Prosthetic Valve Hemolysis

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Int J Cardiol. 2007 Jan 31;115(1):e39-40. Epub 2006 Oct 18.
Transcatheter closure of paravalvular mitral prosthetic leak with resultant hemolysis.
Sivakumar K, Shahani J.

Reoperations for mitral prosthetic paravalvular leaks presenting with heart failure or hemolysis are associated with significant morbidity and mortality. Transcatheter options offer an attractive alternative, though the method is under evolution and outcome is varied. This report gives procedural details of transcatheter closure of mitral paravalvular leak with Amplatzer septal occluder device.

Ann Thorac Surg. 2006 Apr;81(4):1291-6.
Hemolysis in mechanical bileaflet prostheses: experience with the Bicarbon valve.
Josa M, Castellį M, Paré C, Bedini JL, Cartańį R, Mestres CA, Pomar JL, Mulet J.
Cardiovascular Service, Hospital Clinic and University of Barcelona, Barcelona, Spain.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Ann Thorac Cardiovasc Surg. 2005 Dec;11(6):413-5.
A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.
Sezai A, Shiono M, Hata M, Saito A, Hattori T, Wakui S, Soeda M, Kasamaki Y, Tokai K, Saito S, Negishi N, Sezai Y.
Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.

J Biomech. 2005 Aug;38(8):1557-65. Epub 2005 Jan 19.
Comment in:
J Biomech. 2006;39(13):2542; author reply 2542-4.
Prosthetic heart valves' mechanical loading of red blood cells in patients with hereditary membrane defects.
Grigioni M, Caprari P, Tarzia A, D'Avenio G.
Department of Technology and Health, Istituto Superiore di Sanitą, Viale Regina Elena 299, 00161 Rome, Italy.

Implantable cardiovascular devices such as prosthetic heart valves (PHVs) are widely applied clinical tools. Upon implantation, the patient can suffer from anemia as a result of red cell destruction and hemolysis can be more relevant whenever the patient is also affected by red cell disorders in which erythrocytes are more susceptible to mechanical stress such as hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). Considering the typical morphological alterations observed in HS and HE, a study of the influence of cell geometry on the distribution of the shear stress on red cells in biological fluids was carried out. A numerical simulation of the loading caused by Reynolds shear stresses on a prolate spheroid was performed, with the ellipticity of the particle as the independent parameter. The average shear stress on a particle in the blood stream was found to depend on the particle's geometry, besides the stress field produced by the prosthetic device. The relevance of an increasing particle ellipticity on the global load is discussed. The model was applied to erythrocytes from implanted patients with HE or HS, enabling to explain the occurrence of moderate or severe anemia, respectively. The clinical data support the relevance of the proposed global parameter as erythrocyte trauma predictor with regard to the fluid dynamics of artificial organs.

Chest. 2004 Jun;125(6):2115-20.
Evaluation of intravascular hemolysis with erythrocyte creatine in patients with cardiac valve prostheses.
Okumiya T, Ishikawa-Nishi M, Doi T, Kamioka M, Takeuchi H, Doi Y, Sugiura T.
Department of Laboratory Medicine, Faculty of Medicine, Kochi Medical School, Nankoku, Japan.

STUDY OBJECTIVES: To detect intravascular hemolysis in patients with cardiac valve prostheses. Erythrocyte creatine, a marker of erythrocyte age that increases with shortening erythrocyte survival, was evaluated with other hemolytic markers and hemodynamic parameters. DESIGN: Prospective study. Patients and measurements: Erythrocyte creatine was enzymatically assayed in 33 patients with prosthetic valves, including 15 patients with aortic valve replacement, 13 patients with mitral valve replacement, and 5 patients with double-valve (aortic and mitral) replacement, and 33 control subjects. Blood flow velocity and valvular regurgitation were determined by Doppler echocardiography. Other hemolytic markers (lactate dehydrogenase [LDH], reticulocyte count, and haptoglobin) and cardiac muscle markers (myoglobin and myosin light chain 1) were also measured. RESULTS: Erythrocyte creatine and LDH levels were significantly higher (p < 0.0001) and the haptoglobin level was lower (p < 0.0001) in patients with a prosthetic valve as compared with control subjects. However, there were no significant differences in these markers between those with (n = 17) and without (n = 16) regurgitation. Patients with high erythrocyte creatine levels (> 1.8 micro mol/g hemoglobin) exhibited significantly higher total peak flow velocity (sum of peak flow velocities at mitral and aortic valves) than those with normal erythrocyte creatine levels (p = 0.006). Erythrocyte creatine had a significant correlation with total peak flow velocity (r = 0.64, p < 0.0001), but LDH and haptoglobin had no significant correlation with total peak flow velocity. Patients with high LDH levels (> 460 IU/L) showed significantly higher myoglobin (p = 0.008) and myosin light chain 1 (p = 0.02) than those with normal LDH levels, whereas erythrocyte creatine was not related to cardiac muscle markers. CONCLUSIONS: Erythrocyte creatine is a quantitative and reliable marker for intravascular hemolysis in patients with prosthetic valves. Mild hemolysis is ascribable to valvular flow velocity rather than regurgitation.

