[A Successful Surgical Treatment of Hemolytic Anemia Caused by Aortic Valve Perivalvular Leakage and Severely Kinked Elephant Trunk:Report of a Case].

Both perivalvular leakage and kinked prosthetic graft may cause hemolysis. A 72-year-old man was refereed to our hospital because of hemolytic anemia. He has past histories of total aortic arch replacement and repeat aortic valve replacement for aortic aneurysm and prosthetic valve endocarditis. Pre-operative examinations demonstrated aortic valve perivalvular leakage and severe graft kinking of the elephant trunk. Repeat aortic valve replacement and axillo-femoral bypass were performed successfully. Hemolysis got better after the operation and the patient discharged home in stable condition.

Evaluation of haematological parameters in haemolytic anaemia caused by tick-borne pathogens in grazing cattle.

BACKGROUND: No tick-borne pathogens (TBPs) causing haemolytic anaemia in cattle have been reported, except Theileria orientalis and complete blood count (CBC) profile is the only haematological parameter to determine the severity of regenerative haemolytic anaemia. OBJECTIVES: To identify the causative agents of TBP-induced haemolytic anaemia and determine haematological parameters that indicate haemolytic anaemia in grazing cattle. METHODS: Eighty-two Korean indigenous cattle (Hanwoo) were divided into two groups: grazing (n = 67) and indoor (n = 15) groups. CBC and serum biochemistry were performed. PCR was conducted using whole blood-extracted DNA to investigate the prevalence of TBPs. RESULTS: TBP-induced haemolytic anaemia was observed in the grazing group. In grazing cattle, co-infection (43.3%, 29/67) was most frequently detected, followed by T. orientalis (37.6%, 25/67) and Anaplasma phagocytophilum infections (1.5%, 1/67). In indoor cattle, only co-infection (20%, 3/15) was identified. Grazing cattle exhibited regenerative haemolytic anaemia with marked monocytosis, mild neutropenia, and thrombocytopenia. According to grazing frequency, the 1st-time grazing group had more severe anaemia than the 2nd-time grazing group. Elevations in indirect bilirubin and L-lactate due to haemolytic anaemia were identified, and correlations with the respective markers were determined in co-infected grazing cattle. CONCLUSIONS: Quantitative evaluation of haematocrit, mean corpuscular volume, and reticulocytes (markers of regenerative haemolytic anaemia in cattle) was performed for the first time. Our results show that, in addition to T. orientalis, A. phagocytophilum is strongly associated with anaemia. The correlation between haemolytic anaemia severity and haematological parameters (indirect bilirubin, reticulocytes, and L-lactate) was confirmed.

Clinical Evaluation and Management of Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and organ injury that stems from endothelial damage and vascular occlusion. There are several disease states with distinct pathophysiological mechanisms that manifest as TMA. These conditions are associated with significant morbidity and mortality and require urgent recognition and treatment. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are traditionally considered to be primary forms of TMA, but TMA more commonly occurs in association with a coexisting condition such as infection, pregnancy, autoimmune disease, or malignant hypertension, among others. Determining the cause of TMA is a diagnostic challenge because of limited availability of disease-specific testing. However, identifying the underlying etiology is imperative as treatment strategies differ. Our understanding of the conditions that cause TMA is evolving. Recent advances have led to improved comprehension of the varying pathogenic mechanisms that drive TMA. Development of targeted therapeutics has resulted in significant improvements in patient outcomes. In this article, we review the pathogenesis and clinical features of the different TMA-causing conditions. We outline a practical approach to diagnosis and management and discuss empiric and disease-specific treatment strategies.

Mitapivat: A Quinolone Sulfonamide to Manage Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency.

BACKGROUND: Pyruvate kinase (PK) deficiency is a rare enzyme-linked glycolytic defect resulting in mild-to-severe chronic persistent erythrocyte hemolysis. The disease is an autosomal recessive trait caused by mutations in the PK liver and red blood cell gene characterized by insufficient erythrocyte PK activity. PK deficiency is most diagnosed in persons of northern European descent and managed with packed red blood cell transfusions, chelation, and splenectomy with cholecystectomy. Mitapivat is the first approved therapy indicated for hemolytic anemia in adults with PK deficiency with the potential for delaying splenectomy in mild-moderate disease. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Mitapivat is a PK activator that acts by allosterically binding to the PK tetramer and increases PK activity. The red blood cell form of PK is mutated in PK deficiency, which leads to reduced adenosine triphosphate, shortened red blood cell lifespan, and chronic hemolysis. The half-life of elimination is 3-5 hours, with 73% bioavailability, 98% plasma protein binding, and a median duration of response of 7 months. CLINICAL TRIALS: Mitapivat has been investigated through various clinical trials for different therapeutic indications. Pivotal trials that serve the primary focus throughout this article are ACTIVATE, ACTIVATE-T, and RISE. ACTIVATE is a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of mitapivat in adult patients who were not receiving regular blood transfusions. Contrarily, ACTIVATE-T explored the safety and efficacy of mitapivat in adults with PK deficiency who received regular blood transfusions. Both trials demonstrated favorable use of mitapivat in PK deficiency. Focusing on another indication, the ongoing RISE trial investigates the optimal dosage of mitapivat in sickle cell disease. THERAPEUTIC ADVANCE: Mitapivat is an appropriate treatment for adults with PK deficiency requiring transfusions and may be considered for patients with symptomatic anemia who do not require transfusions and/or PK deficiency with compensated hemolysis without overt anemia.

