Negative Coomb Research Articles

THROMBOTIC MICROANGIOPATHIC HEMOLYTIC ANEMIA IN SYSTEMIC LUPUS ERYTHEMATOSUS IN A 25 YEARS OLD FEMALE IN CHENNAI, INDIA

Systemic lupus erythematosus (SLE) is an autoimmune condition, affecting multiple organs and tissues by autoantibodies and immune complexes. Hematologic manifestations of SLE include anemia, thrombocytopenia and leukopenia. The most common type of anemia seen in SLE is anemia of chronic disease. Thrombotic microangiopathic hemolytic anemia (TMHA) in SLE is very rare. Incidence of TMHA in children with SLE is common compared to adult cases of SLE. Manifestations of TMHA include presence of schistocytes in the peripheral smear, elevated bilirubin levels, elevated LDH and negative coombs test. This case report focuses on 25-year-old female diagnosed concomitantly with SLE and TMHA, and treated with steroids, blood transfusions, megakaryocyte growth factors and antibiotics.

A 5-year-old child with hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency: a case report

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that plays an essential role in the human body cell. It is found in the cytoplasm of cells and functions to prevent cellular damage from reactive oxygen species. G6PD deficiency can be highly variable in its clinical presentation. It can cause acute or chronic hemolytic anemia and hyperbilirubinemia. Severe hemolytic can cause mortality in children. So, it is crucial to be aware during the diagnosis of hemolytic anemia at any age. The hemolytic occurred is usually precipitated by exposure to medication or intake of fava bean. This report is aimed to describe the diagnosis and treatment of a child who appears with acute hemolytic anemia due to favism.Case description: A 5-year-old boy came to the emergency department with a chief complaint of pale and fatigue since a day before admission in PKU Muhammadiyah Gamping Hospital. No family history of hemolytic anemia or parental consanguinity. He appeared icteric and with severe anemia. We found that he consumed fava beans twelve hours prior to the onset of the symptoms was reported. The laboratory findings were as follows: Hb 4.9 g/dl, total bilirubin 6.17 mg/dl, indirect bilirubin 5.49 mg/dl and a negative Coomb’s test result then obtained. The patient then is transfused with PRC, and the level of Hb became 9.2 g/dl and total bilirubin 0.2 mg/dl. The blood smear result was met hemolytic anemia and bacterial infection. The level of G6PD result obtained four days after was low, 7.5 U/gr Hb (10.0-14.2).Conclusion: The severe hemolytic anemia in the patient was proven caused by G6PD deficiency.

Dehydrated Hereditary Stomatocytosis: A Rare Inherited Hemolytic Anemia

Background: Dehydrated hereditary stomatocytosis (DHSt), also known as hereditary xerocytosis, is a rare congenital hemolytic anemia with an autosomal dominant inheritance. It is often misdiagnosed for other hemolytic conditions, such as hereditary spherocytosis. Herein, we present the case of a young female presenting with hemolytic anemia, who was found to have a mutation in PIEZO1 gene and was subsequently diagnosed with DHSt.Case Presentation: A 39-year-old woman of Asian origin presented to the hematology clinic for evaluation of anemia diagnosed on blood work performed by primary care physician for symptoms of fatigue. She was adopted and had no information about her family history. A complete blood count revealed: hemoglobin 8.2 g/dL, mean corpuscular volume (MCV) 121.6 fL, absolute retic counts 0.08 M/mcL, lactate dehydrogenase 851 units/L and a negative coombs test. Iron profile revealed iron saturation 85% and ferritin 1961.4 ng/mL (see table 1 for laboratory work up). The peripheral blood smear showed anisopoikilocytosis, macrocytes, spherocytes and several stomatocytes along with polychromatophils. An ultrasound of the abdomen was subsequently performed, and which revealed hepatomegaly and biliary stones. Enzyme assay for glucose-6-phosphate dehydrogenase and flow cytometry for paroxysmal nocturnal hemoglobinuria were also sent and were negative. Red blood cells osmotic fragility was decreased. The bone marrow biopsy showed full spectrum trilineage hematopoiesis with no mutations on molecular testing. Based on the blood smear and clinical presentation, a diagnosis of DHSt was suspected. Genetic testing was performed and which revealed Sc.2842C>T; p.Arg948Cys mutation in the PIEZO1 gene by massively parallel sequencing and confirmation by Sanger sequencing. This confirmed the diagnosis of DHSt. Patient was started on high dose folic acid with improvement in her hemoglobin in one month. She did not require any blood transfusions. MRI liver T2* scan measured quantitative liver iron of 31 mM/g, which was at the high normal range.Discussion: DHSt is caused by gain of function mutation in PIEZO1 gene or KCCN4 gene which encode the transmembrane cation ion channel and Gardo's channel respectively on red blood cell membrane. This results in delayed inactivation of the channel. The disease presents as a spectrum from asymptomatic anemia to massive hemolysis, and many patients present later in life. Patients may manifest clinical signs of jaundice, pallor, fatigue, splenomegaly, gallstones and iron overload. Labs are typically significant for elevation in mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW) and MCV, with classic slit cells red blood cells seen on peripheral blood smear (see image 1). PIEZO1 is expressed early in erythroid progenitor cells and may delay erythroid differentiation and reticulocyte maturation, which may be the cause of low reticulocyte count such as in our patient. While treatment is supportive with blood transfusions, only a minority of DHSt patients ever require regular transfusions. Interestingly, hyperferritinemia, high transferrin saturation or clinical iron overload are quite frequent in DHSt and iron chelation is recommended. Splenectomy is contraindicated due to increased risk of thrombosis.Conclusions: DHSt as a rare inherited hemolytic anemia and its diagnosis warrants maintaining a high index of clinical suspicion based on supportive laboratory findings. Diagnosis involves thorough testing earlier in the disease as patients may be asymptomatic until adulthood. Delaying the diagnosis may lead to severe iron overload and consequent organ damage. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cancer Associated Microangiopathic Hemolytic Anemia: A Rare Paraneoplastic Syndrome

