Transcranial Color Doppler Sonography and Magnetic Resonance Imaging In Adult Patients With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2245-2245
Author(s):  
Giovanna Graziadei ◽  
Francesca Marta Casoni ◽  
Pietro Ridolfi ◽  
Antonella Costa ◽  
Alessia Marcon ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Doppler Sonography ◽  
Color Doppler ◽  
Adult Patients ◽  
Resonance Imaging ◽  
Advisory Committees ◽  
Angle Correction ◽  
Stop Trial ◽  
Blood Flow Velocities ◽  
Transcranial Color Doppler

Abstract Introduction Stroke is a serious complication in Sickle Cell Disease (SCD) with an incidence of 11% by age 16 yrs and 24% by 45 yrs. In the Stroke Prevention Trial (STOP Trial) validity of the TransCranial Doppler (TCD) and threshold velocity ≥200 cm/sec were demonstrated to be useful in the prevention of stroke in pediatric patients with SCD. At present few data are available in adult patients. It is known that blood flow velocities detected with TransCranial Doppler (TCD) and TransCranial Color Doppler (TCCD) are comparable. Aim To compare transcranial blood flow velocities between SCD adult patients and healthy controls using TCCD with the insonation angle correction; to identify by TCCD the maximum mean Peak Systolic Velocity (PSV) in SCD adult patients as potential predictor of acute event or as an indicator of chronic progression of the disease; to evaluate Magnetic Resonance Imaging/Angiography (MRI/MRA) findings. Patients and Methods Fifty adult patients with SCD (aged >16 years) were enrolled, including14 Sickle Cell Anemia (SCA), 24 Sickle Cell Thalassemia (HbS-βThal) and 12 HbS/HbC. SCD adult patients and healthy subjects matched by gender, age and ethnicity (ratio of 2:1) were compared. SCD patients with epilepsy, pregnancy, HIV infection and bone marrow transplantation were excluded. The study was approved by Ethics Committee and all subjects gave written informed consent. Clinical evaluation, blood cell count, hemoglobin fractions by High Performance Liquid Chromatography (HPLC) and biochemical tests were evaluated. In both patients and controls Color and Duplex Doppler Sonography (CDDS) and TransCranial Color Doppler (TCCD) with angle correction were performed by the same physician to evaluate PSV, Pulsatility Index (PI) of the extracranial vessels (ICA and VA) and middle (MCA), anterior (ACA), posterior (PCA) cerebral arteries, carotid siphon (SIPH), vertebral (VA intracranial) and basilar (BAS) arteries following the STOP protocol. Furthermore, in all the patients 3.0T MRI/MRA was performed. Results Significant differences in Hb levels, Hct%, WBC, RBC, MCV, HbA2% and HbF% (p<0.001) were found comparing SCD group and controls, with a mean Hb values of 9.9±1.8 and 13.8±1.4 g/dl respectively. No neurological signs were reported, despite history of sickle crisis. PSVs in MCA, ACA, SIPH, PCA, intracranial VA, BAS were higher in SCD patients (p<0.001), in particular the mean PSV in MCA was 129.89±21.22 cm/sec in SCD patients and 110.71±14.96 cm/sec in controls. In SCD patients MCA velocities were correlated with Hb values, Ht%, RBC and HbS% (p<0.01), but independent from MCV, HbA2%, HbF%, reticulocytes, erythroblasts, WBC, iron status and hemolysis indices. In SCA patients higher velocities compared to HbS-βThal and HbS/HbC patients (140.55±12.90 cm/sec vs 128.48±22.37, p=0.013 and 119.394±22.51, p<0.011 respectively) were found. PI was normal in both SCD patients and controls, but statistically lower in SCD patients, (MCA, ACA, PCA, SIPH, VA intra- and extracranial, p<0.01). No differences in PI between the 3 SCD subgroups were found. PSVs percentile were calculated, considering pathological those above the 95°: MCA>164.18 cm/s; ACA>135.20 cm/s, SIPH>170.75 cm/s; PCA>99.67 cm/s; VA>101.50 cm/s; BAS>116.12 cm/s. Eight out of 50 SCD patients were found above the 95° percentile in any district, showing a more severe clinical phenotype. No stenosis were found in ICA by CDDS. SCD patients underwent to MRI/MRA to evaluate cerebral parenchymal lesions and vessel abnormalities respectively. In 11 patients (22%) vascular lesions, in 17 patients (34%) white aspecific lesions and in 9 patients (18%) cerebral atrophy were found. In 2 patients (4%) mild focal stenosis were detected. Conclusions TCCD velocities in adults SCD patients are lower than those provided by the STOP trial in children, confirming that the speeds disclose an age-related decline, however are higher than in healthy controls, in particular in SCA patients. According to our data, we could suggest as pathological cut off a MCA PSV value >160 cm/s. Moreover stenosis detected by MRA are not frequent as in young SCD patients. The peculiar alterations observed at MRI require further investigations. Disclosures: Cappellini: Novartis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity’s Board of Directors or advisory committees.

