Fragmented Erythrocytes Research Articles

Congenital thrombotic thrombocytopenic purpura: Upshaw–Schulman syndrome: a cause of neonatal death and review of literature

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder in children characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The classic Moschcowitz Pentads of TTP include hemolytic anemia, with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decrease renal function and fever. We report a newborn who was diagnosed with congenital TTP. The newborn was admitted at age of 40 h, in our hospital, in view of respiratory distress with impending respiratory failure and red colored urine. On examination, the newborn was febrile, tachypneic, had deep icterus, pallor and no hepatosplenomegaly. Family history was significant with one unexplained neonatal death at age of 24 with symptoms of red colored urine. Examination of peripheral smear was diagnostic with the presence of fragmented RBCS, giant but fewer platelets consistent with a diagnosis of MAHA. The diagnosis of TTP was confirmed with low ADAMTS activity and gene analysis showed c 2203 G > T-p.Glu735X (domain TSP1-2) mutation in exon 18 of ADAMTS 13 gene. The newborn had rapid deterioration, with respiratory distress and refractory shock leading to death. Post-mortem bone marrow done showed marrow hyperplasia.

Post-partum management in a patient affected by thrombotic thrombocytopenic purpura: case report and review of literature

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially lethal syndrome characterized by severe thrombocytopenia, microangiopathichaemolytic anaemia, and aspecific neurologic symptoms. This syndrome is the result of an abnormal intravascularplatelet aggregation which induces transient ischemia in various organs, especially in the central nervous system. Platelet aggregationcauses also fragmentation of erythrocytes, thus leading to the characteristic anaemia. The exact cause of TTP is unknown, but a largebody of evidence suggest that this syndrome might be due to acquired (immunological) or congenital ADAMTS13 deficiency. The dysregulationof ADAMTS13 activity could promote massive release of high molecular weight multimers of von Willebrand factor (VWF)from endothelium and, as a consequence, could cause intravascular platelet aggregation. Pregnancy is commonly associated with numerousmetabolic, immunological, and haemostatic changes which could increase thrombotic risk: during pregnancy, in fact, it is generallyobserved an increase of procoagulant activity and a decrease of fibrinolytic activity; moreover, at the end of pregnancy, it is notrare to find thrombocytopenia. All these reasons lead us to consider pregnancy itself as a triggering event for the onset of TTP. The authorsdescribe a case of TTP occurred during puerperium, in a patient who underwent caesarean section.

Von Willebrand factor-cleaving protease activity in thrombotic microangiopathy: first report from iran.

Background:Thrombotic microangiopathy (TMA) is a rare but devastating small vessels disorder that is characterized by intravascular platelet thrombi, thrombocytopenia, and various degrees of organ ischemia and anemia, which is due to erythrocyte fragmentation in microcirculation.Objectives:The Aim of this study was to determine the von Willebrand factor-cleaving protease (ADAMTS13) activity during the acute phase of TMA. We also investigated inhibiting antibodies against ADAMTS13 in these patients.Patients and Methods:In a collaborative work with Mario-Negro institute of pharmacological research in Bergamo-Italy, we registered the clinical and laboratory data, collected the serum samples, and transferred the samples to the laboratories. Serum samples were taken before the start of plasmapheresis or at least 15 days after the final exchange.Results:We recruited 40 patients (14 males and 26 females) with the mean age of 46.12 ± 17.26 years. The mean activity of ADAMTS13 was 34.58% ± 21.83%. Two patients had inhibitory antibodies against ADAMTS13 with profound deficiency of ADAMTS13 activity (< 6%). Infectious diseases were the most common underlying condition, followed by systemic lupus erythematous.Conclusions:Majority of patients had an underlying condition and had various ADAMTS13 activity. The presence of inhibiting antibodies and accompanied complete deficiency of ADAMTS13 activity is an indicator of severity.

