Moderate Hemolysis Research Articles

Guidelines for the diagnosis and management of hereditary spherocytosis

Hereditary spherocytosis (HS) is a heterogeneous group of disorders with regard to clinical severity, protein defects and mode of inheritance. It is relatively common in Caucasian populations; most affected individuals have mild or only moderate haemolysis. There is usually a family history, and a typical clinical and laboratory picture so that the diagnosis is often easily made without additional laboratory tests. Atypical cases may require measurement of erythrocyte membrane proteins to clarify the nature of the membrane disorder and in the absence of a family history, occasionally molecular genetic analysis will help to determine whether inheritance is recessive or non-dominant. It is particularly important to rule out stomatocytosis where splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 years and with appropriate counselling about the infection risk. In all cases careful dialogue between doctor, patient and the family is essential. Laparoscopic surgery, when performed by experienced surgeons, can result in a shorter hospital stay and less pain.

An experimental model of hemolysis-induced acute pancreatitis.

The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

Temporary donor-derived B-lymphocyte microchimerism leading to hemolysis in minor AB0-incompatible renal transplantation

AT THE BEGINNING of the 21st century the term “compatibility” took on new relevance. The compatibility in the ABO system should mean “identity”. The nonidentical transfusions, bone marrow and solid organ transplants, should be divided into minor and major incompatible groups with unambiguous distinctions in our procedure manuals. To date, the most important principle in transfusion and transplantation medicine has been to avoid the transmission of any incompatible antigen of the ABO system. There has been even less concern regarding the transfusion of incompatible antibodies. A unique way of transmitting incompatible antibodies is by transplantation of antibody-producing B lymphocytes through bone marrow or solid organ transplantation. This kind of microchimerism may be followed by incompatible antibody production leading to delayed moderate hemolysis. Donor-derived ABO antibodies have a tendency to destroy the recipient’s red blood cells.

Use of a new HemoCue system for measuring haemoglobin at low concentrations.

In many photometers and spectrometers used in routine practice Beer's law (relating absorbance to concentration) fails at low concentrations. A refinement of the HemoCue haemoglobin system (HemoCue AB, Sweden) provides a facility for accurate measurement of haemoglobin at the lower end of the scale. This study confirmed excellent linearity of the photometer response of the HemoCue Plasma/Low Hb photometer to haemoglobin concentration by direct measurement on whole blood samples, thus providing a reliable method when laboratory facilities are limited and where critical patient management may be dictated by the severity of anaemia. Furthermore, measurements on plasma and on samples of urine containing haemoglobin demonstrated the utility of the device for reliable quantification of plasma haemoglobin and haemoglobinuria, thus providing a useful method in investigating moderate or severe intravascular haemolysis. A study of plasma haemoglobin on stored samples of ethylenediamine tetraacetic acid (EDTA) blood showed that a small but measurable degree of lysis occurs after two days at room temperature and after four days when stored at 4 degrees C. This effect on the red cell count will reflect on the reliability of using such blood as a quality control preparation.

Clinical experience with nine patients supported by the continuous flow Debakey VAD

Introduction: Pulsatile left ventricular assist devices (LVADs) have been established for bridging of selected patients with advanced congestive heart failure to transplantation. Their clinical application, however, has been complicated by bleeding, thromboembolic and infectious adverse events. Recently, continuous flow LVADs have been introduced. They are expected to be associated with a reduced risk for such complications. Here we report our experience with 9 patients on the continuous flow DeBakey VADTM. Patients and Methods: Since February 2000, 9 patients have been supported by the continuous flow DeBakey VADTM at our institution (all male, 38.6613.1 years, 3 DCM, 3 ICM, 1 congenital, 1 postcardiotomy, 1 myocardial infarction). Before implantation, patients were in severe heart failure (NYHA IV) requiring inotropic support. Cardiac index was 1.6460.49 l/min/m2. All patients fulfilled the requirements for listing to heart transplantation and were put on the waiting list at the time of LVAD implantation. Results: Current total support time (as of October 17, 2000) amounts to 900 patient days (14 2 232 days). One patient was transplanted 226 days following LVAD implantation, six patients are currently still on LVAD support. One patient died on postoperative day (POD) 14 due to multiorgan failure developing following preoperative cardiogenic shock due to myocardial infarction, one patient died on POD 15 after a thrombus generated from the left ventricle had caused the pump to stop. Bleeding complications requiring rethoracotomy occurred in 3 patients. There was no thromboembolic event. No driveline or device infection was observed. Moderate hemolysis was seen in 3 patients. In 4 patients, the LVAD was replaced (POD 76, 76, 137, 170) for another DeBakey VADTM. Device exchanges were associated with thrombus; however, its origin could not be determined. Conclusion: Our experience with the DeBakey VADTM indicates that it is associated with a low risk for bleeding, hemolysis, thromboembolic and infectious complications which makes it a valuable alternative to pulsatile LVADs. Thrombus in the pump may be addressed with improved anticoagulation and platelet inhibition.

Therapy of thromboembolic blockages in the crural arteries: Clinical experience with the Angiojet thrombectomy catheter

To investigate the clinical impact of a new hydrodynamic thrombectomy catheter in thromboembolic occlusion of tibial arteries. 10 patients with thromboembolic occlusion of all tibial arteries were treated with the Angiojet thrombectomy device in order to reestablish blood flow. Depending on angiographic and clinical results of thrombectomy, additional thrombolysis, PTA, recanalization, or surgical bypass grafting was performed. Antegrade blood flow in at least one tibial artery was reestablished in 6 cases with the thrombectomy device. However, additional treatment modalities were used in order to improve the outcome and to resolve adherent thrombi or to treat vessel stenoses and occlusions: thrombolysis (n = 9), PTA (n = 3), recanalization (n = 1), bypass grafting (n = 3), suction thromboembolectomy (n = 1), replacement of popliteal aneurysm (n = 1). The limb salvage rate was 7/10. The ratio of injected volume to aspiration volume was 1.04 +/- 0.07 indicating that the system works isovolumetrically. The device induced moderate hemolysis with plasma free hemoglobin rising by the factor 12.91 +/- 11.59, (P < 0.01). In cases with thromboembolic occlusions of tibial arteries the Angiojet thrombectomy catheter is a valuable addition to the interventional instrumentarium. It works isovolumetrically but induces moderate hemolysis and thereby may compromise renal function. However, in most cases additional treatment modalities are required.

Amniotic fluid nitric oxide metabolites, cyclic guanosine 3′,5′ monophosphate and dimethylarginine in alloimmunized pregnancies

Objective: To determine the relationship between gestational age or the Liley index (the severity of fetal hemolysis) and the amniotic fluid total nitrite (NOx), cyclic guanosine 3′,5 ′monophosphate (cGMP) and dimethylarginine (DMA) concentrations. We hypothesized that the concentrations of these components change because of fetal growth or adaptation to fetal anemia. Study Design: Amniotic fluids ( n=64) were obtained between 23 and 37 weeks from fifty-three patients at risk for alloimmunization. Amniotic fluids from the pregnancies with a Liley index=1 were considered as controls ( n=17). Creatinine (C, μMol) was determined with the Jaffé reagent, nitrite (NOx, μMol) with the Griess reagent, cGMP (nMol) by an enzyme immunoassay and DMA (μMol) after HPLC. Multiple regression analysis was used for separating the effects of growth and the estimated degree of anemia. Results: The concentration of NOx, cGMP and DMA was not related to the Liley index or whether or not the fetuses needed blood transfusions. The concentrations of creatinine (C), NOx and cGMP increased during pregnancy (in weeks;W) (C=−69.2+6.28W; r 2=0.532; P<0.0001, NOx=−17.6+ 1.29W; r 2=0.106; P=0.01, cGMP=−20.9+1.05W; r 2=0.414; P<0.0001). The DMA concentration (3.8±0.8(SD) and the NOx/creatinine ratio (181±110 mM/M) did not change with gestational age. The cGMP/creatinine ratios (μM/M) increased (cGMP/C=−41.8+4.31W; r 2=0.134; P=0.007) whereas the DMA/creatinine ratio (mM/M) declined during pregnancy (DMA/C=73.1−1.34W; r 2=0.278; P=0.0002). Consequently, the NOx/DMA and cGMP/DMA ratios increased (NOx/DMA=−6.96+0.43W; r 2=0.105; P=0.02, cGMP/DMA=−5.9+0.29W ; r 2=0.391; P<0.0001). Conclusions: The concentrations in amniotic fluid of cGMP and NOX, but not of DMA increase during gestation. The cGMP/creatinine ratio increases also whereas that of DMA decreases. The changes in products of the NO–cGMP pathway are independent of mild to moderate fetal hemolysis and may result from fetal growth as well as from reduced inhibition of NO synthase by DMA. Gestational age related effects should be taken into account when analyzing nitric oxide metabolites in amniotic fluids.

