今日の臨床サポート

血栓性血小板減少性紫斑病

概要・推奨   

  1. 後天性TTPでは、診断後早期に血漿交換を開始することが重要である(推奨度1)
  1. 後天性TTPの治療には、血漿交換にステロイド治療を追加することが推奨される(推奨度2)
  1. 難治性や再発性の後天性TTPにリツキシマブは有効である。また、後天性TTPの急性期にリツキシマブを使用することで再発率を減少させることができる(推奨度2)
  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
  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
  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
  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
  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。
  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
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:
松本雅則 : 特許使用料(アルフレッサファーマ),講演料(武田薬品,サノフィ),奨学(奨励)寄付など(中外製薬,旭化成ファーマ)[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. ADAMTS13活性と自己抗体測定が保険適用となった。
  1. 保険診療上の後天性TTPに対する血漿交換の実施回数が変更となった。
  1. リツキシマブが後天性TTPの難治、再発例に対して保険適用となった。

病態・疫学・診察

疾患情報  
  1. 血栓性微小血管症(thrombotic microangiopathy、TMA)は、①微小血管症性溶血性貧血、②血小板減少、③細血管内血小板血栓、を特徴とし、このなかには血栓性血小板減少性紫斑病(thrombotic thrombocytopenic purpura、TTP)と溶血性尿毒症症候群(hemolytic-uremic syndrome、HUS)が含まれる。
  1. TTPは血小板減少溶血性貧血、腎機能障害、発熱、精神神経障害の古典的5徴候で知られている。
  1. HUSは血小板減少、溶血性貧血、急性腎不全の3徴候で診断される。
  1. 両疾患を臨床的に鑑別することは困難な場合があり、TMAと診断される場合がある。
  1. 最近では、von Willebrand因子切断酵素(ADAMTS13)活性著減により、TTPと診断される。
  1. TTPには、先天性(Upshaw-Schulman症候群、USS)と後天性があるが、大部分は後天性である。
  1. Upshaw-Schulman症候群は、遺伝的にADAMTS13活性が著減し、後天性TTPはADAMTS13に対するIgG型の自己抗体産生が病因である。
  1. TTP/HUSの診断と治療方針:アルゴリズム
  1. 後天性TTPは、無治療の場合は致死率90%以上であるが、血漿交換の導入により致死率は20%程度となった。
  1. HUSの90%は、志賀毒素産生大腸菌(Shiga-toxic producing E.coli: STEC; O157:H7など)感染に伴うHUS(STEC-HUS)である。残りの10%はatypical(a) HUSと呼ばれている。
  1. STEC-HUSでは支持療法のみであるが、aHUSは血漿交換などの血漿療法を行う。aHUSは補体関連因子の異常が明らかであれば、エクリズマブの使用を考慮する。
  1. STEC-HUSの予後は比較的良好である。aHUSは約半数が末期腎不全になるとされている。
  1. 血栓性血小板減少性紫斑病(後天性TTP、先天性TTPともに)、非典型HUSはいずれも指定難病であり、中等症以上の場合などは、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。なお、指定難病の診断基準では、TTPはADAMTS13活性10%未満の症例のみ、aHUSは補体系、凝固系異常によるTMAのみが対象となっている。(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  
  1. 下痢の有無を確認し、STEC-HUSを診断する。

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: Yoshitaka Mori, Hideo Wada, Esteban C Gabazza, Nobuyuki Minami, Tsutomu Nobori, Hiroshi Shiku, Hideo Yagi, Hiromichi Ishizashi, Masanori Matsumoto, Yoshihiro Fujimura
雑誌名: Transfusion. 2002 May;42(5):572-80.
Abstract/Text BACKGROUND: Severe deficiency of vWF-cleaving protease (vWF-CPase) activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). Although the survival of patients with TTP has been dramatically improved with plasma exchange (PE), there are still many patients who are refractory to PE and immunosuppressive therapy.
STUDY DESIGN AND METHODS: The activities of vWF-CPase and its inhibitor were measured in 27 patients with nonfamilial TTP and hemolytic-uremic syndrome (HUS) to examine the relationship between the clinical variables and vWF-CPase activity.
RESULTS: Eight of nine patients with HUS had more than 40 percent of vWF-CPase activity, whereas one had 28 percent of the normal level at the acute phase. Ten of 12 TTP patients with a good outcome had a severe deficiency of vWF-CPase activity and its inhibitor, whereas four of six patients with a poor outcome had a moderate deficiency of vWF-CPase activity along with a lack of the inhibitor. PE produced normalization of the vWF-CPase activity and neutralization of the inhibitor in TTP patients with a good outcome; however, some TTP patients with vWF-CPase inhibitor had relapsed and required an immunosuppressive therapy. The response to the combination therapy with PE and immunosuppressive treatment was poor in TTP patients without a severe deficiency of vWF-CPase activity.
CONCLUSION: Assays of vWF-CPase activity and its inhibitor may be useful for predicting the response to therapy and the outcome of patients with TTP. In some patients, nonfamilial TTP with a poor prognosis may not be caused by a constitutional or acquired deficiency of vWF-CPase with its inhibitor. Although PE and immunosuppressive therapy are effective in patients with nonfamilial TTP and a vWF-CPase inhibitor, other therapeutic modalities may be needed for nonfamilial TTP with unknown etiology.

