Defining a reference range for cold agglutinin titers

Bendix, Brenda J.; Tauscher, Craig D.; Bryant, Sandra C.; Stubbs, James R.; Jacob, Eapen K.

doi:10.1111/trf.12453

Cited by 11 publications

(12 citation statements)

References 6 publications

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“…The activity of a CA is usually assessed by the titer, measured at 4 o C and defined as the inverse of the maximum serum dilution at which agglutination can be seen. Nearly all patients with CAD have a CA titer > 64; we found a median titer of 512 (range, 16-819200) (3,13,18,67). A titer as high as 168 million has been reported (68).…”

Section: Immunological Properties Of Cold Agglutininsmentioning

confidence: 56%

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: Immunological Properties Of Cold Agglutininsmentioning

confidence: 56%

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

2020

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“…In a minority of healthy people, blood tests will detect CA that have no clinical significance (Bendix et al , ; Mauro et al , ). A frequency of positive screening tests at 0·3% was reported in a large cohort of patients with nonrelated disorders, but only 43% of these had demonstrable CA by titration (Jain et al , ).…”

Section: Diagnosis and Clinical Featuresmentioning

confidence: 99%

“…Thus, incidentally detected CA occur more frequently than CAD; and patients with demonstrable CA without haemolysis or circulatory manifestations do not have CAD. The normally occurring CA are polyclonal, have a low TA and are found in low titres, usually below 64 and rarely exceeding 256 (Dacie, ; Bendix et al , ). In contrast, among 172 subjects with monoclonal IgM in serum and CA titre between 512 and 65 500, haemolysis was found in every case (Stone et al , ).…”

Section: Diagnosis and Clinical Featuresmentioning

confidence: 99%

How I manage patients with cold agglutinin disease

Berentsen

2018

Br J Haematol

111

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Cold agglutinin disease (CAD) is an uncommon autoimmune haemolytic anaemia in which a well-defined, clonal low-grade lymphoproliferative disorder of the bone marrow results in erythrocyte destruction mediated by the classical complement pathway. The pathogenesis, clinical features and diagnostic criteria are reviewed. Although anaemia is mild in some patients, approximately one-third of untreated patients have a haemoglobin level of ≤80 g/l, and about 50% have been considered transfusion dependent for shorter or longer periods. Therapy has improved greatly during the last 15 years. Mild disease can be managed by avoidance of cold and adequate precautions in specific situations, without drug therapy. Corticosteroids should not be used to treat CAD. Patients requiring pharmacological therapy should be considered for prospective trials. Outside clinical studies, the rituximab-bendamustine combination or rituximab monotherapy is recommended in the first line, depending on individual patient characteristics. Second-line options are rituximab-fludarabine in fit patients or, although less strongly documented, a bortezomib-based regimen. Therapies targeting the classical complement pathway are promising, and the complement C1s inhibitor, BIVV009, has shown favourable results in preliminary studies.

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“…3,4,12,30 Usually, the CA titer is much higher, but it should nonetheless be acknowledged that occasional patients with otherwise typical CAD may have a CA titer <64. 4,30,31 An additional diagnostic criterion is the absence of known causes of secondary CAS, for example, specific infections or aggressive lymphoma. A bone marrow low-grade clonal LPD (discussed below) can be demonstrated in a majority of patients, but confirmation of an LPD is sometimes a matter of sensitivity and not required for diagnosis.…”

Section: Diagnostic Criteriamentioning

confidence: 99%

<p>Cold agglutinin disease: current challenges and future prospects</p>

Berentsen¹,

Roth²,

Randen³

et al. 2019

JBM

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Cold agglutinin disease (CAD) is a complement-dependent, classical pathway-mediated immune hemolytic disease, accounting for 15–25% of autoimmune hemolytic anemia, and at the same time, a distinct clonal B-cell lymphoproliferative disorder of the bone marrow. The disease burden is often high, but not all patients require pharmacological treatment. Several therapies directed at the pathogenic B-cells are now available. Rituximab plus bendamustine or rituximab monotherapy should be considered first-line treatment, depending on individual patient characteristics. Novel treatment options that target the classical complement pathway are under development and appear very promising, and the C1s inhibitor sutimlimab is currently being investigated in two clinical Phase II and III trials. These achievements have raised new challenges and further prospects, which are discussed. Patients with CAD requiring therapy should be considered for clinical trials.

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Defining a reference range for cold agglutinin titers

Abstract: Prospective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.

Cited by 11 publications

References 6 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

How I manage patients with cold agglutinin disease

<p>Cold agglutinin disease: current challenges and future prospects</p>

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