Gastrointestinal involvement of passenger lymphocyte syndrome followed by minor ABO-incompatible renal transplantation: A case report.

BACKGROUND: People with group O blood are considered universal organ donors compatible with any other blood group. However, in the case of minor ABO-incompatible transplantation, immune-mediated hemolysis may occur due to concomitant transfer of donor B lymphocytes together with the allograft. These passenger lymphocytes can produce antibodies in the recipients erythrocytes, causing hemolytic anemia known as passenger lymphocyte syndrome (PLS). METHODS: A retrospective chart review was performed. RESULTS: A 6-year-old boy (A+) underwent transplantation of a kidney from his father (O+). On postoperative day (POD) 6, the patient developed fever with no explainable causes. On POD 11, he presented with abdominal pain, hematochezia, and severe diarrhea, with sudden hemolytic anemia. Since then, GI symptoms have continued. On POD 20, direct antiglobulin test (DAT) was positive, and the anti-A IgM/G titer was 2/32. The results of the anti-A antibody elution test were strongly positive (3+). These findings highly suggested PLS. On the same day, the GI symptoms suddenly worsened, and laboratory findings showed hemolysis and thrombocytopenia with disseminated intravascular coagulation (DIC). Abdominal computed tomography (CT) scans suggested ischemic colitis of venous origin, and the patient underwent segmental colectomy with ileostomy formation on POD 23. To remove the anti-A antibodies, the patient underwent therapeutic plasma exchange (TPE) five times until the DAT and anti-A elution test were negative. CONCLUSIONS: We report a case of gastrointestinal involvement of PLS that occurred after minor ABO-incompatible kidney transplantation. This is the first report of ischemic colitis as an atypical manifestation of PLS.

Distinct lipid profile in haemolytic anaemia-related gallstones compared with the general gallstone.

BACKGROUND: Pigment gallstones are not uncommon among patients with chronic haemolytic anaemia. But their clinical characteristics have not been described in detail and not been directly compared with the general gallstone population. METHODS: Patients at Peking Union Medical College Hospital with haemolytic anaemia and subsequent gallstones from January 2012 to December 2022 were included. Cases were matched (1:2) based on age, sex and location of stones to randomly select non-anaemia patients with gallstones (controls). RESULTS: Screening 899 cases of gallstones, we finally included 76 cases and 152 controls. Total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) for cases were 3.02 ± 0.98 mmol/L, 0.89 ± 0.30 mmol/L and 1.58 ± 0.70 mmol/L, respectively, significantly lower than those in the control group (all p < 0.001). TC and HDL were both lower than the normal range, but triglyceride and LDL were within the normal range. Multiple stones were significantly more common for cases (n = 59, 78%) than for controls (n = 44, 29%, p < 0.001). The mean diameter of the maximal gallstone was 1.2 ± 0.6 cm and 1.5 ± 1.0 cm for cases and controls (p = 0.120), respectively. Stones in the elderly (p = 0.002 for univariate analysis, and 0.001 for multivariate analysis) and stones in the bile duct (p = 0.005 for univariate analysis, and 0.009 for multivariate analysis) were found to occur in a shorter period after anaemia. CONCLUSION: The lipid profile of haemolytic anaemia with gallstones was distinct, low TC, low HDL, and increased-to-normal LDL, compared with the general gallstone population. Patients with haemolytic anaemia were recommended an abdominal ultrasound if aged older than 50 years, with more frequent follow-up visits.KEY MESSAGESClinical characteristics of gallstones following chronic haemolytic anaemia were described and compared with the general gallstone population.The lipid profiles were distinctly different between the patients with gallstones following chronic haemolytic anaemia and the general gallstone population.Elder patients were complicated with gallstones in a shorter period after anaemia and thus were recommended an abdominal ultrasound if aged older than 50 years, with more frequent follow-up visits.

Severe Hemolytic Anemia and Metabolic Acidosis at Birth with Glutathione Synthetase Deficiency and Progressive Neurological Symptoms on Follow-Up.