Magnetic Resonance Imaging/Angiography Findings in Adult Patients with Sickle Cell Disease: Correlation with Transcranial Color Doppler Sonography

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4085-4085 ◽  
Author(s):  
Giovanna Graziadei ◽  
Francesca Marta Casoni ◽  
Antonella Costa ◽  
Alessia Marcon ◽  
Fabio Triulzi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Sickle Cell ◽  
Doppler Sonography ◽  
Color Doppler ◽  
Adult Patients ◽  
Resonance Imaging ◽  
Cell Disease ◽  
Vessel Tortuosity ◽  
Blood Flow Velocities ◽  
Transcranial Color Doppler

Abstract Introduction. Stroke is a severe complication of Sickle Cell Disease (SCD). Ischemic strokes are more frequent among patients younger than 20 years of age, whereas older patients experience hemorrhagic strokes. At present few data are available in adult patients. Aim. To evaluate Magnetic Resonance Imaging/Angiography (MRI/MRA) findings and to correlate with Transcranial Color Doppler Sonography (TCCD) in adult SCD patients. Patients and methods. Fifty-one adult patients with SCD (median age 36.2 years, range 17-69 years; M:F 19:32) were enrolled, including 15 Sickle Cell Anemia (SCA), 24 Sickle Cell Thalassemia (HbS-βThal) and 12 HbS/HbC, all followed in a single tertiary Rare Disease Center in Milan, Italy. The study was approved by Ethic Committee and all subjects gave written informed consent. Clinical history and hematological tests were collected. 3.0 T MRI/MRA was performed to detect cerebral parenchyma lesions and vessels abnormalities. Color and Duplex Doppler Sonography (CDDS) and TransCranial Color Doppler (TCCD) following the STOP protocol but with angle correction were performed by the same physician to evaluate mean Peak Systolic Velocity (PSV) and Pulsatility Index (PI) of the extracranial vessels (ICA and VA) and middle (MCA), anterior (ACA), posterior (PCA) cerebral arteries, carotid siphon (SIPH), vertebral (VA intracranial) and basilar (BAS) arteries. Results. In overall SCD adult patients median Hb levels were 9.9±1.7 g/dL, Hct 28.5±4.5%, HbS% 60±18.5% (range 5.5-90.2%), HbF% 8.5±8.6% (range 0.9-33.8%); 68.6% SCD patients had <4 crises/year, 27.5% >4 crises/year, while 3.9% were completely asymptomatic; 37.3% SCD patients were treated with Hydroxycarbamide (HU); 49% were transfused <4 RBCs Units /year and 19.6% >4 RBCs Units/year, while 31.4% had never been transfused; 21.6% were splenectomized. No patient experienced stroke nor ischemic, neither hemorrhagic, despite history of sickle crises. Out of 51 SCD patients, 51% showed cerebral parenchimal lesions, 33.3% aneurisms of the intracranial vessels, 96.1% vessel tortuosity (25.5% mild and 70.6% severe). In only 2 patients (4%) mild focal stenosis were detected. Comparing the three SCD subgroups, in SCA patients the percentage of cerebral parenchimal lesions (60%), aneurisms (53%) and tortuosity vessels (100%, 13.3% mild and 86.7 severe) were significantly higher than in HbS-βThal and HbS/HbC patients (p<0.01), where cerebral parenchimal lesions were respectively 45.8% and 50%, aneurisms 20.8% and 33.3%, and vessels tortuosity 92.6% (33.3% mild and 58.3% severe) and 100% (25% mild and 75% severe). Considering SCD patients with cerebral parenchimal lesions, MCA TAMM and PSV values were lower (87.30±16.88 cm/sec, p <0.002; 123.32±22.36, p <0.013 respectively) then in SCD group without lesions. SCD patients with aneurism showed lower MCA TAMM and PSV values (87.55±16 cm/sec, p <0.049; 123.02±22.2, p <0.08 respectively) then SCD group without lesions, as well. Same correlations were found in SCA, HbS-βThal and HbS/HbC patients. No statistical differences between PI, Hb, HT and HbS and the overall MRI/MRA abnormalities were found. Considering the other intracranic vessels studied, no correlations were found between TCCD blood flow velocities and MRI/MRA cerebral findings. Conclusions. In the studied group of SCD adult patients MRI/MRA findings are characterized by aneurismal enlargement and tortuosity of cerebral vessels, probably due to age-related brain endothelial damage. MCA TAMM and PSV values were lower in SCD adult patients with cerebral parenchimal lesions and aneurisms, in comparison with ones without, indicating a consequent reduced blood flow velocity. According to our data, we could suggest as potentially pathological cut off MCA TAMM <100 cm/sec and MCA PSV value <125 cm/s, measurement close to the normal, but lower than ones found in SCD adult patients. These threshold intracranial blood flow velocities could be an indication to perform MRI/MRA to evaluate vessel tortuosity and mainly life-threatening aneurysms The correlations observed between TCCD values and MRI/MRA findings require further investigations. Disclosures Cappellini: Novartis, Shire, Cellgene, Sanofi: Advisory board Other.

