Evidence Of Intravascular Hemolysis Research Articles

Unclogging the effects of the Angiojet\xae thrombectomy system on kidney function: a case report

BackgroundAngioJet® is an increasingly used method of percutaneous mechanical thrombectomy for the treatment of patients with arterial and venous thromboses. AngioJet® has been shown to cause intravascular haemoylsis universally. We report the case of a 29 year old patient who underwent AngioJet® thrombectomy and post-procedure developed a stage 3 Acute kidney injury (AKI.) requiring renal replacement therapy (RRT), secondary to intravascular haemolysis. We aim to explore the mechanism and potential risk factors associated with developing AKI in these patients and suggest steps to optimise patient management.Case presentationA 29 year old Caucasian male who developed a stage 3 AKI, requiring RRT, following AngioJet® thrombectomy for an occluded femoral vein stent. Urine and laboratory investigations showed evidence of intravascular haemolysis, which was the likely cause of AKI. Following a brief period of RRT he completely recovered renal function.ConclusionsAKI is an increasingly recognised complication following AngioJet® thrombectomy, but remains underappreciated in clinical practice. AKI results from intravascular haemolysis caused by the device. Up to 13% of patients require RRT, but overall short-term prognosis is good. Pre-procedural risk factors for the development of AKI include recent major surgery. Sodium bicarbonate should be administered to those who develop renal impairment. Renal biopsy is high risk and does not add to management. Increased clinician awareness and vigilance for AKI post-procedure can allow for early recognition and referral to nephrology services for ongoing management.

Asian wasp envenomation and acute renal failure: a report of two cases

Acute renal failure is an unusual complication of wasp stings. We report two cases of renal failure after multiple wasp stings (Vespa affinis). Both patients had evidence of intravascular haemolysis, hepatic dysfunction, oligo-anuria and azotaemia and required dialysis. The first patient had severe hemolysis, rhabdomyolysis, pigment and venom nephropathy and died on the 8th day in hospital. The second patient, who recovered completely in 3 weeks time with steroid and antihistaminic therapy, had interstitial nephritis. Although acute renal failure after wasp stings is typically caused by acute tubular necrosis (ATN) in the setting of haemolysis or rhabdomyolysis, in some patients, acute renal failure may result from a direct nephrotoxic effect or acute interstitial nephritis from a hypersensitivity reaction.

Naphthalene Mothballs Poisoning Leading to Intravascular Hemolysis: A Case Report.

Naphthalene is widely used in households as an insect repellent, but its poisoning is rare, especially in adults. Naphthalene is a strong oxidant with a pungent smell. We report a case of a 16-year-old female who ingested three naphthalene mothballs 3days prior to admission and presented with history of recurrent vomiting, severe pallor, jaundice, and hemoglobinuria. Investigation found severe hemolytic anemia, indirect hyperbilirubinemia, acute kidney injury, and evidence of intravascular hemolysis. Her urine output was normal throughout the course of illness. She was managed conservatively with i.v. fluid, oral ascorbic acid, and blood transfusion. With treatment our patient improved completely and was discharged in hemodynamically stable condition. She is doing fine after further follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physician should keep the possibility of poisoning by an oxidizing agent, such as naphthalene, when a patient presents to the emergency department with rapid onset pallor, jaundice, and hemoglobinuria.

Safety of Pressurized Intraosseous Blood Infusion Strategies in a Swine Model of Hemorrhagic Shock

BackgroundCurrent guidelines support intraosseous access for trauma resuscitation when intravenous access is not readily available. However, safety of intraosseous blood transfusions with varying degrees of infusion pressure has not been previously characterized. Materials and methodsAdult female Yorkshire swine (Sus scrofa; n = 36; mean (M): 80 kg, 95% CI: 78-82 kg) were cannulated and then bled approximately 30% total blood volume. Swine were randomly assigned to proximal humerus intraosseous blood infusion with either Rapid Infuser, or Pressure Bag, or Push-Pull methods (n = 12 each). Flow rates, infusion pressures, vitals, biochemical variables, and pulmonary and renal tissue pathology were contrasted between groups. ResultsFlow rates were greater for the Push-Pull strategy than Pressure Bag (96.5 mL/min versus 72.6 mL/min, P = 0.02) or Rapid Infuser (96.5 mL/min versus 60 mL/min, P = 0.002) strategies. The pressures generated during the Push-Pull transfusion (3058 mmHg) were greater than the other strategies (≤360 mmHg). After the observation period, plasma-free hemoglobin levels were higher in the Push-Pull strategy than in the Rapid Infuser (40 mg/dL versus 12 mg/dL, P = 0.02) or Pressure Bag (40 mg/dL versus 12 mg/dL, P = 0.01). Groups did not significantly differ in vitals, biochemical variables, or tissue pathology. ConclusionsPush-Pull conferred the highest flow rates, but with higher infusion pressures and evidence of intravascular hemolysis. Rapid Infuser and Pressure Bag infusions had no increase from baseline in plasma-free hemoglobin. Pressure Bag infusion was noted to confer an advantage in flow rates over Rapid Infuser. Intraosseous blood transfusion with pressure bags can safely bridge toward central access in the early phases of trauma resuscitation.

