scholarly journals High Incidence of Venous Thromboembolism Events during Warm Autoimmune Hemolytic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2448-2448
Author(s):  
Sylvain Audia ◽  
Benoit Bach ◽  
Maxime Samson ◽  
Vanessa Leguy ◽  
Sabine Berthier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Hemolytic Anemia ◽  
Haemolytic Anaemia ◽  
Predictive Factors ◽  
Autoimmune Hemolytic Anemia ◽  
Antiphospholipid Antibodies ◽  
High Incidence ◽  
Thromboembolism Events ◽  
Positive Direct

Abstract Introduction. Thrombotic manifestations are a hallmark of many hemolytic disorders such as sickle cell disease and paroxysmal nocturnal hemoglobinuria. However, the risk of venous thromboembolism events (VTE) associated with warm autoimmune hemolytic anemia (wAIHA) has only been investigated in few studies and reported to occur in up to 15 to 33%.1-4 Moreover, risk factors of VTE during wAIHA have not been clearly identified, except for antiphospholipid antibodies and splenectomy. The aim of this study was to characterize VTE in wAIHA and to determine predictive factors of occurrence. Methods. Medical records of patients with wAIHA taken in charge in our university hospital between March 2006 and March 2016 were retrospectively analyzed. Inclusion criteria were 1) patients older than 18, with 2) wAIHA defined as hemoglobin below 120 g/L, low haptoglobin level and a positive direct antiglobulin test (DAT) for IgG alone or with complement. Exclusion criteria were known constitutional hemolysis, negative DAT or positive DAT for complement alone, or presence of cold agglutinins. Demographic, clinical and biological characteristics of patients and treatments were recorded. All VTE were proven by ultrasound scan for deep vein thrombosis (DVT) or CT scan for pulmonary embolism (PE). Thromboses of the portal system following splenectomy were not considered. The study was approved by the ethical committee. Quantitative data are reported by median [interquartile range] and compared by Mann-Whitney test. Qualitative data are reported as percentage and compared by Khi2. p<0.05 was considered significant. Results. Forty-eight patients were included, among which 26 (54%) had a secondary wAIHA (15 lymphomas, 5 autoimmune diseases, 3 infections, 2 myeloproliferative neoplasms and 1 myelodysplastic syndrome). Median age was 65 [44-78], with 51% of female. Median hemoglobin level was 73 g/L [63-90]. Clinical and biological parameters were not significantly different between primary and secondary wAIHA, notably the frequency of VTE was similar (27.3 vs. 19.2%; p=0.5). Overall, the incidence of VTE was 22.9% (n=11): 3 patients had PE, 3 had DVT alone and 5 had both DVT and PE. Only one patient was splenectomized at the time of VTE. VTE occurred at a median time of 4 weeks [1.7-7] after the diagnosis of wAIHA, with an active hemolysis in 91% cases (10/11). The Padua score was used to quantify clinical risk factors for VTE and was not different between the two groups. The frequency of jaundice was higher in patients with VTE (44.4 vs. 7.1%; p=0.02), confirmed by a higher bilirubin level (41 [32-47.5] vs. 31 [25-39] mmol/L; p=0.04). Despite similar levels of hemoglobin (74 [56-89] vs. 72 g/L [63-89]; p=0.9), hemolysis and erythropoiesis tended to be higher in the VTE group, as the LDH level (768 [464-1254] vs. 461 UI/L [296-704]; p=0.09) and reticulocyte count (288 [147-341] vs. 158x109/L [115-249]; p=0.06) tended to be higher. Platelet count was not different between the two groups (283 [165-364] vs. 228x109/L [156-310]; p=0.5). In the VTE group, a higher leucocyte count was observed (11.9 [8.6-18.1] vs. 7.3x109/L [5.4-10.5]; p=0.02). Antiphospholipid antibodies were screened in 9/11 patients with VTE and were negative. Conclusion. A high incidence of VTE (22.9%) was observed during wAIHA. VTE preferentially occurred in the first weeks of diagnosis. As no clinically relevant predictive factors could be determined, a systematic screening for DVT at diagnosis and the use of a prophylactic anticoagulation until the hemolysis is controlled are recommended. References 1. Roumier M, Loustau V, Guillaud C, et al. Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single-center experience with 60 patients. Am J Hematol. 2014;89(9):E150-155. 2. Pullarkat V, Ngo M, Iqbal S, Espina B, Liebman HA. Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism. Br J Haematol. 2002;118(4):1166-1169. 3. Hendrick AM. Auto-immune haemolytic anaemia--a high-risk disorder for thromboembolism? Hematology. 2003;8(1):53-56. 4. Lecouffe-Desprets M, Neel A, Graveleau J, et al. Venous thromboembolism related to warm autoimmune hemolytic anemia: a case-control study. Autoimmun Rev. 2015;14(11):1023-1028. Disclosures No relevant conflicts of interest to declare.