Microangiopathic hemolytic anemias (MAHA) are secondary to damage of RBCs because of endothelial vascular damage of blood vessels leading to hemolysis. MAHAs are characterized by negative coombs test and are associated with several etiologies that include can be either hereditary complement or ADAMTS13 deficiency or sepsis or malignancy. Cancer associated MAHA (CA-MAHA) is a rare and is seen in patients with advanced metastatic disease. CA-MAHA has significant mortality rate and chemotherapy is the only therapeutic option, however overall survival is poor. Here we, present a rare case of CA-MAHA secondary to metastatic signet ring cell carcinoma with an unknown primary. In patients, when the cause of progressive MAHA is unknown, the possibility of cancer associated MAHA must be considered and a comprehensive work up for an underlying malignancy must be done.

Nucleated red blood cell levels in the diagnosis of patients with indirect hyperbilirubinemia.

Nucleated red blood cells (NRBCs) are progenitores of red blood cells that are physiologically seen in the peripheral blood of the fetus and newborn at birth. The increased numbers of NRBCs in the circulation is associated with pathologic conditions such as prematurity, hemolytic diseases and bleeding, intrauterine growth restriction. We aimed to evaluate the relationship between NRBCs and the demographic and clinical characteristics of the patients with indirect hyperbilirubinemia who were followed up in the neonatal intensive care unit. In this retrospective study we evaluated 134 patients with indirect hyperbilirubinemia between January 2017 and December 2018. Patients were divided into two groups as those with ABO and/or Rh incompatibility and those without. Groups were compared in terms of demographic, clinical characteristics and for the hematological parameters. A total of 134 infants were evaluated in the study, including 68 (50%) infants with ABO incompatibility, 12 (8.9%) with Rh incompatibility and 3 (2.2%) with ABO and Rh incompatibility. Coombs test results were positive for 34 patients. There were no differences between ABO and/or Rh incompatibility group and non incompatibility group with regards to birth weight, gestational age and gender. In terms of hematologic parameters, there were no differences between the hemoglobin, hematocrit and mean platelet volumes of the patients at the time of hospitalization, while red cell distribution width, NRBCs per 100 white blood cells (NRBCs/100 WBCs) and absolute NRBC count were statistically higher in patients with ABO and/or Rh incompatibility. It was found that NRBCs/100 WBC and absolute NRBC count were statistically higher in patients with positive direct coombs test than patients with negative coombs test (p <0.05). Early diagnosis of indirect hyperbilirubinemia is essential, as it can prevent to occur serious neurological sequelas. Elevated levels of NRBCs in infants with blood group incompatibilities could alert clinicians about the severity of jaundice and should increase awareness in terms of hemolysis.