Acute thrombotic thrombocytopenic purpura after pneumococcal vaccination

We report the case of a 68-year-old woman with acute thrombotic thrombocytopenic purpura (TTP) that developed after pneumococcal vaccination. She was found in a confusional state with high fever 15 days after vaccination. Laboratory data showed hemolytic anemia and thrombocytopenia, and blood smear showed fragmented erythrocytes. TTP was diagnosed based on the clinical presentation, and was subsequently confirmed by the absence of ADAMTS13 activity and the presence of inhibitor against ADAMTS13 in serum. She was successfully treated using plasma exchange and corticosteroids, and no recurrence has been identified. This appears to represent the first report of TTP following pneumococcal vaccination.

A novel algorithm based on visual saliency attention for localization and segmentation in rapidly-stained leukocyte images

In this paper, we propose a fast hierarchical framework of leukocyte localization and segmentation in rapidly-stained leukocyte images (RSLI) with complex backgrounds and varying illumination. The proposed framework contains two main steps. First, a nucleus saliency model based on average absolute difference is built, which locates each leukocyte precisely while effectively removes dyeing impurities and erythrocyte fragments. Secondly, two different schemes are presented for segmenting the nuclei and cytoplasm respectively. As for nuclei segmentation, to solve the overlap problem between leukocytes, we extract the nucleus lobes first and further group them. The lobes extraction is realized by the histogram-based contrast map and watershed segmentation, taking into account the saliency and similarity of nucleus color. Meanwhile, as for cytoplasm segmentation, to extract the blurry contour of the cytoplasm under instable illumination, we propose a cytoplasm enhancement based on tri-modal histogram specification, which specifically improves the contrast of cytoplasm while maintaining others. Then, the contour of cytoplasm is quickly obtained by extraction based on parameter-controlled adaptive attention window. Furthermore, the contour is corrected by concave points matching in order to solve the overlap between leukocytes and impurities. The experiments show the effectiveness of the proposed nucleus saliency model, which achieves average localization accuracy with F1-measure greater than 95%. In addition, the comparison of single leukocyte segmentation accuracy and running time has demonstrated that the proposed segmentation scheme outperforms the former approaches in RSLI.

Mitomycin‐C‐Induced Thrombotic Thrombocytopenic Purpura

ABSTRACTBackgroundAlthough mitomycin‐C has been supplanted by other chemotherapeutic drugs, it is still the drug of choice for anus squamous cell carcinoma. Mitomycin‐C has rarely been reported to cause thrombotic thrombocytopenic purpura with or without haemolytic uraemic syndrome (TTP/HUS).AimTo report a case of probable mitomycin‐C‐induced TTP with associated acute renal failure and severe hypertension.Clinical detailsA 60‐year‐old Caucasian female was diagnosed with anus squamous cell carcinoma and started on mitomycin‐C, fluorouracil and targeted radiation therapy. After completing this regimen, the patient developed acute kidney injury, thrombocytopenia and hypertension. Kidney biopsy revealed diffuse endocapillary cell proliferation and one glomerulus contained multiple hyaline thrombi with basement membrane double contours. Focal subendothelial and intramural fragmented erythrocytes were present; all of which suggested TTP. The patient was started on high‐dose corticosteroids followed by plasmapheresis.OutcomesThe patient's blood pressure, and platelets returned to baseline levels, while her renal function improved partially.ConclusionTTP is a rare but serious adverse effect associated with mitomycin‐C. Discontinuing mitomycin‐C does not resolve TTP; a variety of treatments are required, such as corticosteroids, plasmapheresis, chemotherapeutic drugs and rituximab.

Plunder of Human Blood Leukocytes Containing Ingested Material, by Other Leukocytes: Where Is the Fusagen That Allows Preservation of Membrane Integrity and Motile Function?

