Cumulative Incidences and Risk Factors for Intra and Extracranial Cerebral Arteriopathy in Sickle Cell Disease Children

In children with sickle cell disease (SCD), cerebral vasculopathy is responsible for overt strokes and silent cerebral infarcts (SCI). Transcranial Doppler (TCD) detects children at risk of strokes (intracranial time averaged mean of velocities (TAMV) ≥200cm/s). The extracranial portion of the internal carotid artery (eICA) can also be the site of stenosis or occlusion. eICA assessment requires cervical Doppler using a submandibular approach and cervical MRA (cMRA). We previously reported that eICA TAMV≥160cm/s are highly predictive of eICA stenosis and are a risk factor for SCI independently of acute and chronic anemia. However, the kinetics of eICA arteriopathy are unknown. The aim here was to evaluate and compare the cumulative incidence of intra/extracranial arteriopathy and associated risk factors in a longitudinal SCD cohort. Children born between 01/1988 and 01/ 2018, followed at our center at least until 06/2012 and up to 09/2019, annually assessed by TCD imaging and at least once by cervical Doppler were included, resulting in 493 SCD children (238F-255M) with 398 SCA (385SS,10Sb0,3SDPunjab), and 95 SC/Sb+ children (65SC,30Sb+). Alpha-genes, b-globin haplotypes, G6PD activity, CD36 expression were recorded. The average of baseline biologic parameters recorded between 1 and 3 years of age, a minimum of 3 months away from transfusion, 1 month from a painful episode, and before any intensive therapy was calculated. The median (range) follow-up of the overall cohort was 10.6 years (1.1-22.9), providing 5335 patient-years of follow-up. Six deaths occurred (5 SCA-children at 2, 4, 7, 19 & 20 years and 1 in SB+ patient at 13 years). Three SS patients had an ischemic stroke at 1.5, 3 and 4.3 years. Kaplan-Meier estimates of cumulative incidence (95%CI) are shown (Figure). In SCA-children, abnormal eICA TAMV and/or eICA stenosis were sometimes associated with abnormal intracranial TAMV and/or stenosis, but isolated eICA TAMV≥200cm/s or 160-199cm/s were observed in 19 (4.8%) and 28/398 (7.0%) patients, respectively, and isolated eICA stenoses in 33/294 (11.2%).Thus, risk factors were only analyzed in patients with isolated intra- or extracranial arteriopathy. COX regression analyses are shown (Table). For isolated intracranial TAMV≥200cm/s, multivariate analyses after introducing all significant genetic and biological risk factors retained the number of SEN b-haplotypes [HR=0.547 (95%CI:0.335-0.893); p=0.016], reticulocyte count>400x109/L [HR=1.961 (95%CI:1.119-3.436); p=0.019], and WBC count>20x109/L [HR=2.410 (95%CI:1.340-4.329); p=0.003] as independent risk factors. Isolated eICA TAMV≥160 cm/s were only strongly associated with the presence of tortuosities [HR=8.6 (95%CI :4.3-17.2); p<0.001]. eICA tortuosities were present in 94/284 (33.1%) SCA vs 5/43 (11.6%) SC/Sb+ children (p=0.004), most often seen at the first cMRA but secondarily in 16 patients. Multivariate COX analysis retained genotype [HR/SCA vs SC/Sb+ = 3.6 (95%CI:1.4-9.4); p=0.010], low hemoglobin [HR=1.25 (95%CI:1.04-1.50); p=0.020], and high LDH [HR=1.002 (95%CI:1.001-1.002); p=0.001], as independent risk factors for eICA tortuosities. As expected, the risk of intracranial stenosis was significantly associated with isolated intracranial TAMV≥200 cm/s [HR (95%CI)=4 .255 (2.146-8.475); p<0.001]. After adjustment with isolated intracranial TAMV≥200 cm/s, a-thalassemia, low hemoglobin, high WBC, MCV and LDH remained as significant, but not independent, risk factors for intracranial stenosis. The risk for eICA stenosis was only highly associated with the presence of tortuosities [HR=10.9 (95%CI:4.7-25.0); p<0.001], or a history of eICA≥160cm/s [HR=15.4 (95%CI :7.5-31.2); p<0.001]. This study reports eICA arteriopathy kinetics using a longitudinal cohort of SCD children systematically assessed by Doppler and cMRA. While we confirm that only SCA and not SC/Sb+ children are at risk of intra/extracranial arteriopathy, we show for the first time that extracranial arteriopathy progressively develops as early as 2 years old in SCA-children and reaches a plateau around 10 years of age, as for intracranial arteriopathy. Furthermore, eICA tortuosities, which are the risk factor for eICA arteriopathy, are themselves significantly and independently associated with the SCA genotype and the severity of hemolytic anemia. Figure Disclosures Bernaudin: BlueBirdBio: Consultancy; AddMedica: Honoraria, Other; GBT: Membership on an entity's Board of Directors or advisory committees. Verlhac:BlueBirdBio: Consultancy; AddMedica: Honoraria.