PMID 12084165  Transfusion. 2002 May;42(5):572-80.
著者: Sara K Vesely, James N George, Bernhard Lämmle, Jan-Dirk Studt, Lorenzo Alberio, Mayez A El-Harake, Gary E Raskob
雑誌名: Blood. 2003 Jul 1;102(1):60-8. doi: 10.1182/blood-2003-01-0193. Epub 2003 Mar 13.
Abstract/Text Initial management of patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic criteria, high mortality without plasma exchange treatment, and risks of plasma exchange. Although severe ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) deficiency may be specific for TTP, the role of ADAMTS13 activity measurements for initial management decisions is unknown. ADAMTS13 was measured before beginning plasma exchange treatment in 142 (88%) of 161 consecutive patients with clinically diagnosed TTP-HUS with assignment to 1 of 4 categories: less than 5% (severe deficiency), 5% to 9%, 10% to 25%, and more than 25%. Eighteen (13%) of 142 patients had severe ADAMTS13 deficiency. Among 6 predefined clinical categories (stem cell transplantation, pregnant/postpartum, drug association, bloody diarrhea, additional/alternative disorder, idiopathic), severe deficiency occurred only among pregnant/postpartum (2 of 10) and idiopathic (16 of 48) patients. The presenting features and clinical outcomes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinct from the 32 patients with idiopathic TTPHUS who did not have severe ADAMTS13 deficiency. Many patients in all ADAMTS13 activity categories apparently responded to plasma exchange treatment. Therefore, severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment.

PMID 12637323  Blood. 2003 Jul 1;102(1):60-8. doi: 10.1182/blood-2003-・・・
著者: Y Fujimura, M Matsumoto, A Isonishi, H Yagi, K Kokame, K Soejima, M Murata, T Miyata
雑誌名: J Thromb Haemost. 2011 Jul;9 Suppl 1:283-301. doi: 10.1111/j.1538-7836.2011.04341.x.
Abstract/Text Upshaw-Schulman syndrome (USS) is an extremely rare hereditary deficiency of ADAMTS13 activity, termed congenital TTP. The clinical signs are usually mild during childhood, often with isolated thrombocytopenia. But their symptoms become more evident when patients have infections or get pregnant. We identified 43 USS-patients in Japan, who ranged in age from early childhood to 79 years of age. Analysing the natural history of these USS patients based on ADAMTS13 gene mutations may help characterise their clinical phenotypes. Severe neonatal jaundice that requires exchange blood transfusion, a hallmark of USS, was found in 18 of 43 patients (42%). During childhood, 25 of 43 patients were correctly diagnosed with USS without gender disparity. These 25 patients were categorised as having 'the early-onset phenotype'. Between 15 and 45 years of age, 15 were correctly diagnosed, and, interestingly, they were all female. The remaining three patients were male and were diagnosed when they were older than 45 years of age, suggesting that they were 'the late-onset phenotype'. Two of these three males developed sudden overt TTP when they were 55 and 63 years old, respectively. These two men had two different homozygous ADAMTS13 gene mutations, p.R193W/p.R193W and p.C1024R/p.C1024R, respectively. Both of which were not discovered in the US or Western countries. In vitro expression studies showed that these two proteins were consistently secreted into the culture medium but to a lesser extent and with reduced activity compared to the wild-type protein. Our results indicate that 'the late-onset phenotype' of USS is formed with ethnic specificity.

