Association of Annexin A5 Resistance with Silent Infarct in Sickle Cell Disease

Abstract Background: In sickle cell disease (SCD) abnormally shaped RBCs interact with white blood cells and the endothelium, leading to a vasculopathy and thrombotic/ prothrombotic complications such as stroke and pulmonary hypertension. About 10 % of patients with a thrombotic event in the general population will have the presence of an antiphospholipid (aPL) antibody (Andreoli et al. 2013). One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of annexin A5. Annexin A5 is a potent anticoagulant protein that has an affinity to phospholipids. In the presence of aPL antibodies, annexin A5 is unable to form its crystallized anticoagulant shield (annexin A5 resistance). There is a paucity of data which assesses the association of aPL antibodies with vasculopathic complications of SCD, and there have been no studies investigating the annexin A5 resistance assay (A5R). We designed a pilot study assessing aPL antibody levels and A5R in a pediatric sickle cell population. Methods: Patients with a history of stroke, abnormal transcranial doppler (TCD) and elevated TR gradient by echocardiography (>25mm of Hg) were eligible. A5R, lupus anticoagulant- DRRVT, anti β2GP1, anti phosphatidylserine and anti cardiolipin antibody (IgG, IgA, IgM) assays were performed on samples obtained prospectively when patients were at a steady state (at least 4 weeks after an acute event). A5R measures coagulation times in the presence and absence of annexin A5. Resistance to the anticoagulant effects of annexin is expressed as a reduction in this ratio (Rand et al. 2004). Statistical analysis assessed multiple variables including age, gender, hemoglobin, reticulocyte count, LDH, hydroxyurea therapy, transfusion therapy, elevated TR gradient, stroke and silent stroke. Univariate analysis and multivariate logistic regression was performed with abnormal annexin A5 as the outcome variable. Results:There were a total of 39 patients: 12 patients with a history of stroke, 6 with an elevated TCD velocity and 15 patients with an elevated TR gradient. Of the 27 patients that did not have a stroke, 25 had a screening MRI in the prior year, and 9 of these patients had silent infarcts. Only 1 of 39 patients had elevated anticardiolipin IgG antibodies and 1 had an abnormal lupus coagulant (DRVVT). In contrast, 5/39 patients (12.8%) had low or abnormal annexin A5 resistance, 7/39 (18%) were in the borderline range and 27/39 (69%) were normal. This frequency of abnormality was unexpected in the antiphospolipid antibody and lupus anticoagulant negative population. None of the patients, except the one with the positive lupus anticoagulant, developed any thrombotic events in 3.5 years of follow up. None of the patients with overt stroke or abnormal TCDs had an abnormal A5R. Multivariate logistic regression analyses showed statistically significant association of hemoglobin (p= 0.037, OR 0.25, CI 0.07-0.92)), age (p =0.047, OR 1.43, CI 1.01-2.04) and silent infarct (p =0.015, OR 28.5, CI 1.9-420.5) with abnormal annexin A5 resistance. A multivariate analysis using linear regression with annexin A5 resistance as a continuous outcome variable (Table 1), showed persistence of the significant association of silent infarcts (p =0.037). Conclusion: We report an association between annexin A5 resistance and low hemoglobin, older age and presence of silent infarct in a subgroup of SCD patients. Prevalence of abnormal aPL antibody assays and lupus anticoagulant was strikingly low in this cohort. A potential role for perturbed annexin A5 resistance in the pathophysiology of silent infarction in SCD will need to be evaluated further in carefully designed prospective studies and may be a novel therapeutic target. Table 1. Hemoglobin, Age and Silent Stroke are Associated with Abnormal Annexin A5 Resistance Characteristic Odds Ratio Odds Ratio Confidence Interval p-value Hemoglobin* 0.25 0.07-0.92 0.037 Reticulocyte count 0.77 0.54-1.08 0.13 LDH 1.00 0.99-1.00 0.51 Age* 1.43 1.01-2.04 0.047 Monocyte count 1.00 1.00-1.00 0.34 Silent infarct* 28.5 1.9-420.5 0.015 Stroke 0.47 0.05-4.88 0.53 Elevated TR gradient 0.34 0.03-3.49 0.36 Gender 0.47 0.05-4.88 0.53 Allosensitization 0.56 0.05-5.86 0.63 HU vs no treatment 0.46 0.03-6.93 0.58 Transfusion vs no treatment 0.18 0.01-4.26 0.29 Disclosures No relevant conflicts of interest to declare.

