IgG proved to be sensitive (71.4%) and specific (87.8%) when using these cutoffs. Using these cutoffs for 41 patients with negative DAT referred to our laboratory in 2006, all the pseudonegative cases were treated with steroids before the test. The 31 untreated cases could be grouped using one cutoff value of 78.5 and showed 100% sensitivity and 94% specificity, independent of gender and age. Results indicate that RBC-IgG could become a standard approach for the diagnosis of Coombs-negative AIHA, when measured before treatment.
特発性造血障害に関する調査研究班：自己免疫性溶血性貧血診療の参照ガイド 令和4年度改訂版.
W Walker
Splenectomy in childhood: a review in England and Wales, 1960-4.
Br J Surg. 1976 Jan;63(1):36-43.
Abstract/Text
An investigation was carried out of 821 children under the age of 16 years who were subjected to splenectomy in England and Wales during the 5 years 1960-4. A postal follow-up study provided satisfactory information concerning 96 per cent of these. Excluding early postoperative deaths, practically all the cases were followed up for 2 years or more and 70 per cent for more than 5 years. Forty-nine children had died since operation, 32 from underlying disease and 17 from infection. Fifty children (6 per cent of the survivors) had major infections considered to be due to the primary condition aggravated by splenectomy. Seven died, all from the primary disease. Sixteen children (2 per cent) developed septicaemic illnesses and 10 died. In these the effect of splenectomy was considered to be the primary factor. Fourteen of the 16 had been operated on in the first 4 years of life. Practically all the serious infections occurred within 3 years of operation and pneumococcus was the organism most frequently implicated. Ninety per cent of the splenectomies in childhood were performed for accidental injury, congenital haemolytic anaemia or idiopathic thrombocytopenic purpura. Accidental injury to the spleen rarely occurs in very young children, and in the other two conditions splenectomy can usually be safely delayed untile over the age of 3 years. If this is achieved it is estimated that the unavoidable risk of dangerous infection is less than 1 per cent. One in 10 splenectomies will be carried out for severe and potentially fatal illnesses and in this situation the risk from operation is of secondary importance. Many such conditions carry increased susceptibility to infection per se or because corticosteroids or other immune suppressants are used in their management. It is recommended that splenectomy be avoided if at all possible during the early years of life. It is further recommended that prophylactic penicillin be administered for 3 years following operation whatever its indication and whatever the age of the patient. If the underlying condition itself carries risk of infection more active and more prolonged prophylaxis may be indicated.
A J Eraklis, R M Filler
Splenectomy in childhood: a review of 1413 cases.
J Pediatr Surg. 1972 Aug-Sep;7(4):382-8.
Abstract/Text
H B Konradsen, J Henrichsen
Pneumococcal infections in splenectomized children are preventable.
Acta Paediatr Scand. 1991 Apr;80(4):423-7.
Abstract/Text
Through the Danish National Patient Registry we identified all children 0-15 years old who had been splenectomized during the period 1979-87 and all children of the same age who, during the same period of time, had been admitted to a hospital because of either meningitis or bacteraemia caused by Streptococcus pneumoniae. We wanted to see whether any of the splenectomized children had developed invasive pneumococcal infection during the observation period. A similar Danish study covering the period 1969-78, when pneumococcal vaccine was not available, has already been published (3). Four per cent of the children splenectomized during that period developed invasive pneumococcal infection in contrast to none of the children splenectomized and vaccinated during the period 1979-87. Since 1982 antibiotic treatment of splenectomized patients running a fever has been recommended, and we show that the program of pneumococcal vaccination and defined antibiotic prophylaxis has been highly efficacious in preventing post-splenectomy infections in children.
