Primary autoimmune haemolytic anaemia is associated with increased risk of ischaemic stroke: A binational cohort study from Denmark and France.

Primary autoimmune haemolytic anaemia (AIHA) causes the destruction of red blood cells and a subsequent pro-thrombotic state, potentially increasing the risk of ischaemic stroke. We investigated the risk of ischaemic stroke in patients with AIHA in a binational study. We used prospectively collected data from nationwide registers in Denmark and France to identify cohorts of patients with primary AIHA and age- and sex-matched general population comparators. We followed the patient and comparison cohorts for up to 5 years, with the first hospitalization of a stroke during follow-up as the main outcome. We estimated cumulative incidence, cause-specific hazard ratios (csHR) and adjusted for comorbidity and exposure to selected medications. The combined AIHA cohorts from both countries comprised 5994 patients and the 81 525 comparators. There were 130 ischaemic strokes in the AIHA cohort and 1821 among the comparators. Country-specific estimates were comparable, and the overall adjusted csHR was 1.36 [95% CI: 1.13-1.65], p = 0.001; the higher rate was limited to the first year after AIHA diagnosis (csHR 2.29 [95% CI: 1.77-2.97], p < 10-9 ) and decreased thereafter (csHR 0.89 [95% CI: 0.66-1.20], p = 0.45) (p-interaction < 10-5 ). The findings indicate that patients diagnosed with primary AIHA are at higher risk of ischaemic stroke in the first year after diagnosis.

Medical therapy to attenuate fetal anaemia in severe maternal red cell alloimmunisation.

Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of fetal mortality with potential neonatal and longer-term morbidity. HDFN is caused by maternal red cell alloimmunisation, with IgG antibodies crossing the placenta to destroy fetal erythroid cells expressing the involved antigen. Intrauterine fetal blood transfusion is the therapy of choice for severe fetal anaemia. Despite a strong evidence base and technical advances, invasive fetal therapy carries risk of miscarriage and preterm birth. Procedure-related risks are increased when invasive, in utero transfusion is instituted prior to 22 weeks to treat severe early-onset fetal anaemia. This review focuses upon this cohort of HDFN and discusses intravenous immunoglobin (IVIg) and novel monoclonal antibody (M281, nipocalimab) treatments which, if started at the end of the first trimester, may attenuate the transplacental passage and fetal effects of IgG antibodies. Such therapy has the ability to improve fetal survival in this severe presentation of HDFN when early in utero transfusion may be required and may have wider implications for the perinatal management in general.

Marked reduction in haemoglobin levels secondary to ceftizoxime-induced immune haemolytic anaemia in diabetic patients.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced immune haemolytic anaemia (DIIHA) is rare and difficult to diagnose. In diabetic patients, the diagnosis of DIIHA is even harder. In the current study, we report on two cases of ceftizoxime-induced immune haemolytic anaemia in diabetic patients. CASE DESCRIPTION: Two diabetic patients (suffering from type 1 and type 2 diabetes mellitus, respectively) presented with rapid reduction in haemoglobin levels when exposed to ceftizoxime (2g q12h). They both achieved symptom improvement after switching to another antibiotic. WHAT IS NEW AND CONCLUSION: The persistently reduced haemoglobin levels in diabetic patients may contribute to DIIHA. Reviewing patients' medical records might provide some valuable clues as to the causes of DIIHA.

Bortezomib and dexamethasone, an original approach for treating multi-refractory warm autoimmune haemolytic anaemia.

We report the off-label use of bortezomib combined with dexamethasone in eight adults with severe and multi-refractory warm auto-immune haemolytic anaemia (wAIHA). After six cycles of induction therapy, 6 of the 8 patients achieved response (3 complete response, 3 response). Response was obtained after a median of 2 (1-4) cycles. After a median follow-up of 14 (6-36) months, six patients maintained a response (bortezomib/dexamethasone maintenance, n = 4); five patients experienced at least one moderate adverse event, including peripheral neuropathy (n = 2). These results suggest that bortezomib/dexamethasone combination is a promising approach with acceptable toxicity for treating severe refractory wAIHA in adults.