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Hospital Readmission within 30 Days: A New Benchmark for Quality Care among Children with Sickle Cell Disease.

Blood ◽

10.1182/blood.v110.11.3403.3403 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3403-3403

Author(s):

Melissa J. Frei-Jones ◽

Michael R. DeBaun

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Quality Of Care ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Hospital Readmission ◽

Cell Disease ◽

First Admission

Abstract The National Association of Children’s Hospitals and Related Institutions (NACHRI) has established benchmarks for measuring quality of care in children that are hospitalized. Readmission within 30 days of discharge is the benchmark chosen to assess the quality of care for patients with Sickle Cell Disease (SCD). Limited data exist to determine risk factors for re-admission and whether such risk factors are modifiable. We performed a retrospective case-control study to identify risk factors for hospital readmission in children with SCD. All hospital admissions of patients with SCD for one year were reviewed. Cases were defined as children with SCD who were readmitted within 30 days of their first admission during the 12 month study period. Controls were defined as children with SCD who were not readmitted within 30 days of their first admission. A total of 30 cases and 70 controls were identified. The average time between admissions was 10.7 days with 50% readmitted within 8 days and 77% readmitted within 21 days. No difference in demographic data was found between cases and controls. The most common admission and readmission diagnosis was pain, 78% and 70%, respectively. The greatest risk factor for readmission was no follow-up appointment within 30 days after discharge in the SCD clinic (OR 7.7, 95% CI 2.4–24.4). The second highest risk factor was severity of disease, defined as patients with ≥ 3 hospitalizations in the previous 12 months versus patients with ≤ 2 hospitalizations in the previous 12 months (OR 7.3, 95% CI 2.8–18.9). A diagnosis of asthma was also a risk factor for readmission (OR 2.9, 95% CI 1.2–7.3). Patients who initially required supplemental oxygen to maintain their oxygen saturation in the normal range and were subsequently on room air for ≤ 24 hours at discharge were also more likely to be readmitted (OR 3.3, 95% CI 1.1–9.7). Steroid administration was not a risk factor for readmission (OR 1.2, 95% CT 0.5–3.2). Potential modifiable risk factors exist to decrease the rate of readmission. Specifically, strategies targeted at the modification of disease severity, aggressive management of asthma, and outpatient follow-up after hospitalization may decrease the 30 day readmission rate.

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Reproductive Behaviour of Couples at Risk for Sickle Cell Disease in Cuba: a Follow-Up Study

Prenatal Diagnosis ◽

10.1002/(sici)1097-0223(199708)17:8<737::aid-pd137>3.0.co;2-v ◽

1997 ◽

Vol 17 (8) ◽

pp. 737-742 ◽

Cited By ~ 10

Author(s):

Aida Dorticós-Balea ◽

Marcos Martin-Ruiz ◽

Piedad Hechevarria-Fernández ◽

Martha S. Robaina-Castellanos ◽

Manuel Rodriguez-Blanco ◽

...