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Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study

Stroke ◽

10.1161/strokeaha.121.035338 ◽

2021 ◽

Author(s):

Alejandro N. Santos ◽

Laurèl Rauschenbach ◽

Dino Saban ◽

Bixia Chen ◽

Annika Herten ◽

...

Keyword(s):

Logistic Regression ◽

Brain Stem ◽

Odds Ratio ◽

Pediatric Patients ◽

Cox Regression ◽

Cerebral Cavernous Malformations ◽

Multivariate Logistic Regression ◽

Cavernous Malformations ◽

History Of

Background and Purpose: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. Methods: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. Results: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15−8.63], P =0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04−5.86], P= 0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18−8.99], P= 0.022 and odds ratio, 2.53 [95% CI, 1.07−5.98], P =0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80−110.39], P= 0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%−23.6%) for the entire cohort, 30.2% (20.2%−42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%−51.1%) for children with brain stem CCM. Conclusions: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

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Predictors of Adverse Outcomes in Hospitalized Adult Patients with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3197.3197 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3197-3197

Author(s):

Fahd Rahman ◽

Roy N. Gay ◽

Samir K. Ballas ◽

Juan C. Zubieta ◽

Zekarias Berhane ◽

...

Keyword(s):

At Risk ◽

Logistic Regression ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Acute Pain ◽

Reticulocyte Count ◽

Laboratory Data ◽

Adverse Outcomes ◽

Acute Chest Syndrome ◽

Cell Disease

Abstract The identification of patients with sickle cell disease at risk of serious complications at the time of hospital admission can help stratify patients who will need aggressive management. We identified predictors associated with adverse outcomes such as frequent hospitalizations, acute pain crises and acute chest syndromes. To that end, we retrospectively reviewed medical records of 265 adult sickle cell disease patients, hospitalized between 1/1/98 and 2/3/05 at Mercy Catholic Medical Center, with complete clinical and laboratory data. 195/73.6% had HbSS and the rest had HbSC, HbSβ-thal0,HbS-βthal+or HbSOarab disease. 59 variables were considered including demographic, hematological, biochemical, clinical and treatment data. Logistic regression models were used to obtain associations between variables, and to adjust for confounding effects. Analysis showed that adverse events during admission included acute pain crises in 249/94%, acute chest syndromes in 25/9.4% and strokes in 5/1.9% patients. Other outcomes were a greater than 2 hospitalizations per year 82/31.9%, more than 2 pain crises per year 145/54.7%, transfusion required during admission 72/27.2%, length of hospital stay more than 5 days 105/39.6% and death during hospitalization 13/4.9%. Multivariate logistic regression analysis revealed 21 factors with statistically significant associations. A reticulocyte count greater than 1.5 (OR 3.98, CI 1.48–10.69, P.006) and employment status (OR .31, CI .13-.75, P.009) were associated with more admissions per year. History of acute chest syndrome (OR 5.33, CI 1.7–16.77, P.004), reticulocyte count greater than 1.5 (OR 3.46, CI .91–13.11, P.067) and care provided by a nonhematologist (OR 5.04, CI 1.7–14.95, P.0035) were linked with more pain crises per year. Pain crises during admission were associated with HbSS disease (OR 9.31, CI 2.17–39.9, P.01) and out patient folate therapy(OR 6.23, CI 1.45–26.84, P.003). Patients with leukocytosis (OR 3.41, CI 1.2–9.67, P.02) and a higher serum glucose level (OR 7.54, CI 2.6–21.86, P.0002) were linked to more acute chest syndromes. Females (OR .1, CI .03–.37, P.0004) were at lower risk of having acute chest syndromes. Outpatient folate therapy (OR .07, CI .007–.69, P.02) was associated with lower numbers of acute neurological events. Patients with initial hemoglobin levels less than 7 g/dL (OR 1.99, CI 1–4, P.0007) and prolonged hospitalization (OR 7.06, CI 3.63–13.74, P.0001) frequently required transfusions. Variant diseases (OR .28, CI .13–.58, P.05) required fewer transfusions. Deaths during hospitalization were lower with folate therapy (OR .18, CI .05–.63, P.007) and a transfusion requirement during admission (OR 5.07, CI 1.45–17.64, P.01) predicted more deaths. HbSS patients (OR 2.52, CI 1.1–5.8, P.03), substance abusers (OR 2.93, CI 1.21–7.08, P.01), those requiring antihistamines during admission (OR 3.33, CI 1.38–8.03, P.007), or requiring more than 2 hospitalizations per year (OR 2.62, CI 1.26–5.43, P.009) had hospital stays longer than 5 days while in females odds were low for this outcome (OR .30, CI .15–.59, P.0005). In conclusion, simple tools like a complete history, physical examination, demographic and laboratory data can help clinicians and health care providers to gauge severity of the illness and deliver tailored management protocols targeting these “at risk” sickle cell disease patients.