Pregnancy in Paroxysmal Nocturnal Hemoglobinuria

Pregnancy and childbirth associated with a high risk of severe maternal and fetal complications in women with paroxysmal nocturnal hemoglobinuria (PNH). Recently the management of PNH during pregnancy has been challenging and childbearing was practically contraindicated in these patients. Eculizumab treatment improved the prognosis in PNH and made it possible to minimize complications during pregnancy. Establishment of effective and safe algorithms for the management of pregnancy, delivery and postpartum period in PNH patients is crucial to their lives.Since 1999, we have analyzed 15 pregnancies in six women with PNH. The median age at PNH diagnosis was 22 years (18-27), the median age at the start of pregnancy - 25 years (21-34). All of them were diagnosed with PNH following treatment for aplastic anemia (AA) with antithymocyte globulin, cyclosporine A and splenectomy in two cases before pregnancy. The median of PNH granulocyte clone at the start of pregnancy was 74,7% (17,8-94,1). Pregnancy occurred during complete remission of AA with PNH clinical signs in 5 (33,3%) cases. Most patients were in partial remission at the time of pregnancy-7 (46,7%) or continued to receive immunosuppressive therapy with minimal effect-3 (20%). Progression of aplasia observed during 4 (26,7%) pregnancies, but it was not severe and special treatment delayed until the completion of pregnancy. Two patients exposed to eculizumab before conceiving and remained on the treatment during pregnancy. Other women received only symptomatic therapy. Anticoagulation with low molecular weight heparin was used in 5 (33,3%) pregnancies. No thrombotic events during pregnancy and postpartum have been observed. Skin hemorrhages were revealed in 2 (13,3%) patients. During 4 (26,7%) gestations patients underwent erythrocytes and/or platelets transfusion. Pregnancies resulted in the birth of healthy infants in 7 (46,7%) cases - two girls and five boys. There were no adverse effects in the newborns from PNH patients both on eculizumab and without it. Successful outcomes were in 2/2 pregnancies on eculizumab treatment and in 5/13 (38,5%) cases without the drug. Caesarean sections were performed in all of births, early surgical delivery (30-34 weeks)-in 4/7 cases (preeclampsia-2, placenta previa-1, breakthrough hemolysis-1). Adverse pregnancy outcomes occurred only in patients not receiving eculizumab and amounted to 8/13 (61,5%). Only three patients had planned the pregnancy, other 12 cases were unplanned. Consequently, in 4 (30,8%) cases of pregnancy in the midst of illness was performed the abortion for medical reasons. Spontaneous miscarriage was registered in 2 (15,4%) patients. Two pregnancies (15,4%) ended in fetal death on 27th and 20th gestation weeks. Transfusion requirements increased in two pregnancies with symptomatic therapy, but did not increase on eculizumab. One of patients had first pregnancy without eculizumab and developed complications such as preeclampsia, postpartum severe epistaxis and high transfusion requirement (an average of 1,2 units per month). During second pregnancy on eculizumab she had no obstetric complications and transfusion requirements were less (0,5 units monthly). Second patient continued to have evidence of intravascular hemolysis despite the treatment, and so received eculizumab more frequent (one time in 10 days) in the third trimester. PNH granulocyte clone size decreased in both cases of eculizumab treatment during pregnancy.The risk of complications in PNH patients during pregnancy may be minimized by applying the management algorithm with eculizumab treatment. Despite the small number of observations, we can safely conclude that pregnancy outcomes in PNH patients with eculizumab are better than with only symptomatic therapy. Our experience confirms that eculizumab can be safely used in PNH throughout pregnancy to reduce the risk of complications and adverse outcomes. There is no difference in health between infants born by mothers with PNH and the newborns from general population. DisclosuresNo relevant conflicts of interest to declare.