Keyword(s):

At Risk ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Reproductive Behaviour ◽

Cell Disease ◽

Follow Up Study

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Abstract T MP110: Central Retinal Artery Occlusion in Patients with Sickle Cell Disease

Stroke ◽

10.1161/str.46.suppl_1.tmp110 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Hashim Khan ◽

Morad Chughtai ◽

Ahmed A Malik ◽

Adnan I Qureshi ◽

Fareed K Suri

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Central Retinal Artery Occlusion ◽

Retinal Artery Occlusion ◽

Artery Occlusion ◽

Cell Disease ◽

History Of ◽

Retinal Artery

Objective: To determine the rate of and risk factors for incident central retinal artery occlusion (CRAO) among patients with sickle cell disease enrolled in a large cohort with longitudinal follow-up. Background: Sickle cell disease increases the risk of ischemic stroke among women but the risk of CRAO is not studied. Design/Methods: A total of 4085 patients from newborns to 77 years-old, were enrolled in Phase 1 of Cooperative Study of Sickle Cell Disease from 23 centers across the US. Participants underwent a baseline examination for assessment of demographics, prior medical history, lab assessments, and clinical data. Post baseline data included routine follow-up examinations, measures of organ damage, and collection of acute and chronic complications. The risk factors for CRAO were identified using Cox Proportional Hazards analysis. Results: A total of 9 (0.002%) of 4085 patients with sickle cell disease developed CRAO over a mean follow-up of 5.2 (95% CI 0.9 - 11.3) months, with an estimated incidence of 0.02 per 100 patient years. The incidence of CRAO was 0.03 per 100 patient years and 0.05 per 100 patient years in men and women, respectively. The history of previous stroke (2.6% versus 0.0%, p=0.7) and the proportion of patients diagnosed with large arterial occlusive disease (55.6% versus 7.7%, p=<0.001) was greater in those who developed CRAO compared to those who did not develop CRAO. History of exchange transfusions (2.7 % versus 22.2 %, p=0.02) and cigarette smoking (13.7 % versus 22.2 %, p =0.4) were more common among patients who developed CRAO. The hematocrit (%) (mean ± SD) was similar between patients who did or did not develop CRAO (29.5 ± 9.6 versus 27.3 ± 5.6, p=0.3). At completion of follow-up, 22.2% (n=2) patients with CRAO reported disability compared with 11.1% (n=455) patients without CRAO (p=0.7) Conclusions: The incidence of CRAO is relatively high among patients with sickle cell disease and was associated with disability.

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Low Mortality In Sickle Cell Patient Cohort with Elevated Tricuspid Regurgitant Jet Flow Velocity

Blood ◽

10.1182/blood.v116.21.1641.1641 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1641-1641

Author(s):

Eduard J. Beers van ◽

Charlotte F.J. Tuijn ◽

Erfan Nur ◽

Anita W. Rijneveld ◽

M. R. Mac Gillavry ◽

...

Keyword(s):