In studying phagocytosis of zymosan particles by human blood monocytes in phase-contrast videomicroscopy, we found that monocytes loaded with zymosan particles became chemotactic for polymorphonuclear leukocytes (PMN) which closed on them and purloined their particle content. This despoliation usually occurred in monocytes that had begun to swell—prefiguring their death. The violent seizure of their contents by the aggressing PMN often tore the monocytes apart. However, some apparently healthy monocyte survived the removal of zymosan content by PMN or, more commonly, its removal by another monocyte. PMN—a much hardier cell in slide preparations—that were similarly loaded with zymosan particles, also attracted PMN. The latter could remove zymosan from the target cell without killing it. Thus, leukocytes were sacrificing significant portions of themselves without losing residual membrane integrity and motile function. Their behavior with respect to other particles (e.g., bacteria) will be of interest. We suggest that the membrane fusagen resides in the inner membrane leaflets when they are brought together in an extreme hourglass configuration. This event may be similar to the fragmentation of erythrocytes into intact pieces, the formation of cytokineplasts, the rear extrusion of content by migrating cells on surfaces, and the phagocytic process itself.

Pressure-induced hemolysis of in vivo aged human erythrocytes is enhanced by inhibition of water transport via aquaporin-1

Human erythrocytes are fractionated into young, intermediate, and old cells according to their densities. Pressure-induced hemolysis reflects sensitively membrane perturbations. Therefore, the hemolysis of erythrocytes at 200 MPa was examined using fractionated cells. Pressure-induced hemolysis of old (or in vivo aged) erythrocytes was enhanced, compared with those of young and intermediate cells which showed the same hemolytic values. Flow cytometric analysis showed less fragmentation of old erythrocytes under pressure. Moreover, the water transport through the membrane was suppressed in old erythrocytes than intermediate ones. The low permeability of water in old erythrocytes was confirmed by osmotic hemolysis using a hypotonic buffer. These results suggest that water transport via aquaporin-1 (AQP1) is inhibited in old erythrocytes. As the number of AQP1 molecules remained constant in old erythrocytes, the function of AQP1 may be reduced.

Babesiosis-Induced Acute Kidney Injury With Prominent Urinary Macrophages

Babesia is an obligate intracellular erythrocyte parasite that can infect humans. Severe symptomatic disease from massive hemolysis and multiorgan system failure, including acute kidney injury (AKI), occurs. Acute tubular injury from a combination of volume depletion and heme pigment toxicity from profound hemolysis is the most common cause of AKI. We present a case of severe babesiosis complicated by dialysis-requiring AKI with the unique finding of large macrophages containing engulfed erythrocyte fragments in urine sediment. This urinary finding raised the possibility of another diagnosis distinct from acute tubular injury. Subsequent kidney biopsy demonstrated infection-associated acute interstitial nephritis.

Uremia and Thrombotic Microangiopathy: Conditions That May Havethe Same Manifestation

In this article, we present the case of a man with uremia. Laboratory testing revealed thrombocytopenia, erythrocyte fragmentation, elevated lactate dehydrogenase, and malignant hypertension, manifestations that are similar to thrombotic microangiopathy (TMA). Thromboasthenia, manifested as a decrease in the platelet aggregation rate, was also noted. Regular hemodialysis (3 times per week) improved the patient’s thrombocytopenia and thromboasthenia. This case supports the conclusion that uremic toxin, which can be removed by hemodialysis, inhibits the quantity and quality of platelets. We believe that the platelet aggregation rate can be a useful tool in distinguishing uremia from TMA.

The role of Kupffer cells in the morphogenesis of nonalcoholic steatohepatitis – ultrastructural findings. The first report in pediatric patients

