Subclinical Hemolysis Research Articles

Inferior Vena Cava Filters as a Potential Non-immune Cause of Low Serum Haptoglobin

Objective: Serum haptoglobin level is commonly used as a marker of hemolysis. We hypothesized that inferior vena cava (IVC) filters may be a potential non-immune etiology for subclinical hemolysis and low haptoglobin in some patients, after encountering a patient with an IVC filter, mild macrocytic anemia and unexplained severe haptoglobinemia. IVC filters can be associated with pressure gradients and turbulent blood flow in the presence of trapped clots and thrombus formation. Methods: Prospective study in patients undergoing IVC filter placement at our institution over a 3-month period in 2008. All patients had a haptoglobin level prior to filter placement, and then daily for a period of 3-14 days. The absolute and relative change in haptoglobin compared to pre-procedure levels was determined. Results were evaluated by t-test (paired, 2-tail). Statistics and graphics were performed with commercial software. Results: A total of 22 patients underwent IVC filter placement. Four patients were excluded due to low preprocedure haptoglobin levels. At least one post-procedure haptoglobin values was available until day 3 in 18/18 eligible patients. Nine patients were followed for a period of 1-2 weeks. Although the majority of patients had an increase in haptoglobin after IVC filter placement, 3/9 (30%) had >50% decrease in haptoglobin by day 7, including one patient with severe haptoglobinemia by day 14. Patients with decreased haptoglobin levels also had decreases in platelet count over the same period. Conclusion: These results suggest that IVC filters may be another non-immune, device-related cause of decreased haptoglobin in some patients.

Simultaneous transcatheter closure of an atrial septal defect and patent ductus arteriosus in an adult case, followed by thrombocytopenia and subclinical hemolysis

Simultaneous transcatheter closure of an atrial septal defect and patent ductus arteriosus in an adult case, followed by thrombocytopenia and subclinical hemolysis

Erythrocyte creatine as a marker of intravascular hemolysis due to left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

BackgroundErythrocyte creatine, a marker of erythrocyte age that increases with shortening of erythrocyte survival, has been reported to be a quantitative and reliable marker for intravascular hemolysis. We hypothesized that hemolysis could also occur due to intraventricular obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the presence of subclinical hemolysis and the relation between intravascular hemolysis and intraventricular pressure gradient (IVPG). Methods and resultsWe measured erythrocyte creatine in 92 HCM patients. Twelve patients had left ventricular outflow tract obstruction (LVOTO), 4 had midventricular obstruction (MVO), and the remaining 76 were non-obstructive. Erythrocyte creatine levels ranged from 0.92 to 4.36μmol/g hemoglobin. Higher levels of erythrocyte creatine were associated with higher IVPG (r=0.437, p<0.001). If erythrocyte creatine levels are high (≥1.8μmol/g hemoglobin), subclinical hemolysis is considered to be present. Half of LVOTO patients and no MVO patients showed high erythrocyte creatine levels. Although non-obstructive patients did not show significant intraventricular obstruction at rest, some showed high erythrocyte creatine levels. When LVOT-PG was measured during the strain phase of the Valsalva maneuver in 20 non-obstructive patients, 7 of those 20 patients showed LVOTO. In the 20 patients, there was no relation between erythrocyte creatine levels and LVOT-PG before the Valsalva maneuver (r=0.125, p=0.600), whereas there was a significant correlation between erythrocyte creatine and LVOT-PG provoked by the Valsalva maneuver (r=0.695, p=0.001). ConclusionsThere is biochemical evidence of subclinical hemolysis in patients with HCM, and this hemolysis seems to be associated with LVOTO provoked by daily physical activities.