Ital Heart J Suppl. 2003 Oct;4(10):807-13.
Hemolysis following valve surgery
Soccio M, D'Ambrosio C, De Caterina R.
Cattedra di Cardiologia e Centro per gli Studi sull'Invecchiamento, Universitą degli Studi "G. d'Annunzio", Chieti.

Hemolysis is a frequent complication of the implant of prosthetic valves, and is conditioned by a variety of factors, most of which related to the type of valve implanted and to the hemodynamic conditions following implantation. If sufficiently severe, it may lead to varying degrees of hemolytic anemia. The following laboratory tests are useful to diagnose and assess the severity of hemolytic anemia: hemoglobin levels; reticulocyte count; the demonstration of schistocytes on a blood smear; serum levels of lactic dehydrogenase, haptoglobin and iron. Treatment of hemolysis includes the supplementation of iron and folate when their deficiency is evident. Transfusions are necessary only in cases of severe anemia refractory to treatment. The use of beta-blockers appears to decrease the severity of hemolysis, likely because of the induction of bradycardia and of their negative inotropic effects. Some cases have been described of erythropoietin treatment for hemolytic anemia in these conditions, with favorable outcome. However erythropoietin use should currently be restricted to patients with severe hemolytic anemia in whom surgical repair or transfusions should be avoided or deferred. The recognition and the estimation of severity of hemolysis after valve implantation are important steps in the patients' follow-up and the premise for a rational treatment.

Acta Cardiol. 2003 Oct;58(5):379-83.
The effect of pentoxifylline on haemolysis in patients with double cardiac prosthetic valves.
Golbasi I, Turkay C, Timuragaoglu A, Ozdem SS, Belgi A, Akbas H, Bayezid O.
Department of Cardiovascular Surgery, Akdeniz University, Medical Faculty, 07070 Antalya, Turkey.

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.

J Am Soc Echocardiogr. 2003 Feb;16(2):188-90.
An unusual cause of hemolysis in a patient with an aortic valved conduit replacement.
Allman C, Rajaratnam R, Kachwalla H, Hughes CF, Bannon P, Leung DY.
Department of Cardiology, Liverpool Hospital, University of New South Wales, Australia.

Hemolytic anemia is a well-known but uncommon complication in patients with prosthetic heart valves. It is most commonly a result of prosthetic valve dysfunction, periprosthetic valvular regurgitation, or both. We report a case of a 41-year-old man who had a previous aortic valve and root replacement for acute proximal aortic dissection, now presenting with hemolytic anemia. This was a result of flow obstruction at the distal anastomosis of the aortic conduit by the presence of multiple dissection flaps resulting in severe flow turbulence. Although the pathology was at the blind spot for transesophageal echocardiography, the dissection flaps, the flow turbulence, and the degree of obstruction were well-demonstrated by this technique after careful manipulation of the probe and a high index of suspicion.

Int J Cardiol. 2004 May;95(1):89-93.
Hemolysis parameters of St. Jude Medical: Hemodynamic Plus and Regent valves in aortic position.
Suedkamp M, Lercher AJ, Mueller-Riemenschneider F, LaRosee K, Tossios P, Mehlhorn U.
Department of Cardiothoracic Surgery, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.

BACKGROUND: Elevated plasma lactate dehydrogenase (LDH) concentration may reflect hemolysis due to mechanical heart valve dysfunction. Thus, knowledge of LDH levels in patients with properly working prostheses is required. Because hemolysis parameters for the SJM Hemodynamic Plus (HP) and Regent series are currently not available, the purpose of our study was to determine these data. METHODS: At 12-19 months follow-up after isolated aortic valve replacement with SJM HP(R) or Regent prostheses, we examined 102 patients by transthoracic echocardiography and determined plasma LDH, haptoglobin, bilirubin and hemoglobin. RESULTS: Five patients with properly working prostheses were excluded because of increased LDH due to non-cardiac reasons. In four patients with paravalvular leakage, LDH was 244, 307, 446 and 628 U/l, respectively. In patients with properly working prostheses, LDH was 287+/-52 (range: 163-374) U/l for HP(R) (n=33) and 274+/-48 (151-386) U/l for Regent valves (n=60, p=0.2). Haptoglobin was <1g/l in all patients; in 91% of HP and 75% of Regent valves, haptoglobin was below detection limit. Bilirubin and hemoglobin as well as red blood cell count (RBC) were normal in all patients except for five patients with renal anemia, two patients with paravalvular leakage and four patients with macrocytosis due to alcohol abuse. There was no correlation between LDH and transvalvular gradient (r=-0.02) or valve size (r=0.25). CONCLUSIONS: In patients with SJM HP(R) or Regent valves in aortic position, LDH values > 400 U/l indicate valvular dysfunction or leakage if non-cardiac causes for hemolysis are excluded. However, paravalvular leakage can be present without substantially increased LDH. Haptoglobin has no diagnostic value as it is almost always markedly reduced. Hemolysis does not correlate with transvalvular gradient or prosthesis size.

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