Transcranial color Doppler in stroke-free adult patients with sickle cell disease

2017 ◽  
Vol 96 (9) ◽  
pp. 1547-1555 ◽  
Author(s):  
G. Graziadei ◽  
F. M. Casoni ◽  
F. Annoni ◽  
I. Cortinovis ◽  
P. Ridolfi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Color Doppler ◽  
Adult Patients ◽  
Cell Disease ◽  
Transcranial Color Doppler

Rituximab for Preventing Delayed Hemolytic Transfusion Reaction (DHTR) in Sickle CELL Adult Patients: Outcome of Transfusion and SIDE Effects in 58 CASES

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3687-3687
Author(s):  
Fabian Zanchetta-Balint ◽  
France Pirenne ◽  
Marc Michel ◽  
Armand Mekontso-Dessap ◽  
Matthieu Mahevas ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Sickle Cell ◽  
High Probability ◽  
Previous History ◽  
Clinical Signs ◽  
Adult Patients ◽  
Advisory Committees ◽  
The Third ◽  
History Of ◽  
Low Probability

Background: Transfusion is a major therapeutic of sickle cell disease (SCD); however, DHTR is one of the most feared complications . Prevention of allo immunization, by extended RBC matching is insufficient to prevent all cases of DHTR. Therefore, B cell depletion therapy should be also useful, especially in previously immunized patients to avoid the emergence of new allo-antibodies. Rituximab (RTX) is used for preventing alloimmunization for patients with a history of DHTR. Therefore, secondary prevention with rituximab prior a new exposure to transfused RBCs could be a relevant option. Here, we will report our experiences of RTX use in SCD adult patients with a previous history of DHTR. Methods: In this retrospective observational study, the data from 58 consecutive RTX infusion in 44 SCD patients with history of DHTR in our French referral center for SCD were analysed. Medical, biological and blood bank records of patients, clinical signs, rate of hemoglobin A (HbA) after transfusion (TF) were collected. To evaluate the persistence of transfused RBCs, the DHTR risk probability on days 15 and 30 after TF was evaluated according to Mekontso Dessaps nomogram. We also reported serious adverse events like infections in the year after RTX infusion. In cases of programmed surgery, 1 gramme of RTX was administred at day 1 and 15 few weeks before or one injection in emergency situation, with low dose of steroides. Adjuvant measure to avoid transfusion like EPO, Iron injection and hydroxyurea was decided in some cases. Results: We analyzed 58 cases of RTX administered to 44 adult patients with SCD, 10 of whom received two or more times this drug. A transfusion (TF) was required in 33/58 cases (56%). We distinguished three groups of patients. In the first group of 21 cases (36%), rituximab was used preventively before planned surgery at risk of bleeding, only 8 cases were transfused. In the second group of 30 cases (53%) during an acute event, in 19 cases patients received a transfusion. The third group of 7 patients received RTX during an active DHTR with hyperhemolysis requiring transfusion to protect an imminent transfusion and finally 6 of them was transfused. To evaluate the efficacy of transfusion we analyzed group 1 and 2 together and separately the third group with active DHTR and hyperhemolysis. In the first and second groups, HbA measurements was not available or interpretable in 11,1% of cases. On day 15 after TF, 77,8% of cases were classified as having a low probability of hemolysis, 7.4 % as intermediate probability and 3.7% as high probability. On day 30 after TF: 55,6% were into the low probability of hemolysis subgroup, 11,1% in the intermediate probability and 22,2% in the high probability group. (Figure 1) In group 3, HbA measurement wasn't available in 2 cases. On day 15 after TF, no cases were classified as having a low probability of hemolysis, 33,3 % as intermediate probability and 33.3% as high probability. On day 30 after TF: 33,3% were in the intermediate probability and 50 % in the high probability group. (Figure 2) Infection requiring intravenous antibiotic were observed in 19 cases/58 (32.7%) with a bacterial documentation in 73,7 %. In 63% of these cases, patients have been hospitalized in intensive care unit for acute events before RTX administration and had other risk factors of infection. The median time of apparition of infection was 28 days [11.5-46.5]. We report 4 deaths (6,8%), two patient died due to a hyperhemolysis syndrome with multiorgan failure that started before RTX administration, two other were due to an end stage cancer. These deaths are not related to the use of RTX. Conclusion: This study suggests that RTX can be safely used for preventing DHTR in patients with a previous history of DHTR and detected antibodies. We show that transfusion efficiency at day 15 post TF is better than days 30 postTF. The effectiveness of TF in active DHTR with h yperhemolysis is much lower, as most patients lose the transfused units at day 30 post TF.Beyond the use of RTX, the use of other measures such as hydroxyurea and erythropoietin to avoid the need of transfusion in these patients must be emphasized. Infection risk after RTX therapy is difficult to assess. In most cases an active inflammatory event was in process. Additional prospective studies are needed to improve the management of this challenging clinical situation. Disclosures Michel: Novartis: Consultancy; Amgen: Consultancy; Rigel: Consultancy. Galactéros:Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci:Novartis: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Causes of Death in 198 Sickle Cell Adult Patients: Old and New Trends