scholarly journals Autoimmune Hemolytic Anemia Confers Risk of Thromboembolism That Is Not Attributable to Usual Thrombosis Risk Factors: A Longitudinal, Retrospective Cohort Study Using the "Stride" Database

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1258-1258 ◽  
Author(s):  
Evan C. Chen ◽  
Pooja D. Loftus ◽  
Susan C. Weber ◽  
Nhat Minh Hoang ◽  
James Gilbert ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Venous Thromboembolism ◽  
Hemolytic Anemia ◽  
Retrospective Cohort Study ◽  
Autoimmune Hemolytic Anemia ◽  
Odds Ratio ◽  
Research Funding ◽  
Retrospective Cohort ◽  
Thrombosis Risk

Abstract INTRODUCTION Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disorder in which auto-antibodies target red blood cell surface antigens, causing hemolysis. The incidence is estimated to be 0.8 per 100,000 (Lechner and Jager, Blood 2010). Depending on the temperature at which the auto-antibodies are most active, AIHA is classified as warm, cold, or mixed. Main risk factors include malignancy, viral infection, and rheumatologic disorders. Thromboembolism is an important complication of AIHA that has received increasing attention in case series and small observational reports. However, there has not yet been a study that compares the risk of thromboembolism in AIHA with that of matched, non-AIHA patients in a longitudinal fashion. OBJECTIVES 1) To assess the risk of arterial and venous thromboembolism in AIHA patients using a longitudinal, retrospective cohort study. 2) To define the contribution from usual thrombosis risk factors (defined in Methods section) in the development of thromboembolism in AIHA patients. METHODS We derived our cohorts from Stanford University's Standards-Based Translational Research Informatics Platform (STRIDE). The STRIDE database houses records since 2003 for over 2.1 million patients who receive their care at Stanford Hospital and Clinics. We identified 156 patients diagnosed with AIHA of any type and matched them with 312 non-AIHA patients (control) in a 1:2 ratio. To achieve stringent matching, patients in the control group were selected to have known risk factors for AIHA--malignancy, viral infections, and rheumatologic diseases--without developing AIHA itself. We assessed the incidence of arterial and venous thromboembolism in the AIHA and non-AIHA groups. Within each group, we assessed the association between thromboembolism and the presence of thrombosis risk factors, which we based on the PADUA criteria (Barbar et al, J Throm Haemost 2010). The PADUA risk factors comprise a weighted sum known as the PADUA score (max score of 20), and we compared the median PADUA score between AIHA and non-AIHA patients with thromboembolism using the Mann-Whitney rank sum test. Interquartile ranges (IQR) of PADUA scores were calculated. Finally, using inverse-probability weighting to achieve matching thromboembolism propensity scores between AIHA and non-AIHA patients, we derived an odds ratio for the development of thromboembolism given a diagnosis of AIHA. RESULTS A significantly higher proportion of AIHA patients developed arterial and venous thromboembolism than non-AIHA patients (29% vs. 19%, respectively; p < 0.05). Notably, the median PADUA score was not different between AIHA and non-AIHA patients with thromboembolism (4, IQR [2-7] vs 4.5, IQR [3-7], respectively, n.s.), despite the aforementioned difference in thromboembolism incidence. However, the distribution of PADUA risk factors in each group did differ: malignancy was seen in a smaller proportion of AIHA patients with thromboembolism than in non-AIHA counterparts (31% vs 57%, respectively; p < 0.05), while acute infection and/or rheumatologic disorders was seen in a larger proportion of AIHA patients with thromboembolism than non-AIHA counterparts (53% vs 25%, respectively; p < 0.05; see Table 1). After additional analysis to ensure propensity score matching, we found that AIHA confers an odds ratio of 2.44 (95% CI [1.16-5.10], p < 0.05) for the development of thromboembolism. CONCLUSION Different thrombosis risk factors contribute to the development of thromboembolism in AIHA patients than in non-AIHA patients. However, AIHA patients carry a significantly higher risk of thromboembolism than non-AIHA patients, and this risk is not attributable to the usual thrombosis risk factors considered in the PADUA criteria. Our finding suggests a need for clinical trials to study the role of thrombo-prevention in AIHA patients. Table 1 Percentage of PADUA risk factors in AIHA and non-AIHA patients with thromboembolism. Table 1. Percentage of PADUA risk factors in AIHA and non-AIHA patients with thromboembolism. Disclosures Chen: True North Therapeutics: Research Funding. Loftus:True North Therapeutics: Research Funding. Weber:True North Therapeutics: Research Funding. Hoang:True North Therapeutics: Research Funding. Gilbert:True North Therapeutics: Employment. Kummar:True North Therapeutics: Research Funding.