Risk Factor ◽

Sickle Cell Disease ◽

Mortality Rate ◽

Pulmonary Function ◽

Brain Natriuretic Peptide ◽

Sickle Cell ◽

Plasma Levels ◽

Early Death ◽

Cell Disease

Abstract Abstract 1641 Elevated tricuspid regurgitant jet flow velocity (TRV) occurs in approximately 30% of adults with sickle cell disease (SCD) and is reported to be an independent risk factor for early death with a mortality rate as high as 40% after 4 years. We previously presented the results on a cohort of 85 consecutive ambulatory sickle cell patients that were prospectively screened for elevated TRV (2.5 m/sec) using trans-thoracic echocardiography. We aimed to determine the mortality rate in relation to TRV and associated factors in a well characterized cohort of sickle cell disease patients in the Netherlands. Follow up consisted of regular outpatient visits including laboratory testing and repeated echocardiography every 2 years. Baseline hemoglobin (Hb), lactate dehydrogenase (LDH), brain natriuretic peptide (BNP), N-terminal pro brain natriuretic peptide (NT-proBNP), asymmetric dimethylarginine (ADMA) and arginine plasma levels were related to outcome, as were baseline pulmonary function tests and coagulation studies. The prevalence of elevated TRV in the cohort at baseline was 30% (41% in HbSS/HbS0-thalassemia patients and 13% in HbSC/HbS+-thalassemia patients). Median (IQR) follow-up for the whole group was 53 months (50-57). No patients were lost to follow-up. Four patients (3 HbSS and 1 HbSβ0-thalassemia) died during follow-up. Two of these patients had an elevated TRV at baseline while the other two initially had immeasurable TRV, resulting in a death rate for patients with an elevated TRV of 8% and a ratio for early death in of 2.3 (95 percent confidence interval, 0.3 to 16.6; p=0.40) However, the two patients with immeasurable TRV at baseline had an elevated TRV (2.55 m/sec and 2.92 m/sec) on repeated echocardiography two years later. Median age of the patients who died was 48 (34-58) years compared to 29 (21-44) years of those who survived (p=0.18). Baseline plasma levels (medians (IQR)) of Hb and LDH in the deceased were 4.7 (4.3-5.0) mmol/L and 676 (575-801) U/L compared to 5.4 (4.8-6.0) and 410 (341-629) in the survivors (p=0.075 and p=0.049) respectively. Baseline median NT-proBNP plasma levels in the deceased were 278 (131-686) pg/mL and 520 (154-3957) pg/mL compared to 45 (26-94) and 91 (52-150) in the survivors (p=0.007 and p=0.03) respectively. Pulmonary function testing, coagulation studies and plasma levels of ADMA and arginine were not associated with mortality in this cohort. Conceding the relative young age of our cohort, we conclude that the mortality in sickle cell patients with elevated TRV values was far lower as compared to the published literature. Although an elevated TRV could still be an important risk factor for early death, mortality may in fact be much lower than previously reported which is in line with more recent observations by other groups. With respect to biomarkers, we confirmed that NT-pro BNP and BNP levels were significantly higher in patients who died, with a trend toward a higher rate of hemolysis as well. Disclosures: No relevant conflicts of interest to declare.

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Survival of Children with Sickle Cell Disease: An Update from the Dallas Newborn Cohort.

Blood ◽

10.1182/blood.v106.11.3812.3812 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3812-3812

Author(s):

Charles T. Quinn ◽

Nancy J. Lee ◽

Zora R. Rogers ◽

George R. Buchanan

Keyword(s):

At Risk ◽

Overall Survival ◽

Sickle Cell Disease ◽

Newborn Screening ◽

Sickle Cell ◽

Standard Error ◽

Additional Patient ◽

Acute Chest Syndrome ◽

Cell Disease

Abstract The Dallas Newborn Cohort is the largest newborn inception cohort of individuals who have sickle cell disease (SCD), and it has provided modern pediatric SCD survival data (Blood2004;103:4023–7). The Cohort includes subjects who were diagnosed at birth by universal newborn screening and followed at our center up to 18 years of age. All subjects with sickle cell anemia (SS) or sickle-β° thalassemia (Sβ°) were prescribed prophylactic penicillin until 5 years of age. The first report from the Cohort showed an overall survival of 85.6% at 18 years for individuals with SS or Sβ°. The standard error of this estimate was high because only 8 individuals remained at risk at 18 years of age at the time of the analysis, which included follow-up until July 2002. Accrual and follow-up of cohort members has continued. We therefore sought to update the survival estimates through age 18 by including three further years of follow-up. By definition the Dallas Newborn Cohort includes all individuals with SS, Sβ°, sickle-hemoglobin C disease (SC), or sickle-β+-thalassemia (Sβ+) who were born in Texas after November 1, 1983, diagnosed by the newborn screening program of Texas, and seen at least once in our center. New members of the Cohort who came to our center between July 2002 and July 2005 were identified. Follow-up of existing members was updated. All deaths and their causes were determined. Subjects were analyzed in two separate groups because of known clinical similarities: SS/Sβ° and SC/Sβ+. Overall survival was analyzed by the Kaplan-Meier method. Subjects were censored at the time of their last clinical encounter. We identified 115 new subjects, and included 1627 additional patient-years of follow-up. The cohort now includes 826 subjects (SS 503, Sβ° 18, SC 247, Sβ+ 58; male:female 427:399) and it provides 7275 patient-years of follow-up. Mean follow-up was 8.9 years (range 0.9–19.5 years). 62 patients (7.5%) were lost to follow-up. There were 25 deaths in the cohort; none was new and all were previously reported. Of the deaths, 15 were likely related to SCD (5 sepsis, 3 acute chest syndrome, 2 multi-organ failure syndrome, 5 other) and 10 were apparently unrelated to SCD (4 trauma or accidental death, 6 other diseases). There were 22 and 3 deaths in the SS/Sβ° and SC/Sβ+ groups, respectively. All the SC/Sβ+ deaths were apparently unrelated to SCD. Overall survival at 18 years for SS/Sβ° and SC/Sβ+ subjects was 92.4% (standard error [SE] 1.9; 52 at risk) and 98.1% (SE 1.3; 12 at risk), respectively. The overall incidence of death through 18 years of age was 0.46 and 0.12 per 100 patient-years, respectively. In conclusion, this updated survival analysis of the Dallas Newborn Cohort now shows that over 90% of children with SS/Sβ° survive childhood, and nearly 100% of children with SC/Sβ+ become adults.