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Clinical and Laboratory Predictors for Renal Damage in Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.3252.3252 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3252-3252

Author(s):

Santosh L Saraf ◽

Robert Molokie ◽

Johara Hassan ◽

Michel Gowhari ◽

James Lash ◽

...

Keyword(s):

Logistic Regression ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Reticulocyte Count ◽

Female Gender ◽

P Value ◽

Cell Disease ◽

Intravascular Hemolysis ◽

Indirect Bilirubin ◽

Laboratory Variables

Abstract Abstract 3252 Renal failure is an independent marker for developing other forms of chronic organ damage and for early mortality in sickle cell disease (SCD). We conducted a retrospective, cross-sectional chart review of 292 adults with SCD (type SS or S-beta thal) treated at the University of Illinois Medical Center to assess the prevalence and factors related to kidney damage. Data was recorded from a clinic visit at least four weeks from a vaso-occlusive pain episode or red blood cell transfusion. The glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease formula. Hemoglobinuria was defined by dipstick urinalysis showing trace, small, or moderate blood and <2 RBC/high power field. Urine albumin to creatinine ratios of 30 to 300 mg/g and >300 mg/g were categorized as microalbuminuria and macroalbuminuria, respectively. The median age was 33 years and 46% of patients were on hydroxyurea. We observed microalbuminuria in 41%, macroalbuminuria in 20%, hemoglobinuria in 41% and GFR <90 mL/min in 20% of adults with SCD. Univariate associations with GFR <90 mL/min are summarized in Table 1. By logistic regression, macroalbuminuria (OR 7.5, 95% CI: 2.5–22.2; p<0.0001) and age (OR 1.11, 95% CI: 1.06–1.16; p <0.0001) were independent predictors of GFR <90 mL/min (r2 = 0.23). Given the strong correlation of macroalbuminuria with GFR <90 mL/min, we explored factors related to degree of albuminuria. Univariate associations with degree of albuminuria are shown in Table 2. Logistic regression showed that independent predictors for macroalbuminuria were the presence of hemoglobinuria (OR 93.7, 95% CI: 15.2–576.5; p<0.0001) and age (OR 1.07, 95% CI: 1.01–1.14; p=0.03) (r2=0.28, p<0.0001). We further explored predictors of hemoglobinuria given its independent association with macroalbuminuria. By logistic regression, the strongest predictor of hemoglobinuria was the natural log LDH (OR 32.4; 95% CI: 8.4–124.9; p<0.0001) (r2=0.22), but other markers of hemolysis including higher absolute reticulocyte count, greater indirect bilirubin concentration and lower hemoglobin concentration were also associated with hemoglobinuria in univariate analyses. In summary, increasing age and macroalbuminuria were independent factors associated with GFR < 90mL/min in this cohort of adults with SCD, and intravascular hemolysis as reflected in hemoglobin-positive urine dipstick with negative microscopy was associated with macroalbuminuria. Further research is needed to determine if measures to decrease intravascular hemolysis and to prevent the development of macroalbuminuria can preserve renal function in patients with SCD. Investigation is also needed to identify genomic and genetic markers that put patients at risk for kidney disease and might serve as targets for preventive and therapeutic interventions. Table 1: Correlation of GFR to clinical and laboratory variables. Variable N >90 N <90 p-value Age (years) 234 30 (25–39) 58 45 (37–54) <0.0001 Female gender 234 141 (60%) 58 38 (65%) 0.63 MAP 231 86 (90–93) 58 91 (86–98) <0.0001 HU therapy 110 48 (44%) 30 16 (53%) 0.35 Hemoglobin (g/dL) 234 8.9 (7.9–10) 58 8.1 (7.4–8.9) <0.0001 LDH (u/L) 146 309 (235–425) 41 375 (251–481) 0.11 Absolute Reticulocyte Count (×103/μL) 111 332 (234–444) 29 302 (197–368) 0.001 Hgb F (%) 218 5.5 (2.9–9.8) 52 5.5 (2.5–9.8) 0.98 Albuminuria: Microalbuminuria Macroalbuminuria 112 46 (41%) 30 11 (36.7%) 0.001 15 (13%) 13 (43.4%) Table 2: Correlation of Albuminuria to clinical and laboratory variables. Variable N Normal N Micro-albuminuria N Macro-albuminuria p-value Age (years) 57 32 (26–42) 58 38 (28–48) 28 35 (27–45) 0.20 Female gender 57 43 (75%) 58 34 (59%) 28 18 (64%) 0.16 MAP (mmHg) 56 86 (80–97) 58 88 (84–92) 28 91 (84–98) 0.24 HU therapy 56 24 (42.9%) 57 24 (42.1%) 28 17 (60.7%) 0.22 Hemoglobin (g/dL) 57 8.9 (8.1–10.3) 58 8.1 (7.5–9.4) 28 8.5 (6.9–9.4) 0.008 LDH (u/L) 54 270 (212–358) 49 363 (251–434) 27 377 (355–488) <0.0001 Indirect bilirubin (mg/dL) 56 1.7 (1.2–2.5) 57 2.4 (1.4–3.3) 28 2.0 (1.3–4.3) 0.03 Absolute reticulocyte count (×103/μL) 57 256 (213–399) 56 332 (243–448) 28 369 (276–466) 0.06 Hgb F (%) 52 6.6 (2.7–9.7) 56 5.1 (2.8–11.7) 26 7.8 (3.7–13) 0.54 Hemoglobinuria 53 3 (5.7%) 54 29 (53.7%) 26 22 (84.6%) <0.0001 Disclosures: No relevant conflicts of interest to declare.