Significance of the detection of paroxysmal nocturnal hemoglobinuria clones in patients with multiple myeloma undergoing autologous stem cell transplantation

There are reports about the presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in multiple myeloma (MM), but these have been demonstrated only in red blood cells (RBCs) and the previous reports utilized an obsolete diagnostic method. We carried out a study to identify the clones by flow cytometry (FC) and to understand their clinical significance. A prospective study on consecutive patients with newly diagnosed MM who were candidates for autologous stem cell transplantation (ASCT) from 2008 to 2012. We screened peripheral blood samples by FC for CD55- and/or CD59-deficient RBC, neutrophils, and monocytes. PNH testing was carried out at diagnosis, before ASCT and 3 months after ASCT, as well as sporadically during MM remission and at disease relapse. A total of 31 patients were included in the study. PNH clones reaching a median size of 10.8% (range 4.0-18.7%) were found in 10 patients (32.3%). Clones were detected at diagnosis in nine patients and 3 months after ASCT in one patient. A correlation between the presence of the clones and subclinical hemolysis was observed. Nevertheless, the presence of the clones did not influence the overall management and prognosis of the patients. We confirmed findings of previous reports with current diagnostic guidelines and showed that although the size of the clones may be relatively large, their presence is probably not detrimental. The clinical significance of these clones and the possible mechanisms underlying their expansion in MM must be a subject of further investigation.

Incidence and Risk Factors of Hemolysis After Transcatheter Aortic Valve Implantation With a Balloon-Expandable Valve

There are currently no data evaluating the hematologic and biocompatibility profile of transcatheter aortic valves invivo. We evaluated the incidence, predictive factors, and clinical consequences associated with hemolysis post-transcatheter aortic valve implantation (TAVI). A total of 122 patients who underwent TAVI with a balloon-expandable valve were included. Baseline blood sampling and echocardiography, followed by early post-TAVI echocardiography and repeat blood sampling, at 6 to 12months post-TAVI were performed. Hemolysis post-TAVI was defined according to the established criteria. The incidence of hemolysis post-TAVI was 14.8% yet no patient experienced severe hemolytic anemia requiring transfusion. Compared with the nonhemolysis group, those with hemolysis demonstrated significant reductions in hemoglobin (p= 0.012), were more frequently women (67% vs 34%, p= 0.016), and had a higher incidence of post-TAVI severe prosthesis-patient mismatch (PPM) (44% vs 17%, p= 0.026). The rate of mild or more prosthetic valve regurgitation did not significantly differ between those patients with and without hemolysis (56% vs 37%, p= 0.44). Wall shear rate (WSR) and energy loss index (ELI), both indirect measures of shear stress, were higher (p= 0.039) and lower (p= 0.004), respectively, in those patients with hemolysis. Increasing PPM severity was also associated with significant stepwise WSR increments and ELI decrements (p <0.01 for both). In conclusion, subclinical hemolysis occurred in 15% of patients following TAVI. Although prosthetic valve regurgitation had no impact on hemolysis, a novel association between PPM and hemolysis was found, likely driven by higher shear stress as determined by WSR and ELI. These hematologic and biomechanical findings may have long-term clinical implications and could affect future transcatheter aortic valve design.

Two Patients with Low HbA1c Levels Due to Subclinical Hemolysis

Two Patients with Low HbA1c Levels Due to Subclinical Hemolysis

Cation Leak in Red Blood Cells of Patients with Wiskott-Aldrich Syndrome Leads to Non-Immunologic Hemolysis

