今日の臨床サポート

溶血性貧血

著者: 杉原尚 川崎医科大学 総合内科学4

著者: 中西秀和 川崎医科大学 総合内科学4

監修: 木崎昌弘 埼玉医科大学総合医療センター

著者校正/監修レビュー済:2021/03/24
患者向け説明資料

概要・推奨   

  1. 特発性の温式AIHAの治療では、ステロイド薬が第1選択である(推奨度2)
  1. 特発性の温式AIHAの治療において、ステロイド薬の禁忌例や無効例では摘脾術、免疫抑制薬が第2選択として考慮される(推奨度2)
  1. 特発性の温式AIHAの発症/診断から5年後の生存率は約80%であり、高齢者の予後は相対的に不良である。続発性では、3年までに約50%の死亡が記録され、基礎疾患が主要な予後因子である。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
杉原尚 : 特に申告事項無し[2021年]
中西秀和 : 特に申告事項無し[2021年]
監修:木崎昌弘 : 講演料(ブリストル・マイヤーズスクイブ,ヤンセンファーマ,ノバルティスファーマ,セルジーン,MSD,小野薬品,武田薬品,大日本住友製薬),研究費・助成金など(武田薬品),奨学(奨励)寄付など(協和キリン,中外製薬,武田薬品,小野薬品,第一三共)[2021年]

改訂のポイント
  1. 定期レビューを行い、参考ガイドラインについて更新を行った。

病態・疫学・診察

疾患情報  
  1. 溶血性貧血(hemolytic anemia)とは、何らかの原因によって赤血球の崩壊が亢進した状態の総称であり、多くの疾患を包括する一種の症候群である。赤血球崩壊といっても、赤血球が末梢血液中で、まさに溶ける疾患群(血管内溶血)もあれば、赤血球が脾臓などに捕捉され流血中から取り除かれる疾患群(血管外溶血)も存在する。いずれにせよ、赤血球崩壊が亢進し赤血球寿命が短縮してくると、骨髄はその産生能力を高め、通常よりも多くの赤血球を産生する。この産生の程度が赤血球の崩壊の範囲内にある場合には貧血がみられず(代償性溶血)、赤血球崩壊に産生能が追いつかない場合にはじめて貧血を生じることになる(非代償性溶血)。したがって、実際には貧血を呈さない症例もあり、溶血性疾患と呼ぶのが適切と考えられる[1]
  1. 自己免疫性溶血性貧血は、指定難病であり、重症度分類においてStage3以上(薬物療法を行っていてヘモグロビン濃度10g/dl以上の者は除く)の場合などでは、申請し認定されると、保険料の自己負担分の一部が公費負担として助成される。([ https://www.nanbyou.or.jp/wp-content/uploads/upload_files/File/061-201704-kijyun.pdf 平成27年1月施行])
  1. 難病法に基づく医療費助成制度
問診・診察のポイント  
ポイント:
  1. 貧血に伴う一般症状や身体所見、および溶血に伴う症状や身体所見について問診や診察で確認する。また経過が急であるのか緩徐であるのか、あるいは先天性を疑わせる経過や家族歴があるのかについても聴取する。貧血に伴う自覚症状は、貧血の程度よりも、むしろ貧血の進行速度により左右される。慢性に経過する貧血では、6~7g/dl程度の貧血であっても自覚症状に乏しいことが多い。進行の早い貧血は急性出血か急性溶血発作を疑う。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: 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
雑誌名: 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.

PMID 15287938  Br J Haematol. 2004 Aug;126(4):455-74. doi: 10.1111/j.1・・・
著者: François Mullier, Elodie Lainey, Odile Fenneteau, Lydie Da Costa, Françoise Schillinger, Nicolas Bailly, Yvan Cornet, Christian Chatelain, Jean-Michel Dogne, Bernard Chatelain
雑誌名: 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.

PMID 21181161  Ann Hematol. 2011 Jul;90(7):759-68. doi: 10.1007/s00277・・・
著者: L A Michaels, A R Cohen, H Zhao, R I Raphael, C S Manno
雑誌名: 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.

PMID 9202619  J Pediatr. 1997 Jun;130(6):957-60.
著者: A Salama, H Berghöfer, C Mueller-Eckhardt
雑誌名: 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.

PMID 1361607  Lancet. 1992 Dec 19-26;340(8834-8835):1515-7.
著者: Toyomi Kamesaki, Takashi Oyamada, Mitsuhiro Omine, Keiya Ozawa, Eiji Kajii
雑誌名: 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.

PMID 19105232  Am J Hematol. 2009 Feb;84(2):98-101. doi: 10.1002/ajh.2・・・
著者: W Walker
雑誌名: 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.

PMID 1267873  Br J Surg. 1976 Jan;63(1):36-43.
著者: A J Eraklis, R M Filler
雑誌名: J Pediatr Surg. 1972 Aug-Sep;7(4):382-8.
Abstract/Text
PMID 5049847  J Pediatr Surg. 1972 Aug-Sep;7(4):382-8.
著者: H B Konradsen, J Henrichsen
雑誌名: 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.

PMID 2058391  Acta Paediatr Scand. 1991 Apr;80(4):423-7.
著者: 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
雑誌名: 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.
PMID 22055020  Br J Haematol. 2012 Jan;156(1):37-49. doi: 10.1111/j.13・・・
著者: 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
雑誌名: 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.

PMID 21080168  Ann Hematol. 2011 Jun;90(6):625-34. doi: 10.1007/s00277・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから