Evidence Of Hemolysis Research Articles

Refractory Autoimmune Cytopenias, Either Associated with Lymphoproliferative Diseases or Idiopathic in Adult Patients, Treated with Anti-CD20 Monoclonal Antibody (Rituximab).

Immune cytopenias (IC) frequently require prolongued administration of immunosupressors, especially when associated with lymphoproliferative disorders (LPD). Rituximab causes in vivo selective destruction of B lymphocytes and supresses the production of antibodies. Three mechanisms are involved; complement dependent cytotoxicity, antibody dependent cellular citotoxicity and the induction of apoptosis. We present 10 patients with IC: 8 autoimmune hemolytic anemia (AIHA), and 2 AIHA plus immune thombocytopenia (Evans' syndrome). Seven patients had IC associated with LPD, and 3 were idiopathic. LPD were: 3 follicular lymphoma (1 Grade 1, 1 Grade 2, 1 Grade 3), 1 small lymphocytic lymphoma, 3 chronic lymphocytic leukemia. Three patients with idiopathic cytopenias had a long history of recurrent AIHA (2) and Evans' syndrome (1). Ages ranged between 43 and 81 (median 63 yrs); 6 were female gender and 4 male. All AIHA cases, except 1 pts with cryogrobulins, presented with warm IgG antibodies. Previous evolution included splenectomy in 2 pts and all pts received multiple courses of immunosupression with steroids and others, like azathioprine and cyclophosphamide. All patients with LPD received one or more chemotherapeutic regimens with alkylating agents, fludarabine or CHOP combination. Median time to IC in 7 pts with LPD was 75 months (2–228). Idiopathic cases had 12, 132 and 204 months of previous evolution. Rituximab was administered at 375 mg/m2 every 1 to 3 weeks for 3 to 8 doses (median 4). Six pts received rituximab as monotherapy and 4 pts in combination with chemotherapy. Toxicity was mainly related to the first cycle of rituximab and consisted in chills and fever grade I-II in three pts. Clinical resolution of cytopenia occured in 9/10 pts (90%). 4 of them (44%) resolved with negative direct antiglobuline test. Median time to response was 4 weeks (2–8). One AHIA died with hemolysis progression, six months after rituximab, and 1 pts with AHIA and follicular lymphoma died 8 months after rituximab treatment with progression of LPD without evidence of hemolysis. The rest of the patients remained without IC for 2–42 months (median 18). Rituximab, originally designed to treat B-cell neoplasms, is an active immunosupressive agent in either lymphoproliferative associated or idiopathic autoimmune cytopenias even in non splectomized pts. Its use may avoid the secondary effects of long term administration of steroids, alkylating agents or transfusions.

SUCCESSFUL ABO INCOMPATIBLE PEDIATRIC LIVER TRANSPLANTATION UTILIZING SELECTIVE PLASMAPHERESIS

O160 Aims: It has been reported that ABO incompatible grafts during liver transplantation results in lower patient and graft survival. Also it is believed that ABO incompatible liver grafts will have an increase in incidence and severity of acute cellular rejection. The aim of this study is to report our experience of emergent transplantation of pediatric recipients utilizing ABO incompatible, mismatched grafts while using selective plasmapheresis with an induction protocol using daclizumab with tacrolimus, mycophenolate and steroids. Methods: From July 1998 to November 2003, 115 liver transplants in 101 pediatric recipients were prospectively followed for outcomes of which 11 (10.8%) of the children received an ABO incompatible liver allograft emergently. ABO incompatible liver allograft (n=11) consisted of group pairings which included blood type B donors to type A liver recipient (B to A, n = 4), A to B (n = 2), A to O (n=4), and AB to A (n =1). All patients received similar immunosuppression with induction therapy of daclizumab. Additional intravenous methylprednisolone (10-20 mg/kg per dose) was administered when evidence of hemolysis was confirmed by increased AB antibody titers on serial isohemagglutinins assay, evidence of hemolysis was suggested by increased indirect bilirubin, hematuria, or increased haptoglobin. If the titers did not respond to methylprednisolone, plasmapheresis was instituted plasmapheresis. Total plasma exchange and splenectomy were not used for pre-transplant or post-transplant as induction treatment. Results: Two of eleven (18%) children with ABO incompatible allografts had three rejection episodes compared with 48/91 (53%) children with 111 rejection episodes in ABO compatible allograft placement. The incompatible liver group was similar in age (8.1 ± 6.2 years vs. 6.5 ± 6.2 years; p = NS), time to first rejection (135 ± 178 days vs. 340 ± 396 days; p = NS), with the compatible group having longer mean follow-up (573 ± 372 days vs. 930 ± 568 days, p = 0.013). Only one patient received plasmapheresis that demonstrated anti-B titers of 1:32 or less at baseline and increased to 1:1024 with hemolysis, an increase in serum total bilirubin to 8.4 mg/dl from 3.7mg/dl and hematuria on POD #6 with unresponsive steroid therapy. Plasmapheresis was instituted for 10 days, 80% total blood replacement for three days and 150% replacement for 7 days. There were no post-operative complications of hepatic arterial or portal venous thrombosis, or vena caval occlusion in the ABO incompatible group. One child lost their allograft following a percutaneous transhepatic cholangiogram due to a intra-hepatic hematoma. Patient actuarial survival for ABO matched children vs ABO incompatible children was 84/90(93.3%), versus 11/11 (100%) and graft survival was 84/101 (89.7%) vs 10/11 (91%) at one year. Conclusions: ABO mismatched grafts can be used without an increase in patient/graft mortality or an increase in rejections when an enhanced immunosuppressive protocol of daclizumab/tacrolimus/mycophenolate/prednisone is used. Plasmapheresis may be reserved for times of increased anti-ABO titers with clinical hemolysis for graft salvage.

Posttransfusion recovery of stored red blood cells in very low birth weight infants using a hemoglobin balance model.

A Hb balance model was used in very low birth weight (VLBW) infants to predict posttransfusion Hb levels from which we inferred allogeneic RBC recovery after transfusion of RBCs stored for varying periods of time. Premature VLBW infants receiving RBC transfusions during the 1st month of life were evaluated retrospectively for RBC survival of stored donor blood. Actual Hb levels measured in infant blood 1 and 2 days after RBC transfusions were compared to those predicted using a Hb balance model based on factors affecting blood Hb loss and gain. Transfusions were subgrouped according to whether or not infants were clinically stable at the time of RBC transfusion. Model-predicted RBC recovery was also evaluated relative to duration of RBC storage. Model-predicted mean (+/- SD) Hb levels 2 days after transfusion among the 30 VLBW infants receiving a total of 57 RBC transfusions were only 4 percent higher than actual values observed (15.2 +/- 1.2 g/dL vs. 14.7 +/- 1.4, respectively; p < 0.05). The infant's clinical status at the time of transfusion did not affect predicted 1- and 2-day posttransfusion RBC recovery. Model-predicted recovery of transfused RBCs was modestly, but significantly, decreased with increasing duration of donor RBC storage (i.e., 10% lower by 42 days-the maximal allowed storage period for donor blood [p < 0.01]). Our model-predicted RBC survival results are consistent with-but not direct evidence of-hemolysis of donor blood after RBC transfusion. Although observed post-RBC Hb levels 2 days after transfusion averaged only 4 percent less than predicted, model-predicted survival of donor RBCs at 42 days suggested a modest decrease (i.e., by 10%).

Recurrent vomiting and acute renal failure after HUS: Question

An 18.5-year-old boy was first referred to our hospital at the age of 11 years with acute renal failure secondary to (D+) hemolytic uremic syndrome. Peritoneal dialysis was necessary for 19 days. The catheter was inserted surgically without any complications. He recovered completely without any sequelae. His past medical history is remarkable for a right nephrectomy that was performed in early infancy at another hospital. A tumor of the right kidney was suspected and apparently the kidney was surgically removed. However, microscopic evaluation revealed adrenal bleeding but no tumor. His further development was normal. At the age of 12 years, 1 year after suffering from acute renal failure, he presented with recurrent episodes of abdominal distention, vomiting, diarrhea, and slight discomfort after fatty meals. No infectious etiology could be found. A mild exocrine pancreatic insufficiency was suspected (normal serum pancreatic enzymes, pancreatic elastase in stool reduced to 89 g/g, normal >200 g/g) and enzyme replacement was started. Atypical cystic fibrosis was unlikely because of negative molecular analysis. In the following 4 years, several episodes of nausea and vomiting occurred, lasting 1 or occasionally several days. At the age of 16 years, two such episodes with marked dehydration occurred, making hospitalization with intravenous rehydration necessary. The vital signs at the time of his last admission were as follows: blood pressure 116/ 73 mmHg, heart rate 98/min, afebrile, weight 49.3 kg (10th percentile), and height 175.5 cm (50th percentile). Laboratory results included a hemoglobin level of 18.3 g/ dl with a normal complete blood count and platelets, creatinine of 4 mg/dl [glomerular filtration rate (GFR) 24 ml/min per 1.73 m], no evidence of hemolysis, a metabolic alkalosis with a bicarbonate level of 33 mmol/l and pH of 7.42, a potassium level of 3.0 mmol/l, and an intact parathyroid hormone level of 361 pg/ml (normal 10–69 pg/ml). Urinalysis was normal, with a specific gravity >1,030. A metabolic disorder was unlikely due to normal values for aminoaciduria, normal ammonia concentration, and the absence of lactic acidosis and ketoacidosis. An ultrasound scan of the kidney was within normal limits. A renal biopsy was performed showing no glomerular abnormalities. However, tubular changes with interstitial edema and microcalcifications were noted [often seen with high doses of diuretics (furosemide)]. After intravenous rehydration his renal function returned to normal and he was clinically stable. Further diagnostic investigation revealed no signs of a possible metabolic disorder, chronic pancreatitis, or celiac disease. Magnetic resonance imaging of the head was normal. He and his parents denied any medication abuse and his past medical history was negative for any mental or adjustment problems. Prior to his 18th birthday, nausea and vomiting with weight loss occurred and he was again hospitalized. His renal function was only mildly reduced with a creatinine of 1.6 mg/dl (GFR 61 ml/min per 1.73 m). Further laboratory results included blood urea nitrogen 38 mg/dl, hemoglobin 16.9 g/dl, and bicarbonate 30 mmol/l. An abdominal ultrasound scan was performed and showed signs of constipation and meteorism, some fluid in the colon, but no masses or obstruction. However, for the first time the patient complained of abdominal pain, especially in the lower right part of the abdomen. The answer to this question can be found at http://dx.doi.org/ 10.1007/s00467–004–1534–9

The effect of pentoxifylline on haemolysis in patients with double cardiac prosthetic valves

Objective — Intravascular haemolysis frequently occurs in patients with mechanical heart valve prostheses. In this prospective study, we investigated whether pentoxifylline (PTX) has an effect on haemolysis following prosthetic valvular replacement in 40 patients who underwent double valve (mitral and aortic) replacement.Methods and results — The patients were randomly assigned to two groups as control (n = 20) and PTX group (n = 20). PTX was given in a daily oral dose of 1200 mg (3 times 400 mg) for 120 days. Laboratory tests for evidence of haemolysis namely, haemoglobin (Hb), haematocrit (Hct), plasma total bilirubin, indirect bilirubin and haptoglobin levels, corrected reticulocyte percent and serum lactic dehydrogenase activity (SLDH) were performed before and after the PTX treatment. PTX treatment caused significant increases in Hb, Htc, and haptoglobin levels (P < 0.05, P<0.05 and P<0.01, respectively).Additionally, there were significant decreases in SLDH, total and indirect bilirubin levels, and corrected reticulocyte percent in patients receiving PTX as compared with their respective control values (P<0.01, for all). PTX treatment caused a significant improvement, to different extents, in signs of haemolysis in 60% of the patients. On the other hand, the response rate was 5% in the placebo-treated control group (P<0.05).Conclusions — These findings suggest that PTX may be an effective agent in the management of haemolysis in patients with prosthetic heart valves.

ABO mismatch increases transplant-related morbidity and mortality in patients given nonmyeloablative allogeneic HPC transplantation.

ABO mismatch has not been thought to affect the outcome of patients undergoing myeloablative conditioning and allogeneic HPC transplantation. Data on transplant-related complications after ABO-mismatched transplantation after nonmyeloablative conditioning are limited. Therefore, 40 patients were analyzed after nonmyeloablative conditioning with regard to ABO compatibility. Eleven received a minor and bidirectional and 8 a major ABO-mismatched graft. Four patients had evidence of hemolysis during engraftment, being lethal in one, and three developed pure RBC aplasia. Six patients in the ABO-mismatched group developed thrombotic microangiopathy, and three of them died. ABO-identical and ABO-mismatched patients had a similar incidence of GVHD. Viral infections occurred in both groups in equal shares. Patients with an ABO-mismatch had to be rehospitalized until Day 100 for a median of 19 days versus 0 days in the identical group (p < 0.05). Overall survival was 60 and 57 percent in the ABO-identical and ABO-mismatch groups, respectively. The probability of transplant-related mortality was 0 versus 28 percent in the identical group compared to patients with an ABO mismatch (p < 0.05). The probability of relapse or progression was 76 versus 25 percent in the ABO-identical group compared to the ABO-mismatched group, respectively. Significantly more patients with ABO mismatch showed transplant-associated complications and died as a result of transplant-related causes.

Anemia hemolítica autoinmune: una rara complicación de la colitis ulcerosa

Anaemia is a common problem in patients with ulcerative colitis, and its etiology is usually multifactorial. It can be produced by chronic blood loss, nutritional deficiencies, drugs such as salazopyrine, or it can be related to those chronic disease. However, ulcerative colitis is known to be associated with several immune disorders, as autoimmune haemolytic anaemia. Nevertheless, this rare complication can be found in 0.2 to 0.7% of patients affected by ulcerative colitis, and although 1.82% of patients with ulcerative colitis have a positive direct Coombs test without evidence of hemolysis. We report one new case of ulcerative colitis associated with autoimmune anaemia haemolytic, and a review the literature.

Bartonella quintana in human erythrocytes.

Bartonella quintana is transmitted by body lice among homeless people. Infection with this organism leads to chronic bacteraemia with few symptoms. We looked for B quintana in erythrocytes in a population of homeless people in Marseille, France. In this report we show the intraerythrocytic presence of B quintana in people with symptomless bacteraemia, by use of a specific monoclonal antibody and laser confocal microscopy. Presence of at least 5 x 10(4) colony-forming units per mL was predictive of intracellular infection. However, such infection was not associated with evidence of haemolysis. Colonisation of erythrocytes could allow efficient transmission of B quintana by body lice.

Murine models of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by chronic intravascular hemolysis, cytopenia, and an increased tendency to thrombosis. All patients with PNH studied so far have a somatic mutation of phosphatidyl inositol glycan complementation group A (PIG-A), an X-linked gene involved initially in the biosynthesis of the glycosyl phosphatidylinositol (GPI) molecule, which serves as an anchor for many cell surface proteins. The mutation occurs in a hematopoietic stem cell, and consequently, all cells derived from the mutated stem cell are devoid of GPI-linked proteins. The absence of GPI-linked proteins explains some clinical symptoms of the disease but not the mechanism that allows the expansion of the mutated clone. By using targeted disruption of the PIG-A gene in mouse embryonic stem cells, some mice models of PNH have been generated. These animals have a discrete proportion of blood cells devoid of GPI-linked proteins, and although not anemic, they have evidence of hemolysis. The clinical course of these animals is benign, and there are no signs of a substantial expansion of the PNH clone, as observed in human patients. The fact that these animals do not develop the disease strongly supports the notion that a mutation of PIG-A is not sufficient per se to cause PNH and that another factor, namely, bone marrow failure, is necessary to allow proliferation and expansion of the PNH clone.

Breast-feeding, neonatal jaundice and kernicterus

Despite the many advantages of breast-feeding, there is ample documentation of the strong association between breast-feeding and an increase in the risk of neonatal hyperbilirubinaemia. Breast-fed infants have higher bilirubin levels than formula-fed infants. Suggested mechanisms for these findings include poor fluid and caloric intake, inhibition of hepatic excretion of bilirubin, and intestinal absorption of bilirubin (enterohepatic circulation). On rare occasions, breast-fed infants without evidence of haemolysis have developed extreme hyperbilirubinaemia and kernicterus. Because almost all of the cases of kernicterus reported in the last 15 years have occurred in fully or partially breast-fed newborns, it is important that these infants be followed closely. Appropriate support and advice must be provided to the lactating mother so that successful breast-feeding can be established and the risk of severe hyperbilirubinaemia reduced.

Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model.

This study was undertaken to assess the acute safety and feasibility of rapidly inducing, maintaining, then reversing hypothermia using a novel heat transfer catheter and a closed-loop automatic feedback temperature control system to overcome limitations imposed by current clinical practices used for perioperative cooling and warming. Six swine (mean mass, 53.8 +/- 3.6 kg) were studied. The heat transfer catheter was placed in the inferior vena cava via the femoral vein. Hypothermia to 32 degrees C was induced, maintained for 6 hours, then reversed to 36 degrees C. The time needed to induce and reverse hypothermia was recorded via continuous temperature monitoring of the lower esophagus, cerebrum, and rectum. Electrocardiography provided continuous monitoring, and blood draws were made at baseline and at 2-hour intervals. Examination of the catheter in situ was performed after the animals were killed. Cooling from 36.2 to 32.0 degrees C was rapid and uniform (mean, 7.3 +/- 0.7 degrees C/h), with animals reaching the target temperature within 60 minutes. Rewarming was also easily controlled, with animals' temperatures reaching 36 degrees C within 130 minutes. No arrhythmia was observed, and all hematological variables were within the normal range for swine. There was no evidence of hemolysis or platelet changes. Little to no thrombosis was observed. The data presented here suggest that rapid induction and reversal of hypothermia are technically possible using a core intravenous cooling catheter; this method would provide a safe, rapid, and exquisitely reproducible way to induce hypothermia with subsequent restoration of normothermia.

ABO mismatch may affect engraftment in multiple myeloma patients receiving nonmyeloablative conditioning.

Blood group incompatibility does not appear to affect the overall outcome in patients undergoing myeloablative conditioning before allogeneic BMT. Data on ABO-mismatched transplantation in the nonmyeloablative setting are limited. A retrospective analysis of the effects of ABO mismatches in multiple myeloma patients who received a nonmyeloablative conditioning regimen was conducted. Three of 27 patients received a minor ABO-mismatched graft, all with evidence of hemolysis before converting to donor ABO group on Days 10, 15, and 6. Six patients received a major ABO-mismatched graft; of these, three developed GVHD of more than grade 2 and subsequently converted to the ABO blood group of the donor on Days 38, 33, and 43. Of the three patients without GVHD, one rejected the allograft and had autologous reconstitution. One remained a mixed chimera to Day 100 despite three donor lymphocyte infusions, and one developed pure RBC aplasia. None of the ABO-matched patients rejected the graft, whether they developed GVHD or not. RBC transfusions were significantly higher in the major and minor ABO-mismatched patients than in the ABO-matched patients, with medians of 12 units (range, 2-35), 13 units (range, 5-18), and 4 units (range, 2-15), respectively (p = 0.02). ABO-matched patients had a similar incidence of GVHD, with 5 of 9 ABO-mismatched patients (56%) having more than grade 2 versus 10 of 18 (56%). Four of 9 ABO-mismatched patients (44%) were mixed chimeras up to Day 100 versus 2 of 18 ABO-matched patients (11%), and the difference was significant (p = 0.01). Patients with ABO mismatch had problems with engraftment, including graft rejection, pure RBC aplasia, and mixed-lineage chimerism. RBC transfusions were significantly higher in the ABO-mismatched recipients. GVHD may play a role in engraftment, possibly by facilitating the disappearance of native ABO antibodies via graft-versus-plasma cell effect. A prospective study to evaluate the effects of ABO mismatch on engraftment in the nonmyeloablative setting is needed.

Safety and Performance of a Novel Intravascular Catheter for Induction and Reversal of Hypothermia in a Porcine Model

OBJECTIVE: This study was undertaken to assess the acute safety and feasibility of rapidly inducing, maintaining, then reversing hypothermia using a novel heat transfer catheter and a closed-loop automatic feedback temperature control system to overcome limitations imposed by current clinical practices used for perioperative cooling and warming. METHODS Six swine (mean mass, 53.8 ± 3.6 kg) were studied. The heat transfer catheter was placed in the inferior vena cava via the femoral vein. Hypothermia to 32°C was induced, maintained for 6 hours, then reversed to 36°C. The time needed to induce and reverse hypothermia was recorded via continuous temperature monitoring of the lower esophagus, cerebrum, and rectum. Electrocardiography provided continuous monitoring, and blood draws were made at baseline and at 2-hour intervals. Examination of the catheter in situ was performed after the animals were killed. RESULTS Cooling from 36.2 to 32.0°C was rapid and uniform (mean, 7.3 ± 0.7°C/h), with animals reaching the target temperature within 60 minutes. Rewarming was also easily controlled, with animals’ temperatures reaching 36°C within 130 minutes. No arrhythmia was observed, and all hematological variables were within the normal range for swine. There was no evidence of hemolysis or platelet changes. Little to no thrombosis was observed. CONCLUSION The data presented here suggest that rapid induction and reversal of hypothermia are technically possible using a core intravenous cooling catheter; this method would provide a safe, rapid, and exquisitely reproducible way to induce hypothermia with subsequent restoration of normothermia.

Nimesulide-Induced Severe Hemolytic Anemia and Acute Liver Failure Leading to Liver Transplantation

We present the case of a 63-year-old woman who had undergone 7 months of treatment with Nimesulide (100 mg/b.i.d.) for symptomatic osteoarthritis. The patient was admitted to our unit with a clinical picture of progressive jaundice over 3 weeks. Clinical and analytical studies revealed acute liver failure, this being confirmed by liver biopsy, which showed submassive necrosis. Serological tests for different viral agents causing hepatitis were all negative. In addition, she presented a picture of severe haemolytic anaemia resistant to several treatments and needed multiple transfusions. Twenty-three days after admission, the patient presented hepatic encephalopathy and received an orthotopic liver transplant on day 25. The evolution after transplantation was good and the patient continues in good health with no evidence of haemolysis almost 2 years later. Liver toxicity due to Nimesulide is well known, but to our knowledge the occurrence of haemolytic anaemia has not been related to this drug previously. For these reasons, Nimesulide has been restricted or removed from the market in several countries in recent months.

An animal model for delayed hemolytic transfusion reactions1

Delayed hemolytic transfusion reactions (DHTRs) are a well-known complication of transfusion that may be defined as immune-mediated hemolysis of allogeneic donor red cells that occurs approximately 3 to 5 days after transfusion. In general, DHTRs occur in patients who have been alloimmunized previously, but the antibody titers have fallen below serologically detectable levels. Transfusion of seemingly compatible blood and exposure to the putative alloantigen results in an anamnestic immune response that may lead to in vivo accelerated destruction of donor red cells. Symptoms may include a drop in hemoglobin and hematocrit, fever, jaundice, and renal insufficiency. More recent studies have shown that there is a subset of cases called delayed serologic transfusion reactions (DSTRs) when there are serologic findings consistent with DHTRs but no clinical evidence of hemolysis. In both DHTRs and DSTRs, direct antiglobulin tests are often persistently positive long after the transfused donor red cells should have been removed from the circulation. Because the studies required to investigate the immunologic and clinical aspects of these reactions are precluded in humans, we developed an animal model for the study of DHTRs and DSTRs. Our article provides a comprehensive review of DHTRs and DSTRs, the role of complement and cytokines in these reactions, and the phenomenon of bystander hemolysis. We describe our studies using the rabbit as a model for the study of DHTRs and bystander hemolysis.