scholarly journals EPIDEMIOLOGY AND RISK FACTORS OF WARM AND COLD AUTOIMMUNE HEMOLYTIC ANEMIA

InterConf ◽  
2021 ◽  
pp. 225-232
Author(s):  
Vasile Musteata ◽  
Aslam Thoufeeq
Keyword(s):  
Risk Factors ◽  
Hemolytic Anemia ◽  
Clinical Features ◽  
Haemolytic Anaemia ◽  
Autoimmune Hemolytic Anemia ◽  
Medical Literature ◽  
Current Medical ◽  
Autoimmune Haemolytic Anaemia ◽  
Coombs Test ◽  
Different Types

Even though clinical features in autoimmune haemolytic anaemia vary according to the type of AIHA, anaemic syndrome stays common for most of the cases. A positive Coombs test or direct anti-globulin test developed in 1945 by Coombs, Mourant and Race, is the most deciding factor in AIHA diagnosis. Since the immunologic mechanisms causing erythrocyte destruction vary between AIHAs, treatment is also different. Empirical approach with glucocorticoids is the main treatment of AIHA overall, but less effective in CAD. However, the current medical literature is still with gaps concerning the management, presentation and diagnosis of the different types of AIHA altogether.

scholarly journals Clinical Patterns and Hematological Spectrum in Autoimmune Hemolytic Anemia

2010 ◽  
Vol 2 (01) ◽  
pp. 017-020 ◽  
Author(s):  
Vanamala Alwar ◽  
Shanthala Devi A M. ◽  
Sitalakshmi S. ◽  
Karuna R K.
Keyword(s):  
Connective Tissue ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Severe Anemia ◽  
Red Cell ◽  
Connective Tissue Disorders ◽  
Red Cell Membrane ◽  
Antiglobulin Test ◽  
Circulating Autoantibodies ◽  
Positive Direct

ABSTRACT Background: Autoimmune hemolytic anemia (AIHA) results from red cell destruction due to circulating autoantibodies against red cell membrane antigens. They are classified etiologically into primary and secondary AIHAs. A positive direct antiglobulin test (DAT) is the hallmark of diagnosis for AIHA. Methods and Results: One hundred and seventy-five AIHA cases diagnosed based on positive DAT were included in the study. The cases showed a female predilection (M: F = 1:2.2) and a peak incidence in the third decade. Forty cases were found to be due to primary AIHA, while a majority (n = 135) had AIHA secondary to other causes. The primary AIHA cases had severe anemia at presentation (65%) and more often showed a blood picture indicative of hemolysis (48%). Forty-five percent of primary AIHAs showed positivity for both DAT and indirect antiglobulin test (IAT). Connective tissue disorders were the most common associated etiology in secondary AIHA (n = 63). Conclusion: AIHAs have a female predilection and commonly present with symptoms of anemia. AIHA secondary to other diseases (especially connective tissue disorders) is more common. Primary AIHAs presented with severe anemia and laboratory evidence of marked hemolysis.

scholarly journals Complement Blockade with C1 Esterase Inhibitor in Severe C3d Positive Autoimmune Hemolytic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4817-4817 ◽  
Author(s):  
Jasmin Desai ◽  
Catherine Broome
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Standard Therapy ◽  
Classical Pathway ◽  
Severe Anemia ◽  
Complement Protein ◽  
C1 Esterase Inhibitor ◽  
Rbc Membrane ◽  
Positive Direct ◽  
Esterase Inhibitor

