We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in five countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate 4-fold differences between cold and warmer climates regarding prevalence (20 versus 5 cases/million) and incidence (1.9 versus 0.48 cases/million/year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin < 8 g/dL. Identification of typical features of 'CAD-associated lymphoproliferative disorder' in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work included a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift towards deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.

Background The COVID‐19 vaccine from AstraZeneca (AZD1222) is one of several vaccines introduced to provide immunity against SARS‐CoV‐2. Recently, more than 50 cases have been reported presenting a combination of thrombosis, thrombocytopenia, and remarkably high levels of anti‐platelet factor 4 (PF4)/polyanion antibodies post‐AZD1222 vaccination. Now linked to the vaccine, the condition is referred to as vaccine‐induced immune thrombotic thrombocytopenia. The European Medicines Agency still recommends vaccination with AZD1222, but several European countries have temporally paused and/or restricted its use because of the perceived risk of this severe side effect. Because there is no description of PF4/polyanion antibody testing in the clinical trials, knowledge about the prevalence of such antibodies in a vaccinated cohort is needed. Objectives To investigate prevalence of thrombocytopenia and anti‐PF4/polyanion antibodies in a population recently vaccinated with AZD1222. Patients/Methods Four hundred and ninety‐two health care workers recently vaccinated with the first dose of AZD1222 were recruited from two hospitals in Norway. Study individuals were screened for thrombocytopenia and the presence of anti‐PF4/polyanion antibodies with a PF4/PVS immunoassay. Side effects after vaccination were registered. Results The majority of study participants had normal platelet counts and negative immunoassay. Anti‐PF4/polyanion antibodies without platelet activating properties were only detected in six individuals (optical density ≥0.4, range 0.58–1.16), all with normal platelet counts. No subjects had severe thrombocytopenia. Conclusions We found low prevalence of both thrombocytopenia and antibodies to PF4/polyanion‐complexes among Norwegian health care workers after vaccination with AZD1222.

Whole genome analysis of genetic alterations in small DNA samples using hyperbranched strand displacement amplification and array-CGH.

No abstract

Primary chronic cold agglutinin disease (CAD) is an autoimmune haemolytic anaemia in which a specific bone marrow lymphoproliferative disorder causes production of cold agglutinins (CA). Binding of CA to erythrocyte surface antigens results in a predominantly extravascular haemolysis that is entirely complement dependent. Because of complement activation, exacerbations are common during febrile infections, trauma or major surgery. Involvement of the terminal complement pathway with C5-mediated intravascular haemolysis is probably not prominent in stable disease but is supposed to be of importance in exacerbations following acute phase reaction.We report on a patient with CAD prone to exacerbation of haemolysis during acute phase reactions who was scheduled for cardiac surgery. To prevent her having an exacerbation of haemolysis, we chose to treat her prophylactically with eculizumab along with the usual perioperative precautions. Aortic valve replacement was undertaken with full cardiopulmonary bypass at normothermia. The procedure was successful; no exacerbation of haemolysis was observed, and transfusion requirements did not exceed what could be expected.

Objectives Every year, several patients are bitten by the common European adder (Vipera berus). The aim of this study is to present a large consecutive case series of patients bitten by V. berus, and to identify signs and symptoms indicative of complicated illness. Patients and methods This is a retrospective case series from the Hospital of South West Jutland, Denmark. All 219 patients bitten by V. berus (diagnosed by history or clinical findings) from 1994 to 2012 were identified through hospital databases. A severity grading from 1 to 5 was applied, and epidemiology, symptoms and signs, complications, treatment and laboratory data were extracted from the hospital databases. Results The most common complaints on admission were pain, nausea, abdominal pain, diarrhoea and dizziness, with discoloration and oedema being the most common symptoms. Few patients experienced syncope, palpitations or respiratory distress. Fifteen percent of all patients were transferred to the ICU and 2% (all children) were suspected of having compartment syndrome. Leucocytosis, gastrointestinal symptoms and hypotension were risk factors for complicated disease. Conclusion Most patients only showed symptoms of no or mild envenomation. Fifteen percent were transferred to the ICU and five patients (all children) required fasciotomy because of suspected compartment syndrome. Only 10 patients received antivenom.

Purpose:The incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real-world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry Population:The Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow-up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits.

Summary RITP was a double‐blind randomized, 78‐week follow‐up trial in which 109 adults with immune thrombocytopenias (ITP) who failed to achieve adequate response to steroids, were randomized to receive rituximab or placebo. Here, we provide the duration of response, splenectomy and mortality rates based on extended follow‐up after completion of the RITP study. Extended follow‐up data were retrospectively collected for 72 (83%) patients out of the 84 patients who were not splenectomized during the initial RITP study. For the present analysis, median [interquartile range] duration of follow‐up after randomization was 72 [62–82] months. Median duration of response among patients who achieved an initial response was significantly longer in patients who received rituximab (8·2 [5·5–16·7] months) as compared to placebo (1·8 [1·3–3·6] months), P = 0·036. Overall, 35 patients underwent splenectomy (13 in the rituximab, and 22 in the placebo arm, P = 0·12). Eleven patients (10%) died during the study: five in the rituximab and six in the placebo arms, including four deaths from severe bleeding. Although most rituximab‐treated patients eventually relapsed, a longer duration of response and a trend towards lower splenectomy rate were observed in rituximab‐treated patients.