A Novel Case of Direct Antiglobulin Test-Negative Intravascular Hemolysis in a Patient with Smoldering Myeloma

▪Objectives:1. Describe a case of severe DAT-negative intravascular hemolysis in plasma cell dyscrasia.2. Discuss a potential novel mechanism of light-chain mediated hemolysis.A 34-year old woman was admitted to hospital with fatigue and severe iron deficiency anemia (hemoglobin 47 g/dL, MCV 59 fL, ferritin 2 mcg/L). Her medical history included a presumptive diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) from five years prior. She was transfused 2 units of red cells, started on oral iron and folate, and was discharged symptom-free with a hemoglobin of 71 g/dL. She returned three days later with abdominal pain, dark urine, and evidence of intravascular hemolysis. She was admitted for empiric treatment of PNH with high-dose glucocorticoids and therapeutic enoxaparin for presumed intra-abdominal thrombosis. Her flow cytometry, including granulocytes, was negative for PNH. Her direct antiglobulin test (DAT) was negative for IgG antibodies but positive for C3 complement. A thorough hemolysis workup was negative, including schistocytes and Donath Landsteiner testing. ADAMTS13 testing was uninterpretable due to high plasma free hemoglobin.Despite corticosteroids, brisk hemolysis continued with 10 units of RBCs required over 5 days to maintain a stable hemoglobin. Plasma free hemoglobin reached 1147 mg/L, prompting therapeutic plasmapheresis for renal protection by the end of day 5. She deteriorated clinically after her first plasmapheresis with acute confusion (GCS 10) and lactic acidosis. She was empirically treated for seizure with levetiracetam. CT and MRI scans of her brain and lumbar puncture were normal. Her consciousness improved with daily plasmapheresis. A bone marrow biopsy performed on day twelve of glucocorticoid therapy found monoclonal plasma cell proliferation of 15% with marked lambda light chain predominance (20:1) (Figure 1). Repeat bone marrow biopsy 3 months post-steroid therapy still revealed 10% clonal plasma cells.Hemolysis can be a rare presentation of plasma cell dyscrasia. Case reports of both autoimmune hemolytic anemia and microangiopathic hemolytic anemia associated with multiple myeloma exist. In our case, there was no evidence of a microangiopathic process, making thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic-uremic syndrome (aHUS) unlikely. DAT was negative for IgG but did demonstrate C3 complement molecules bound to red cells. No previous case reports of complement-mediated hemolysis and multiple myeloma were found on literature review.We report the first in vivo association between complement-mediated hemolysis and plasma cell dyscrasia. Complement pathways bridge the innate and acquired immune systems by helping select cells to be targeted by the acquired immune system. The alternative complement pathway does not require an antigen-antibody interaction to become active; rather, it is controlled by direct binding of complement and regulated by cofactor molecules. Jokiranta et al. (J Immunol 1999) identified a monoclonal Ig-lambda dimer that efficiently activated the alternative pathway of complement, triggering complement molecules to enhance hemolysis of serum in vitro. This "miniautoantibody" specifically bound and blocked the function of complement factor H, inhibiting enzymatic inactivation of fluid-phase C3b with uncontrolled activation of the alternative pathway. It is possible that the relative immune dysfunction in this patient's plasma cell dyscrasia led to a disturbance in the alternate complement pathway, perhaps due to dimerization of abnormal lambda light chains, resulting in complement-mediated intravascular hemolysis. Glucocorticoids and plasmapheresis may have helped manage hemolysis in this case.By diagnostic criteria, this patient has smoldering myeloma, with urine monoclonal protein (1.2 g/24 hours), clonal bone marrow plasma cells (10-15%), and absence of myeloma-defining events. We have elected to manage her as such, with close observation. Further work-up performed for her plasma cell dyscrasia included a normal MRI of spine and pelvis. Over a year later, there has been no recurrence of hemolysis. Consideration will be given to treatment if she progresses to overt multiple myeloma. [Display omitted] DisclosuresSandhu:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

Iron metabolism following intravenous transfusion with stored versus fresh autologous erythrocyte concentrate in healthy dogs.

