The Effect of Splenectomy on Development of Cerebral Vasculopathy in Children with Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3647-3647
Author(s):  
Azada Ibrahimova ◽  
Bruce Bernstein ◽  
Rida Abid ◽  
Nataly Apollonsky
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Protective Effect ◽  
Sickle Cell ◽  
Cerebral Artery ◽  
Cell Disease ◽  
Increased Risk ◽  
Significant Difference ◽  
History Of

Abstract Splenic complications are often seen in pediatric patients with sickle cell disease and could lead to an increase in morbidity and mortality. The most common splenic event is acute splenic sequestration crisis (ASSC) which has been often managed with surgical splenectomy. Although splenectomy has been the treatment of choice for years, the long term complications of splenectomy on vascular events has not been broadly assessed. It has been reported that splenectomy could lead to vascular complications and increased risk of thrombosis in chronic hemolytic conditions. As it was proposed, it could be partially due to the shift form extravascular hemolysis to intravascular leading to the scavenging of nitric oxide (Kato et al, 2007). In terms of cerebral vasculopathy in children with sickle cell disease, screening is usually done by measuring blood flow velocity in the main cerebral arteries using Transcranial Doppler Ultrasonography (TCD). In 2014 Peter Soh and Abdul Siddiqui reported an increased risk of cerebrovascular complications in splenectomized patients with sickle cell disease (3), but it has not been confirmed by other publications. The aim of our study is to evaluate how splenectomy affects cerebral blood flow measured by TCD in patients with homozygous HbS. The secondary aim is to evaluate if Hydroxyurea (HU) has a protective effect on the development of cerebral vasculopathy in splenectomized patients. We performed a retrospective chart review of patients with sickle cell disease Hb SS and Hb S beta thalassemia followed at the Marian Anderson Center at St. Christopher's Hospital for Children, Philadelphia between 1999 and 2016. In the final analysis we included TCD data on 153 patients, of which 36 had undergone splenectomy. A total of 516 TCD studies were collected, of which 145 patients had a history of splenectomy. Of the 516 TCD assessments in this sample, 70 (13.6%) patients were on HU of which 21 had undergone splenectomy. Pearson correlations were calculated to explore linear associations of mean cerebral blood flow velocities (CBFV) with age at the time of TCD assessment, time since splenectomy, and TCD values. Associations of CVFV with splenectomy and with HU administration for splenectomy patients were analyzed with analysis of covariance (ANCOVA). The association of time elapsed since splenectomy to TCD measure, adjusting for age at TCD assessment, was explored with multiple linear regression models. Statistical analysis was conducted with SPSS ver. 24.0. Age at the time of TCD was significantly correlated with mean right cerebral artery (RMCA) (r = -.199, p < .001), LMCA (r = -.181, p < .001), RDICA (r = -.110, p = .047), LDICA (r = -.142, p = .01) and Basilar (r = -.186, p = < .001) velocities. Tables 1 and 2 present estimated mean TCD values (calculated adjusting for age at the time of TCD). In analysis of all TCDs, the estimated mean (RMCA) velocity was significantly higher in patients with history of splenectomy than in patients without splenectomy, (Table 1). There was also significant difference in LDICA, RDICA and right posterior cerebral artery (RPCA) velocities, all of which were higher in splenectomized patients (Table 1). When analyzing the velocities according to time since splenectomy, there were significant associations between years since splenectomy (0-5, 5-10 and >10years) and with both RMCA and LMCA abnormalities. Analysis of TCD results in splenectomized patients on HU versus non-HU, indicates all estimated mean TCDs except for RPCA, are lower for the patients on HU (Table 1), with RMCA and LMCA statistically significant. Based on our analysis we conclude that in patients with homozygous HbS disease history of surgical splenectomy increases the risk for cerebral vasculopathy. It remains unclear if cerebral vasculopathy develops as a result of splenectomy or if there is a preexisting factor leading to the development of both complications. The other important finding of our study is a protective effect of hydroxyurea on the development of cerebral vasculopathy in splenectomized patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Middle cerebral artery blood velocity and cerebral blood flow in sickle cell disease.