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Predictors of In-Hospital Mortality and Charges in Sickle Cell Disease: Results from the California Discharge Databases 1998–2005.

Blood ◽

10.1182/blood.v110.11.432.432 ◽

2007 ◽

Vol 110 (11) ◽

pp. 432-432 ◽

Cited By ~ 1

Author(s):

John J. Strouse ◽

Carlton Haywood ◽

Sophie Lanzkron

Keyword(s):

Logistic Regression ◽

Sickle Cell Disease ◽

Hospital Mortality ◽

Sickle Cell ◽

Odds Ratio ◽

Private Insurance ◽

Charlson Index ◽

Cell Disease ◽

Increased Risk ◽

Age Of Death

Abstract Most studies of survival in sickle cell disease (SCD) include only patients followed at referral centers. We used the public set of the California Patient Discharge Databases (1998–2005) to compare in-hospital mortality and charges by patient characteristics. We included discharges with any diagnostic code for SCD (282.41–2, 282.60–69). We used the Charlson index (adapted for administrative data) to adjust for comorbid conditions. Hospital charges were adjusted to 1998 levels. Statistical methods included ANOVA, Wilcoxon rank-sum, and multivariate linear and logistic regression. We identified 57,887 admissions for SCD and 376 in-hospital deaths (0.65%) from 1998–2005. The mean age of death was 40 years (95% CI 38–42) for sickle cell anemia (HbSS) and 48.3 years (95% CI 44.1–52.5, p<.0005) for all other SCD. Median length of stay was 4 days (IQR 2–7 days) and charges were $10,027 (IQR 5547–18,302) for HbSS and 4 days (IQR 2–6 days) and $8045 (IQR 4375–16,253) for all other SCD (p<.0001). Women with SCD were older at the time of death (43.6 years) than men (41.4 years, p=.29) and age of death increased from 40.6 years in 1998–2000 to 44.2 in 2004–2005 (p=.17) but these differences were not significant. Mortality was increased with a Charlson Index of 1 or 2, older age, private insurance, a diagnosis of HbSS, and transfusion during the admission (Table 1). Women had a lower odds of death than men (OR 0.7, p<.05). Average annual charges for hospitalization in patients with SCD, adjusted to 1998 values, were $117,000,000 and decreased $1,960,000/year (−4.1%, p<.0001) for children and increased $1,150,000/year (1.4% p<0.05) for adults. Adjusted charges for all children were stable and increased 1.5% per year for adults. Charges per admission were $3167 higher for adults than children, $5608 higher per comorbid diagnosis, $6506 higher in transfused patients, and $3595 higher with a diagnosis of crisis (p<.0001 for all). Compared to MediCal, charges were $1186 higher for Medicare (p<.05), $2651 lower for other government insurance (p<.0001), and $3521 lower for self-pay (p<.05). Government (77%) and private insurance (21%) paid for most admissions. We identified a greatly increased risk of in-hospital morality with comorbid diagnoses and older age and moderately increased risk with private insurance, HbSS genotype, and transfusion during the admission. The increased risk with private insurance was surprising, as higher socioeconomic status is often associated with better health outcomes. This may reflect more stringent requirements for admission or financial barriers to outpatient and preventive services for SCD. Total charges decreased dramatically in children, possibly reflecting increased use of hydroxyurea for frequent pain and chronic transfusions for primary stroke prevention. Table 1: Odds Ratio for In-Hospital Death Based on Multivariate Logistic Regression Variable Odds Ratio (95% CI) P-Value NS indicates not significant Charlson Index=1 3.3 (2.4–4.6) <.0001 Charlson Index=2 12.9 (9.3–18) <.0001 Age (per year) 1.04 (1.03–1.05) <.0001 Private Insurance vs. MediCal 1.6 (1.2–2.2) <.0005 Medicare vs. MediCal 0.9 (0.7–1.3) NS Other SCD vs. HbSS 0.7 (0.5–0.9) <.0005 Transfusion 1.6 (1.2–2.0) <.0001

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Predictors of hospital mortality among patients with COVID-19 in Tehran, Iran

SAGE Open Medicine ◽

10.1177/20503121211051573 ◽

2021 ◽

Vol 9 ◽

pp. 205031212110515

Author(s):

Fatemeh Esfahanian ◽

SeyedAhmad SeyedAlinaghi ◽

Nazanin Janfaza ◽

Marcarious M. Tantuoyir

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Laboratory Data ◽

Hospitalized Patients ◽

Multivariate Logistic Regression ◽

Predictors Of Mortality ◽

Laboratory Test Results ◽

History Of

Objective: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Timely and effective predictors of survival and death rates are crucial for improving the management of COVID-19 patients. In this study, we evaluated the predictors of mortality based on the demographics, comorbidities, clinical characteristics, laboratory findings, and vital signs of 500 patients with COVID-19 admitted at Imam Khomeini Hospital Complex, the biggest hospital in Tehran, Iran. Methods: Five hundred hospitalized laboratory-confirmed COVID-19 patients were included in this study. Subsequently, electronic medical records, including patient demographics, clinical manifestation, comorbidities, and laboratory test results were collected and analyzed. They were divided into two groups: expired and discharged. Demographics, clinical, and laboratory data were compared among the two groups. The related factors with death in the patients were determined using univariate and multivariate logistic regression approaches. Results: Among the 500 hospitalized patients, most patients were male (66.4% versus 33.6%). The expired group had more patients ⩾70 years of age compared with the discharged group (32.9% versus 16.3%, respectively). Almost 66% of the expired patients were hospitalized for ⩾5 days which was higher than the discharge group (26.9%). Patients with a history of opium use in the expired group were significantly higher compared to the discharged group (14.8% versus 8.6%, p = 0.04) as well as a history of cancer (15.5% versus 4.7%, p < 0.001). Out of the 500 patients with COVID-19, four patients (2.6%) were HIV positive, all of whom expired. Dyspnea (76.4%), fever (56.6%), myalgia (59.9%), and dry cough (67%) were the most common chief complaints of hospitalized patients. Age ⩾70 years (adjusted odds ratio = 2.49; 95% confidence interval, 1.02–6.04), being female (adjusted odds ratio = 2.06; 95% confidence interval, 1.25–3.41), days of hospitalization (adjusted odds ratio = 5.73; 95% confidence interval, 3.49–9.41), and having cancer (adjusted odds ratio = 3.23; 95% confidence interval, 1.42–7.39) were identified as independent predictors of mortality among COVID-19 patients. Conclusion: Discharged and expired COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principal component analysis. The mortality risk factors for severe patients identified in this study using a multivariate logistic regression model included elderly age (⩾70 years), being female, days of hospitalization, and having cancer.