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Outpatient Follow-up and Rehospitalization for Sickle Cell Disease in Wisconsin Medicaid.

Blood ◽

10.1182/blood.v114.22.2489.2489 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2489-2489

Author(s):

Jack M Leschke ◽

Julie A. Panepinto ◽

Raymond G Hoffmann ◽

Ke Yan ◽

David Brousseau

Keyword(s):

At Risk ◽

Sickle Cell Disease ◽

Disease Severity ◽

Sickle Cell ◽

Outpatient Visit ◽

Index Hospitalization ◽

Cell Disease ◽

Outpatient Visits ◽

Sickle Cell Crisis

Abstract Abstract 2489 Poster Board II-466 Elevated hospitalization rates for patients with sickle cell disease are largely a result of frequent vaso-occlusive crises. Recent hospital utilization concerns have placed increasing emphasis on rehospitalization as a cost saving and quality of care measure. For sickle cell disease, 30 day rehospitalization has become a benchmark for care quality. Previous reports have shown 30 day rehospitalization rates as high as 30-47% and propose outpatient follow-up as a preventive measure. However, these studies have been limited to single centers and have focused only on specific age groups. Our study sought to examine the efficacy of outpatient follow-up on 30 day rehospitalization prevention across all ages in a statewide Medicaid program. We hypothesized that a post-discharge outpatient visit is associated with lower rehospitalization rates for patients with sickle cell disease. The study is a retrospective cohort using Wisconsin Medicaid claims data for hospitalized children and adults with sickle cell disease from January 1, 2003 to December 31, 2007. Patients at risk for rehospitalization were identified using sickle cell disease-related ICD-9 diagnosis codes (28241, 28242, 28260-28269) at inpatient discharge. The first hospitalization with a sickle cell diagnosis for each individual was extracted and then only those hospitalizations with a diagnosis of sickle cell crisis (28242, 28262, 28264, 28269) were included. Each patient participated in the study only once. The main outcome measure was a rehospitalization within 30 days of discharge from the previous hospitalization. Individuals were considered to have had an outpatient follow-up visit based on a claim for an outpatient visit within 30 days of discharge or prior to a rehospitalization if the rehospitalization occurred in fewer than 30 days. Outpatient visits that occurred on the same day as the rehospitalization were not included. Outpatient visits were calculated as rates to avoid the bias of those not being rehospitalized having more time for an outpatient visit. Multiple logistic regression was performed to evaluate the association between having an outpatient visit, disease severity, and asthma on the outcome of rehospitalization. Severe cases were defined as individuals with 3 or more hospitalizations within 1 year beginning 2 months after the index hospitalization. Patients were excluded from our study if the index hospitalization resulted in death, as they were not at risk for rehospitalization. Four hundred and eight patients with a hospitalization for sickle cell crisis were included in the analysis. Of these 408 patients, 70 (17%) were rehospitalized within 30 days following discharge from the index hospitalization. Of the 70 re-hospitalized patients, 35 (50%) were re-hospitalized within 11 days, and 54 (77%) were rehospitalized within 22 days from discharge. Multiple regression revealed that severe disease was associated with rehospitalization (4.693, 95% CI (2.674, 8.236)), but neither the outpatient visit rate (OR 0.970, 95% CI (0.367, 2.560)) nor a diagnosis of asthma (OR 0.862, 95% CI (0.467, 1.592)) were associated with rehospitalization. Of note, when the unadjusted analysis using the simple existence of an outpatient visit prior to rehospitalization was used, outpatient visits did show an association with decreased rehospitalizations; however this association was no longer significant when adjusted for the increased time for an outpatient visit in those not rehospitalized within 30 days. Contrary to our hypothesis, outpatient follow-up was not associated with fewer rehospitalizations in our study, when the outpatient follow-up rate was used to correct for the increased time for outpatient visits in those not rehospitalized. Disease severity was found to be the only statistically significant predictor of rehospitalization for patients with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

