The erythrocyte alloimmunisation in patients with sickle cell anaemia: a systematic review

Transfusion therapy is a common practice in the treatment of anaemia and can cause erythrocyte alloimmunisation. To systematise data related to erythrocyte alloimmunisation in patients with sickle cell disease (SCD), a bibliographic search was carried out in September 2017 to search for studies in four electronic databases. (i) Referring to the original work, (ii) being cohort or case–control, (iii) having been developed with individuals with SCD and (iv) having evaluated the erythrocyte alloimmunisation. Two reviewers identified the articles for inclusion in the study, extracted the predetermined data and carried out the evaluation of the methodological quality of the work. 21 studies were selected; the studies included data on 20 636 individuals (children and adults), were mostly published in the last 10 years, were developed in the United States and had high methodological quality. The occurrence of erythrocyte alloimmunisation ranged from 4·4 to 76%, and there was a higher rate of alloimmunisation against antigens of the Rh system. The risk factors for alloimmunisation were age; gender (female); red blood cell (RBC) units received; presence of ≥1 autoantibodies, TNF‐α, interleukin (IL1B), human leukocyte antigens (HLA)‐DRB1 gene polymorphisms; first blood transfusion (BT) after 5 years of age, transfusion episodic, multiple or during inflammatory events, acute chest syndrome (ACS) and vase‐occlusive crisis (VOC); increased percentage of CD41 T memory cells; and positive direct antiglobulin test. Transfusion policies should be developed to protect the patient and his or her health based on the main factors associated with its incidence.     

The prevention and management of stroke in sickle cell anaemia

Perhaps the most important clinical complication of sickle cell anaemia is stroke, an event that occurs in ～ 5 – 10% of children who inherit this disorder. To prevent recurrent or progressive CNS damage, the institution of regular red blood cell (RBC) transfusions is the standard of care. In addition, children at high risk of developing stroke, as screened by transcranial Doppler, also benefit from regular RBC transfusions for stroke prevention. In this review, standard and novel techniques of RBC transfusion, and also alternative therapies to treat children with or at risk for stroke are considered. In addition, haematopoietic cell transplantation, the only curative option for sickle cell anaemia, is considered, and speculation about its present and future application in this clinical setting is discussed.     

Changes in global longitudinal strain during rest and exercise in patients treated with cardiac resynchronization therapy

Relatively few data have been reported on prospective changes in global longitudinal strain (GLS) following cardiac resynchronization therapy (CRT), and none are available on GLS during physical exercise. We investigated the effects of CRT on GLS, assessed by speckle tracking two-dimensional (2D) echocardiography, at rest and during exercise after a mid-term follow-up. Twenty consecutive CRT patients (45% ischaemic) were assessed prospectively by speckle tracking 2D echocardiography before implant (at rest) and at mid-term follow-up (during rest and bicycle exercise). GLS, septum and lateral wall longitudinal strain, left ventricular ejection fraction (LVEF), and conventional functional variables were evaluated at baseline and follow-up. All patients completed the study protocol at rest. Exercise images were available in 90% of the patients. At follow-up, GLS improved at rest from -7.1 ± 2.6% to -9.1 ± 4.5% (P<0.01), with a further increase to -11 ± 5.1% during exercise (P<0.001). Longitudinal strain increased at rest both in the septum and in the lateral wall, with an additional increase during exercise in the lateral wall (P<0.05). GLS correlated with LVEF both at rest (r= -0.55 and r= -0.91 at baseline and 3 months, respectively; P<0.05) and during exercise (r= -0.89, P<0.05). Improvement in GLS during rest and exercise can be observed in CRT patients at mid-term follow-up and seems to correlate with changes in LVEF. GLS may be a valuable method to assess left ventricular function during rest and exercise.     

Predicting risk factors for thromboembolic complications in patients with sickle cell anaemia – lessons learned for prophylaxis

ObjectiveTo assess the clinical and laboratory predictors of venous thromboembolism (VTE) in patients with sickle cell anaemia (SCA) and its relationship to morbidity and mortality.MethodsThis retrospective case–control study analysed data from patients with SCA that experienced VTE compared with matched control patients with SCA but no VTE (2:1 ratio).ResultsA total of 102 patients with SCA were enrolled (68 cases with VTE and 34 controls). Amongst the 68 cases (median age, 29.5 years), 26 (38.2%) presented with isolated pulmonary embolism (PE). A higher prevalence of splenectomy (73.5% versus 35.3%) was observed in the cases compared with the controls. A significantly higher prevalence of central venous catheter (CVC) insertion (42.6% versus 8.8%) was observed in the cases compared with the controls. High white blood cell counts, serum lactic dehydrogenase (LDH), bilirubin and C-reactive protein (CRP) and low haemoglobin (Hb) and HbF were significant risk factors for VTE. Forty-two cases (61.8%) developed acute chest syndrome, 10 (14.7%) had a stroke and seven (10.3%) died.ConclusionsVTE in patients with SCA has a high impact on morbidity and mortality. PE was the leading presentation of VTE, with CVC insertion, high LDH, bilirubin, CRP and white blood cell counts along with low Hb and HbF constituting other significant risk factors.     