BACKGROUND Glutathione synthetase deficiency (GSD) is a rare autosomal recessive disorder caused by glutathione synthetase (GSS) gene variants that occur in 1 in 1 million individuals. The severe form of GSD is characterized by hemolytic anemia, metabolic acidosis with 5-oxoprolinuria, progressive neurological symptoms, and recurrent bacterial infections. This case report presents a male Japanese infant with severe hemolytic anemia and metabolic acidosis at birth caused by GSD, who developed progressive neurological symptoms on follow-up. CASE REPORT A Japanese male term infant developed severe hemolytic anemia and metabolic acidosis in the early neonatal period. We suspected GSD based on his symptoms and a high 5-oxoproline urine concentration. We began correcting his metabolic acidosis and administering vitamins C and E supplements. The patient required blood transfusion twice during the acute phase for hemolytic anemia. After age 1 month, he maintained good control of metabolic acidosis and hemolytic anemia. A definitive diagnosis of GSD was made based on high concentrations of 5-oxoproline in urine, low concentrations of glutathione and GSS activity in erythrocytes, and genetic testing. Several episodes of febrile convulsions were started at age 11 months, but none occurred after 2 years. At the last follow-up at age 25 months, metabolic acidosis and hemolytic anemia were well controlled, but he had mild neurodevelopmental delay. CONCLUSIONS This case report shows that GSD can present with severe hemolytic anemia and metabolic acidosis at birth, and manifest with subsequent neurological impairment despite early diagnosis and treatment. Therefore, a careful long-term follow-up that includes neurological evaluation is essential for patients with GSD.

Acute hemolytic anemia after hematopoietic stem cell transplantation: An unusual invader.

69-year-old man with a history of diffuse large B-cell lymphoma (DLBCL) presented with severe acute hemolytic anemia 27 months after an autologous hematopoietic stem cell transplantation. Bone marrow aspirate revealed intracellular micro-organisms (arrows) located within the cytoplasm of red blood cells confirming the diagnosis of severe babesiosis.

A thorny matter: Spur cell anemia.

Spur cell anemia (SCA) is an acquired form of non-autoimmune hemolytic anemia that occurs in advanced liver disease. It is characterized by the presence of acanthocytes or spur cells, spiculated erythrocytes whose shortened life span causes anemia that is unresponsive to transfusion. SCA has been regarded as a rare condition with an ominous prognosis for which the only known cure is liver transplantation, but recent prospective studies have demonstrated the existence of a milder form of SCA in which there are smaller numbers of acanthocytes, but which is nevertheless associated with hemolysis and poor outcomes. This form of SCA appears to be considerably more common than the severe classical variant. The conventional understanding of the pathogenesis of SCA is that abnormalities of lipid metabolism are the primary event driving the formation of spur cells. However, the studies that underpin this theory are based on small numbers of patients with heterogeneous clinical features and inconsistent use of nomenclature for dysmorphic red blood cells. In this review, we discuss the evolution of the current understanding of SCA and therapeutic strategies that have been employed based on this understanding. Our goal is to raise awareness of this understudied condition that has significant implications for patient outcomes. Furthermore, we highlight the need for rigorous, contemporary research into the underlying cause or causes of SCA in order to develop an effective therapy for this disorder.

Hemolytic anemia caused by kinked graft 6 months after aortic dissection repair.

BACKGROUND: Clinically insignificant hemolytic anemia is occasionally a complication of prosthetic valve replacement. However, hemolysis related to kinked grafts is a very rare complication after central repair for acute aortic dissection. CASE PRESENTATION: A 42-year-old man had undergone replacement of the ascending aorta and a root repair for type A aortic dissection 6 months previously. Laboratory data showed mild hemolysis 5 months later, and he began to complain of fatigue on exertion. The serum hemoglobin level reduced to 8.6 g/dL, and lactate dehydrogenase levels increased to 3071 IU/L with gross change in urine color, indicating hemoglobinuria. We diagnosed mechanical hemolytic anemia caused by a kinked graft and planned a repeat operation. The kinked graft was resected and graft-graft anastomosis was performed. Postoperatively, the clinical course was uneventful, and the hemolytic anemia completely resolved. CONCLUSION: We herein report a case of hemolytic anemia caused by kinking of the graft 6 months after acute aortic dissection repair. The diagnosis was swiftly made, and the patient was successfully managed with redo surgery.

Therapeutic plasma exchange in gastric signet ring cell carcinoma presenting as microangiopathic hemolytic anemia: A rare case report.

Microangiopathic hemolytic anemia (MAHA) defines a group of disorders characterized by the formation of microthrombi in capillaries and arterioles and the fragmentation of erythrocytes that pass through. Cancer-related MAHA is a rare but serious condition that is encountered in patients diagnosed with a malignancy. This clinical picture is thought to be linked to certain tumor characteristics; particularly, adenocarcinoma histology, vascular invasion, and bone marrow infiltration. MAHA is most commonly associated with tumors of gastric, prostate, and breast origin. The optimal treatment is not clear; however, there is evidence for the importance of promptly starting an effective antineoplastic regimen and it was also reported that administering therapeutic plasma exchange (TPE) therapy for immunocomplex removal could be beneficial for patients with symptoms of bleeding and thrombosis. Here, we present a case that presented a picture of MAHA secondary to gastric signet-ring cell adenocarcinoma (SRCC). The clinical picture was initially evaluated as thrombotic thrombocytopenic purpura and the patient benefited significantly from the TPE treatment administered before the adenocarcinoma diagnosis was confirmed. In this period, epistaxis stopped, platelet count increased from 25 × 109 /L to 162 × 109 /L, fragmented erythrocyte rate in the peripheral smear decreased by more than 75% and other laboratory findings of hemolysis (LDH, bilirubin, etc.) significantly improved.