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Screening of the Mother During Early Pregnancy

PEDIATRICS ◽

10.1542/peds.83.5.884 ◽

1989 ◽

Vol 83 (5) ◽

pp. 884-885

Author(s):

Yolanda Rooks

Keyword(s):

At Risk ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Screening Program ◽

Medical Center ◽

Medical Community ◽

Cell Disease ◽

Sample Collection ◽

The Family

Screening for the early diagnosis of sickle cell disease has been advocated as essential for reducing infant mortality and morbidity. The provision of comprehensive and preventive care optimizes the chance for a longer and more healthy life by minimizing the detrimental complications that often occur in early life. Accordingly, the goals of early identification and intervention include preventing complications through the anticipation of medical problems, educating the family so that they become knowledgeable about sickle cell disease and how it may affect their child, and assisting the family in identifying specialized medical centers where appropriate care and follow-up will occur. MATERIALS AND METHODS The target population in New Haven, CT, was defined as black and Puerto Rican gravida women giving birth at Yale Medical Center. Screening these at-risk pregnant women and the fathers permitted prior identification of the newborn at risk. This was perceived to be a method of decreasing the number of cord blood specimens to be screened as well as increasing the yield. Screening guidelines mandated education, informed consent, and appropriate follow-up for parents whose infants were identified to be heterozygous or homozygous for a sickle variant. The protocols for sample collection and sample testing were established. Hemoglobin electrophoresis was performed by the following two techniques: (1) cellulose acetate at pH 8.4 and (2) citrate agar gel at pH 6.2. The latter technique facilitates the identification of Hb S and Hb C in the presence of large amounts of Hb F3. The screening program was introduced to the medical community and support staff.

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PROGRAM EFFECTS ON DECREASING MORBIDITY AND MORTALITY

PEDIATRICS ◽

10.1542/peds.83.5.819 ◽

1989 ◽

Vol 83 (5) ◽

pp. 819-822

Author(s):

Ranjeet Grover

Keyword(s):

At Risk ◽

Sickle Cell Disease ◽

Sickle Cell ◽

High Standard ◽

Disease Diagnosis ◽

Test Results ◽

Cell Disease ◽

Test Procedures ◽

The Public

Our experience demonstrates that the diagnosis of sickle cell disease at birth along with early intervention can reduce mortality among identified patients. However, accurate screening of newborns in the absence of a comprehensive follow-up program is of limited value. Our experience with trait follow-up indicates that couples at risk should be sought both by testing the parents of trait newborns and by testing the mothers in the prenatal period. Our recommendations are that programs for sickle cell screening of newborns should be structured on the basis of clearly defined goals and should ensure the following services: a newborn screening laboratory under strict quality control with backup facilities for special test procedures and interpretation of test results; an efficient and effective mechanism for recall of infants with presumptively positive results and referral of patients with the sickle cell disease diagnosis; treatment centers with a high standard of medical care to provide comprehensive care to patients with sickle cell disease and their families; skilled genetic counseling for the families of newborns with sickle cell disease and trait, including the information available concerning prenatal diagnosis for couples at risk; broadbased and ongoing education for professionals, paraprofessionals, and the public at large to enhance their understanding and cooperation; means to evaluate the effectiveness and success of the program in achieving the goals set forth.