Atrial fibrillation is associated with decreased cardiac sympathetic response to isometric exercise in CHF in comparison to sinus rhythm

Background: The presence of atrial fibrillation (AF) in congestive heart failure (CHF) is accompanied by increased mortality, although the exact mechanism is unclear. In previous studies, we have demonstrated cardiac baroreceptor abnormalities in association with AF and CHF. In this study, we sought to examine the effect of cardiac rhythm on the cardiac sympathetic response to exercise in CHF.
Methods: In 13 CHF patients (six AF, seven SR, left ventricular ejection fraction 31 ± 2%, age 61 ± 1 years), we measured the hemodynamic and cardiac sympathetic response isometric handgrip (IHG) exercise.
Results: At baseline the groups were well matched. Baseline hemodynamics and cardiac sympathetic activity did not significantly differ between the cohorts. In response to IHG exercise, both groups demonstrated significant hemodynamic responses. In conjunction, the sinus rhythm (SR) group demonstrated a significant increase in cardiac sympathetic response to exercise (P = 0.04) while in contrast the AF group did not (P = 0.6).
Conclusion: In this study, we demonstrate for the first time that the combination of AF and CHF is accompanied by a marked attenuation of the cardiac sympathetic response to acute hemodynamic stress. This implies AF is associated with a further impairment of baroreceptor response in CHF compared to SR. These findings present possible insights to the associated increased mortality and pathogenesis of AF with CHF.     

Use of erythrocytapheresis in the treatment of patients with sickle cell anemia

We performed exchange transfusions, utilizing the technique of automated erythrocytapheresis, for the treatment of patients with sickle cell anemia. In an attempt to determine guidelines for the use of erythrocytapheresis, we studied the use of this procedure in three distinct clinical situations in nine patients with sickle cell disease. Patients with dangerous complications of sickle cell disease such as acute respiratory distress and priapism responded well to erythrocytapheresis, showing marked improvement within 24-48 hours. Patients with prolonged painful vasoocclusive crises showed only variable improvement after erythrocytapheresis therapy, insufficient to justify exposing the patient to the risks of the procedure. Patients treated to decrease the frequency of painful crises demonstrated no prolongation in symptom-free intervals between crises. Therefore, erythrocytapheresis has its main value in the management of acute, dangerous complications of sickle cell disease.     

Exhaled nitric oxide during incremental and constant workload exercise in chronic cardiac failure

BACKGROUND: Nitric oxide (NO) is present in exhaled breath and produced by the pulmonary vascular endothelium as a potent vasodilator. Exercise is normally associated with pulmonary vasodilatation and a decrease in pulmonary vascular resistance to accommodate the increase in cardiac output. If production of NO is impaired in patients with chronic congestive cardiac failure (CCF), this might contribute to their exercise intolerance. PATIENTS AND METHODS: We quantified NO production (V NO) in 12 patients with chronic stable CCF and 12 controls, at rest and during incremental cardiopulmonary exercise on a treadmill, and at a later date during constant workload exercise. RESULTS: Patients had reduced V NO compared with controls during incremental exercise [381 (180) vs. 777 (275) nL min-1; mean (SD); P < 0.0001] but at constant workload V NO was similar between the two groups [353 (124) vs. 389 (189) nL min-1; P = 0.25]. Plasma levels of nitrate, the stable end-product of NO production, were significantly higher in patients [resting value 46.1 (21.6) vs. 23.0 (10.0) microM; P = 0.004] and were not influenced by exercise. CONCLUSION: Impaired NO-mediated pulmonary vasodilatation does not appear to contribute to exercise limitation in CCF. Alternatively, the lower NO production observed during maximal exercise in the patient group compared with controls may reflect a reduced incremental response of a system that is already abnormally activated in heart failure.     