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1031-1031
Author(s):  
Anoosha Habibi ◽  
Stephanie Ngo ◽  
Etienne Audureau ◽  
Armand Mekontso-Dessap ◽  
Keyvan Razazi ◽  
...  
Keyword(s):  
Organ Failure ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Causes Of Death ◽  
Adult Patients ◽  
Therapeutic Education ◽  
Renal Diseases ◽  
Age At Death ◽  
Advisory Committees ◽  
Aged Patients

Introduction: Over the past decades, there have been substantial improvements in the medical care of sickle cell patients, leading to an increase in life expectancy, despite the fact that the latest studies in adults do not see any change in age at death. Pediatric mortality has declined significantly with the introduction of systematic antibiotics, the preventive care cerebral vasculopathy and therapeutic education for families. It seems important to analyze the morbidity and mortality risks to decide the necessary preventive measures. In this study we will describe the circumstances of death, the profiles of the patients and the risk factors in SCD adult patients. Materiel and method: We retrospectively reviewed the records of patients which died between 2001 and 2019 and treated in our national referral center (Henri Mondor Hospital) where 3500 patients are followed. Basic biological parameters, chronic and acute complications present in these patients as well as their treatment, median age at death, causes and circumstances of death were identified when the information was available. Results: During this period, 198 deaths were recorded or reported by families of patients. 54% were men. Patients ranged in age from 16 to 69 years and median age at death was 37 years IQR [30-47]. Concerning the type of hemoglobinopathy there were 158 homozygous patients (77%), 28 SC (14%), 11 heterozygous Sβ0 (5%) and 4 heterozygous Sβ+(2%).The causes of death are summarized in the Table 1. Patients had chronic terminal stage organ failure in more than 30% of cases, with indication for organ transplantation (renal, hepatic or cardiac) in 60 of them and 10 precapillary PAHs. 18% of patients were dialyzed. The diagnosis of DHTR was not reported in previous studies and probably under-diagnosed but 12 (6%) patients died of hyperhemolysis with multi-organ failure in this study. Nine deaths occurred during pregnancy and 17 during a travel. Biological, echo graphics data and risk factor analysis is ongoing. Discussion: The median age of death does not seem to improve from the study of Platt et al, however our cohort appears to age, we observed an increase in the number of aged patients over 45. The causes of death have evolved compared to data avaliable from previous studies, chronic organ failures are the leading cause of mortality especially in patients with renal impairment. The prevention of the onset of these complications is one of the new challenges especially renal diseases which was associated with premature mortality. DHTR and brain hemorrhages are new entities probably previously under-diagnosed. Pregnancy remains a risk period, which should strengthen its monitoring. Table 1 Disclosures Michel: Novartis: Consultancy; Rigel: Consultancy; Amgen: Consultancy. Galactéros:Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci:Roche: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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