S2384 Post-TIPS Hemolytic Anemia Due to Polytetrafluoroethylene Stent

INTRODUCTION: Transjugular intrahepatic portosystemic shunt (TIPS) procedures are performed to decrease the complications of portal hypertension in cirrhosis including salvage for variceal bleeds, medically refractory ascites, and hepatic hydrothorax. Although generally well-tolerated, encephalopathy and liver failure are major complications which can occur after the procedure. One of the lesser known complications of TIPS, however, is a transient hemolytic anemia, which we discuss here. It occurs in approximately 10% of cases. CASE DESCRIPTION/METHODS: A 65-year-old male with history of alcoholic cirrhosis decompensated by esophageal and gastric varices was referred to our facility after recent gastrointestinal hemorrhage to evaluate for a TIPS procedure. After being deemed a candidate, a 90 mm total length (70 mm covered / 20 mm uncovered) Viatorr (GORE, Flagstaff, AZ, USA) polytetrafluoroethylene (PFTE) stent-graft was successfully placed, and the portosystemic gradient decreased from 16 mmHg to 5 mmHg. Post-procedure, however, the patient developed worsening jaundice. Laboratory data demonstrated anemia with hemoglobin of 6.0 gm/dL, reticulocytosis with a reticulocyte index of 7.9%, hyperbilirubinemia with up-trending total bilirubin from 6.5 mg/dL to 18.9 mg/dL and an indirect bilirubin of 8.0 mg/dL, and findings consistent with hemolysis with an elevated LDH of 254 units/L, low haptoglobin of < 15 mg/dL, and a negative Coomb’s test. Peripheral smear showed anisocytosis, Burr cells, and target cells; no schistocytes were observed. This led to a diagnosis of non-immune hemolytic anemia. During the remainder of the patient’s hospital course, his hyperbilirubinemia slowly improved prior to discharge. DISCUSSION: Hemolytic anemia is one of the lesser known complications following TIPS. It was first described in the 1990s when bare metal stents (BMS) were commonly used. Literature refers to the hemolytic process with BMS as the “Naked Stent” syndrome due to injury of red blood cells after colliding with the exposed mesh of the stent. In order to improve stent patency and decrease complications, PFTE stents were introduced; however, hemolytic anemia may still occur as described in our case. The pathogenesis remains the same due to stent-related trauma to red blood cells as the covered PFTE stents have areas which remain exposed. With complete endotheliazation of the stent, the hemolytic anemia generally resolves without further intervention in 8–12 weeks.

MM-098: A Case Report: Acquired Pure Red Cell Aplasia Associated with Monoclonal Gammopathy of Undetermined Significance

Background: Pure Red Cell Aplasia (PRCA) is a rare disorder characterized by profound anemia and absence of erythroid precursor in the bone marrow, and it can be genetic or acquired; the acquired form can be idiopathic or secondary and one of these causes is monoclonal gammopathy (MG). In review of the literature, we found a few cases that were treated in different ways. Case Presentation: We will report a case of pure red cell aplasia associated with monoclonal gammopathy of undetermined significance; the patient admitted for severe anemia with hemoglobin 5.4 g/dl, MCV 120 fl, and white blood count (WBC) was 3750/mm3 with 67% neutrophils and a normal platelet count. The workup was done and showed a reticulocyte count of 0.03%, negative coombs (direct and indirect), negative ANA, and anti-double stranded DNA (dsDNA). Vitamin B12 was 900 pg/ml and folate 7.66 ng/ml; serology for HIV, HBV, and HCV found to be negative. TSH, LDH, liver function tests were all normal. Erythropoietin level was 11.79 IU/L. Bone marrow aspirate revealed a cellular bone marrow (60-70%) with less than 5% plasma cells expressing excess lambda light chain. Immunohistochemistry using CD138 confirmed the result and flow cytometry revealed a small population of plasma cells with aberrant phenotype. Serum protein electrophoresis showed a monoclonal gamma peak and immunofixation showed high light lambda chains. Total body MRI showed diffuse infiltrative marrow disorder. Patient was treated with Lenalidomide 25 mg daily on days 1-21 of repeated 28-day cycles and Dexamethaxone 8 mg twice weekly with excellent response. After 6 months of treatment and follow-up, patient had normal bone marrow cytology, normal hemoglobin, and normal reticulocyte count.