Red blood cell membrane disorders.

The recent discovery of the specific molecular defects in many patients with hereditary spherocytosis and hereditary elliptocytosis/pyropoikilocytosis partially clarifies the molecular pathology of these diseases. HE and HPP are caused by defects in the horizontal interactions that hold the membrane skeleton together, particularly the critical spectrin self-association reaction. Single gene defects cause red cells to elongate as they circulate, by a unknown mechanism, and are clinically harmless. The combination of two defective genes or one severe alpha spectrin defect and a thalassaemia-like defect in the opposite allele (alphaLELY) results in fragile cells that fragment into bizarre shapes in the circulation, with haemolysis and sometimes life-threatening anaemia. A few of the alpha spectrin defects are common, suggesting they provide an advantage against malaria or some other threat. HS, in contrast, is nearly always caused by family-specific private mutations. These involve the five proteins that link the membrane skeleton to the overlying lipid bilayer: alpha and beta spectrin, ankyrin, band 3 and protein 4.2. Somehow, perhaps through loss of the anchorage band 3 provides its lipid neighbours (Peters et al, 1996), microvesiculation of the membrane surface ensues, leading to spherocytosis, splenic sequestration and haemolysis. Future research will need to focus on how each type of defect causes its associated disease, how the spleen aggravates membrane skeleton defects (a process termed 'conditioning'), how defective red, cells are recognized and removed in the spleen, and why patients with similar or even identical defects can have different clinical severity. Emphasis also needs to be given to improving diagnostic tests, particularly for HS, and exploring new options for therapy, like partial splenectomy, which can ameliorate symptoms while better protecting patients from bacterial sepsis and red cell parasites, and perhaps from atherosclerosis (Robinette & Franmeni, 1977) and venous thrombosis (Stewart et al, 1996).

PLASMID MEDIATED DRUG RESISTANCE IN VIBRIO CHOLERAE 0139 BENGAL

Sixteen strains of Vibrio cholerae were isolated from cases of diarrhoea. Out of these, 12 (75%) were identified as Vibrio cholerae 0139 synonym Bengal and 4 (25%) as Vibrio cholerae El Tor by standard biochemical and serological tests. Modified CAMP reaction in sheep blood agar showed that 0139 produced moderate hemolysis, El Tor produced wider zone of hemolysis whereas Classical Vibrio cholerae produced no zone of hemolysis (CAMP negative). Break point minimum inhibitory concentration (MIC) by agar dilution method showed that all 0139 strains were resistant to ampicillin 8 mg/L, streptomycin 1 mg/L, chloramphenicol 8 mg/L, sulphamethoxazole 32 mg/L and trimethoprim 0.3-128 mg/L, 58.3% were sensitive to gentamicin 1 mg/L, and all were sensitive to norfloxacin 1 mg/L and cefotaxime 1 mg/L. Resistance to trimethoprim, sulphamethoxazole, ampicillin and gentamicin in 5 strains could be transferred to E coli K-12 by conjugation experiment at a rate of 5×10-6 to 4×10-3. Distinct plasmid bands of 35.8 mega daltons could be seen in agarose gel electrophoresis.

Hereditary xerocytosis: a report of six unrelated Spanish families with leaky red cell syndrome and increased heat stability of the erythrocyte membrane.