Current status of the AbioCor implantable replacement heart

Background. The AbioCor implantable replacement heart (IRH) has been developed as an alternative to transplant (ie, destination therapy). We report our experience with the AbioCor IRH in a bovine model at the University of Louisville. Methods. Male Holstein cows were used (85 to 115 kg). The internal controller, battery, and secondary transcutaneous energy transfer coil were implanted in the right flank. After cardiopulmonary bypass, the thoracic unit was implanted orthotopically. After removal of air and weaning from cardiopulmonary bypass, the AbioCor was connected to internal components and energy transfer through transcutaneous energy transfer coils was achieved. Results. Nineteen animals underwent implantation of the AbioCor IRH for a proposed 30-day duration. There were 6 deaths, none related to device malfunction. All animals demonstrated normal hemodynamics with normal pressures in the aorta, pulmonary artery, left atrium, and right atrium. There was no significant hemolysis and all animals demonstrated normal end organ function. The internal battery allowed for brief periods of untethered mobility. Conclusions. The AbioCor IRH has resulted in normal hemodynamics and normal end organ function without evidence of hemolysis in a bovine model.

Tacrolimus: The good, the bad, and the ugly

The aim of this study was to evaluate the efficacy and side-effects of tacrolimus in pediatric transplant patients previously receiving cyclosporin A (CsA). This study was a retrospective chart review strengthened by a concomitant patient interview. Eleven pediatric cardiac or renal transplant patients, who had been converted from CsA to tacrolimus from October 1995 to January 1999 at The Cleveland Clinic Foundation, were included; there were six renal and five cardiac transplant patients. Each chart was reviewed to assess transplanted organ function pre- and post-conversion. For the six renal transplant patients, creatinine levels and biopsy findings were evaluated. For the five cardiac transplant patients, cardiac catheterization and routine biopsy data were analyzed likewise. Epstein Barr virus (EBV) status was also evaluated in each patient. In addition, each parent or patient was interviewed to ascertain dates of transplant, current medications, and side-effects. The patients' ages ranged from 6 to 20 yr (mean age 14.6 yr). All patients had been converted to tacrolimus. Eight patients were converted for treatment of refractory rejection, two were converted because of CsA-associated side-effects, and one patient was converted empirically for a history of multiple previous transplant rejections. Seven out of eight patients who received tacrolimus for rejection therapy improved. One patient had complete resolution of gingival hyperplasia. Another patient who previously developed hemolytic uremic syndrome on CsA had no further evidence of hemolysis. Four patients were weaned off steroid therapy. Despite conversion, two renal transplant patients progressed to chronic rejection. Five patients exhibited no side-effects. Side-effects experienced included transient hyperglycemia in conjunction with steroid use, headaches, and tremors that subsided rapidly. Four of 11 patients developed post-transplant lymphoproliferative disease (PTLD). Fortunately, reducing the dose of tacrolimus and/or surgical resection of the mass (if present), eradicated the disease. In conclusion, conversion therapy successfully provides an alternate treatment for acute rejection. It also enabled some patients to discontinue steroid therapy, maximizing growth potential. PTLD is a severe, potentially life-threatening complication that needs to be recognized and monitored closely. In conclusion, tacrolimus has been shown to be a very effective agent for the treatment of refractory organ rejection, but must be used cautiously.

Clinical performance of an in-line point-of-care monitor in neonates.

To evaluate the bias, precision, and blood loss characteristics of an ex vivo in-line point-of-care testing blood gas and electrolyte monitor designed for use in critically ill newborn infants. Study participants included consecutive neonates with an umbilical artery catheter (UAC) in use for clinical laboratory testing. The in-line monitor (VIA LVM Blood Gas and Chemistry Monitoring System, VIA Medical, San Diego, CA) was directly connected to the participant's UAC and the monitor's determinations of pH, PCO(2), PO(2), sodium, potassium, and hematocrit (Hct) were compared with those simultaneously drawn and measured with a standard bench top laboratory instrument (Radiometer 625 ABL; Radiometer America, Inc, Westlake, OH). The bias (the mean difference from the reference method) and precision (1 standard deviation of the mean difference) performance criteria of the in-line monitor were derived using standard laboratory procedures. Sixteen neonates monitored for a total of 37 days had a total of 229 paired blood samples available for comparison by the 2 methods. Bias and precision performance characteristics of the in-line monitor were similar to reports of other point-of-care devices (ie, pH: -.003 +/-.024; PCO(2):.35 +/- 2.84 mm Hg; PO(2):.39 +/- 7.30 mm Hg; sodium:.52 +/- 2.34 mmol/L; potassium:.17 +/-.18 mmol/L; and Hct:.61 +/- 2.80%). The range of values observed for each parameter included much of the range anticipated among critically ill neonates (ie, pH: 7.15-7.65; PCO(2): 25-75 mm Hg; PO(2): 25-275 mm Hg; sodium: 127-150 mmol/L; potassium: 2.6-5.5 mmol/L; and Hct: 32%-60%). Mean blood loss (+/- standard deviation) per sample with the in-line monitor was approximately one-tenth that of the reference method: 24 +/- 7 microL versus 250 microL, respectively. There was no evidence of hemolysis and no patient related safety issues were identified with use of the in-line monitor. Repeated laboratory testing of critically ill neonates using an ex vivo in-line monitor designed for use in neonates provides reliable laboratory results. The blood loss and hemolysis data obtained suggests that this monitoring device offers potential for reducing neonatal blood loss-and possibly transfusion needs-during the first weeks of life. Before this promising technology can be routinely recommended for care of critically ill neonates, greater practical experience in a variety of clinical settings is needed.