Objective. Until now studies concerning the involvement of hepatic nonparenchymal cells (NPCs), particularly Kupffer cells/macrophages (KCs/MPs), in the pathogenesis of human nonalcoholic steatohepatitis (NASH) have been limited to adult patients; there are no similar reports referring to children. This study aimed to explore, based on ultrastructural analysis, the role of KCs/MPs in the morphogenesis of nonalcoholic steatohepatitis (NASH) in children. Material and methods. Ultrastructural investigations of KCs were conducted on liver bioptates obtained from 10 children, aged 2–14 years, with clinicopathologically diagnosed NASH. Bioptatic material was fixed in solution of paraformaldehyde and glutaraldehyde in cacodylate buffer, routinely processed for transmission-electron microscopic analysis and examined using an Opton EM microscope. Results. The current ultrastructural study revealed within the hepatic sinusoids the presence of numerous enlarged KCs with increased phagocytic activity, which reduced or blocked vascular lumen. Interestingly, the activated KCs not only contained primary and secondary lysosomes, altered mitochondria, and well-developed Golgi apparatus, but also absorbed fragments of erythrocytes. Such macrophages were frequently seen very close to the transformed hepatic stellate cells (T-HSCs) and progenitor/oval cells. Intensive fibrosis was observed in the vicinity of activated KCs/MPs. Bundles of collagen fibers were seen directly adhering to these cells and to other NPCs, especially T-HSCs. Conclusions. KCs are involved in the morphogenesis and development of pediatric NASH. Engulfment of erythrocytes by hepatic macrophages may lead to the accumulation of iron derived from hemoglobin in liver and play a role in triggering the generation of oxidative stress in the disease course.

Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies

AbstractThrombotic microangiopathies (TMAs) are a group of life-threatening disorders characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors for TMAs, but an additional, unknown trigger is needed to bring about acute disease. Recent studies suggest that DNA and histones are released during inflammation or infection and stimulate coagulation, thrombosis, thrombocytopenia, and organ damage in mice. We show that extracellular DNA and histones as well as markers of neutrophils are present in acute TMAs. Analysis of plasma from TMA patients of different clinical categories revealed elevated levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol. During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often associated with severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were inversely correlated with platelet counts, and their levels indicated amelioration or exacerbation of the disease. ADAMTS13 deficiency together with increased levels of plasma DNA and MPO were characteristic for acute thrombotic thrombocytopenic purpura. A minor infection often precedes acute TMA and extracellular DNA and histones released during the inflammatory response could provide the second hit, which precipitates acute TMA in patients with pre-existing risk factors.

Management of Chenopodium polyspermum toxicity with plasma exchange and hemodialysis

A 45-year-old male patient was admitted to our emergency department complaining of fatigue, headache, mild confusion, nausea, and vomiting. He had had Type 2 diabetes mellitus for 10 years that was managed with insulin injections. Two days before the onset of symptoms, he had consumed the natural herb Chenopodium polyspermum to regulate his blood glucose levels. Upon examination, he was found to be experiencing tenderness in the upper left abdominal area, icteric sclera, and pallor conjunctivas. Laboratory tests revealed that he was anemic and had increased levels of indirect bilirubin, lactic dehydrogenase, and creatinine in blood. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The best supportive care was provided, and therapeutic plasma exchange (TPE) treatments were administered. TPE was performed five times and hemolytic findings improved. The patient then developed chronic renal failure and was transferred to the dialysis program and discharged. In this article, we present a case with hemolytic and renal toxicity induced by the ingestion of Chenopodium polyspermum that was managed with TPE and hemodialysis.

Life-threatening hemorrhagic shock after laparoscopic surgery: a case of postoperative thrombotic thrombocytopenic purpura

We report the successful management of a female patient who developed postoperative thrombotic thrombocytopenic purpura (TTP) after an uneventful laparoscopic oophorocystectomy. The patient underwent uneventful laparoscopic surgery for ovarian cystoma. One hour after completion of surgery, the patient suddenly went into shock, with her blood pressure dropping to 60/40 mmHg. Hemorrhage into the abdominal cavity with an estimated blood loss of 2,000 ml was confirmed by exploratory laparotomy. Initially, anemia and thrombocytopenia were attributed to blood consumption or disseminated intravascular coagulation (DIC). However, blood tests revealed evidence of hemolytic anemia, with fragmented erythrocytes observed on peripheral blood smear examination. Serum levels of lactate dehydrogenase, blood urea nitrogen, and creatinine were elevated. Based on the findings, postoperative TTP was suspected. High-dose steroids and plasma infusions were administered but proved ineffective. Plasma exchange was performed three times, resulting in resolution of postoperative TTP. TTP is an idiopathic disorder, known to be triggered by surgical trauma. Postoperative TTP is difficult to distinguish clinically from DIC because of its close similarity with the latter and subtle differences from other postoperative hematological complications. It is important to bear in mind the possibility of postoperative TTP in patients with unexplained hemorrhagic shock after uneventful surgery.