Wiskott-Aldrich Syndrome (WAS) is a primary immunodeficiency that is associated with microthrombocytopenia. Autoimmunity is one of the defining characteristics of severe WAS, and can contribute to the decision to proceed to hematopoietic cell transplantation. Autoimmune Hemolytic Anemia (AIHA) is one of the most common autoimmune syndromes found in WAS. Even in the absence of AIHA, some patients with WAS have anemia, and this is often of unclear etiology.We studied 29 patients with WAS, 6 of whom had had splenectomy, on 46 occasions. All patients were found to have anisopoikilocytosis. Common red blood cell (RBC) variants included stomatocytes, xerocytes, eccentrocytes, dacryocytes, spherocytes and target cells. Two WAS knockout mice whose blood smears were studied also had poikilocytosis, with dacryocytes predominating. The average hemoglobin in humans with WAS was 13.3 g/dL. In 19/46 measurements, hemoglobin was below the lower limit of normal for age. LDH was elevated in 1/43 measurements, and bilirubin was elevated in 7 of 46 measurements, 4 measurements being from a patient with molecularly diagnosed Gilbert’s syndrome. Average MCHC was 34.7 g/dL, with MCHC being elevated in 3/43 measurements. Despite these unremarkable screening assays, haptoglobin was decreased in 10/45 measurements and undetectable in 6 of these 10. The average plasma free hemoglobin and plasma free oxyhemoglobin were elevated to 21.4 and 14.7 mg/dL respectively. Analysis of osmotic fragility revealed average numbers near the lower end of the normal range, with fragility in 0.6 g/dL NaCl being abnormally low in 29/35 specimens and fragility in 0.65 g/dL NaCl being abnormally low in 9/35 specimens. A standard Coomb’s test was positive in 6/39 specimens. 4 such assays were positive for IgG, 1 for C3 and 1 for neither molecule despite a positive screening assay. Using enhanced methodology, 1/5 specimens was positive only with polyspecific serum. Overall, immune mediated hemolysis was detected by either method in 6/39 specimens. These data were interpreted to be consistent with a subclinical non-immune hemolysis in 33/41 specimens from 28/29 patients.In order to evaluate these findings further, ektacytometry was performed in 5 specimens from 5 patients and intracellular cations were measured in 4 of these specimens. Ektacytometry revealed Omin of 135.8±5.1 mOsm/kg in patients with WAS and 156.4±5.3 mOsm/kg in control specimens (P=0.0002). Sodium and potassium concentrations in patients were 53.3±12.7 mmol/kg hemoglobin and 282.3±13.1 mmol/kg hemoglobin respectively. In control specimens, the concentrations were 4.4±10.5 mmol/kg hemoglobin and 297.5±14.4 mmol/kg hemoglobin (P=0.3196 and 0.1684).These data are consistent with non-immune hemolysis in most patients with Wiskott-Aldrich syndrome. This hemolysis is associated with a xerocytic ekatacytometry curve, although cation concentrations in the small number of specimens tested only trended to statistical significance. This is the first intrinsic red cell defect described in patients with WAS, emphasizing that this disease truly affects all hematopoietic lineages and not only cells of the immune system. Whether the roles of the WAS protein in actin polymerization or signal transduction are involved in these abnormal functions remains unclear and requires additional research. These findings also have implications for clinical management of WAS as they indicate that hemolysis is commonly present without necessarily defining the autoimmune, severe clinical phenotype in these patients. As autoimmunity is often an important consideration in the decision to proceed to hematopoietic cell transplantation, these data should inform the decision-making process toward this and other therapeutic modalities for WAS. DisclosuresNo relevant conflicts of interest to declare.

O-MAX Chemotherapy: High Activity in Metastatic Esophagogastric Adenocarcinoma and Possible Relation to Subclinical Hemolysis

Objectives: Our objectives were to confirm the activity of O-MAX chemotherapy in adenocarcinoma of the stomach and esophagus, particularly the high rate of complete remission (CR) and the relation of subclinical hemolysis to CR. Patients and Methods: Twenty-five patients with metastatic esophagogastric adenocarcinoma were treated with O-MAX. Two developed cancer-related hemolytic-uremic syndrome (C-HUS); both achieved CR. Subsequent patients were monitored for serum haptoglobin for subclinical hemolysis. Results: Median survival was 16.5 months. The objective response rate was 90%, with 38% CR. Three patients achieving CR relapsed in the central nervous system and died (2 without systemic disease). Four patients have remained alive, off therapy, the longest for 20 years. Two patients developed clinical C-HUS and 5 of 8 monitored patients developed subclinical hemolysis based on abnormal serum haptoglobin. Four of the patients with subclinical hemolysis achieved CR. Of the 7 patients developing clinical C-HUS or subclinical hemolysis, 6 (86%) achieved CR. Conclusions: O-MAX appears highly active in esophagogastric adenocarcinoma. A few long-term survivors of metastatic disease are being seen. CR and long-term survival appear to correlate with the development of hemolysis. Although highly promising, these results should be considered only as hypothesis-generating and require confirmation in a prospective trial.

Baseline red blood cell osmotic fragility does not predict the degree of post-LVAD hemolysis.