Acute kidney injury with dark urine: the case of paroxysmal nocturnal hemoglobinuria

In this case report; we describe a patient with severe attack of paroxysmal nocturnal hemoglobinuria (PNH) following Ciprofloxacin therapy. He presented with recurrent abdominal pain, repeated vomiting and dark urine. Physical examination revealed severe pallor and jaundice. Laboratory investigations showed severe intravascular hemolysis with negative Coomb’s test, progressive acute kidney injury (AKI), sterile blood cultures and negative serology for autoimmune diseases. Subsequently, he developed pancytopenia. Ham test was positive and flow cytometry, later on, confirmed PNH. He was supported with multiple transfusions of packed blood cells and hemodialysis. Ciprofloxacin was discontinued and his PNH was treated with Solumedrol 1 g daily for 3 days followed by Prednisone 60 mg/day for 2 months. Two weeks later; his hemolysis abated and his AKI improved. Up to 5 years later, he still has minor PNH clone yet without disease activity. In conclusion; our patient had acute drug-induced hemolytic crisis associated with minor PNH clone. With drug-vigilance; no further relapses were reported and his PNH clone remained stable for 5 years. The case expands the spectrum of PNH phenotypes and its triggering factors.&#x0D; Keywords: AKI, anemia, autoimmune, flow cytometry, hemolysis, PNH.

P0392AHUS ASSOCIATED WITH IGA NEPHROPATHY

Abstract Background and Aims IgAN is characterized by the presence of intense deposits of C3 accompanying IgA. As documented in several studies this is due to the activation of the complement system by pathological IgA; the mechanism of IgA–mediated complement activation remains poorly understood but is thought to act with different mechanisms such as the stabilization of the C3 convertase, the activation of the lectin pathway through polymeric IgA and eventually inherited partial deficiencies of complement regulatory genes [Maillard N, Wyatt RJ, Julian BA, Kiryluk K, Gharavi A, Fremeaux-Bacchi V, Novak J.J Current Understanding of the Role of Complement in IgA Nephropathy.Am Soc Nephrol 26:, 2015] . Dysregulation of the C3 convertase is a recognized cause of thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS). The association between aHUS and IgAN has been sporadically described . In this study we report a series of 6 patients, observed in our department, with biopsy proven IgAN, who developed aHUS during the follow-up. We report a series of aHUS associated IgA nephropathy. Method This report describes 6 patients with aHUS IgAN who were identified among all patients with biopsy proven IgAN observed at the Department of Nephrology, University of Parma, from March 2010 to March 2015. The diagnosis of aHUS was suspected in the presence of renal biopsy with documented typical signs of TMA (glomerular or arteriolar thrombi, onion skin lesions) associated with non-immune microangiopathic haemolytic anemia, increased reticulocyte count, negative Coomb test, thrombocytopenia (platelets &amp;lt;150000/mm3). Results Data collected on the 6 patients with IgA nephropathy associated with aHUS are described in Figure 1. All the cases of aHUS-IgAN were characterized by worsening of nephrotic proteinuria and reduced serum C3. Pathogenetic variant of CFH, predisposing for aHUS were identified in 2/6 cases; in the remaining patients a predisposing risk aplotype for aHUS was documented. All patients were treatment resistant for IgA nephropathy, had persistent proteinuria and progressed to ESRD. Conclusion It is known that most cases of aHUS are associated with the presence of genetic or acquired alterations of the regulation of the complement AP. However overlapping of other triggering conditions was documented in 70% of aHUS cases [Noris M, Caprioli J, Bresin E, et al. Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype. Clin J Am Soc Nephrol. 2010;5: 1844–1859]. Our case series shows that the presence of genetic factors predisposing to uncontrolled activation of the C3 convertase associated to continuous activation of the same enzyme from pathological IgA, could lead to sC3 consumption, development of aHUS and consequent rapid progression towards ESRD. In conclusion during the natural history of IgAN, appearance of hemolysis, thrombocytopenia, serum C3 reduction and increasing proteinuria would suggest to search for aHUS, allowing to early treatment with plasmapheresis and/or new available complement targeted inhibitors to prevent renal failure.

Haemolytic Anaemia: A Diagnostic Dilemma

It is sometime difficult to find out the cause of haemolysis in haemolytic anaemia due to inconclusive results of investigation. Diagnosis of immune haemolytic anaemia is often difficult when Coomb’s test is negative. Here we present such a case of fourteen years old girl who presented with haemolytic anaemia with negative Coomb’s test. Due to high clinical suspicion we labelled her as a case of Coomb’s negative immune haemolytic anaemia and she responded well to steroid.

