Successful Management of Refractory Autoimmune Hemolytic Anemia with Cold Agglutinin Disease with Splenectomy: A Case Report with Review of Literature.

BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by agglutination of red blood cells at temperatures below the normal core body temperature. In patients with CAD, splenectomy is not indicated because of its low therapeutic effect on hemolytic anemia induced by extravascular hemolysis. Herein, we report a case of refractory hemolytic anemia with CAD successfully managed with splenectomy. CLINICAL CASE: A 60-year-old man visited a municipal hospital with the chief complaint of fatigue. He was found to have hemolytic anemia and icterus with increased cold agglutination and was diagnosed with CAD. Malignant lymphoma was suspected as the underlying disease; however, no clear underlying disease was identified. Hemolytic anemia progressed during the subsequent winter seasons, and he was treated with temperature control, warming, and weekly blood transfusions. However, despite the blood transfusions, his hemoglobin level did not improve during the summer 2 years after diagnosis, and his previously observed splenomegaly had progressed. He was referred to our department, and a splenectomy was performed to diagnose any occult malignant lymphoma and improve the refractory hemolytic anemia. Because histopathological examination revealed no evidence of malignant lymphoma, a diagnosis of primary CAD was made. The hemolytic anemia improved, and no blood transfusion was required after splenectomy. CONCLUSIONS: Splenectomy significantly improved the patient's refractory hemolytic anemia due to primary CAD. Thus, it may be an effective treatment option in such cases, although further cases and studies are required to evaluate the effects of splenectomy.

Splenectomy in the management of primary immune-mediated hemolytic anemia and primary immune-mediated thrombocytopenia in dogs.

BACKGROUND: Current reports about the use of splenectomy for the management of immune-mediated hemolytic anemia (IMHA) or immune-mediated thrombocytopenia (ITP) or both in dogs are limited. OBJECTIVES: To retrospectively describe the use of splenectomy as part of the management for IMHA, ITP, and concurrent IMHA and severe thrombocytopenia (CIST) in dogs. It was hypothesized that splenectomy would be beneficial in allowing for reduction of dose of immunosuppressive drugs or discontinuation in 1 or more of these groups. ANIMALS: Seventeen client-owned dogs (7 with IMHA, 7 with ITP, and 3 with CIST) were identified across 7 UK-based referral hospitals from a study period of 2005 to 2016. METHODS: Data were collected retrospectively via questionnaires and included information about diagnosis, management and treatment response before and after splenectomy. Based on clinical outcome, treatment with splenectomy as part of the management protocol was classified as either successful or unsuccessful. RESULTS: Six of 7 dogs with ITP were managed successfully with splenectomy as part of their management protocol (3 complete and 3 partial responses), although 1 subsequently developed suspected IMHA. Of the 7 dogs with IMHA, splenectomy was part of a successful management protocol in 4 dogs (2 complete and 2 partial responses). In the CIST group, 1 case (1/3) responded completely to management with splenectomy as part of the management protocol. CONCLUSIONS AND CLINICAL IMPORTANCE: Splenectomy was considered successful and well tolerated in most cases of isolated ITP. Whether there is a benefit of splenectomy in cases of IMHA and CIST could not be determined in the current study.

Clinical and surgical outcomes of splenectomy for autoimmune hemolytic anemia.

INTRODUCTION: We investigated short and long-term remission rates after splenectomy in patients with primary and secondary autoimmune hemolytic anemia (AIHA). METHODS: All adults who underwent splenectomy for primary or secondary AIHA at a single center (2004-2018) were retrospectively reviewed. Short-term response was determined at 30-day postoperatively and long-term at one year. Complete response was defined as hemoglobin > 10 g/dL without hemolysis, transfusions, or need for additional medical therapy for > 6 months. RESULTS: Short-term complete response was attained in 22 of 36 patients (61%), partial response in 3 (8%), no response in 11 (31%). The response rate at 1 year was complete in 14/36 (39%), partial in 14 (39%), and 8 non-response (22%). At last available follow-up (median 33.1 months (IQR 19-59), 16/37 patients had experienced a complete response (43%), 14 partial response (38%), 7 non-response (19%). 80% of partial responders with primary AIHA required maintenance therapy compared to 100% with secondary AIHA. CONCLUSION: Splenectomy is associated with short- and long-term improvement in anemia and hemolysis in the majority of patients with AIHA. Immunosuppressants remain important supplemental therapy.

Perioperative Management of a Patient With Severe Cold Agglutinin Disease Undergoing Total Hip Arthroplasty With a Cemented Stem: A Case Report.

Patients with cold agglutinin disease who undergo total hip arthroplasty (THA) are rarely encountered. Patients with cold agglutinin disease are very sensitive to cold ambient temperatures and require scrupulous perioperative body-temperature management. However, THA requires a cementing procedure that exposes patients to cold temperatures during surgery and may result in autoimmune hemolytic anemia in these patients. Thus, perioperative management of patients with cold agglutinin disease undergoing THA requires more than just scrupulous systemic temperature management. Here, we present the successful perioperative management of a patient with severe cold agglutinin disease who underwent THA with a cemented stem.