Continuous-flow left ventricular assist devices (LVADs) subject elements of the blood to significant stress, resulting in clinically significant and subclinical hemolysis. We sought to prospectively determine whether baseline red-cell osmotic fragility of an advanced heart-failure patient influences the hemolytic response to LVAD support. Osmotic fragility assesses the degree of red-blood-cell hemolysis under varying degrees of osmotic stress. Assays were prospectively obtained on 50 consecutive patients prior to placement of continuous-flow LVADs: HeartMate II (n = 34), Jarvik 2000 (n = 5), HeartWare (n = 6). The mean age of the patients was 60.2 years and 87% were male and 47% were nonischemic. The overall median post-LVAD lactate dehydrogenase (LDH) was 583 (427-965), and there was no difference between devices. Mean hemolysis was 15.68 ± 12.96% at 0.45% NaCl (the inflection point of the osmotic fragility hemolysis curve). A scatter plot did not reveal any relationship between preoperative osmotic fragility and postoperative LDH. Linear regression confirmed no predictive relationship (p = 0.71). In conclusion, preoperative variations in osmotic fragility do not appear to account for differences in hemolysis following ventricular assist device placement. Mechanical forces generated by existing LVADs result in similar levels of biochemical hemolysis, as assessed by LDH, despite baseline differences in a patient's osmotic red-cell fragility.

Increases in beta-lipoproteins in hyperlipidemic and dyslipidemic dogs are associated with increased erythrocyte osmotic fragility.

The capacity of RBCs to traverse endothelium and deliver oxygen to tissues is dependent on a mechanically stable yet flexible plasma membrane. The lipid composition of the RBC membrane is crucial in maintaining its structure and fluidity. Lacking a nucleus and having minimal synthetic capacity, RBCs are exquisitely sensitive to changes in plasma lipids. The objective of this study was to investigate the effects of plasma lipids on RBC fragility in hyperlipidemic and dyslipidemic dogs. Osmotic fragility of RBCs, plasma lipoprotein fractions, and cholesterol and phospholipid content of RBC membranes were measured in hyperlipidemic, dyslipidemic, and healthy control dogs. Osmotic fragility of normal canine RBCs incubated in phosphate-buffered saline and in both intact and lipid-depleted plasma from diabetic dogs was also measured. RBCs from hyperlipidemic and dyslipidemic dogs with diabetes mellitus and dogs treated with glucocorticoids were significantly more fragile than RBCs from healthy control dogs. RBCs from hyperlipidemic dogs with cholestatic disease tended to be more stable relative to RBCs from controls. RBC osmotic fragility was positively correlated with beta-lipoprotein levels, but was only weakly correlated with serum cholesterol concentration. Incubation in plasma from hyperlipidemic diabetic dogs rendered RBCs from healthy dogs osmotically fragile, whereas lipid-depleted plasma from the same diabetic dogs had no effect. RBCs from hyperlipidemic and dyslipidemic dogs are osmotically fragile, and fragility is highly correlated with increases in beta-lipoproteins. Future studies are planned to address the consequences of lipid-induced fragility and subclinical hemolysis on endothelial cells, platelets, and coagulation.

Abstract 508: Heme-Loaded Microparticles May Connect Subclinical Intravascular Hemolysis to Endothelial Cell Injury in Type 2 Diabetes

Rational: Type 2 Diabetes induces heavy hemoglobin glycation and discrete red blood cell (RBC) fragility. Intravascular hemolysis in type 2 diabetes is not a paramount clinical feature of the disease and it receives little attention. But hyperglycemia favors hemolysis and diabetes is associated to raised circulating levels of submicrometric cell membrane fragments from RBCs, called microparticles (MPs). We hypothesized that circulating diabetic MPs could be loaded with heme and participate in oxidative vascular injury. Material and Methods: A type 2 diabetic blood collection was assembled. Diabetic and healthy RBCs were separated from platelet-free plasma (PFP) by centrifugation. We purified MPs from native PFP, or from RBCs made to vesiculate in vitro with the thrombospondin-1-derived peptide 4N1-1. We characterized the size of MPs by dynamic light scattering, and quantified the heme contained in MPs by spectrophotometry, before and after MP depletion by ultracentrifugation. We exposed vascular endothelial cells to these different MP preparations and determined radical oxygen species (ROS) production with a fluorescent probe, as well as apoptosis by fluorescence microscopy and flow cytometry. Results: Purified diabetic and healthy RBCs released MPs expressing surface phosphatidylserine. MPs from type 2 diabetic RBCs were generally larger than healthy RBC MPs and contained significantly more heme. In cultured endothelial cells, MPs from diabetic RBCs stimulated the production of ROS in a dose- and time-dependant fashion, at concentrations observed in diabetic plasma. In contrast, healthy RBC MPs and hemoglobin or heme alone had little effects at such concentrations. Moreover, overproduction of ROS was followed by endothelial apoptosis after 24h, revealed by pyknotic nuclei and degraded chromatine, as well as reduced DNA contents by flow cytometry. Conclusion: Diabetic RBC can release MPs that are loaded with heme and trigger oxydative cell injury and apoptosis in cultured endothelial cells. These results identify for the first time the fact that heme-loaded MPs vector oxidative cell injury in type 2 diabetes. Diabetic RBC MPs may thus form a novel bridge between RBC glycation, sub-clinical intravascular hemolysis and diabetic vasculopathy.