OBJECTIVE To determine effects of IV transfusion with fresh (3-day-old) or stored (35-day-old) autologous erythrocyte concentrate on serum labile iron concentration, iron-binding capacity, and protein interaction with iron in dogs. ANIMALS 10 random-source healthy dogs. PROCEDURES Dogs were randomly assigned to receive autologous erythrocyte concentrate stored for 3 days (n = 5) or 35 days (5). One unit of whole blood was collected from each dog, and erythrocyte concentrates were prepared and stored as assigned. After erythrocyte storage, IV transfusion was performed, with dogs receiving their own erythrocyte concentrate. Blood samples were collected from each dog before and 5, 9, 24, 48, and 72 hours after transfusion. Serum was harvested for measurement of total iron, labile iron, transferrin, ferritin, hemoglobin, and haptoglobin concentrations. RESULTS For dogs that received fresh erythrocytes, serum concentrations of the various analytes largely remained unchanged after transfusion. For dogs that received stored erythrocytes, serum concentrations of total iron, labile iron, hemoglobin, and ferritin increased markedly and serum concentrations of transferrin and haptoglobin decreased after transfusion. CONCLUSIONS AND CLINICAL RELEVANCE Transfusion with autologous erythrocyte concentrate stored for 35 days resulted in evidence of intravascular hemolysis in healthy dogs. The associated marked increases in circulating concentrations of free iron and hemoglobin have the potential to adversely affect transfusion recipients.

Paroxysmal cold hemoglobinuria in an elderly patient: A rare case with poor prognosis

Introduction: Paroxysmal cold hemoglobinuria (PcH) is a very rare type of cold-mediated autoimmune hemolytic anemia causing direct intravascular hemolysis and hemoglobinuria, typically after exposure to cold. the reaction is caused by an IgG antibody known as DonathLandsteiner (D-L), which binds specifically to the P antigen of red blood cells at low temperatures, leading to complement activation and red cell lysis. case report: We report a case of rare occurrence of acute syphilitic paroxysmal cold hemoglobinuria in an elderly female with evidence of intravascular hemolysis complicated with peripheral gangrene and multiple organ dysfunctions. conclusion: the prognosis of PcH associated with syphilis is usually considered excellent and benign. However, we encountered a syphilitic PcH in an elderly female with a grave prognosis who passed away within five months after her first episode. based on our case experience, we recommend that acute episodes of PcH in an elderly patient should be treated in a closely monitored setting with high dose of steroids and warm blankets.

Acute extravascular hemolytic transfusion reaction due to anti-Kpa antibody missed by electronic crossmatch

BackgroundKpa antigen is a low incidence red blood cell antigen within the Kell system. Anti-Kpa alloantibody may be associated with acute and delayed hemolytic transfusion reactions. Case StudyWe report a case of a clinically significant acute extravascular hemolytic transfusion reaction mediated by previously unrecognized (and undetected) anti-Kpa alloantibody. This reaction occurred in a patient who met all criteria for electronic crossmatch, resulting in the transfusion of an incompatible red cell unit. ResultsPost-transfusion investigation showed the transfused red cell unit was crossmatch compatible at the immediate spin phase but was 3 + incompatible at the antiglobulin phase. No evidence of intravascular hemolysis was observed upon visual comparison of the pre- and post-transfusion peripheral blood plasma. Further testing showed the presence of anti-Kpa antibody. The clinical course of the patient included acute febrile and systemic reaction. ConclusionAcute extravascular hemolytic transfusion reaction may occur due to undetected anti-Kpa alloantibody. Various strategies for crossmatching are discussed in the context of antibodies to low incidence antigens.

A patient with severe body aches without fever progressing to dengue shock syndrome

Investigations showed that the patient had severe haemolytic anaemia on presentation, the haemoglobin was 6.2 g/dl, with a positive haemolytic screen of reticulocytosis, indirect hyperbilirubinaemia and erythroid hyperplasia in the bone marrow. According to the blood picture it is a spherocytic anaemia and the positive DAT indicates that it is immune mediated. Since it is positive for both C3d and IgG, it is considered as warm autoimmune hemolytic anaemia. However, subsequently her urine was strongly positive for haemosiderin which showed evidence of intravascular haemolysis. References

A case of warm autoimmune haemolytic anaemia with intravascular haemolysis: a rare presentation

Autoimmune haemolytic anaemia (AIHA) is a rare (prevalence 0.2 -1.0 per 100,000 population) but a potentially fatal condition. Diagnosis of AIHA is based mainly on Direct Agglutination Test (DAT/Coomb's test). AIHA is classified into warm (optimal autoantibody reactivity at 37°C) and cold (optimal autoantibody reactivity at 4°C) types. Based on the presence or absence of an underlying cause, it is divided into primary (idiopathic) and secondary (secondary to lympho proliferative disorders, autoimmune disease, drugs and non-haematological malignancies). Warm type accounts for about 70% of cases with AIHA. It can occur at any age, but mostly after 40 years. Haemolysis in warm AIHA is mediated by IgG alone or IgG with complement. Once immunoglobulins are bound, the red cells are taken up by the macrophages of the reticulo-endothelial system which has receptors for the Fc fragments of the immunoglobulins. As the red cells are haemolysed extravascularly this occurs mainly in the spleen. Intravascular haemolysis is unusual in warm AIHA, although it can occur rarely, as warm autoantibodies can fix complements. We report severe warm AIHA in an adult with evidence of intravascular haemolysis, which is an unusual presentation.

Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria

Acute renal failure (ARF) is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH). The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN) developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham's test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

Persistent complement-dependent anti-AnWj in a lymphoproliferative disorder: a case study and review

AnWj is a high-incidence antigen present on the red blood cells (RBCs) of greater than 99 percent of the general population. A 58-year-old man underwent autologous hematopoietic stem cell transplantation (HSCT) for stage IVa mantle cell lymphoma. This procedure was complicated by failure to engraft, necessitating ongoing support with blood components. After a 2-month period of uneventful transfusion support, the patient experienced increasingly severe reactions with fever and evidence of intravascular hemolysis, including hemoglobinuria. Testing revealed a complement-dependent anti-AnWj. Phenotyping confirmed the AnWj- phenotype. Anti-AnWj was persistent despite immunosuppression, including treatment with allogeneic HSCT. Of interest, the pathogenesis of the downregulation of the graft AnWj in this patient is unclear.

AN UNUSUAL TOXIC CAUSE OF HEMOLYTIC-UREMIC SYNDROME

Hemolytic uremic syndrome (HUS) has been associated with a variety of infective as well as non-infective causes. HUS as a toxic manifestation of exposure to herbicides/pesticides has not been reported so far in literature. We report a subject who presented with clinical features of features of HUS after intentional suicidal ingestion of the herbicidal agent monochloroacetic acid (MCA). A 55-year-old farmer was admitted with a history of consumption of monochloroacetic acid with vomiting, hematochezia and oligo-anuria. Our investigations revealed severe renal failure, metabolic acidosis, anemia, and thrombocytopenia with evidence of intravascular hemolysis. He was treated for HUS with plasma transfusions and haemodialysis in view of renal failure. During the course of hospital admission he developed acute antero-septal myocardial infarction and subsequently succumbed to the disease. MCA is used as an herbicidal agent and also a bleaching agent for silkworm cocoons. The toxicity of MCA has included metabolic acidosis, rhabdomyolysis and renal failure; however HUS has not been described in the literature. Extra -renal manifestations of HUS such as cardiomyopathy have also been infrequently described. This case is presented to highlight an as yet unknown toxicity of MCA.

Anti-human erythrocyte antibodies in horse-derived antivenoms used in the treatment of snakebite envenomations

This work examined the presence of antibodies reacting with human erythrocytes in horse-derived antivenoms used in the treatment of snakebite envenomations, and assessed the efficacy of various fractionation protocols in the elimination of agglutinating antibodies. A number of antivenoms produced by various fractionation protocols were tested for direct agglutination of human erythrocytes. Reactions were observed visually and microscopically, and an indirect anti-equine globulin test was also used. In addition, rabbits and mice were injected intravenously with antivenoms to observe possible intravascular hemolysis and erythrocyte sequestration. All tested antivenoms agglutinated human erythrocytes, albeit to different extent, and also gave a positive anti-globulin test. Agglutination was due to IgG(T) subclass of antibodies. Pepsin digestion of horse IgG, to obtain F(ab′) 2 fragments, reduced the direct agglutination, but not the indirect anti-globulin test. Ion-exchange chromatography of IgG in a strongly basic quaternary ammonium cellulose membrane abrogated direct agglutination and reduced the indirect anti-globulin test. Binding of antivenom antibodies to erythrocytes in vivo was demonstrated in rabbits, although there was no evidence of intravascular hemolysis or erythrocyte sequestration in rabbits and mice. It is concluded that anti-human erythrocyte antibodies are present in horse-derived antivenoms, and that fractionation of horse plasma by pepsin digestion, and especially by anion-exchange chromatography, reduces the titer of these antibodies. Our in vivo experimental results do not support a role for these antibodies in early adverse reactions occurring after antivenom administration.