© 2011 International Society on Thrombosis and Haemostasis.
PMID 21781265  J Thromb Haemost. 2011 Jul;9 Suppl 1:283-301. doi: 10.1・・・
著者: G A Rock, K H Shumak, N A Buskard, V S Blanchette, J G Kelton, R C Nair, R A Spasoff
雑誌名: N Engl J Med. 1991 Aug 8;325(6):393-7. doi: 10.1056/NEJM199108083250604.
Abstract/Text BACKGROUND: Thrombotic thrombocytopenic purpura is an uncommon disease with a high mortality rate even with current treatment. The cause of the syndrome and its optimal treatment are unknown. Although both plasma exchange and plasma infusion have been useful treatments, it is not clear which is superior. In this report we describe a prospective randomized trial comparing plasma exchange with plasma infusion for the treatment of thrombotic thrombocytopenic purpura.
METHODS: One hundred two patients with thrombotic thrombocytopenic purpura were randomly assigned to receive either plasma exchange or plasma infusion with fresh-frozen plasma on seven of the first nine days after entry into the trial. The total volume of plasma received by patients undergoing plasma exchange was three times that received by patients undergoing plasma infusion. All the patients also received aspirin and dipyridamole. The outcomes in the two groups were compared at the end of the first treatment cycle (day 9) and after six months.
RESULTS: At the end of the first treatment cycle patients receiving plasma exchange had a higher rate of response as defined by an increase in the platelet count (24 of 51 patients) than those who received plasma infusion (13 of 51, P = 0.025). Of the 51 patients treated with plasma exchange, 2 died, whereas 8 of the 51 patients who received plasma infusion died (P = 0.035). After six months the outcome in the plasma-exchange group was still superior, with a response observed in 40 of 51 patients, whereas 25 of 51 patients in the plasma-infusion group responded (P = 0.002). Eleven patients in the plasma-exchange group died, as did 19 patients in the plasma-infusion group (P = 0.036). The overall mortality was 29 percent.
CONCLUSIONS: Plasma exchange is more effective than plasma infusion in the treatment of thrombotic thrombocytopenic purpura.

PMID 2062330  N Engl J Med. 1991 Aug 8;325(6):393-7. doi: 10.1056/NEJ・・・
著者: Masanori Matsumoto, Hideo Yagi, Hiromichi Ishizashi, Hideo Wada, Yoshihiro Fujimura
雑誌名: Semin Hematol. 2004 Jan;41(1):68-74.
Abstract/Text A total of 290 Japanese patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) were analyzed with respect to ADAMTS-13 activity and its inhibitor. Twenty-one patients (17 families) had Upshaw-Schulman syndrome, and 12 patients (six families) had familial HUS of undetermined etiology. The number of patients with acquired HUS and TTP was 44 and 213, respectively. In acquired TTP, patients with severe deficiency of ADAMTS-13 activity secondary to the presence of an inhibitor were high responders to plasma exchange, but others were low responders to plasma exchange. The former patients were associated with "idiopathic" TTP, drugs, and pregnancy, and the latter patients with malignancy and stem cell transplantation. Patients with autoimmune disease-associated TTP fit into both groups.

PMID 14727261  Semin Hematol. 2004 Jan;41(1):68-74.
著者: A Pereira, R Mazzara, J Monteagudo, C Sanz, L Puig, A Martínez, A Ordinas, R Castillo
雑誌名: Ann Hematol. 1995 Jun;70(6):319-23.
Abstract/Text The aim of this study was to investigate pretreatment prognostic factors that could be useful in predicting the response to plasma exchange in thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994, were studied. The main clinical and laboratory data at the beginning of plasma exchanges were analyzed by the Cox stepwise logistic regression, applied to either treatment failure or death. Seventeen (53%) patients attained a complete remission and 22 (69%) survived (five in advanced renal failure and long-term hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or coma, and higher creatinine levels at the beginning of plasma exchanges were independent predictors of treatment failure. Stupor or coma at the beginning of plasma exchanges was the only predictor of mortality from unremitted TTP/HUS. Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as markers of disease activity, neither correlated with previous duration of TTP/HUS nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of intensive plasma exchange emerged from this study as the most effective interventions for improving the prognosis of TTP/HUS patients.