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Hydroxyurea Is Associated with Lower Prevalence of Albuminuria in Adults with Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.3211.3211 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3211-3211

Author(s):

Louis-Philippe Laurin ◽

Patrick H. Nachman ◽

Payal C. Desai ◽

Kenneth I. Ataga ◽

Vimal K. Derebail

Keyword(s):

Logistic Regression ◽

Logistic Regression Model ◽

Systemic Hypertension ◽

Multivariate Logistic Regression Model ◽

Acute Chest Syndrome ◽

Lower Prevalence ◽

Cell Disease ◽

Multivariate Logistic Regression ◽

History Of ◽

Univariate Analyses

Abstract Abstract 3211 Background: Albuminuria is an early manifestation of sickle cell disease (SCD) nephropathy, denoting glomerular injury. Minimal clinical data exist on the association of hydroxyurea (HU) use with albuminuria in adults with SCD. Methods: A cross-sectional study was performed to evaluate the association of HU with the prevalence of albuminuria among adults with SCD using clinical data collected from 2000 to 2011. HU exposure was defined as ≥3 months of therapy prior to assessment of albuminuria. Albuminuria was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g and/or ≥1+ proteinuria on two dipstick measurements at least 2 months apart. A multivariate logistic regression model was constructed from univariate analyses and with covariates previously identified to be associated with albuminuria in SCD, including history of acute chest syndrome, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) use, age, and elevated tricuspid regurgitation jet velocity (TRV). Backward elimination of covariates was used to produce the most parsimonious model. Results: 149 adult patients (mean age 38±13 years; 113 with HbSS, 10 HbSß0, 7 HbSß1, 18 HbSC, and 1 HbSD) were included. The prevalence of albuminuria was lower among patients on HU therapy than those not on HU [26/75 (34.7%) vs. 41/74 (55.4%); p=0.01]. Among 112 patients with a measured UACR, median albumin excretion was lower in patients on HU [17.9 (6.0–53.0) vs. 40.5 (7.0–204.9) mg/g; p=0.04]. In univariate analyses, ACEi/ARBuse, hemoglobin level and percent reticulocytes were also related to albuminuria. By multivariate logistic regression model, HU use was associated with a lower risk of albuminuria (odds ratio 0.31, 95% CI 0.12 to 0.81; p=0.02), adjusting for age, ACEi/ARB use, TRV ≥2.5 m/s, systemic hypertension and history of acute chest syndrome. Conclusion: The use of HU was associated with lower prevalence of albuminuria, after controlling for age, ACEi/ARB use, TRV ≥2.5 m/s, systemic hypertension and history of acute chest syndrome. Based upon these findings, the potential of HU to prevent overt nephropathy or the progression of SCD nephropathy to end-stage renal disease merits further investigation. Disclosures: No relevant conflicts of interest to declare.

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FCGR2B B2.4 Haplotype Predicts Increased Risk of Red Blood Cell Alloimmunization in Sickle Cell Disease Patients

Blood ◽

10.1182/blood-2018-99-113896 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1255-1255

Author(s):

Abel Costa Neto ◽

Flávia Leite Santos ◽

Ingrid Helena Ribeiro ◽

Valeria Brito Oliveira ◽

Marcia Regina Dezan ◽

...

Keyword(s):