Hereditary xerocytosis (HX) is a rare haemolytic disease due to dehydrated red blood cells (RBCs). A unique feature of this syndrome is that affected members often show normal or near normal haemoglobin levels despite clinical and laboratory evidence of mild to moderate haemolysis. The diagnostic clue is the association of markedly increased RBC Na+ + K+ fluxes with low total cation (Na+ + K+) content. 11 patients of six unrelated families of Spanish origin with HX have been studied from clinical, genetical and biological points of view. In addition, we have investigated the sensitivity of RBC membrane to heat at three different incubation times (15, 30 and 60 min) and two different temperature values (46 degrees C and 49 degrees C). Under these conditions control RBCs (50 normal subjects) exhibited at 49 degrees C and 30 min a maximum of 30% fragmented RBCs. This value increased to 80% after 60 min of incubation. In contrast, patients with HX showed significantly lower percentages of fragmented RBCs at both 30 and 60 min of incubation (maximum 10% and 30%, respectively). In an attempt to determine if increased heat stability was unique to HX RBCs, several other congenital membranopathies with haemolytic anaemia were also studied. The degree of fragmentation, except in one case of HPP (which was strongly increased), did not differ from the control group. Electrophoretic studies of membrane proteins performed in RBCs of all the patients with HX did not explain any qualitative nor quantitative abnormality. In addition to its physiopathological interest, study of RBC heat stability, together with other haematological parameters (increased MCHC and decreased RBC osmotic fragility), may be useful for HX diagnosis, especially in laboratories which are not equipped to evaluate RBC membrane permeability.

Hemolysis in primary lipoprotein lipase deficiency

A slight to moderate hemolysis is often present in plasma from patients with primary lipoprotein lipase (LPL) deficiency. To determine the nature of this hemolysis, we measured erythrocyte hypo-osmotic fragility, plasma free hemoglobin, and phospholipid composition in 26 patients with primary LPL deficiency and 21 unrelated controls. In some patients, these investigations were completed by erythrocyte cytoskeletal protein determinations and abdominal echography. Osmotic fragility was similar between control subjects and patients. However, there was a significantly increased concentration of plasma free hemoglobin in primary LPL deficiency (0.282 ± 0.331 v 0.048 ± 0.038 g/L in controls, P < .005). In LPL-deficient patients, an increase of plasma lysophosphatidylcholine concentration (12.6% ± 5.8% v 6.4% ± 1.9% in controls, P < .0001) was also found. The protein composition of the erythrocyte membrane skeleton was abnormal in some LPL-deficient patients and splenomegaly was present in 12, but these abnormalities did not correlate with plasma free hemoglobin levels. Bilirubin and haptoglobin levels were also within physiologic ranges in these patients, suggesting that the observed hemolysis did not result from hypersplenism. It appears likely that the accumulation of lysophosphatidylcholine was due to an impairment in the reverse metabolic pathway converting lysophosphatidylcholine back to phosphatidylcholine. Collectively, these data, along with a positive correlation between plasma free hemoglobin and lysophosphatidylcholine levels ( r = .58, P = .0001), suggest that the hemolysis observed in primary LPL deficiency is mediated to some extent by the abnormally elevated concentration of lysophosphatidylcholine.

A Deletional Frameshift Mutation of the β-Spectrin Gene Associated With Elliptocytosis in Spectrin Tokyo (β220/216)

AbstractA novel spectrin variant carrying a truncated β-chain and designated Spectrin Tokyo (β220/216) is presented. It was associated with elliptocytosis and moderate uncompensated hemolysis. The dimer self-association was reduced. An increase of the al 74-Kd fragment was detected upon partial trypsin digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon 2059 (GCC AGC → GCA GCT; Ala-Ser → Ala-Ala) that belongs to exon X of spectrin β-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a potential phosphorylation site, was replaced by alanine. The shortened β-chain failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (β220/216), which is caused by a dinucleotide insertion in codon 2046 and contains 2076 amino acids. However, for some reason, Spectrin Tokyo had a lower incorporation level into the membrane than Spectrin Nice.