Successful Treatment of an Adolescent Male With Severe Refractory Evans Syndrome Using Bortezomib-based Therapy.

Evans syndrome is defined by bilineal autoimmune cytopenia, typically coombs positive hemolytic anemia and thrombocytopenia. Corticosteroids are the mainstay of treatment, with rituximab and/or mycophenolate mofetil often used in steroid-refractory cases. However, no treatment methodology has ever evaluated by a randomized clinical trial. We present a 15-year-old boy with Evans syndrome and common variable immunodeficiency who experienced a severe, refractory flare 16 months postsplenectomy. After failing to respond to multiple other agents, he achieved a durable response to a bortezomib-based regimen. Bortezomib may be a reasonable second or third line option, especially before high-morbidity therapies such as splenectomy or stem cell transplantation.

Long-term remission rates after splenectomy in adults with Evans syndrome compared to immune thrombocytopenia: A single-center retrospective study.

OBJECTIVE: Evans syndrome, the combination of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) or autoimmune neutropenia, is associated with a high rate of relapsed/refractory disease. There are limited data on the efficacy of splenectomy for this condition. We reviewed patient outcomes after splenectomy for Evans syndrome compared to ITP at our institution. METHODS: We performed a retrospective analysis of patients who underwent splenectomy for autoimmune cytopenias over a 23-year period with the intention of comparing disease relapse rates after splenectomy in patients with Evans syndrome and in those with ITP. RESULTS: During the study period, 77 patients underwent splenectomy for ITP and seven underwent splenectomy for Evans syndrome. In the Evans cohort, splenectomy led to an 85.7% initial response rate with a 42.8% rate of relapse within one year and a long-term (one-year) response rate of 42.8%. In the ITP cohort, the initial response rate was 90.9% with a long-term response rate of 70.1%. CONCLUSION: Our data suggest that long-term remission rates after splenectomy are lower in adults with Evans syndrome compared to those with ITP, although splenectomy may still be an acceptable treatment for certain patients with Evans syndrome. Our findings underscore the need for further research and development of additional therapeutic strategies for this patient population.

A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia.

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10-11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2-6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3-12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6-15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

Splenectomy and the incidence of venous thromboembolism and sepsis in patients with autoimmune hemolytic anemia.

INTRODUCTION: The impact of splenectomy on venous thrombosis (VTE), abdominal thrombosis (abVTE) and sepsis in autoimmune hemolytic anemia (AIHA) is unclear. METHODS: Using the California Discharge Dataset 1991-2014, 4756 AIHA patients were identified. Cumulative incidences (CI) of VTE, abVTE, and sepsis were determined in patients with and without splenectomy. Using propensity score matching adjusted for competing risk of death, the association between VTE, abVTE and sepsis with splenectomy was determined. RESULTS: In those without splenectomy, the CIs of VTE, abVTE, and sepsis were 1.4%, 0.2%, and 4.3% respectively, compared to 4.4%, 3.0% and 6.7% with splenectomy. Splenectomy was associated with increased risk for VTE in immediate (HR 2.66, CI 1.36-5.23) and late (HR 3.29, CI 2.10-5.16) post-operative periods. AbVTE was increased in immediate post-operative period (HR 34.11, CI 4.93-236.11). Sepsis was only increased in late post-operative period (HR 2.20, CI 1.75-2.77). In multivariate models, older age, having >1 comorbidity and having VTE, abVTE, and sepsis were associated with increased mortality. Splenectomy was not associated with increased mortality. DISCUSSION: Splenectomy in AIHA was associated with significant early thrombotic risk and long-term morbidity. Future research should evaluate the role of splenectomy in AIHA patients, and potential long-term thrombotic and antibiotic prophylaxis.

Successful cardiac surgery in a patient with Evans syndrome.

Evans syndrome is a rare haematological disease that may cause several complications during heart surgery. Herein we documented heart valve surgery in a patient with Evans syndrome who was receiving monoclonal antibody therapy, and valve replacement was successfully performed via prophylactic measures against haemolysis.

[Digital necrosis revealing cold agglutinin disease: Treatment with rituximab]. / Nécroses digitales révélant une maladie des agglutinines froides : traitement par rituximab.

BACKGROUND: Digital necrosis is rarer than lower limb necrosis and constitutes a medical or surgical emergency. Etiological evaluation is required. Cold agglutinin disease is a cause of digital necrosis but diagnosis is difficult. PATIENTS AND METHODS: Herein we report the case of a 57-year-old man presenting recent paroxysmal acrosyndrome of the left hand subsequently complicated by digital necrosis following occupational exposure to cold in his work as a forklift driver. After etiological evaluation, a diagnosis of primary cold agglutinin disease was made. Intravenous rituximab and topical treatment resulted in complete healing. DISCUSSION: Cold agglutinin disease is a rare type of auto-immune hemolytic anemia. Following exposure to cold, paroxysmal cutaneous signs are frequent. The disease may be either primary or secondary with B-cell lymphoproliferative disorder, auto-immune disease or infection. A thorough workup is required. To date, the treatment combining the best positive response rate and good safety is rituximab in weekly perfusions over a 1-month period.