Autoimmune hemolytic anemia (AIHA) is defined as the development of autoantibodies against red blood cell (RBC) antigens. AIHA is diagnosed in the presence of hemolysis and a positive direct antiglobulin test (DAT) for IgG and/or complement C3d. AIHA is classified as warm, cold or mixed based on the temperature at which the autoantibody is most active. The most clinically severe anemia is usually associated with AIHA in which C3d is detected on DAT. The classical complement pathway is activated in AIHA when antigen-autoantibody complexes on the RBC surface bind to the complement protein C1q. This ultimately results in the generation of C3b. C3b is both an opsonin and an additional proteolytic enzyme. C3b deposition targets the RBC for phagocytosis by macrophages of the reticuloendothelial system resulting in extravascular hemolysis. C3b can also continue activation of complement on the RBC membrane resulting in formation of the membrane attack complex (MAC) and cell lysis. C3b is degraded into C3d, which is identified by the DAT (Bartolmas 2015). Severe anemia and its immediate consequences, the difficulty identifying suitable units for acute RBC transfusion, the likelihood of causing additional hemolysis as well as concerns for stimulating additional antibody production with transfusion make these patients particularly challenging to treat. Current standard treatment consists of steroids with or without rituximab. This treatment paradigm does not, however, address the acute and urgent management of life threatening anemia in many of these patients. C1 esterase inhibitor (C1-INH) is a member of the serine protease inhibitor family and interacts with C1 esterase to block activation of the classical pathway of complement. Case reports have demonstrated that C1-INH can prevent C3-mediated lysis of PNH erythrocytes (DeZern 2014) and augment survival of transfused RBCs in a patient with DAT C3d positive autoimmune hemolytic anemia (Wouters 2013). We hypothesized that minimizing or inhibiting the generation of C3b with C1-INH in patients with either severe cold autoantibody AIHA or a mixed AIHA would rapidly reduce acute hemolysis. We report our clinical experience using a novel approach in the acute management of severe AIHA using the commercially available C1-INH, Berinert. The four patients we identified with either cold or mixed AIHA (Table 1) were between the ages of 58 and 63. All patients presented with clinically severe anemia and required urgent management. Three of the 4 had a co-morbid condition associated with AIHA. All patients received prednisone (1mg/kg) and the commercially available C1-INH at a dose of 20mcg/kg daily from the day of admission for a minimum of 6 days to a maximum of 20 days. Patients 2, 3, and 4 also received 4 weekly doses of rituximab during the course of treatment. The average increase in mean hemoglobin was 79% (presentation mean 4.5gm/dL- end of C1-INH mean 7.95gm/dL) during C1-INH administration. An average of 1.25(0-2) units of packed RBC per patient were transfused during C1-INH administration. Additional measures of ongoing hemolysis including mean LDH which decreased by an average of 72% (presentation mean 1358u/L to end of C1-INH mean 356u/L) and mean haptoglobin which increased in all patients from < 8mg/dL to 111mg/dL after C1-INH. Of note, patient 1 had cold agglutinin titers measured prior to C1-INH administration at 1:128 and repeated after two days of C1-INH administration revealed a decrease to 1:32. This retrospective review of patients demonstrates that utilizing C1-INH in conjunction with standard therapy is safe and results in rapid improvement of hemoglobin levels in patients with DAT/C3d positive AIHA. We hypothesize the inhibition of C1q-C4 interaction rapidly reduces C3b deposition on the RBC membrane decreasing both extra and intravascular RBC destruction. CI-INH therapy allowed successful management of these acutely ill patients with minimal RBC transfusions. We hypothesize that decreasing the exposure to additional antigenic stimulation may shorten the acute exacerbation of hemolysis. The optimal form and schedule of C1-INH therapy for AIHA remains to be determined. Based on these observations the role of inhibitors of the classical pathway of complement as both a single modality and in conjunction with standard therapy in the management of AIHA deserves further investigation. Table Table. Disclosures Broome: Alexion Pharmaceuricals: Honoraria; True North Therapeutics: Honoraria.

scholarly journals Sepsis-induced Autoimmune Hemolytic Anemia: A Case Report

2020 ◽  
Vol 4 (4) ◽  
pp. 668-670
Author(s):  
Zach Edwards ◽  
Stephen DeMeo
Keyword(s):  
Risk Factors ◽  
Emergency Department ◽  
Case Report ◽  
Hemolytic Anemia ◽  
Patient Outcomes ◽  
Autoimmune Hemolytic Anemia ◽  
Rare Complication ◽  
Signs And Symptoms ◽  
Emergency Physicians ◽  
Colonic Diverticula

Introduction: Sepsis commonly brings patients to the emergency department (ED). Patient outcomes can vary widely. In some cases, rare complications of sepsis such as autoimmune hemolytic anemia can occur. Case Report: A 68-year-old female presented with sepsis secondary to infected nephrolithiasis. The patient had signs and symptoms consistent with hemolysis upon arrival to the ED. Her hemolysis progressively worsened over a two-day period leading to a diagnosis of warm autoimmune hemolytic anemia. She responded well to treatment; however, her condition began to worsen due to a new infection caused by perforated colonic diverticula. The patient ultimately expired from complications of her perforated colonic diverticula. Conclusion: It is crucial that emergency physicians understand the risk factors, symptoms, pathophysiology, and treatment of this rare complication of sepsis so that favorable patient outcomes can be achieved.