Pre-Transplant Use of Tyrosine Kinase Inhibitors Increases Risk of Transplant Associated Thrombotic Microangiopathy - a Single Centre Analysis of Incidence, Risk Factors and Outcomes

Introduction Transplant associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication post hematopoietic stem cell transplant (HSCT). Epidemiology, risk factors, prognosis and treatment of TA-TMA are not very clear. While type of transplant, and use of calcineurin inhibitors (CNIs) are established risk factors for TA-TMA, not much is known of other risk factors that affect TA-TMA and its outcome. We retrospectively analysed data of all patients who underwent allogeneic transplant for hematological malignancies at our centre to understand its incidence, possible risk factors and treatment outcomes. Methods All consecutive patients who underwent allogeneic HSCT for AML, ALL and CML from January 2008 to March 2019 were included. Conditioning regimens used were either myeloablative (CyTBI or BuCY) or reduced intensity (fludarabine with either melphalan, treosulfan or cyclophosphamide with or without 2 Gy TBI). Rabbit ATG was used at a dose of 2.5-5 mg/kg for patients who underwent matched unrelated donor (MUD) transplants. GVHD prophylaxis for matched sibling donor (MSD) and MUD transplants included CNIs with methotrexate or mycophenolate mofetil (MMF). Patients who underwent haploidentical (haplo) HSCT received post transplant cyclophosphamide (PTCy) on d+3 and d+4 and CNI with MMF from day+5 onwards. Definitive TA-TMA was defined using Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) criteria ie schistocytes ≥2/HPF, elevated LDH, renal compromise (increase in creatinine 2 times baseline or 50 % decrease in creatinine clearance from baseline ) or unexplained neurological manifestations and negative coombs test. Probable TMA was defined as per criteria proposed by Cho et al ie schistocytes ≥2/HPF, elevated LDH, negative coombs test, no coagulopathy, drop in haemoglobin and thrombocytopenia (platelet &lt; 50 x 109/L or &gt; 50 percent decline in platelet count). Risk factors explored for development of TA-TMA were age, gender, diagnosis, type of transplant, acute and chronic GVHD, use of tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib or sorafenib pre transplant and conditioning regimen used. Factors evaluated to affect the outcomes of TA- TMA were gender, baseline LDH, least platelet count, presence of acute GVHD, TA-TMA index (LDHx1000/platelet count per cumm), definitive vs probable TMA, and type of transplant. All categorical data was compared using Chi-square /Fisher exact test. OS probabilities were calculated using Kaplan -Meier method and were compared using log-rank test. Multivariate analysis to assess risk factors for TMA was carried out using logistic regression. Results Total 241 patients, 179 (74.2 %) male and 62 (25.7 %) female, with median age of 28.5 (3- 53) years were analysed. Donors were MSD (6/6 matched -174, and 9/10 matched-1), MUD (16) or haplo (50) donors. Diagnoses were 104(43 %) - AML, 85 (35%) - ALL (of which Ph+ patients --23) and 52 (22%) -CML patients. Conditioning regimens given were myeloablative (MAC; n= 64, 27 %) or reduced intensity (RIC; n=177, 73 %). Total 26 (10.7%) patients developed TA-TMA; 22 (85%) were males. Table 1 shows clinical features at diagnosis of TA-TMA. Median day of diagnosis of TA-TMA was d+102 (range 12- 722) post HSCT. Analysis of potential risk factors for TA-TMA is shown in table 2. Use of pre-HSCT TKI (OR 2.7, p=0.028), haplo HSCT (OR 3.16, p=0.018) and presence of acute GVHD within 30 days of diagnosis of TA-TMA (OR 4.17, p=0.003) were identified to be significant factors on multivariate analysis. CNIs were omitted as soon as TA-TMA was diagnosed. Low dose defibrotide (5mg/kg BD) was used in 4 patients. No patient received plasma exchange. Median follow up for whole cohort was 59.5 months. Median OS for whole cohort was 59.9 months (figure 1). The OS (figure 2) at 5 years was 51.1% in the patients who did not develop TA-TMA vs 29.6% in the group with TA-TMA (P=0.026).Ten (39%) patients with TA-TMA are alive at the time of analysis. No significant factors affecting outcomes of TA-TMA were identified. Conclusion Incidence of TA-TMA was 10% in our cohort. Pre-transplant TKI use, acute GVHD, and haplo HSCT are independent risk factor for TA-TMA. This is the first study in our knowledge to show pre-transplant TKI as a risk factor for development of TA-TMA. Higher index of suspicion of TA-TMA is thus warranted for those patients who receive pre transplant TKI. Disclosures No relevant conflicts of interest to declare.