Long-term survival of a patient with bone marrow gelatinous degeneration of idiopathic origin

TO THE EDITOR: Gelatinous bone marrow transformation (GMT) is a rare bone marrow (BM) disorder of unknown pathogenesis. It is characterized by fat cell atrophy, focal loss of hematopoietic cells, and deposition of extracellular gelatinous substances (mucopolysaccharides rich in hyaluronic acid) [1]. The pathogenesis of GMT involves the deposition of hyaluronic acid, which hampers hematopoiesis by altering the BM microenvironment and stroma and disruption of the interactions between BM cells and cell signaling molecules [1]. GMT has been reported in association with chronic debilitating diseases, such as anorexia nervosa, malnutrition, and human immunodeficiency virus (HIV) infection, and after cytotoxic treatments [2]; in addition, GMT has been described in patients with myelodysplastic syndrome [3], acute myeloblastic leukemia [3], and idiopathic myelofibrosis [4]. However, idiopathic GMT has also been reported [5]. Herein, we report a case of idiopathic GMT in a patient who had an unusual clinical course and long-term survival. The patient was a 64-year-old Caribbean woman who had been living in Rome for more than 30 years. She was referred to our clinic in December 2005 because of anemia. Her past medical history was unremarkable. She did not use alcohol, drugs, or tobacco, and her nutritional status was excellent. Physical examination was unremarkable with the exception of pallor; the patient did not have either spleen or liver enlargement. A complete blood count at admission showed normochromic-normocytic anemia with reticulocytopenia and normal white blood cell and platelet counts. Total and unconjugated bilirubin and serum haptoglobin levels were normal. Direct and indirect indirect Coombs tests were negative. Serological tests for HIV, cytomegalovirus, Epstein-Barr virus, parvovirus B19, and hepatitis B and C viruses were negative. In addition, serum levels of tri-iodothyronine were normal. Moreover, no clinical or laboratory features of autoimmune disease were detected. Examination of peripheral blood smears revealed normal RBC; erythrocyte fragments were not detectable. Radiological examinations, which included a whole-body computed tomography scan, revealed no abnormalities. Occult blood loss was ruled out by fecal and urine analyses. A BM aspirate performed at admission resulted in a dry tap. Therefore, a BM trephine biopsy was taken. Histological examination of the BM sample revealed GMT (Fig. 1). The patient did not respond to any potentially disease-modifying treatment, including erythropoietin, prednisone, and cyclosporine. Therefore, she was managed with supportive measures, primarily transfusions. The clinical course was uncomplicated and her hematological status has remained stable. To date, 80 months after the diagnosis, she is managed only with supportive measures, consisting of 2 units of packed RBC every 3 weeks, along with iron chelation therapy. In addition, her BM features, which have been evaluated annually by BM trephine biopsies, have remained stable. In conclusion, we have described a case of an apparently healthy woman who presented with GMT approximately 7 years ago, in whom anemia was the only clinical manifestation of hematopoietic impairment. To the best of our knowledge, no such case of GMT has been reported previously as an idiopathic primary condition. Fig. 1 Serous atrophy in a diffuse and severe hypocellular background (A). Reduced fat cells, a diffuse extracellular gelatinous amorphous material, small typical lymphocytes, and mature plasma cells were also observed (B). Small islets of hematopoietic cells ...