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High Incidence and Recurrence Rate of Venous Thromboembolic Events in Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2018-99-119343 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2381-2381

Author(s):

Bart J. Biemond ◽

Ewout R. Egner ◽

Erfan Nur ◽

Charlotte F.J. Van Tuijn

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Recurrence Rate ◽

Sickle Cell ◽

Organ Damage ◽

Clinical Risk Factors ◽

Cell Disease ◽

Clinical Risk ◽

High Incidence

Abstract Introduction: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and chronic inflammation resulting in endothelial damage, neutrophil and platelet activation, enhanced cell adhesion and coagulation activation. Due to these conditions, sickle cell disease is considered to be a procoagulant condition. However, limited studies have evaluated the incidence of thrombosis in sickle cell disease and clinical risk factors for thrombosis are not clear. Here we present a retrospective cohort study to determine the incidence of VTE in a well characterized cohort of adult sickle cell patients. The aim of the study was to assess the cumulative incidence of venous thromboembolic events in patients with SCD and to relate this complication with clinical risk factors, genotype, organ damage and laboratory parameters. Methods: All patients with SCD (HbSS, HbSC, HbSβ0 thalassemia, HbSβ+ thalassemia) of ≥ 18 years in a tertiary clinic for SCD at the Amsterdam University Medical Center in the Netherlands were eligible for the study. Patients with a history of prior VTE or VTE or VTE at first presentation were excluded. Patients were divided into a subgroups with a severe genotype (HbSS/HbSβ0 thalassemia) and a mild genotype (HbSC/HbSβ+ thalassemia). Hospital electronic records were analyzed for occurrences of deep vein thrombosis (DVT) or pulmonary embolism (PE) objectified with diagnostic tests (ultrasound, high probability ventilation/perfusion scan or CT angiography). All sickle cell related complications, organ damage and clinical risk factors at the time of the VTE were scored. General laboratory parameters were gathered from patient records in steady state condition. Results: In total 228 patients were included in the study with a mean age of 24 ± 10 years at the start of follow up years and a total follow up of 1548 patient years. Median follow up was 5 years (IQR 2-10). Twenty-one patients suffered one or more VTE episodes (9.2%), resulting in an incidence rate in the entire cohort of 13.6 VTE events per 1000 patient years (95%Cl 9.7-22.0). We recorded 8 recurrences of VTE in 5 patients (1 patient suffered two VTE recurrences, and 1 patient had three VTE recurrences) with a median time to recurrence of 3 years (IQR 1-4). Mean age at the time of first VTE was 29 years. The first VTE episodes consisted of an isolated DVT of the leg/arm in 8/21 patients, an isolated PE in 10/21 patients, and a combined DVT and PE in 3/21 patients. Of these first VTE episodes 9/21 (43%) were found to be idiopathic, 5/21 (24%) occurred during oral contraceptive use and 7/21 (33%) were provoked by recent surgical procedure/hospital admission/central venous catheter. VTE was significantly associated with a previous history of acute chest syndrome (ACS) (OR 10.6 [3.3 - 46.6] P<.001), avascular necrosis (AVN) (OR 5.6 [2.1 - 15.0] P <.001) and a ferritin level >1000 μg/L (OR 3.8 [1.4 - 10.2] P=0.023). No significant association with other forms of organ damage was found. Patients with a severe genotype had a higher incidence of VTE than patients with a mild genotype (11.4% versus 5.6%). In the severe genotype subgroup, lower median HbF levels correlated with an increased risk of VTE (P <.005). Ten patients died during follow-up at a mean age of 40 ± 16 years. Conclusion: Sickle cell patients have a remarkably high incidence rate of VTE (13.6 events per 1000 patients years) with a high recurrence rate (23.8%). This confirms the hypercoagulable state of patients with SCD. Sickle cell related complications like ACS and AVN were associated with VTE. Given the high incidence and recurrence rate, awareness for VTE in SCD patients is warranted and long term anticoagulation may be indicated. Disclosures No relevant conflicts of interest to declare.

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