Background: Drug-induced immune haemolytic anaemia (DIHA) is difficult to diagnose, and its true incidence remains obscure. Here, we present cases of DIHA identified at our institute over the last two decades. Methods: Serological tests were performed according to standard procedures. Detection of drug-dependent antibodies was performed in the presence and absence of the relevant drug and/or their ex vivo antigens. Results: Over the last 20 years, 73 patients have been identified with DIHA in our institute, which was related to 15 different drugs. The most common single drugs identified were diclofenac (n = 23), piperacillin (n = 13), ceftriaxone (n = 12) and oxaliplatin (n = 10). As far as data were available, haemolysis was acute in all patients, and signs of intravascular haemolysis were present in 90% of the cases. Haemolysis resulted in death in 17 patients (23%). The remaining patients recovered, but haemolysis was complicated by transitory renal and/or liver failure or shock in 11 patients. Upon initial evaluation, the antibody screening test was positive in 36 cases. A positive direct antiglobulin test (DAT) at least with anti-C3d was found in 65 cases, with anti-IgG only in 6 cases, and with anti-IgA only in 1 case. Conclusion: DIHA is a rare but potentially life-threatening disorder that should be considered if a patient develops haemolysis under drug treatment. The main serological finding is a positive DAT, primarily with anti-C3d.

Objective: Haemolysis and anaemia related to autoimmune haemolytic anaemia (AIHA) of warm type (wAIHA) and of cold type (cAIHA) are believed to be solely due to antibody and/or complement-mediated destruction and clearance of red blood cells (RBCs). There is evidence that RBCs of affected patients may also undergo eryptosis, the suicidal death of RBCs. Method:RBCs from 24 patients with wAIHA, 7 patients with chronic cAIHA and one patient with AIHA of mixed type were analysed for exposed phosphatidylserine (PS) by treatment with phycoerythrin-labelled Annexin V, and cell-associated fluorescence was measured using a MACSQuant flow cytometer.

Weak or nonagglutinating RBC-bound IgM warm antibodies can be identified by the presented DDAT.

LI-cadherin belongs to the family of 7D-cadherins that is characterized by a low sequence similarity to classical cadherins, seven extracellular cadherin repeats (ECs), and a short cytoplasmic domain. Nevertheless, LI-cadherins mediates Ca2+-dependent cell–cell adhesion and induces an epitheloid cellular phenotype in non-polarized CHO cells. Whereas several studies suggest that classical cadherins cis-dimerize in a Ca2+-dependent manner and interact in trans by strand-swapping tryptophan 2 of EC1, little is known about the molecular interactions of LI-cadherin, which lacks tryptophan 2. We thus expressed fluorescent LI-cadherin fusion proteins in HEK293 and CHO cells, analyzed their cell–cell adhesive properties and studied their cellular distribution, cis-interaction, and lateral diffusion in the presence and absence of Ca2+. LI-cadherin highly concentrates in cell contact areas but rapidly leaves those sites upon Ca2+ depletion and redistributes evenly on the cell surface, indicating that it is only kept in the contact areas by trans-interactions. Fluorescence resonance energy transfer analysis of LI-cadherin-CFP and -YFP revealed that LI-cadherin forms cis-dimers that resist Ca2+ depletion. As determined by fluorescence redistribution after photobleaching, LI-cadherin freely diffuses in the plasma membrane as a cis-dimer (D = 0.42 ± 0.03 μm2/s). When trapped by trans-binding in cell contact areas, its diffusion coefficient decreases only threefold to D = 0.12 ± 0.01 μm2/s, revealing that, in contrast to classical and desmosomal cadherins, trans-contacts formed by LI-cadherin are highly dynamic.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-012-1053-y) contains supplementary material, which is available to authorized users.

The patient's DO genes have a single-nucleotide change, which leads to the absence of the high-prevalence antigen DOYA. The absence of this antigen is associated with 183Asp and silencing of Do(a) and weakening of Gy(a), Hy, and Jo(a) antigens.