Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting

Jäger, Ulrich; Barcellini, Wilma; Broome, Catherine; Gertz, Morie A.; Hill, Anita; Hill, Quentin A.; Jilma, Bernd; Kuter, David J.; Michel, Marc; Montillo, Marco; Röth, Alexander; Zeerleder, Sacha; Berentsen, Sigbjørn

doi:10.1016/j.blre.2019.100648

Cited by 346 publications

(652 citation statements)

References 223 publications

(260 reference statements)

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“…Cold-antibody autoimmune hemolytic anemias (cAIHAs) are mediated by autoantibodies characterized by a temperature optimum of the antigen-antibody (AgAb) reaction at 0-4 o C. These hemolytic disorders account for ∼25-30% of autoimmune hemolytic anemias (AIHAs) (1). Table 1 shows a further classification of cAIHAs (1)(2)(3)(4)(5)(6)(7). Cold agglutinins (CAs) are cold-reactive antibodies that are able to agglutinate red blood cells (RBCs) (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

2020

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Autoimmune hemolytic anemias mediated by cold agglutinins can be divided into cold agglutinin disease (CAD), which is a well-defined clinicopathologic entity and a clonal lymphoproliferative disorder, and secondary cold agglutinin syndrome (CAS), in which a similar picture of cold-hemolytic anemia occurs secondary to another distinct clinical disease. Thus, the pathogenesis in CAD is quite different from that of polyclonal autoimmune diseases such as warm-antibody AIHA. In both CAD and CAS, hemolysis is mediated by the classical complement pathway and therefore can result in generation of anaphylotoxins, such as complement split product 3a (C3a) and, to some extent, C5a. On the other hand, infection and inflammation can act as triggers and drivers of hemolysis, exemplified by exacerbation of CAD in situations with acute phase reaction and the role of specific infections (particularly Mycoplasma pneumoniae and Epstein-Barr virus) as causes of CAS. In this review, the putative mechanisms behind these phenomena will be explained along with other recent achievements in the understanding of pathogenesis in these disorders. Therapeutic approaches have been directed against the clonal lymphoproliferation in CAD or the underlying disease in CAS. Currently, novel targeted treatments, in particular complement-directed therapies, are also being rapidly developed and will be reviewed.

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Section: Introductionmentioning

confidence: 99%

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

2020

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“…First line treatment for primary wAIHA is oral prednisolone. Intravenous methylprednisolone and immunoglobulin may be considered in severe, life-threatening cases [7]. In our case,intravenous methylprednisolone and IVIg were added to her regimen when Hb fell further after transfusion.…”

Section: Discussionmentioning

confidence: 87%

“…This patient was administered with warfarin since VKAs have been the gold standard in oral anticoagulation. NOACs may be an alternative to VKAs in this setting but there is no evidence-based practice [7,9].…”

Section: Discussionmentioning

confidence: 99%

Acute peripheral pulmonary embolism attributed to autoimmune haemolytic anaemia: a case report

Wang

Chen

2020

BMC Cardiovasc Disord

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Background: PE (pulmonary embolism) is a life-threatening complication rarely seen in the AIHA (autoimmune haemolytic anaemia) patients. Herein we reported a rare and serious AIHA-PE patient characterised by extensive peripheral pulmonary embolism on CTPA. Case presentation: A 59-year-old woman presented to our ED (emergency department) complaining of acute chest pain and dyspnea. During her presentation in ED she experienced a sudden syncope and soon developed CA (cardiac arrest). Laboratory studies showed a increase of CK-MB,troponin T,myoglobin and D-dimer. Computed tomography pulmonary angiography (CTPA) showed no large central or segment pulmonary emboli but increased RV (right ventricle)size,enlarged main pulmonary artery and invisible peripheral pulmonary artery. She was diagnosed with acute PE and alteplase was delivered intravenously. After thrombolytic therapy she remained hypotension and developed worsening anaemia. Detailed examination for anaemia revealed AIHA. She was discharged in a stable condition after 5 weeks with methylprednisolone and warfarin. Hb, D-dimer and transthoracic echocardiography showed complete recovery at 3-months follow up. Conclusion: PE attributed to AIHA is characterized by subsegment and distal pulmonary artery embolism which is easily neglected but always life-threatening. This case also highlights the PE as a secondary diagnosis should be evaluated comprehensively in order to identify the underlying pathogenesis.

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“…DAT positivity in the context of hemolysis usually defines "auto-immune hemolytic anemia" (AIHA) [43]. Different subtypes of AIHA can generally be classified according to DAT result: warm AIHA (wAIHA) is usually the result of polyclonal IgG binding on RBC surface, while cold AIHA (cAIHA) is related to the effect of clonal or oligoclonal IgM with further activation of the complement cascade, this latter recognized from C3d fraction bound to RBC [44]. A mixed form, characterized by the recognition of both IgG and C3d on RBCs membrane, has also been described.…”

Section: Discussionmentioning

confidence: 99%

“…Noteworthy, a positive DAT alone does not allow for AIHA diagnosis. The test indeed, can be positive in 0.1% of healthy donors and positivity prevalence can rise up to 1-15% in hospitalized patients affected by acute illnesses, even in absence of hemolysis [43,44]. Moreover, malaria and other systemic infections can be associated with a positive DAT, but the true role of immune mechanisms in contributing to malarial anemia is not easy to determine [45,46].…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Direct Antiglobulin Test Results in Post-artesunate Delayed Hemolysis

Bartoli

Lepore

D’Abramo³

et al. 2020

Preprint

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Background: “Post-Artesunate Delayed Hemolysis” (PADH) is common after severe malaria episodes. PADH is related to the “pitting” phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. However, direct antiglobulin test (DAT) positivity has been reported in several PADH cases, suggesting a contribution of immune-mediated erythrocyte clearance. The aim of the present study was to compare clinical features of cases presenting a positive or negative DAT.Method: Articles reporting clinical data of patients diagnosed with PADH, for whom DAT had been performed, were collected from PubMed database. Data retrieved from single patients were extracted and univariate analysis was performed in order to identify features potentially related to DAT results and steroids use.Results: Twenty-two studies reporting 39 PADH cases were included: median baseline parasitemia was 20.8% (IQR: 11.2-30) and DAT was positive in 17 cases (45.5%). Compared to DAT-negative individuals, DAT-positive patients were older (49.5 vs 31; p=0.01), had a higher baseline parasitemia (27% vs 17%; p=0.03) and were more commonly treated with systemic steroids (11 vs 3 patients, p=0.002). Depth and kinetics of delayed anemia were not associated with DAT positivity.Conclusions: In this case series, almost half of the patients affected by PADH had a positive DAT. An obvious difference between the clinical courses of patients presenting with a positive or negative DAT was lacking. This observation strongly suggests that DAT result is not indicative of a pathogenic role of anti-erythrocytes antibodies in patients affected by PADH, but is rather a marker of immune activation.

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Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting

Cited by 346 publications

References 223 publications

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

Acute peripheral pulmonary embolism attributed to autoimmune haemolytic anaemia: a case report

Systematic Analysis of Direct Antiglobulin Test Results in Post-artesunate Delayed Hemolysis

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