A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216)

A novel spectrin variant carrying a truncated beta-chain and designated Spectrin Tokyo (beta 220/216) is presented. It was associated with elliptocytosis and moderate uncompensated hemolysis. The dimer self-association was reduced. An increase of the alpha I 74-Kd fragment was detected upon partial trypsin digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon 2059 (GCC AGC-->GCA GCT; Ala-Ser-->Ala-Ala) that belongs to exon X of spectrin beta-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a potential phosphorylation site, was replaced by alanine. The shortened beta-chain failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (beta 220/216), which is caused by a dinucleotide insertion in codon 2046 and contains 2076 amino acids. However, for some reason, Spectrin Tokyo had a lower incorporation level into the membrane than Spectrin Nice.

Haptoglobin as a sensitive marker of hemolysis in hellp-syndrome

In a prospective study we measured laboratory variables of hemolysis in 25 patients with HELLP-syndrome. Reduced haptoglobin levels were observed in all 25 patients at diagnosis. Elevated bilirubin and plasma hemoglobin levels were observed in 5 25 patients while an abnormal peripheral blood smear was found in 11 25 patients. Our results suggest that haptoglobin is a sensitive parameter for early detection of moderate hemolysis in HELLP-syndrome and should be included in laboratory screening to aid diagnosis.

1991 Sir Henry Wellcome Medal and Prize Recipient

Studies were carried out to determine the comparative toxicity and pathophysiology of 13 of the more poisonous snakes indigenous to Saudi Arabia. Included were four snakes from the Viperidae family, six from the Elapidae family, and three representative sea snakes from the family Hydrophidae. Anesthetized adult beagle dogs and anesthetized monkeys were used in the study. Vital physiological functions were continuously recorded as were changes in the blood coagulation system and any tissue damage produced by the venom at the site of envenomation. For the intravenous administration of the venom, lyophilized venom was obtained by "milking" each of the live specimens used in the study. Actual envenomation was accomplished by grasping the poisonous reptile and allowing the snake to strike the shaved exposed gluteal muscle of the anesthetized animal. Venom from the snakes of the family Viperidae produced death in an average of 3 hours. The average lethal dose was 1.13 mg/kg. Depression of first and second stage clotting factors was observed with these venoms as well as a decrease in fibrinogen levels and in platelet counts. Findings suggestive of intravascular coagulation were also observed with moderate hemolysis of the formed elements. Some local hemorrhage was seen at the site of envenomation. Venom from the Elapidae family of snakes produced death at an average of 1.7 hours. The average lethal dose was 0.70 mg/kg. Death appeared to be primarily due to respiratory paralysis following blockade at the neuromuscular junction. Only moderate hemolysis was seen with these venoms. No intravascular coagulation or tissue damage was seen. The venom of the family Hydrophidae consistently produced death in less than 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of xanthopterin in chronic renal failure.

Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in hemodialysis patients (p < 0.02). Intermediate levels from patients with renal insufficiency not on dialysis correlated with serum creatinine levels (p < 0.001). Xanthopterin (MW 179) was cleared by hemodialysis at a slightly lower rate than creatinine. It is bound to protein, but the binding, 90 +/- 5% in normal subjects, is decreased in uremia to 60 +/- 15%, p < 0.01. Red cell levels of xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate hemolysis induced by mechanical stress increased plasma xanthopterin levels by 35%, the effect being more pronounced when hemolysis was severe. We conclude that xanthopterin is increased and its binding to protein is decreased in chronic renal failure. The altered ratio of red cell/plasma xanthopterin levels may reflect an abnormality of the red cell membrane in uremia. We are conducting further studies to amplify our preliminary findings that xanthopterin inhibits cellular growth in vitro.