PMID 7632812  Ann Hematol. 1995 Jun;70(6):319-23.
著者: W R Bell, H G Braine, P M Ness, T S Kickler
雑誌名: N Engl J Med. 1991 Aug 8;325(6):398-403. doi: 10.1056/NEJM199108083250605.
Abstract/Text BACKGROUND AND METHODS: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the mortality approached 100 percent. A treatment protocol was introduced in 1979 for patients admitted to Johns Hopkins Hospital with the diagnosis of TTP-HUS. Treatment regimens included 200 mg of prednisone a day, for patients with minimal symptoms and no central nervous system symptoms, and prednisone plus plasma exchange, for patients with rapid clinical deterioration who did not improve after 48 hours of prednisone alone and for patients presenting with central nervous system symptoms and rapidly declining hematocrit values and platelet counts.
RESULTS: A total of 108 patients were treated, and 91 percent survived. Prednisone alone was judged to be effective in 30 patients with mild TTP-HUS (two relapses and two deaths). Plasma exchange plus prednisone was given to 78 patients with complicated TTP-HUS, resulting in 67 relapses and 8 deaths. Relapses occurred in 22 of 36 patients given maintenance plasma infusions. Neither splenectomy nor treatment with aspirin and dipyridamole was effective in those with a poor response to plasma exchange. None of the 71 patients tested had positive cultures for O157:H7 Escherichia coli. Nine percent of the patients were pregnant, and none gave birth to infants with TTP-HUS.
CONCLUSIONS: Effective treatment with 91 percent survival is available for patients with TTP-HUS.

PMID 2062331  N Engl J Med. 1991 Aug 8;325(6):398-403. doi: 10.1056/N・・・
著者: D R Harkness, J J Byrnes, E C Lian, W D Williams, G T Hensley
雑誌名: JAMA. 1981 Oct 23-30;246(17):1931-3.
Abstract/Text A patient with thrombotic thrombocytopenic purpura (TTP) showed for the first time catastrophic signs and symptoms of CNS involvement immediately after infusion of platelets. Postmortem examination revealed extensive deposits of platelet aggregates within the small blood vessels of the brain, whereas lesions elsewhere in the body consisted of platelets as well as fibrin and were associated with endothelial proliferation and microaneurysm formation. These findings are consistent with the view that the initial event in TTP may be platelet aggregation. The plasma of this patient contained platelet-aggregating activity. We conclude that platelet transfusions in patients with TTP may aggravate the disease process.

PMID 7197306  JAMA. 1981 Oct 23-30;246(17):1931-3.
著者: Sarah L Allford, Beverley J Hunt, Peter Rose, Samuel J Machin, Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology
雑誌名: Br J Haematol. 2003 Feb;120(4):556-73.
Abstract/Text
PMID 12588343  Br J Haematol. 2003 Feb;120(4):556-73.
著者: Karen K Swisher, Deirdra R Terrell, Sara K Vesely, Johanna A Kremer Hovinga, Bernhard Lämmle, James N George
雑誌名: Transfusion. 2009 May;49(5):873-87. doi: 10.1111/j.1537-2995.2008.02082.x. Epub 2009 Feb 6.
Abstract/Text BACKGROUND: Reports of deterioration and death after platelet (PLT) transfusions in patients with thrombotic thrombocytopenic purpura (TTP) have led to recommendations that they should not be given except for life-threatening hemorrhage.
STUDY DESIGN AND METHODS: Published reports of PLT transfusions in patients with TTP were systematically reviewed and data from the Oklahoma TTP-HUS Registry, an inception cohort of 382 consecutive patients, 1989 through 2007, were analyzed.
RESULTS: A systematic review identified 34 publications describing outcomes of patients with TTP after PLT transfusions: 9 articles attributed complications to PLT transfusions, 4 suggested that they may be safe, and 21 articles did not comment about a relation between PLT transfusions and outcomes. Fifty-four consecutive patients from the Oklahoma TTP-HUS Registry were prospectively analyzed. ADAMTS13 activity was less than 10 percent in 47 patients; also included were 7 patients whose activity was not measured but who may have been deficient. Thirty-three (61%) patients received PLT transfusions. The frequency of death was not different between the two groups (p = 0.971): 8 (24%) patients who received PLT transfusions died (thrombosis, 5; hemorrhage, 1; sepsis, 2) and 5 (24%) patients who did not receive PLT transfusions died (thrombosis, 4; hemorrhage, 1). The frequency of severe neurologic events was also not different (p = 0.190): 17 (52%) patients who received PLT transfusions (in 5 of these 17 patients, neurologic events only occurred before PLT transfusions) and 7 (33%) patients who did not receive PLT transfusions.
CONCLUSION: Evidence for harm from PLT transfusions in patients with TTP is uncertain.