Logistic Regression ◽

Sickle Cell Disease ◽

Blood Cell ◽

Sickle Cell ◽

Red Blood Cell ◽

Promoter Region ◽

Cell Disease ◽

Increased Risk ◽

Lifetime Number ◽

History Of

Abstract Introduction: Red blood cell (RBC) alloimmunization is an important transfusion complication which is very prevalent among patients with sickle cell disease (SCD). Only part of patients is able to develop alloantibodies following antigen-mismatched transfusions, named the 'immune responders', who should be prospectively transfused with antigen-matched RBC units, comprising the most immunogenic erythrocyte antigens. Auto-immune diseases are a known risk factor for RBC alloimmunization, suggesting that auto-immunity and post-transfusion alloantibody development happen through similar physiopathological pathways. In this context, polymorphisms in FCGR2B gene have already been associated with several auto-immune disorders and, hypothetically, could be associated with RBC alloimmunization and help to identify the 'immune responders' in transfusion practice. Methods: In this case-control study, we enrolled 277 transfused SCD patients with retrospective data on alloimmunization status and transfusion exposure from two Brazilian centers. DNA samples (collected from March, 2017 to June, 2018) were extracted from whole blood samples using commercial kits (PureLink™ Genomic DNA®, Invitrogen, CA), and used for PCR amplification of promoter region of FCGR2B gene containing both -386G/C and -120T/A single nucleotide polymorphisms (SNPs) using gene-specific primer. SNPs of the FCGR2B were genotyped by direct Sanger sequencing (ABI3730XL, Applied Biosystems, CA). Cases had a positive history of alloimmunization with a clinically significant alloantibody and a minimum transfusion exposure of 1 RBC unit. Controls had a negative history of alloimmunization and having received ≥ 2 RBC units. Patients with autoimmune diseases or poor quality of DNA were excluded. Unadjusted and adjusted analyses were conducted by using Logistic Regression models to determine the association of covariates with binary outcome. Since the assumption of linearity in the logit was not supported, continuous covariates were categorized based on optimum cut-off point derived from ROC analysis. All statistical analyses were performed using SAS University Edition. A p-value of <0.05 was considered to be statistically significant. Results: A total of 237 patients met the eligibility criteria, 121 cases (alloimmunized) and 117 controls (non-alloimmunized). Majority of patients were female in cases (61%) and male in controls (86%), with mean age of 27.9 years (SD 15.3). Table 1 list the characteristics between the groups. RBC alloimmunization was associated with female sex (p<0.001), lifetime number of RBC units transfused (p=0.002) and FCGR2B 120T/A SNP (p=0.031). No statistically differences in the allele frequency of c.386C were observed between groups (p=0.602). FCGR2B -386G/C and -120T/A SNPs were in intense linkage disequilibrium. Three haplotypes of promoter region were identified as 2B.1 (-386G-120T), 2B.2 (-386C-120T) and 2B.4 (-386C-120A) with statistical significance (p=0.045). Logistic regression model was performed to assess the effects of age, gender, lifetime number of RBC units transfused and FCGR2B 2B.4 haplotype on the likelihood of RBC alloimmunization in patients with SCD. The analysis identified that female sex (OR 10.03, CI95% 5.16-19.49; p<0.001) and FCGR2B 2B.4 haplotype (OR 4.55, CI95% 1.11-18.65; p=0.035) predict increased risk of RBC alloimmunization in SCD patients as show in Table 2. Conclusions: SCD patients with the FCGR2B 2B.4 haplotype had over a 4-fold higher risk for RBC alloimmunization in comparison with patients without this haplotype and probably may be helpful to identify the 'immune responders'. The presence of FCGR2B 2B.4 haplotype have been associated with increased expression of this inhibitory Fc gamma receptor in immune system cells, that was strongly associated with capacity of immune tolerance, regulating the development of antibodies. Future studies are needed to understand more about the functional and immune mechanism behind alloimmunization in SCD patients and ultimately improve our current preventive strategies. Disclosures No relevant conflicts of interest to declare.

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High Risk of One-year Stroke Recurrence in Patients with Younger Age and Prior History of Ischemic Stroke

Current Neurovascular Research ◽

10.2174/1567202616666190618164528 ◽

2019 ◽

Vol 16 (3) ◽

pp. 250-257 ◽

Cited By ~ 1

Author(s):

Jiann-Der Lee ◽

Ya-Han Hu ◽

Meng Lee ◽

Yen-Chu Huang ◽

Ya-Wen Kuo ◽

...