Letter to the editor Cyclophosphamide-rescued plasmapheresis-unresponsive secondary thrombotic thrombocytopenic purpura caused by Sjögren’s syndrome

Letter to the editor Cyclophosphamide-rescued plasmapheresis-unresponsive secondary thrombotic thrombocytopenic purpura caused by Sjögren’s syndrome

Assessment of the Effect of Aluminium, Lead and Cadmium on Human Erythrocyte Glutathione S‐Transferase Activity In‐vitro

The effects of aluminium, lead and cadmium on the activity of human erythrocyte glutathione S-transferase (GST) have been investigated in-vitro. Erythrocytes from healthy volunteers were incubated with aluminium, lead and cadmium at various amounts (nM-mM). After erythrocyte fragments were removed by centrifugation, GST activity was measured. Aluminium exhibited a maximum inhibition of 38·13% at 45 mM. Lead showed a maximum inhibition of 85·02% at 50 mM, whereas with cadmium a maximum inhibition of 72·68% was detected at 80 mM. Our results show that very high concentrations of these metals can inhibit the activity of human erythrocyte GST. However, aluminium, lead and cadmium at blood levels which are toxic do not inhibit erythrocyte GST activity in-vitro.

Pulmonary Hypertension Is Uncommon In Well-Transfused Thalassemia Major Patients

AbstractAbstract 4273 Introduction:Pulmonary hypertension is a common and serious cardiovascular complication in patients with thalassemia intermedia and sickle cell disease. Circulating platelet and erythrocyte fragments, as well as cell-free hemoglobin from intravascular hemolysis, may contribute to nitric oxide depletion, intimal proliferation, and pulmonary vascular remodeling. Splenectomy has been also been associated with pulmonary hypertension in some studies. Ineffective erythropoiesis, via release of PLGF and elevation of other proinflammitory cytokines, has also been associated with pulmonary hypertension. However, the risk for pulmonary hypertension in thalassemia major patients remains controversial, with prevalence estimates ranging from 10%-60%. We report echocardiography results from 80 thalassemia major patients enrolled in the Early Detection of Iron Cardiomyopathy Trial (EDICT) at Children's Hospital Los Angeles. Methods:Patients were enrolled from August 2004 until May 2009 in a combined cross-sectional and observational trial probing for early predictors of cardiac dysfunction. Patient visits were scheduled within one week of transfusion. All patients underwent echocardiography and cardiac MRI analysis within 4 months of each other; most were performed during the same clinical visit (median time between scans one day). Comprehensive assessments of pulmonary artery pressure (tricuspid and pulmonary regurgitation velocities), systolic function, and diastolic function were performed using two dimensional imaging, M-mode, and routine and tissue Doppler. All images were collected by experienced echocardiography technicians and analyzed by the principal investigator. Three to five beat averages were used to improve measurement stability. Tricuspid regurgitation (TR) jet was only reported if a full envelope was recognized; at our institution, the upper limit of normal for TR jet is 2.7 m/s. Results:Patient demographics are summarized in Table 1. Patients were gender-balanced and well distributed between 11 and 47 years of age. Patients who had been splenectomized (N=34) tended to be older. Iron overload was severe, with a mean liver iron concentration of 12.4 ± 14.2 mg/g dry weight. Roughly half of the patients had detectable cardiac iron and 9% had overt left ventricular dysfunction (LVEF < 56%). TR jet was detectable in 62/80 patients. Only one patient exhibited pulmonary artery hypertension (TR jet 2.9 m/s), however this patient also had severe cardiac iron overload and overt left ventricular systolic and diastolic dysfunction (LVEF 42.7%, E/E' 10). Two patients had TR jets of 2.6 ms and three had TR jets of 2.5 m/s. Pulmonary insufficiency jets were normal in all patients.TR velocity did not correlate with age, cardiac index, cardiac iron or liver iron, but demonstrated a weak (r=0.29, p=0.02) association with left ventricular diastolic dysfunction (E/E′). Discussion:The EDICT patient cohort suggests a low risk for pulmonary hypertension in well-transfused thalassemia major patients. The single elevated TR jet was explained by iron cardiomyopathy and normalized (2.2 m/s) after two years of aggressive chelation therapy. TR velocities at the upper limits of normal (2.5-2.7 m/s) were observed in five patients; these have been associated with poor outcomes in some sickle cell disease cohorts, but not in thalassemia major. Long-term surveillance remains critical as pulmonary hypertension risk may increase with age. Disclosures:Harmatz:Novartis: Research Funding. Coates:Novartis: Research Funding, Speakers Bureau. Wood:Novartis: Research Funding; Ferrokin Biosciences: Consultancy.