Cerebral oximetry in patients with sickle cell disease

BACKGROUND: There is limited information concerning the brain's oxygen supply and demand in patients with sickle cell disease. DESIGN: We measured near-infrared spectroscopy of brain oxygenation in 27 patients with sickle cell disease regardless of vaso-occlusive crisis, 14 normal healthy controls, and five anaemic patients without sickle cell disease. We also measured pre- and post-transfusion cerebral oximetry in 14 additional sickle cell disease patients who were on transfusion programmes. RESULTS: The mean cerebral oxygen saturation in the combined steady-state and vaso-occlusive crisis population was found to be significantly lower than that in the controls and in anaemic patients without sickle cell disease (47.7% vs. 61.3%, 59.8%, P < 0.0001). Cerebral oxygen saturation failed to correlate with the haemoglobin concentration (r = 0.51, P > 0.5). However, cerebral oxygen saturation increased from 40.4% to 49.6% (P = 0.01) and correlated significantly with the haemoglobin level (r = 0.553, P = 0.003) in 14 subjects studied before and after transfusions. In seven subjects who received simple transfusions, cerebral oxygen saturation correlated strongly and positively with the haemoglobin level (r = 0.811, P = 0.001) and with percent normal haemoglobin (r = 0.786, P = 0.002), and negatively with abnormal sickle haemoglobin (r = -0.775, P = 0.003). None of these correlations was found to be statistically significant in the seven subjects given exchange transfusions. Cerebral oxygen saturation measured in the sickle cell disease subjects after transfusions was still significantly lower than in the anaemic subjects without sickle cell disease and in the normal controls (49.6% vs. 59.8% and 61.3%, P = 0.001). CONCLUSIONS: We found that patients with sickle cell disease have subnormal values of cerebral oxygen saturation. Red cell transfusions significantly increased the brain oxygenation in these patients. Cerebral oximetry may be a useful, noninvasive method for assessing the effect of circulating normal red cells in sickle cell patients after transfusions.     

Increased expression of VEGF following exercise training in patients with heart failure

BACKGROUND AND AIMS: During the last decades several angiogenic factors have been characterized but so far it is unknown whether local muscle exercise training increases the expression of these factors in patients with moderate heart failure. Expression of the major putative angiogenic factor vascular endothelial growth factor (VEGF) at the level of messenger RNA (mRNA) and/or protein was therefore studied before and after 8 weeks of training in patient with chronic heart failure. METHODS: VEGF mRNA and protein concentrations were determined in skeletal muscle biopsies before and after 8 weeks of one-legged knee extension training in patients with chronic heart failure (New York Heart Association II-III). RESULTS: Exercise training increased the citrate synthase activity and peripheral exercise capacity by 46% and 36%, respectively, in parallel with a two-fold increase in VEGF at both the mRNA (P = 0.03) and protein (P = 0.02) levels CONCLUSION: The increase in VEGF gene expression in response to exercise training indicates VEGF to be one possible mediator in exercise-induced angiogenesis and may therefore regulate an important and early step in adaptation to increased muscle activity in patient with chronic heart failure.     

Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity

Objectives: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT.
Methods: Eighty-nine patients (74.1 ± 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up.
Results: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 ± 1.0 vs 22 ± 0.1%), functional (peak VO₂ 10.2 ± 0.2 vs 6.9 ± 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 ± 15.7 vs 147.6 ± 10.ms, BRS 4.9 ± 0.2 vs 3.6 ± 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO₂ was the strongest predictor of responders.
Conclusions: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO₂) was the strongest predictor of responders to CRT.     

Noninvasive imaging in cardiac resynchronization therapy--part 1: selection of patients

Cardiac resynchronization therapy (CRT) is an established therapy for patients with advanced heart failure, depressed left ventricular function, and wide QRS complex. However, individual response varies, and a substantial amount of patients do not respond to CRT. Recent studies observed that assessment of inter- and particularly intraventricular dyssynchrony may allow identification of potential responders to CRT. In addition, presence of scar tissue and venous anatomy may play a role in the selection of candidates. In this review, an extensive overview of the available dyssynchrony measurements is provided using echocardiography as well as magnetic resonance imaging (MRI) and nuclear imaging. Furthermore, other information derived from MRI, nuclear imaging, and computed tomography useful for the selection of potential candidates for CRT will be discussed.     

Effects of an exercise adherence intervention on outcomes in patients with heart failure.

The purpose of this study was to determine how an exercise adherence intervention affects the physiological, functional, and quality of life outcomes of patients with heart failure (HF). Sixteen HF patients were randomly assigned to an exercise-only group (n = 8) or to an exercise-with-adherence group (n = 8). Two of the 16 people died from nonexercise related causes during the study and were not included in the analysis. The intervention was tested over a 24-week period in which patients participated in a 12-week supervised exercise program (Phase 1) followed by 12 weeks of unsupervised home exercise (Phase 2). The intervention format was one of individualized graphic feedback on exercise goals and participation and problem-solving support by nurses. Results indicate that patients who received the intervention exercised more frequently and experienced improved outcomes during both phases. The adherence intervention may encourage HF patients to continue to exercise and thereby maintain the health benefits gained in both phases of an exercise program.     

Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty‐nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow‐up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted. J. Clin. Apheresis 30:353–358, 2015. © 2015 Wiley Periodicals, Inc.