Keyword(s):

Logistic Regression ◽

Ischemic Stroke ◽

Multivariate Logistic Regression Analysis ◽

Stroke Recurrence ◽

Prior History ◽

Multivariate Logistic Regression ◽

Cart Analysis ◽

Younger Age ◽

History Of ◽

One Year

Background and Purpose: Recurrent ischemic strokes increase the risk of disability and mortality. The role of conventional risk factors in recurrent strokes may change due to increased awareness of prevention strategies. The aim of this study was to explore the potential risk factors besides conventional ones which may help to affect the advances in future preventive concepts associated with one-year stroke recurrence (OSR). Methods: We analyzed 6,632 adult patients with ischemic stroke. Differences in clinical characteristics between patients with and without OSR were analyzed using multivariate logistic regression and classification and regression tree (CART) analyses. Results: Among the study population, 525 patients (7.9%) had OSR. Multivariate logistic regression analysis revealed that male sex (OR 1.243, 95% CI 1.025 – 1.506), age (OR 1.015, 95% CI 1.007 - 1.023), and a prior history of ischemic stroke (OR 1.331, 95% CI 1.096 – 1.615) were major factors associated with OSR. CART analysis further identified age and a prior history of ischemic stroke were important factors for OSR when classified the patients into three subgroups (with risks of OSR of 8.8%, 3.8%, and 12.5% for patients aged > 57.5 years, ≤ 57.5 years/with no prior history of ischemic stroke, and ≤ 57.5 years/with a prior history of ischemic stroke, respectively). Conclusions: Male sex, age, and a prior history of ischemic stroke could increase the risk of OSR by multivariate logistic regression analysis, and CART analysis further demonstrated that patients with a younger age (≤ 57.5 years) and a prior history of ischemic stroke had the highest risk of OSR.

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Gastrointestinal involvement and its association with the risk for nephritis in IgA vasculitis

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x211024828 ◽

2021 ◽

Vol 13 ◽

pp. 1759720X2110248

Author(s):

Mario Sestan ◽

Nastasia Kifer ◽

Marijan Frkovic ◽

Matej Sapina ◽

Sasa Srsen ◽

...

Keyword(s):

Logistic Regression ◽

Odds Ratio ◽

Biochemical Parameters ◽

Upper Extremities ◽

Iga Vasculitis ◽

Older Children ◽

Multivariate Logistic Regression ◽

Gastrointestinal Involvement ◽

Chronic Complications ◽

Gi Symptoms

Background: We analysed clinical and biochemical parameters in predicting severe gastrointestinal (GI) manifestations in childhood IgA vasculitis (IgAV) and the risk of developing renal complications. Methods: A national multicentric retrospective study included children with IgAV reviewed in five Croatian University Centres for paediatric rheumatology in the period 2009–2019. Results: Out of 611 children, 281 (45.99%) had at least one GI manifestation, while 42 of 281 (14.95%) had the most severe GI manifestations. Using logistic regression several clinical risk factors for the severe GI manifestations were identified: generalized rash [odds ratio (OR) 2.09 (95% confidence interval (CI) 1.09–4.01)], rash extended on upper extremities (OR 2.77 (95% CI 1.43–5.34)] or face [OR 3.69 (95% CI 1.42–9.43)] and nephritis (IgAVN) [OR 4.35 (95% CI 2.23–8.50)], as well as lower values of prothrombin time (OR 0.05 (95% CI 0.01–0.62)], fibrinogen [OR 0.45 (95% CI 0.29–0.70)] and IgM [OR 0.10 (95% I 0.03–0.35)]] among the laboratory parameters. Patients with severe GI involvement more frequently had relapse of the disease [OR 2.14 (CI 1.04–4.39)] and recurrent rash [OR 2.61 (CI 1.27–5.38)]. Multivariate logistic regression found that the combination of age, GI symptoms at the beginning of IgAV and severity of GI symptoms were statistically significant predictors of IgAVN. Patients in whom IgAV has started with GI symptoms [OR 6.60 (95% CI 1.67–26.06)], older children [OR 1.22 (95% CI 1.02–1.46)] with severe GI form of IgAV (OR 5.90 (95% CI 1.12–31.15)] were particularly high-risk for developing IgAVN. Conclusion: We detected a group of older children with the onset of GI symptoms before other IgAV symptoms and severe GI form of the IgAV, with significantly higher risk for acute and chronic complications of IgAV.

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To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

Transfusion Medicine and Hemotherapy ◽

10.1159/000512644 ◽

2021 ◽

pp. 1-5

Author(s):

Justin E. Juskewitch ◽

Craig D. Tauscher ◽

Sheila K. Moldenhauer ◽

Jennifer E. Schieber ◽

Eapen K. Jacob ◽

...

Keyword(s):

Pregnant Woman ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pregnancy Termination ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Childbearing Age ◽

Procedural Complications ◽

History Of ◽

Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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