Effect of delayed centrifugation or reading on the detection of ABO incompatibility by the immediate‐spin crossmatch

The immediate-spin (IS) crossmatch is a method that detects ABO incompatibility. However, under certain circumstances, this test may show unwanted negative or weak results, even though the red cells (RBCs) and serum being tested are ABO incompatible with each other. The present study investigated the potential effect of delayed centrifugation or reading on the IS crossmatch test performance. When the centrifugation step of the IS crossmatch between group O sera and group A1 RBCs was delayed for 2 minutes, 5 of 200 crossmatches showed no agglutination with only trace (n = 2) or moderate (n = 3) hemolysis, and one crossmatch showed only weak, macroscopic agglutination, but moderate hemolysis. All six sera contained A antibodies that were lytic in vitro and, therefore, probably were capable of causing in vivo hemolysis of transfused A1 RBCs. Delaying the reading of the IS crossmatch test for 2 minutes had no apparent effect on test performance. These data demonstrate the importance of technologists' recognition of hemolysis as a positive result on IS crossmatches, especially if the performance of the centrifugation step of the test is delayed. Furthermore, the unwanted negative agglutination results were abolished by suspending the group A1 RBCs in saline containing EDTA. The authors' laboratory has modified its IS crossmatch procedure so that donor RBCs are routinely suspended in saline containing EDTA before testing. This procedural change should increase the safety of the IS crossmatch.

A study of the necrotic actions of the venom of the wolf spider, Lycosa godeffroyi, on mouse skin

1. 1. The venom of the wolf spider, Lycosa godeffroyi, caused cutaneous necrosis when injected into mice. 2. 2. A strong inflammatory response and total loss of epidermal cellularity were features of this in vivo necrosis. 3. 3. Mouse skin envenomated while in tissue culture showed epidermal detachment and reduced cellular adhesion. 4. 4. Triprolidine and methysergide, used together, indomethacin, heparin and human and mouse sera all failed to inhibit the necrosis significantly. 5. 5. The venom caused moderate haemolysis, complement consumption and inhibition of clotting, these apparently not being the main reasons for the necrosis. 6. 6. Neither Atrax infensus venom nor hyaluronidase caused similar epithelial damage.

Pathogenesis of anemia due to kidney disease

Several factors contribute to the pathogenesis of anemia due to renal failure. Hypoproliferation of red cell progenitors may be caused partially by an inhibitory effect of some 'uremic toxins' whose existence certainly is very controversial. Iron deficiency due to gastrointestinal and dialysis-related blood losses and occasionally aluminum intoxication may interfere with the maturation of the erythron. Moderate hemolysis with shortening of red cell survival to some 50% of normal may be an additional factor. The main cause of anemia is, however, inadequate production of erythropoietin by the diseased kidney. This latter factor has now become amenable to treatment.

Clinical and hemodynamic assessment of the Omniscience prosthetic heart valve

From 1980 to 1985, 154 Omniscience valve prostheses were implanted in 132 patients (mitral in 72, aortic in 33, and both in 27), 81 women and 51 men, aged 22 to 72 years. There were 13 early deaths (30 day mortality of 9.8%) and nine late deaths. The actuarial survival rate was 79.1% after 4 years, and survival rates after aortic, mitral, and multiple valve replacement were 71.8%, 80%, and 85.2%, respectively. After a postoperative follow-up period averaging 27 months, 96% of the survivors were in Class I or II. The linearized incidence of thromboembolism, hemorrhagic episodes, and reoperation was 3.8%, 3.4%, and 2.3% per patient-year, respectively. After 4 years, freedom from valve-related mortality, valve-related mortality and reoperation, thromboembolic episodes, and all valve-related complications was 93%, 89%, 88%, and 70%. Moderate hemolysis with increases of reticulocyte count and serum lactic dehydrogenase above normal values was found in 80% of the patients, but only one had hemolytic anemia. In 22 patients, the maximal opening angle of the prosthetic disc averaged 54 +/- 11 degrees. Postoperative hemodynamic evaluation was obtained in five patients with aortic prostheses and in 13 with mitral prostheses. Mean aortic gradient and effective orifice area averaged 17.6 mm Hg and 1.2 cm2 at rest and increased to 18.8 mm Hg and 1.7 cm2 with exercise. With mitral prostheses, these values averaged 6.5 mm Hg and 1.9 cm2 at rest and 15.4 mm Hg and 2.1 cm2 with exercise. Thus excellent clinical improvement is obtained with the Omniscience prosthesis; however, the hemodynamic performance of the valve and opening of the tilting disc are suboptimal, causing the prosthesis to be moderately obstructive to blood flow.