Successful bone marrow transplantation in a child with red blood cell pyruvate kinase deficiency

We report the first successful use of BMT for the treatment of RBC pyruvate kinase (PK) deficiency in a boy who developed neonatal jaundice and severe transfusion-dependent hemolytic anemia a few months after birth. He received a BMT at the age of 5 from an HLA-identical sister who has normal PK activity after conditioning with busulfan and cyclophosphamide. The post-transplant course was uneventful. At present, 3 years after transplant, he is 8 years old and has a normal hemoglobin level and normal RBC PK activity without evidence of hemolysis. DNA analysis has confirmed full engraftment.

Pre-eclampsia and eclampsia

LTHOUGH pre-eclampsia and eclampsia affect only a small proportion of all pregnancies, they account for substantial obstetric morbidity and mortality.l2 Pre-eclampsia affects approximately 6% to 8% of all pregnancies, whereas eclampsia has an incidence of 1/1,000 to 1/2,000 deliveries in the United States. However, hypertension during pregnancy is responsible for up to 19% of maternal deaths in the United States. Most maternal deaths in pre-eclamptic women occur from either cerebral hemorrhage or adult respiratory distress syndrome. These complications are usually related to substandard care, the most common factor being a delay in treating the disease aggressively. Other lapses in care include poorly controlled hypertension, delayed delivery to allow fetal maturity, neglect of worsening symptoms, and inadequate postpartum management. Inadequate control of hypertension with subsequent cerebral hemorrhage remains a common, preventable cause of maternal death. Inadequate prophylaxis and treatment of eclamptic seizures is also a common contributor to maternal death. Although the exact etiology of pre-eclampsia is unknown, several factors predispose to preeclampsia, including nulliparity (85% of cases), African-American race, history of previous preeclampsia, family history of pre-eclampsia, obesity, lupus erythematosus, protein S and protein C deficiency, chronic hypertension, renal disease, insulin-dependent diabetes, and conditions associated with rapid uterine growth (eg, macrosomia). Hypertension is commonly an isolated finding with no further complications. However, some women also develop renal, central nervous system, cardiovascular, and/or hematologic dysfunction. The American College of Obstetricians and Gynecologists (ACOG) categorize hypertensive disorders of pregnancy as follows: (1) pregnancy induced hypertension~women who develop hypertension during pregnancy; pre-eclampsia-hypertensive women who also develo p proteinuria; eclampsia--preeclamptic women who also experience seizures/or coma; HELLP syndrome--thrombocytopenia with evidence of hemolysis and increased liver enzymes in pre-eclamptic women; (2) chronic hypertension--hypertension that precedes pregnancy; and (3) chronic hypertension with superimposed pre-eclampsia/eclampsia. With regard to anesthetic management, improper selection of anesthesia and inadequate control of hypertension during anesthesia are the most common reasons for morbidity and mortality. To minimize the possibility of a poor outcome, anesthesiologists must understand pre-eclampsia and eclampsia with their complex pathophysiology and variable presentation and have an optimal plan for anesthetic management.