Expression of CD47, CD35, CD55 and CD59 on Red Cells from Patients with Warm Autoimmune Hemolytic Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3738-3738
Author(s):  
Melca O. Barros ◽  
Mihoko Yamamoto ◽  
Maria S. Figueiredo ◽  
Elisa Y. Kimura ◽  
Jose Orlando Bordin
Keyword(s):  
Hemolytic Anemia ◽  
Lupus Erythematosus ◽  
Autoimmune Hemolytic Anemia ◽  
Experimental Studies ◽  
Red Cells ◽  
High Dose ◽  
Healthy Controls ◽  
Life Threatening ◽  
Positive Direct ◽  
Cd59 Expression

Abstract Autoimmune hemolytic anemia (AIHA) is defined as an increased destruction of red cells (RBC) in the presence of anti-RBC autoantibodies. CD47 is an integrin-associated protein expressed on all cells including RBCs. Animal models show that CD47 deficiency contributes to accelerated development of AIHA, while CD35 (CR1- complement receptor 1), CD55 (decay accelerating factor), and CD59 (membrane inhibitor of reactive lysis) are complement inhibitory proteins. Using flow cytometry analysis, in this study we evaluated the expression of CD47, CD35, CD55, and CD59 on RBCs of patients with warm AIHA before any treatment had been initiated. The study population consisted of 12 patients with active AIHA [M:F = 6:6, median age: 32 yrs (3 – 73)], and 20 healthy controls [M:F = 9:11, median age: 36 yrs (25 – 71)]. Ten patients presented idiopathic AIHA while 2 subjects had secondary AIHA (systemic lupus erythematosus and non-Hodgkin’s lymphoma). At presentation the median Hb level was 6.6 mg/dL (range: 2.9 to 10 mg/dL), and the median absolute reticulocyte count was 324 × 109/L (range: 215 to 756 × 109/L). At the time of the analyses, all 12 patients had a positive direct antiglobulin test (DAT), 12 (100%) had IgG on their RBCs, 5 (41.7%) had IgG plus C3, and none had C3 alone. The strength of agglutination of all positive DATs showed a strong reaction. The RBC eluates prepared by a dichloromethane technique from the cell samples were positive in all 12 patients, but the retrieved autoantibodies were pan-reactive showing no specific reactivity. The mean fluorescence intensity (MFI) of the expression of CD47, CD35 and CD55 on RBCs of AIHA patients and healthy individuals were not statistically different (CD47 = 464.4 and 464.4; CD35 = 186.8 and 194.3; CD55 = 396.9 and 381.1, respectively). Four patients with life-threatening AIHA were treated with high dose of steroids and RBC transfusions, but 3 patients evolved to death. Two patients who died presented low CD55 expression on their RBCs at diagnosis. AIHA patients showed significant lower CD59 expression on RBCs than healthy controls (MFI = 512.3 ± 28.0 and 553.7 ± 36.6, P = .03). Although CD59 expression in patients that evolved to remission was not significantly different from healthy controls (MFI = 538.5 ± 14.4 and 553.7 ± 36.6), the expression of CD59 on RBCs of 3 AHAI patients who died were significantly lower than that seen on RBCs of healthy controls (MFI = 433.6 ± 69.6 and 553.7 ± 36.6, P = .0001). Although experimental studies have suggested that CD47 has a profound influence on the severity of AIHA in mice, our preliminary data on 12 patients with AIHA did not demonstrate difference on the expression of CD47 on RBCs of patients with warm AIHA or healthy indibiduals. On the other hand, complement regulatory proteins (CD35, CD55, and CD59) may play an important role in protecting RBC destruction through the activation of complement. Our results suggest that patients with life-threatening warm AIHA may present significant CD59 deficiency on their RBCs that may increase the susceptibility of cells to complement-mediated lysis resulting in severe clinical hemolysis.

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