Stroke ◽  
1991 ◽  
Vol 22 (1) ◽  
pp. 27-30 ◽  
Author(s):  
L M Brass ◽  
I Prohovnik ◽  
S G Pavlakis ◽  
D C DeVivo ◽  
S Piomelli ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Middle Cerebral Artery ◽  
Sickle Cell ◽  
Cerebral Artery ◽  
Blood Velocity ◽  
Cell Disease

scholarly journals Mechanisms of Stroke in Sickle Cell Disease: Sickle Erythrocytes Decrease Cerebral Blood Flow in Rats After Nitric Oxide Synthase Inhibition

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4591-4599 ◽  
Author(s):  
James A. French ◽  
Dermot Kenny ◽  
J. Paul Scott ◽  
Raymond G. Hoffmann ◽  
James D. Wood ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Endothelium ◽  
Cell Disease ◽  
Cerebral Microvessels ◽  
Doppler Flowmetry ◽  
Cranial Window

Abstract The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF ) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-ω-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

Relationship between skin microvascular reactivity, cerebral blood flow and hypoxaemia in children with sickle cell disease

2010 ◽  
Vol 95 (Suppl 1) ◽  
pp. A5.2-A5
Author(s):  
VS L'Esperance ◽  
F Kirkham ◽  
C Hill ◽  
S Cox ◽  
J Makani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Microvascular Reactivity

Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3628-3632 ◽  
Author(s):  
Alina Ferster ◽  
Parvine Tahriri ◽  
Christiane Vermylen ◽  
Geneviève Sturbois ◽  
Francis Corazza ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Significant Difference ◽  
History Of ◽  
Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P &lt; .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

Nifedipine Increases Cerebral Blood Flow in Sickle Cell Disease: A Case Study

1994 ◽  
Vol 9 (3) ◽  
pp. 337-338 ◽  
Author(s):  
Stephen Ashwal ◽  
Antranik Bedros ◽  
Joseph Thompson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease

scholarly journals Assessment of Cerebral Blood Flow and Oxygen Extraction in Pediatric Sickle Cell Disease with Non-Invasive Diffuse Optical Spectroscopies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Seung Yup Lee ◽  
Eashani Sathilingam ◽  
Kyle R. Cowdrick ◽  
Rowan O. Brothers ◽  
Wilbur A. Lam ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Cost ◽  
Oxygen Extraction ◽  
Signal Quality ◽  
Cell Disease ◽  
Non Invasive