A Case of Liver Abscess Presenting as Acute Hemoglobin Drop in a Patient With History of Gastrointestinal Bleeding (GIB)

Objective: A liver abscess can be caused by multiple organisms including c. perfringens. It is also known to cause a variety of other clinical manifestations, including gas gangrene, cellulitis, fasciitis, and gastroenteritis. Additionally, c. perfringens is a rare but well-documented cause of intravascular hemolysis. This acute drop in hemoglobin can mimic GIB in pt with h/o bleed and can lead to extensive and invasive workup. It should be suspected especially in a patient who initially presented with gastrointestinal manifestations or liver abscess. Methods: Our patient was a 90-year-old male with a recent history of upper GIB who was presented with right upper quadrant pain, fever, and jaundice for 5 days. Laboratory data showed a hemoglobin of 9.9 g/dl, platelet count of 304,000 /mm3, total bilirubin of 8.4 mg/dl, and direct bilirubin of 3.4 mg/dl. On computed tomography (CT) scan of the abdomen, there was a collection of an abscess within the right lobe of the liver which was emergently drained by interventional radiology and 15 ml of purulent fluid drained and sent for culture. Follow-up laboratory results after drainage revealed a hemoglobin of 6.1 g/dl. With concern for post-procedure perihepatic hematoma, a stat CT scan was done. This showed only regression of abscess with no hematoma. An urgent upper GI endoscopy(ss pt had h/o recent GIB) was also negative for any acute bleed. It was found that pt had hemolytic anemia with negative coomb's test. Later pt's blood culture grew c. perfringens and it was thought to be the culprit of acute Hb drop. He was transfused once and was continued on appropriate antibiotics. His Hb stayed stable after antibiotics treatment.Figure: Initial CT Abd/pelvis: There was a gas containing structure with debris present within the right lobe of liver suspicious for an abscess. A necrotic mass (such as a hepatic metastasis) was an additional possibility.Figure: Stat CT Abd/pelvis s/p IR Drainage of Abscess: Indication: Acute Hb Drop There was Small amount of free air and free fluid around the liver which was related to the recent liver abscess drainage. No retroperitoneal or intraperitoneal hematoma was noted.Figure: Initial USG Abd: A Gas containing right lobe of liver lesion with a second fluid containing lesion at the extreme dome of the right lobe of liver suspicious for abscesses.Conclusions: C. perfringens is a normal GI flora which is a rare but well-documented cause of intravascular hemolysis. This acute drop in hemoglobin can mimic GIB especially in a patient with h/o GIB. This case report highlights the importance of early identification of C-perfringens infection which can help us prevent further C-perfringens associated complication and unnecessary workup.

Paroxysmal Nocturnal Hemoglobinuria: A Chronic Rare Acquired Hemolytic Anemia in a Middle-aged Female with Thrombotic Complications and Multi-system Involvement

Facial flushing is usually not associated with hypoglycemia. Diabetics treated with chlorpropamide can have an antabuse-like flushing with ingestion of alcohol, but flushing secondary to hypoglycemia per se has not been reported. The first case demonstrating that facial flushing can occur in insulin-induced hypoglycemia is described. This patient had marked erythematous facial flushing that was repeatable with each instance of hypoglycemia. Endocrine evaluation revealed no evidence of carcinoid or a pheochromocytoma in this patient and the facial flushing was unrelated to alcohol. Without insulin-induced hypoglycemia, this diabetic patient has had no further facial flushing in one year follow-up.

Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized by the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, fever and neurologic abnormalities. It is associated with infections, malignancy, drugs and autoimmune diseases. TTP and systemic lupus erythematosus (SLE) rarely present simultaneously and generally constitute a diagnostic dilemma. We present a case of a 42-year-old patient with overlapping features of SLE and TTP, who was admitted to our hospital with complaints of generalized fatigue, epistaxis and bruises. The workup revealed microangiopathic hemolytic anemia (negative Coomb’s test with schistocytes), and thrombocytopenia. The presence of clinical and immunological criteria made the diagnosis of SLE possible. Recognition of TTP in the setting of SLE is important, because the combination of both conditions carries a worse prognosis than SLE alone. Prompt treatment with plasmapheresis and aggressive immunosuppressive therapy is life saving. J Med Cases. 2017;8(1):5-7 doi: https://doi.org/10.14740/jmc2692w

Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized by the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, fever and neurologic abnormalities. It is associated with infections, malignancy, drugs and autoimmune diseases. TTP and systemic lupus erythematosus (SLE) rarely present simultaneously and generally constitute a diagnostic dilemma. We present a case of a 42-year-old patient with overlapping features of SLE and TTP, who was admitted to our hospital with complaints of generalized fatigue, epistaxis and bruises. The workup revealed microangiopathic hemolytic anemia (negative Coomb’s test with schistocytes), and thrombocytopenia. The presence of clinical and immunological criteria made the diagnosis of SLE possible. Recognition of TTP in the setting of SLE is important, because the combination of both conditions carries a worse prognosis than SLE alone. Prompt treatment with plasmapheresis and aggressive immunosuppressive therapy is life saving. J Med Cases. 2017;8(1):5-7 doi: https://doi.org/10.14740/jmc2692w

Phenazopyridine‐Induced Hemolytic Anemia in Advanced Kidney Disease

Phenazopyridine‐Induced Hemolytic Anemia in Advanced Kidney Disease

New serovars of Leptospira in Iran: Australis and Tarassovi

Background: Brucellosis is a chronic granulomatous infection nd neurobrucellosis is a rare neurological complication of brucelosis. Methods:We evaluate 19 patients with neurobrucellosis in our ospitals during 8 years. Neurobrucellosis was diagnosed in 19 atients out of 235 patients with brucellosis at our institutions.We eviewed their symptoms, signs and paraclinical data. All patients ere followed for two years to find any signs and symptoms of elapse. Results: Two hundred thirty five patients were diagnosed as rucellosis and admitted at two tertiary care hospitals during eight ears period. 19 patients (8%) had neurobrucellosis. Of them 14 74%) were male and 5 (26%) were female. The most common igns and symptomswereheadache (79%), fever (84%), neck rigidity 42%), fatigue (37%), drowsiness (31%), inappropriate speech (21%), ausea and vomiting (15%). Ten (58%) patients had focal neurologcal deficits. The duration of symptoms varied from one week to our months before definite diagnosis. CSF analysis showed noral CSF protein in five (26%) patients. CSF glucose was low in nine 47%) patients. Ten (53%) patients had normal CSF glucose. CSF BC count was between 6 cells/dl and 3600 cells/dl with mean ount 403 cells/dl. CSF cultures and Gram-stains were negative in ll patients. Serumanti-brucella IgG and IgMantibodywas checked or patients who had negative Coomb’s wright tests results by nzyme-linked immunosorbant assay (ELISA) method. Neurobruellosis was diagnosed by detection of anti-brucella antibodies in he CSF by either ELISA or Coomb’swright tests. Hydrocephalus and utamen infarctionwasdetected inMRIof twopatients. Eight (42%) atients received 8-14 weeks antibiotic therapy. One patient who howed right lower extremity weakness and peripheral neuropahy in nerve conduction velocity study received 1.5 year antibiotic herapy. Other patients had received 6 months antibiotic therapy. Conclusion: Clinicians in endemic areas should consider the ikelihood of neurobrucellosis in patients with unexplained neuological and psychiatric symptoms.

Acute hemolytic anemia with negative coomb tests and fulminant hepatic failure: the first manifestation of hepatolenticular degeneration in childhood

目的 探讨肝豆状核变性患儿发生暴发性肝功能衰竭的临床特征、发生原因及诊断要点.方法 对23年间收治的9例以Coomb试验阴性的急性溶血性贫血、暴发性肝功能衰竭为首发表现的肝豆状核变性患儿的临床资料和实验室检查结果进行回顾性分析.结果 9例发生暴发性肝功能衰竭者的肝功能ALT平均为12 U/L,血清白蛋白极度降低,均有一种或多种并发症.患儿病情凶险,大部分预后很差,常规治疗无效,发病11～34 d均死亡.结论 对于急性肝功能衰竭患儿应考虑肝豆状核变性的可能,特别是合并急性溶血.Coomb试验阴性的急性溶血性贫血、暴发性肝功能衰竭可能是儿童肝豆状核变性的首发表现.肝移植是目前最佳的治疗手段。

Evaluation of the Role of Flow Cytometry as a Diagnostic Tool for Hereditary Spherocytosis