Rapid clearance of rituximab may contribute to the continued high incidence of autoimmune hematologic complications of chemoimmunotherapy for chronic lymphocytic leukemia

Rituximab is an effective treatment for autoimmune cytopenias associated with chronic lymphocytic leukemia. Despite the incorporation of rituximab into fludarabine-based chemotherapy regimens, the incidence of autoimmune cytopenias has remained high. Inadequate rituximab exposure due to rapid antibody clearance may be a contributing factor. To test this hypothesis, we measured serum rituximab levels in patients treated with fludarabine and rituximab (375 mg/m(2)). All patients had undetectable rituximab trough levels by the end of cycle 1, and one-third had undetectable levels already on Day 6 of cycle 1. Although rituximab trough levels increased progressively with each cycle, only by cycle 4 did the median trough level exceed 10 ug/mL. The median half-life of rituximab during cycle 1 was 27 hours, compared to 199 hours during cycle 4 (P<0.0001). There was a significant inverse correlation between the rituximab half-life in cycle 1 and the degree of tumor burden (P=0.02). Two patients who were identified as having subclinical autoimmune hemolysis prior to therapy were given additional doses of rituximab during the initial cycles of therapy and did not develop clinically significant hemolysis. One patient who developed clinically significant hemolysis during therapy was given additional rituximab doses during cycles 3-5 and was able to successfully complete his treatment. In conclusion, rituximab is cleared so rapidly during the initial cycles of therapy for chronic lymphocytic leukemia that most patients have only transient serum levels. More frequent dosing of rituximab may be required to prevent autoimmune complications in at-risk patients (clinicaltrials.gov identifier:00001586).

Does Red Blood Cell Fragility Predict the Degree of Post-LVAD Hemolysis?

Purpose Continuous-flow LVADs subject elements of the blood to significant shear stress. The balance between hemostasis and thrombosis that challenge all LVAD patients is potentially impacted by the development and high-prevalence of both sub-clinical and clinical hemolysis. Lactate dehydrogenase (LDH) is a readily available marker of hemolysis and can vary significantly between supported patients. While different types of pumps (centrifugal versus rotary) might affect rates of hemolysis, we sought to determine if a patient’s baseline red cell fragility influences their hemolytic response to LVAD support. Methods and Materials Osmotic fragility assesses the degree of red blood cell hemolysis under varying degrees of osmotic stress. Assays were prospectively obtained on 50 consecutive patients prior to placement of continuous flow LVADs. Five patients were excluded as they were already on circulatory support. LDH was obtained post-operatively at 3-5 weeks or at discharge. Results The mean age was 60.2 yrs, 86.6% were male, and 46.6% were nonischemic. Patients were supported with the Jarvik 2000 (n=5), HeartWare (n=6), and HeartMate II (n=34). The mean LDH was 714 (±324) and there was no difference among devices. A scatter plot did not reveal any relationship between pre-op osmotic fragility and post-op LDH. Mean hemolysis was 15.68 ± 12.96% at 0.45%NaCL (the inflection point of the osmotic fragility hemolysis curve). Linear regression confirmed no predictive relationship (p=0.71). Conclusions Pre-op variations in osmotic fragility do not appear to account for differences in hemolysis following VAD placement. Shear forces across existing LVADs create similar levels of biochemical hemolysis, as assessed by LDH, despite baseline differences in a patient’s red cell fragility.