Hepatitis E Virus Infection with Nonimmune Hemolytic Anemia

Hepatitis E Virus Infection with Nonimmune Hemolytic Anemia

Dengue Virus-Associated Hemophagocytic Syndrome and Dyserythropoiesis: A Case Report

A 33-year-old man had dengue hemorrhagic fever with initial presentation of fever, leukocytosis, and thrombocytopenia. The cause of the subsequent rapid decline in red cell counts without evidence of intravascular hemolysis or massive bleeding was confirmed as hemophagocytosis and dyserythropoiesis by bone marrow study. The patient recovered with supportive care and the bone marrow pattern was normal on repeated bone marrow study. To our knowledge, this is the first reported case of dengue virus-associated hemophagocytosis and dyserythropoiesis in Taiwan. Clinicians should consider that the occurrence of hemophagocytosis and dyserythropoiesis could be due to dengue virus infection. That this dengue virus infection was confirmed by a positive serology result at the convalescent stage but not at the acute symptomatic stage underlines the need for a second dengue serology study, as dengue infection can be missed due to an initial negative serology result.

Acute haemolytic crisis in a Thai patient with homozygous haemoglobin Constant Spring (Hb CS/CS): a case report

Acute haemolysis associated with mild upper respiratory tract infection was observed in a Thai boy who presented with a rapid decline in haemoglobin (Hb) levels, haemoglobinuria and evidence of intravascular haemolysis. Several possible causes giving rise to such a condition were excluded including G6PD deficiency, which is extremely common in Thailand. Subsequent haematological and molecular analyses demonstrated that the patient was homozygous for Hb Constant Spring (Hb CS/CS), an a globin haemoglobinopathy. It has been shown previously that patients with homozygous Hb CS had mild haemolytic anaemia secondary to an accumulation of alpha(CS) chains, which are toxic to red blood cell membrane cytoskeletons. Increased body temperature might induce more precipitation of this a globin variant. This report highlights the importance of Hb CS/CS as a potential predisposing cause of acute haemolysis in children that might be aggravated by acute bacterial or viral infections. This is particularly relevant for patients of Southeast Asian descent where this abnormal haemoglobin is highly prevalent.

Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene

Leukocyte adhesion deficiency type 2 (LADII) is characterized by defective selectin ligand formation, recurrent infection, and mental retardation. This rare syndrome has only been described in 2 kindreds of Middle Eastern descent who have differentially responded to exogenous fucose treatment. The molecular defect was recently ascribed to single and distinct missense mutations in a putative Golgi guanosine diphosphate (GDP)-fucose transporter. Here, we describe a patient of Brazilian origin with features of LADII. Sequencing of the GDP-fucose transporter revealed a novel single nucleotide deletion producing a shift in the open-reading frame and severe truncation of the polypeptide. Overexpression of the mutant protein in the patient's fibroblasts did not rescue fucosylation, suggesting that the deletion ablated the activity of the transporter. Administration of oral L-fucose to the patient produced molecular and clinical responses, as measured by the appearance of selectin ligands, normalization of neutrophil counts, and prevention of infectious recurrence. The lower neutrophil counts paralleled improved neutrophil interactions with activated endothelium in cremasteric venules of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, fucose supplementation induced autoimmune neutropenia and the appearance of H antigen on erythrocytes, albeit without evidence of intravascular hemolysis. The robust response to fucose despite a severely truncated transporter suggests alternative means to transport GDP-fucose into the Golgi complex.

Infusion of hot crystalloid during operative burn wound debridement.

Hypothermia exacerbates coagulopathy and is thus a potentially devastating morbidity during operative debridement of burn wounds. Current techniques for maintaining body temperature include warming intravenous fluids at 38 degrees C. The purpose of this study was to assess the safety of infusing saline heated to 55-60 degrees C. Using a modified fluid warmer, saline heated to 60 degrees C was infused through central venous access in eight adult patients undergoing debridement of burn wounds. The temperature of the saline actually entering the patient was measured by a thermocouple attached at the connection to the central line catheter. The actual infusate temperature was 54.0 +/- 1.2 degrees C. Over the first hour, 1,100 mL of hot saline was given, thus delivering 17.6 kcal more heat than fluid warmed to the traditional 38 degrees C. Core temperature measured via esophageal and Foley catheters had an insignificant trend toward increase during the operative procedure. There was no evidence of intravascular hemolysis or coagulopathy. This pilot study suggests that infusion of hot crystalloids given via central venous access is safe and may be an acceptable adjuvant in attenuating hypothermia during operative procedures.