Flow cytometric analysis of eosin-5′-maleimide-labeled red blood cells has been proposed as a method of identifying hereditary spherocytosis (HS). The flow cytometric test measures the fluorescence intensity of intact red cells labelled with the dye eosin-5-maleimide (EMA), which reacts covalently with Lys-430 on the first extra cellular loop of band 3 protein. Patients with HS have reduced fluorescence compared to other patient groups and normal controls. The aim of the present study was to assess the utility of flow cytometry in the diagnosis of hereditary spherocytosis. Fresh peripheral blood from 40 normal controls was collected in Lithium Heparin, stained with the dye EMA and analysed by flow cytometry. The normal range was established as 55–74 channel numbers. On 7 known cases of Hereditary Spherocytosis the MFI range was 35.6–44.6 channel numbers, and therefore samples falling into this range were considered to be positive for a diagnosis of HS by EMA. Equivocal results were defined when the MFI was in the range of 45–54 channel numbers. A total of 98 samples were sent for investigation or exclusion of HS. Clinical problems were grouped into the following categories: peripheral blood spherocytosis with negative Coomb's test and no family history of HS, positive family history of HS, Neonatal hyperbilirubinaemia, haemolytic anaemia of unknown origin.IndicationsCoomb's −ve, Spherocytosis, no FH (n=50) (51%)Positive family history (FH) (n=18) (17%)Neonatal hyperbilirubinemia (NNH) (n=8) (8%)Haemolytic anaemia (HA) (n=16) (17%)Results of EMAPosNegEquiPosNegEquiPosNegEquiPosNegEquiNumber1917139722420142Percentage383426503911255025087.512.5Within this cohort the group with FH of HS had the highest positive and least equivocal results. The group with suspected HS (peripheral blood spherocytosis with negative coomb's test) resulted in positive in 38% and equivocal in 26% cases. The group with NNH had positive results in 25% of cases and the group with HA had no positive results. Equivocal results occurred in 20% of cases suggesting further investigations are required to confirm or exclude HS. The EMA dye method by flow cytometry is a useful test for diagnosing red cell membrane abnormalities due to band 3 defects, but the assay produces a substantial number of equivocal results, and has poor utility in the investigation of haemolytic anaemia of unknown origin.

Immune anemias in patients with chronic lymphocytic leukemia treated with chemoimmunotherapy regimen of fludarabine, cyclophosphamide and rituximab as initial therapy

6604 Background: Auto-immune hemolytic anemia (AIHA) has been reported with the use of fludarabine in the treatment of chronic lymphocytic leukemia (CLL). Since rituximab has been used to treat AIHA, it was anicipated that rituximab might reduce the incidence of AIHA when combined with fludarabine to treat CLL. We analyzed the incidence of immune anemias in 300 patients (pts) with CLL treated with fludarabine, cyclophosphamide and rituximab (FCR) as initial therapy. Methods: Diagnosis of AIHA was based on clinical evidence of hemolysis (elevated indirect bilirubin, reticulocyte count, lactate dehydrogenase) combined with positive Coomb’s test and/or low haptoglobin level. Pure red cell aplasia (PRCA) was diagnosed based on absence of erythroid precursors in bone marrow aspirate and/or biopsy. Results: 29 of 300 (9.5%) pts with CLL treated on a single-arm study of FCR showed evidence of immune anemias (age range18 to 86 years,median 62 years; 24 male and 5 female). 24 pts had AIHA, 3 had PRCA and 2 pts had positive Coomb’s test only (hemoglobin&gt;10 gm/dL). Higher beta2-microglobin and bone marrow lymphocyte percentage were associated with higher risk of developing AIHA in multivariate analysis. Immune anemia was present in 9 pts prior to FCR treatment, developed in 15 on FCR and in 5 after completion of FCR (1 month to 4 years later). AIHA was detected after a median of 4 cycles (range 1 to 6) in pts who developed it while on therapy. Coomb’s test was positive in 14 pts and negative in 15. Haptoglobin levels were low in 16, normal in 10 and not measured in 3 pts. Coomb’s test was negative in 14 of 16 pts with AIHA and low haptoglobin levels. 9 pts were treated with oral prednisone. Others treatments included cyclosporine, intravenous immunoglobulin, rituximab and splenectomy. 3 of 9 pts who had AIHA prior to starting FCR had sustained correction of anemia with FCR treatment alone. 2 pts had inadequate response to treatment of immune anemia; 1 of them developed myelodysplastic syndrome. Conclusions: The incidence of immune anemias in pts treated with FCR is comparable to other series. Low haptoglobin levels in appropriate clinical context can help to establish the diagnosis of AIHA in the face of negative Coomb’s test. [Table: see text]