Raised erythrocyte creatine in patients with pulmonary arterial hypertension – Evidence for subclinical hemolysis

Pulmonary arterial hypertension (PAH) has been associated with hemolytic conditions such as sickle cell disease but the possible role of hemolysis in the pathogenesis or pathophysiology of other forms of PAH has not been studied. Erythrocyte lifespan is the gold-standard test of hemolysis and may be measured by assaying erythrocyte creatine (EC) levels. EC decreases as the erythrocyte ages, so patients with hemolysis have high EC levels. We measured EC and other parameters of hemolysis in patients with idiopathic and connective tissue associated PAH and normal controls. In patients with PAH (n = 40), EC levels were higher than in controls n = 30 (patients EC 1.72mcmol/g HgB 95%CI[1.51, 1.96], controls EC 1.05mcmol/g HgB [0.93, 1.19], p<0.0001). High levels of EC correlated with worse 6min walk (r=-0.42, p<0.0001) and worse functional class (p=0.002). Other indirect indices of hemolysis (total lactate dehydrogenase, red cell distribution width) were also increased in patients with PAH relative to controls. There is evidence of subclinical hemolysis in patients with PAH, and higher levels of hemolysis are associated with poorer exercise capacity.

Unexpectedly low HbA1c levels in two diabetes patients following dapsone use

Unexpectedly low HbA1c levels in two diabetes patients following dapsone use

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Inappropriately Low Glycated Hemoglobin Values and Hemolysis in HIV-Infected Patients

In order to test the accuracy of glycated hemoglobin (HbA1c) in predicting mean glycemia in HIV-infected patients, we recorded consecutive HbA1c measurements from 1238 non-HIV-infected and 112 HIV-infected patients, all devoid of any hemoglobinopathy, in a retrospective, transversal study. Mean fasting glycemia from the six previous weeks (measured-Gly) and HbA1c-estimated glycemia [HbA1c-Gly (1.85x%HbA1c-4.78) mM] were compared. Mean hemoglobin, red cell volume, serum creatinine, CD4 count, and HIV viral load from the same period were collected in HIV-infected patients. Although measured-Gly was not significantly different between non-HIV-infected (6.95+/-3.23 mM) and HIV-infected patients (6.62+/-2.42 mM), HbA1c underestimated the mean fasting glycemia by 12.3% in HIV-infected as compared to non-HIV-infected patients (p=0.0001). The difference "measured-Gly-HbA1c-Gly" was correlated with the red cell volume (p<0.0001) in HIV-infected patients. We then searched for the presence of subclinical hemolysis, a cause of both macrocytosis and reduced HbA1c levels, in HIV-infected patients. To this end, we prospectively measured serum haptoglobin in 249 consecutive samples from HIV-infected subjects without any known cause of hemolysis. A very low haptoglobin level, a marker of hemolysis, was frequent and negatively correlated with the red cell volume in these patients. Treatment with nucleoside analogues was significantly associated with macrocytosis and low haptoglobin. In conclusion, HbA1c could be inappropriately low in HIV-infected patients. Its underestimation of mean fasting glycemia could be due to an antiretroviral-induced subclinical hemolysis, but further studies are needed to explore this hypothesis. Self-monitoring of blood glucose and search for latent hemolysis should be promoted in diabetic HIV-infected patients.

Intravascular hemolysis in patients with normally functioning mechanical heart valves in mitral position

Traumatic intravascular hemolysis has been recognized as a potentially serious problem after heart valve replacement. Chronic subclinical hemolysis in these patients with normally functioning valvular mechanical or biologic prostheses rarely develop decompensated anemia. This prospective study evaluates the presence and severity of hemolysis in patients with normally functioning mitral prosthetic valves. In this prospective study 78 patients with normally functioning mitral prosthetic valves were evaluated for hemolysis postoperatively on 7th,30th and 180th days by clinical evaluation, transthoracic echocardiography, hemoglobin, serum lactic dehydrogenase (LDH), and reticulocyte count. Data was statistically analysed with paired t test and variance test. LDH was elevated in almost all the patients with mechanical valve replacement. None had significant anemia. All the evidence of hemolysis was not observed in any of the recipients. There was no statistically significant difference in the degree of hemolysis among the recipients of various tilting disc valves. There was no significant correlation between the severity of hemolysis and cardiac rhythm or the size of valve. The recipients of bileaflet valve had significantly more severe hemolysis than those of tilting disc valves. Almost all the recipients of mechanical mitral valves had increased LDH values at the follow up. However none had decompensated anemia during 180 days follow up. Bileaflet valves cause more hemolysis than tilting ones. Recipients of Chitra TTK valve prosthesis showed least hemolysis.