A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia.

The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and rituximab combined (N = 32) or prednisolone monotherapy (N = 32). After 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone but in a significantly smaller proportion (36%) of those given prednisolone alone (P = 0·003). Furthermore, relapse-free survival was significantly better after the combined therapy than after prednisolone monotherapy (P = 0·02). After 36 months, about 70% of the patients were still in remission in the rituximab-prednisolone group, whereas only about 45% were still in complete or partial remission in the prednisolone group. There was no significant difference between the two groups regarding adverse reactions to the studied medications. Likewise, serious adverse events were equally distributed, and no allergic reactions to rituximab were recorded. In conclusion, our data show that using rituximab and prednisolone combined rather than prednisolone alone as first-line treatment in WAIHA increases both the rate and the duration of the response.

Copper-induced Haemolytic Anaemia.

Acute copper toxicity is uncommon in Western countries and is often the result of accidental consumption or a suicide attempt. We report the case of a 65-year-old man presenting to the accident and emergency department after a suicide attempt with ingestion of Bordeaux mixture, ibuprofen, acetaminophen and bleach. Primary evaluation showed caustic oesophagitis, toxic hepatitis and acute renal injury, which were treated with supportive care. During admission, he developed a non-immune haemolytic anaemia associated with high levels of copper in urine and blood. Chelation treatment with penicillamine was started and evolution was favourable after 1 month of treatment. Copper poisoning can be lethal. Prompt diagnosis and treatment are key for a favourable prognosis. LEARNING POINTS: Acute copper intoxication is rare and early clinical suspicion and diagnosis are essential to reduce mortality.The diagnosis of copper poisoning should be based on clinical presentation and measurement of urine and blood copper levels in addition to serum ceruloplasmin levels.Treatment includes reduction of absorption, supportive measures, management of complications and chelation therapy.

Chronic lymphocytic leukaemia/small lymphocytic lymphoma treatment with rituximab and high-dose methylprednisolone, revisited.

High-dose methylprednisolone plus rituximab (R-HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients unfit for chemo-immunotherapy and has proven its utility on the treatment of CLL/SLL complicated by auto-immune cytopenias. We performed a retrospective, single-centre study, of CLL/SLL patients treated with R-HDMP for 9 years. Thirty-nine patients were included, median age at time of treatment was 77 years. Most patients had stage Rai III/IV and Binet C disease. Twenty-eight patients had relapsed/refractory disease at time of treatment with a median of 1 previous line of therapy; 53.8% had prior exposure to fludarabine and 25% to rituximab. Grade 3-4 neutropenia and thrombocytopenia were recorded in 10.2% and 17.9% patients, respectively. While on treatment, 51.3% had documented infectious complications, but no other non-haematological toxicities grades 3-4 were identified. Overall response rate was 64%. Median overall survival and progression-free survival were 24 and 13 months, respectively. Twenty four patients relapsed and 16 received another line of treatment after R-HDMP, with median time to next treatment of 13.5 months. Thirteen out of the 24 patients improved performance status and were subsequently considered fit for chemo-immunotherapy. R-HDMP is a valuable option for elderly and frail patients, with low risk of severe myelotoxicity and other severe adverse events. It was shown to work as a bridge to other lines of treatment, including chemo-immunotherapy.

Case Report: Haemolytic anaemia with ceftazidime use in a patient with cystic fibrosis.

Drug-induced Immune Haemolytic Anaemia (DIIHA) is a rare but serious complication of cephalosporin use. Ceftazidime is recognized to be a rare cause of DIIHA. We report and discuss a case of DIIHA in a person with cystic fibrosis who developed severe haemolytic anaemia following use of ceftazidime in the management of an acute pseudomonal pulmonary exacerbation.