[Surgical treatment of an auto-immune hemolytic anemia]. / Traitement chirurgical d'une anémie hémolytique auto-immune.

INTRODUCTION: Auto-immune hemolytic anemia (AIHA) is a rare cause of anemia, characterized by autoantibodies directed against self red blood cells. It can be primary or secondary, in particular due to lymphoproliferative diseases. CASE REPORT: We report the case of a 24-year-old woman who presented with a severe macrocytic anemia associated with an ovarian teratoma. CONCLUSION: Ovarian teratoma is a rare cause of secondary AIHA, with only few cases reported. Its treatment differs from primary AIHA as steroids may be ineffective. Indeed, complete response can only be achieved with surgical excision of the tumor.

Splenectomy in systemic lupus erythematosus and autoimmune hematologic disease: a comparative analysis.

The objective of the study is to analyze the efficacy and safety of splenectomy in the management of refractory autoimmune thrombocytopenia (AT)/autoimmune hemolytic anemia (AIHA) associated or not with systemic lupus erythematosus. Thirty-four patients after splenectomy due to severe AT and/or AIHA were divided into group 1 (G1) 18 SLE/APS patients: 9 AT/SLE patients, 6 SLE/antiphospholipid syndrome (APS), and 3 primary APS. Group 2 (G2): 16 patients without SLE/APS: 2 Fisher-Evans syndrome and 14 AIHA. Surgery approach when (1) platelets ≤ 50,000/ml despite 2 weeks on medical therapy, (2) medically dependent, and (3) medically intolerant or after two hemolytic crises in AIHA patients. Splenectomy response: (1) complete (CR): ≥ 150,000 platelets/ml, (2) partial: 50,000-149,000/ml, or (3) none: ≤ 50,000/ml. CR for AIHA: hemoglobin ≥9 g/dl. STATISTICAL ANALYSIS: descriptive statistics and chi-square test. The mean age was 34.6 years; mean follow-up: 28.5 months. Open splenectomy in 15/34 vs laparoscopy in 19/34 (p = NS). CR in 15/34, G1: 4/18, G2: 11/16, (p = 0.006). Complications in 6/34, 5 from G2 vs 1 from G1 (p = 0.05). Relapse in 7/18 patients in G1 and 3/16 in G2 (p = 0.05). Open and laparoscopic splenectomies in SLE and AT patients are as effective as in those without SLE; however, patients with SLE and APS had more relapses.

Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy. Long-term corticosteroid regimens markedly reduced this response while splenic plasma cells were able to persist, a fraction of them secreting anti-red blood cell IgG in vitro. In wAIHA patients treated by rituximab and who underwent splenectomy because of treatment failure, plasma cells were still present in the spleen, some of them being autoreactive. By using a set of diagnostic genes that allowed us to assess the plasma cell maturation stage, we observed that these cells displayed a long-lived program, differing from the one of plasma cells from healthy donors or from wAIHA patients with various immunosuppressant treatments, and more similar to the one of normal long-lived bone-marrow plasma cells. Interestingly, an increased level of B-cell activating factor (BAFF) was observed in the supernatant of spleen cell cultures from such rituximab-treated wAIHA patients. These results suggest, in line with our previous report on primary immune thrombocytopenia, that the B-cell depletion induced by rituximab promoted a suitable environment for the maturation and survival of auto-immune long-lived plasma cells in the spleen.

Systemic granulomatosis after surgical injection of silicone oil for retinal detachment in a child affected by Fisher-Evans syndrome.

UNLABELLED: Silicone oil is used for complicated retinal detachment, but it can be associated with relevant side effects. We report a 6-year-old South American female admitted to our hospital with steroid-resistant Fisher-Evans syndrome. She also had developed a retinal detachment, managed with intravitreal oil injection. During treatment for Fisher-Evans syndrome, she progressively developed recurrent and refractory bronchospasm, peaks of hypereosinophilia and orbital soft-tissue swelling. Despite the persistent negativity of all microbiologic tests, she was treated empirically with antibiotics. Failure of the treatment led to the execution of a biopsy of the periocular tissue that revealed an intense polymorphous infiltrate constituted by numerous monoclonal population (FR2 monoclonality) of plasma-cells. A diagnosis of lymphoma with plasmacytoid differentiation was suspected and cytotoxic treatment was started without response. For the appearance of swelling in left parotid and laterocervical region, an excisional biopsy was performed and a diagnosis of granulomatous reaction to ocular implant of silicone oil was made. In consideration of the clinical evolution, enucleation was considered, but parents did not consent to the procedure until the child developed cerebral lesions suspected to be silicone localizations. After enucleation, eosinophilic count normalized and the child no longer presented any new episode of fever or swelling. CONCLUSIONS: In this patient a granulomatous reaction is present at distance from the site of oil injection. This case suggests caution in using this substance even in ocular diseases, especially in immunocompromised patients.