Hemolysis in Mechanical Bileaflet Prostheses: Experience With the Bicarbon Valve

Normal functioning mechanical heart valve prostheses are designed to have a certain degree of intrinsic structural regurgitation as a washout mechanism to avoid prosthetic thrombosis. However, intrinsic regurgitation leads to blood cell trauma and hemolysis. Information on hemolysis associated with mechanical bileaflet prostheses is scarce. This study evaluated factors influencing hemolysis in 197 Bicarbon mechanical bileaflet prostheses implanted in 164 patients. Serial office interviews, laboratory studies, and echocardiography evaluations were done in the surviving patients. An assay for measuring lactate dehydrogenase activity was developed, and the presence and severity of subclinical hemolysis was determined using reported criteria and analyzed at 1 and 2 years. Hospital mortality was 5.5%. Follow-up was 98.1% complete. No patient had clinically significant or severe subclinical hemolysis. Serum lactate dehydrogenase levels were significantly higher when a paravalvular leak was documented (282 +/- 85 U/L versus 242 +/- 64 U/L; p = 0.0026). Subclinical hemolysis was significantly more frequent after mitral valve (p = 0.001) and double valve replacement (p = 0.001) than after aortic valve replacement, and was unrelated to prosthetic size or to geometric area index, even in those cases with effective orifice area index equal to or less than 0.85 cm2/m2 (p = 0.298). Mild subclinical hemolysis is frequently associated with normal functioning Bicarbon heart valves. Subclinical hemolysis was significantly influenced by valve position but not by valve size or effective orifice area index and remained stable through time. The magnitude of hemolysis in Bicarbon prostheses compared favorably with that reported for other bileaflet heart valve prostheses.

Intravascular hemolysis in patients with new-generation prosthetic heart valves: A prospective study

Objective: A prospective clinical study was designed to assess the frequency and severity of intravascular hemolysis in patients with new-generation, normally functioning prosthetic heart valves. Methods: Hemolysis was evaluated in 172 patients with a mechanical prosthesis (53 CarboMedics and 119 Sorin Bicarbon) and in 106 patients with a bioprosthesis (15 St Jude Medical Toronto, 19 Baxter Perimount, and 72 Medtronic Mosaic) in the aortic position, mitral position, or both. Aortic valve replacement was performed in 206 patients, mitral valve replacement in 59 patients, and double valve replacement in 13 patients. The presence of hemolysis was assessed on the basis of the level of serum lactic dehydrogenase and serum haptoglobin and the presence and amount of reticulocytes and schistocytes in the peripheral blood. Severity of intravascular hemolysis was estimated on the basis of serum lactic dehydrogenase. Clinical, echocardiographic, and hematologic evaluations were performed 1, 6, and 12 months after discharge. Results: None of the 278 patients experienced decompensated anemia, whereas at 12 months, mild subclinical hemolysis was identified in 49 patients, 44 (26%) with a mechanical prosthesis and 5 (5%) with a bioprosthesis (P <.001). At multivariate analysis, independent predictors of the presence of subclinical hemolysis were mitral valve replacement (P <.001), use of a mechanical prosthesis (P =.002), and double valve replacement (P =.02). Frequency of hemolysis in patients with stented aortic bioprostheses was 3%, whereas it was absent in those with stentless valves. Among mechanical valve recipients, double versus single valve replacement (P =.04) and mitral versus aortic valve replacement (P =.05) were correlated with the presence of hemolysis; double valve recipients also showed a more severe degree of hemolysis (P =.03). In patients with a Sorin Bicarbon prosthesis, hemolysis was less frequent (22% vs 34%, P =.09) and severe (P <.001) than in those with a CarboMedics prosthesis. Conclusions: In normally functioning prosthetic heart valves, subclinical hemolysis is a frequent finding. A low incidence of hemolysis is found in stented biologic prostheses, and it is absent in stentless aortic valves. Modifications of valve design may contribute to minimize the occurrence of hemolysis in mechanical prostheses.J Thorac Cardiovasc Surg 2002;123:550-6