Hemolytic uremic syndrome associated with novel influenza A H1N1 infection

Sirs, During 2009, a pandemic influenza A H1N1 virus emerged end spread all over the world [1]. Renal involvement in influenza A virus infection is rare, but one case of hemolytic uremic syndrome (HUS) during season influenza has been reported [2]. We present a patient with novel A H1N1 virus complicated with HUS. A previously healthy 11-year-old boy was transferred to our Children’s Clinic with a history of fever, coughing, fatigue, jaundice, and oliguria. He had no diarrhea. On admission his temperature was over 38.5°C, and his blood pressure was 130/80 mmHg. He had no edema. Laboratory investigations revealed a sign of hemolysis (with declining hemoglobin to 6.5 g/l, and reticulocytosis) with thrombocytopenia (38,000 mm) and renal failure (serum creatinine 280 μmol/l, blood urea nitrogen 22 mmol/l). Blood smear showed fragmented and damaged erythrocytes. Serum chemistry showed a high level of total bilirubin (48 μmol/ l) and a very high level of lactate dehydrogenase (LDH 4,800 μ/l, normal range 250–480 μ/l). Alanine and aspartate transferases were slightly elevated. Urine analyses revealed 3+ proteinuria, 3+ hemoglobinuria, and erythrocyte casts. Prothrombin time and activated partial thromboplastin time were normal, D-dimer was elevated, and direct and indirect Coombs tests were negative. C3 and C4 were normal. A chest X-ray showed viral, interstitial pneumonia. Two other family members also started coughing and developed fever and fatigue. Based on the above findings the patient was diagnosed with HUS. On the day of admission he was treated with ceftriaxone 100 mg/kg per day and infusion of low doses of dopamine and furosemide. On his second day in hospital we decided to start plasma therapy, which may be recommended in nondiarrheal/nonpneumococcal HUS. However, a few hours after the first doses of fresh-frozen plasma he showed aggravated hemolytic anemia (hemoglobin level decreased to 5 g/l, LDH severely increased). We stopped plasma infusion, and continued with fluid and diuretics. In the meantime we received his respiratory spacemen test, which was positive for novel influenza A H1N1 by real-time reverse transcriptase PCR. Oseltamivir (75 mg every 12 h) was started, and continued for 6 days. Symptoms subsided in the next few days. He gradually recovered, lost the fever, his urine output increased with improving renal function, and his blood count too. He was discharged after 15 days with serum creatinine 77 μmol/l, normal levels of LDH, and hemoglobin 10 g/l. Usually, influenza A H1N1 turns out to be a benign disease. The association of pneumococcal infection with the current and previous influenza pandemics is well known. Pneumococcal HUS is an uncommon condition, with reports of this complication in patients with invasive infections, but also in one patient during influenza A and pneumococcal coinfection [3, 4]. We did not confirm bacterial super infection in throat swab, sputum and blood culture in our patient. It is E. Golubovic (*) : P. Miljkovic Department of Pediatric Nephrology, Children’s Clinic, University of Nis, Zorana Djindjica 48, 18000 Nis, Serbia e-mail: ema.golubovic@gmail.com

Red cell distribution width in chronic heart failure: a new independent marker for prognosis?

Red cell distribution width in chronic heart failure: a new independent marker for prognosis?