PMID 19210323  Transfusion. 2009 May;49(5):873-87. doi: 10.1111/j.1537・・・
著者: Gema Ariceta, Nesrin Besbas, Sally Johnson, Diana Karpman, Daniel Landau, Christoph Licht, Chantal Loirat, Carmine Pecoraro, C Mark Taylor, Nicole Van de Kar, Johan Vandewalle, Lothar B Zimmerhackl, European Paediatric Study Group for HUS
雑誌名: Pediatr Nephrol. 2009 Apr;24(4):687-96. doi: 10.1007/s00467-008-0964-1. Epub 2008 Sep 18.
Abstract/Text This guideline for the investigation and initial treatment of atypical hemolytic uremic syndrome (HUS) is intended to offer an approach based on opinion, as evidence is lacking. It builds on the current ability to identify the etiology of specific diagnostic sub-groups of HUS. HUS in children is mostly due to infection, enterohemorrhagic Escherichia coli (EHEC), Shigella dysenteriae type 1 in some geographic regions, and invasive Streptococcus pneumoniae. These sub-groups are relatively straightforward to diagnose. Their management, which is outside the remit of this guideline, is related to control of infection where that is necessary and supportive measures for the anemia and acute renal failure. A thorough investigation of the remainder of childhood HUS cases, commonly referred to as "atypical" HUS, will reveal a risk factor for the syndrome in approximately 60% of cases. Disorders of complement regulation are, numerically, the most important. The outcome for children with atypical HUS is poor, and, because of the rarity of these disorders, clinical experience is scanty. Some cases of complement dysfunction appear to respond to plasma therapy. The therapeutic part of this guideline is the consensus of the contributing authors and is based on limited information from uncontrolled studies. The guideline proposes urgent and empirical plasmapheresis replacement with whole plasma fraction for the first month after diagnosis. This should only be undertaken in specialized pediatric nephrology centers where appropriate medical and nursing skills are available. The guideline includes defined terminology and audit points so that the early clinical effectiveness of the strategy can be evaluated.

PMID 18800230  Pediatr Nephrol. 2009 Apr;24(4):687-96. doi: 10.1007/s0・・・
著者: C M Legendre, C Licht, P Muus, L A Greenbaum, S Babu, C Bedrosian, C Bingham, D J Cohen, Y Delmas, K Douglas, F Eitner, T Feldkamp, D Fouque, R R Furman, O Gaber, M Herthelius, M Hourmant, D Karpman, Y Lebranchu, C Mariat, J Menne, B Moulin, J Nürnberger, M Ogawa, G Remuzzi, T Richard, R Sberro-Soussan, B Severino, N S Sheerin, A Trivelli, L B Zimmerhackl, T Goodship, C Loirat
雑誌名: N Engl J Med. 2013 Jun 6;368(23):2169-81. doi: 10.1056/NEJMoa1208981.
Abstract/Text BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease.
METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2).
RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period.
CONCLUSIONS: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).

PMID 23738544  N Engl J Med. 2013 Jun 6;368(23):2169-81. doi: 10.1056/・・・
著者: Nay M Tun, Gina M Villani
雑誌名: J Thromb Thrombolysis. 2012 Oct;34(3):347-59. doi: 10.1007/s11239-012-0723-9.
Abstract/Text Idiopathic thrombotic thrombocytopenic purpura (TTP) occurs primarily due to the formation of autoantibody against ADAMTS13, a specific von Willebrand factor-cleaving protease, resulting in low ADAMTS13 activity and subsequent accumulation of large vWF multimers, platelet aggregation and thrombus formation in the microvasculature of tissues. Limited clinical data suggest that the administration of anti-CD20 antibody (rituximab) may be useful in treating acute refractory or chronic relapsing idiopathic TTP. We carried out a systematic review with pooled data analysis using individual patient data to evaluate the efficacy of rituximab in these settings. Fifteen case series and 16 case reports comprising 100 patients were eligible for the study. Median age was 39 years. Male constituted 31 % and female 69 %. Complete remission was seen in 98 %, non-response in 2 % and relapse after complete remission in 9 %. For patients with complete remission, median follow-up was 13 months. Median platelet recovery from the first dose of rituximab was 14 days. ADAMTS13 inhibitor positivity and severe ADAMTS13 deficiency were highly predictive of the response to rituximab, implying that these can be useful markers in predicting response to rituximab in acute refractory or chronic relapsing idiopathic TTP.

PMID 22547089  J Thromb Thrombolysis. 2012 Oct;34(3):347-59. doi: 10.1・・・
著者: Marie Scully, Vickie McDonald, Jamie Cavenagh, Beverley J Hunt, Ian Longair, Hannah Cohen, Samuel J Machin
雑誌名: Blood. 2011 Aug 18;118(7):1746-53. doi: 10.1182/blood-2011-03-341131. Epub 2011 Jun 2.
Abstract/Text The safety and efficacy of weekly rituximab 375 mg/m(2) (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 10(9)/L and 38% > 150 × 10(9)/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.

PMID 21636861  Blood. 2011 Aug 18;118(7):1746-53. doi: 10.1182/blood-2・・・

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