Introduction: Cerebral infarcts and associated cognitive impairments are a devastating consequence of sickle cell disease (SCD). While the underlying mechanisms are poorly understood, infarctions are thought to arise from anemia-induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow (CBF) and oxygen extraction (OEF) may be useful in identifying infarct risk and monitoring therapeutic efficacy. Unfortunately, current modalities that quantify microvascular hemodynamics (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children &lt;6y, making them inappropriate as routine monitoring tools. Transcranial Doppler ultrasound (TCD) is currently the standard screening tool for overt stroke risk in pediatric SCD, but it only measures blood flow velocity in the large arteries, which is a poor surrogate for microvascular perfusion in sickle cell disease. Diffuse optical spectroscopies (specifically near-infrared frequency-domain spectroscopy, FDNIRS, and diffuse correlation spectroscopy, DCS) offer a low-cost, non-invasive alternative for bedside monitoring of tissue-level OEF and CBF. We previously demonstrated that FDNIRS/DCS are sensitive to elevations in resting-state OEF and CBF in children with sickle cell disease compared to healthy controls (Lee, Neurophotonics 2019), consistent with previous studies using MRI and PET. In this feasibility study, we demonstrate these optical techniques are sensitive to altered cerebral hemodynamics in sickle patients who are 1) undergoing chronic transfusion, and 2) experiencing vaso-occlusive pain episodes (VOE). Methods: To date, we have recruited 6 pediatric patients with sickle cell disease undergoing chronic transfusion (5 females and 1 male, 6 - 14 y, mean ± std hemoglobin change pre- to post-transfusion = 1 ± 0.8 g/dL) and 4 patients admitted to the Emergency department for VOE (2 females and 2 males, 8 - 18 y, mean±std hemoglobin on admission = 8.9 ± 1.6 g/dL). For the transfusion cohort, FDNIRS/DCS measurements were made immediately prior to the start of transfusion and again immediately upon completion. For the VOE cohort, FDNIRS/DCS measurements were made upon hospital admission. For all FDNIRS/DCS assessments, a custom sensor was manually held over right and left forehead to assess oxygen extraction fraction (OEF, %) and an index of microvascular cerebral blood flow (CBFi, cm2/s) (Lee, Neurophotonics 2019). Hemispheric results were averaged to yield a mean of each measured parameter. Total measurement time was less than 15 minutes. Results: In the cohort undergoing chronic transfusion, one patient data was excluded due to poor DCS signal quality. Of the remaining 5 patients, OEF and CBFi decreased after transfusion by a median of -6.4% and -30.0%, respectively (Fig 1A, B). The FDNIRS-measured OEF decrease is comparable to previous results with MRI (Guilliams, Blood 2017) that quantified both cortical OEF and CBF response to transfusion in a similarly aged cohort. However, the DCS-measured CBFi decrease is more prominent than previously reported (30% vs. 9%). The enhanced sensitivity of DCS to CBF in sickle cell disease was reported in our recent study and is likely attributed to the confounding influences of hematocrit on the DCS-measured CBFi (Sathialingam, Biomed Opt Exp 2020). In the cohort measured during VOE, one patient data was excluded due to poor FDNIRS data quality. Of the remaining 3 subjects, OEF was elevated compared to healthy controls and was on the upper range of values measured in a cohort of otherwise subjects with sickle cell disease who were without clinical complications and were measured as part of a separate study (Fig. 1C). Conclusion: These data demonstrate how FDNIRS/DCS may be used as a simple, low-cost tool for bedside assessment of cerebral hemodynamics in non-sedated sickle children that could be used to track brain health over time, particularly during periods thought to be prone to hemodynamic instability like transfusion or VOEs. Although ~20% of data was discarded in this dataset due to improper sensor positioning leading to poor signal quality, we have recently implemented real-time quality control feedback to ensure our data passes quality criteria. Disclosures Lam: Sanguina, Inc: Current equity holder in private company.

scholarly journals The molecular basis for the prothrombotic state in sickle cell disease

Haematologica ◽  
2020 ◽  
Vol 105 (10) ◽  
pp. 2368-2379
Author(s):  
Arun S. Shet ◽  
Maria A. Lizarralde-Iragorri ◽  
Rakhi P. Naik
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Molecular Basis ◽  
Cell Disease ◽  
Prothrombotic State ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Innovative Therapies ◽  
History Of

The genetic and molecular basis of sickle cell disease (SCD) has long since been characterized but the pathophysiological basis is not entirely defined. How a red cell hemolytic disorder initiates inflammation, endothelial dysfunction, coagulation activation and eventually leads to vascular thrombosis, is yet to be elucidated. Recent evidence has demonstrated a high frequency of unprovoked/recurrent venous thromboembolism (VTE) in SCD, with an increased risk of mortality among patients with a history of VTE. Here, we thoroughly review the molecular basis for the prothrombotic state in SCD, specifically highlighting emerging evidence for activation of overlapping inflammation and coagulation pathways, that predispose to venous thromboembolism. We share perspectives in managing venous thrombosis in SCD, highlighting innovative therapies with the potential to influence the clinical course of disease and reduce thrombotic risk, while maintaining an acceptable safety profile.

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