Increased Levels and Activities of Matrix Metalloproteinases in Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1220-1220
Author(s):  
Carla F. Franco-Penteado ◽  
Stephen Hyslop ◽  
Nicola Conran ◽  
Sara T.O. Saad ◽  
Fernando F. Costa
Keyword(s):  
Sickle Cell Disease ◽  
Matrix Metalloproteinases ◽  
Sickle Cell ◽  
Plasma Concentrations ◽  
Gelatin Zymography ◽  
Control Group ◽  
Cell Disease ◽  
Cell Counts ◽  
Significant Difference ◽  
Leukocyte Counts

Abstract Sickle cell disease is characterized by a chronic inflammatory state, however, the mechanism underlying this inflammation is unclear. Elevated basal leukocyte counts, endothelial activation, altered availability of vaso-active factors, increased adhesion molecule expression and cytokines are found in this disease. Matrix metalloproteinases (MMPs) play an important role in physiological and pathological processes, participating in the extracellular matrix turnover as well as tissue degradation, repair mechanisms and cell migration. Since MMPs are important modulators of inflammation and the activity of cytokines and chemokines, our aim was to compare MMP and tissue inhibitor of matrix metalloproteinases (TIMP; inhibitors of MMP) levels and the activities of MMPs in the plasma of healthy subjects and in SCD patients on or off HU therapy (20–30 mg/kg/day, 3 month minimum duration). Gelatin zymography was used to measure MMP-2 and MMP-9 activities and ELISA was used for MMPs and TIMPs determination. After densitometric analysis of zymograms, a significant increase (p=0.03) in the activity of pro-MMP-9 was observed in the plasma of SCD patients (27.09 ± 1.99 average pixel, n=30) compared with the control group (20.96 ± 1.35 average pixel, n=29). Pro-MMP-9 activity in the plasma of SCD patients on HU (SCDHU) was greater (27.2 ± 1.35 average pixel, n=17); however this difference was not quite significant (p=0.07). With regard to MMP-2 activity, no significant difference (P>0.05, data not shown) between groups of patients and control individuals was observed. MMP-9 levels were significantly increased in the plasma of SCD patients (20.99 ± 1.52, n=32) compared to healthy controls (13.96 ± 1.64, n=16, p=0.02), although no effect of HU therapy on these augmented levels was observed (SCDHU; 23.66 ± 2.93, n=22, P>0.05). MMP-9 levels correlated significantly with total WBC counts (r=0.4221, p=0.01) in SCD patients (on and off HU), as well as with neutrophil counts (r=0.4436, p<0.001), but not with mononuclear cell counts. TIMP-1 and TIMP-2 levels were significantly (p<0.0001) higher in SCD patients not on HU therapy (83.69 ± 6.73, n=15; 95.49 ± 4.99, n=14, respectively) compared to control individuals (41.26 ± 3.75, n=11; 62.84 ± 3.43, n=10, respectively). HU therapy had no significant effect on increased TIMP-1 levels (84.14 ± 4.69, n=12, p>0.05) when compared to SCD patients not on HU. TIMP-2 levels were higher in SCD patients treated with HU (87.62 ± 9.39, n=12) than those observed in control subjects, however this difference was not quite significant (p=0.059). In contrast, MMP-2 and MMP-8 plasma concentrations were not significantly different in SCD individuals compared to controls (P>0.05). Data demonstrate, for the first time, that the level and activity of plasma MMP-9 are significantly increased in SCD, and that these levels are not affected by HU therapy. Importantly, MMP-9 levels correlate with leukocyte counts in SCD, indicating that MMP-9 may be a useful marker for inflammation in SCD.

Hydroxyurea Affects T-Lymphocyte Subsets in Sickle Cell Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3726-3726
Author(s):  
Devaki Sivasubramaniam ◽  
Osei Bekoe ◽  
Bharat Motwani ◽  
Sandra Allen ◽  
Lori Feldman ◽  
...  
Keyword(s):  
Treatment Group ◽  
Sickle Cell Disease ◽  
T Lymphocytes ◽  
Blood Cell ◽  
Sickle Cell ◽  
T Lymphocyte ◽  
Cd4 Count ◽  
Control Group ◽  
Cell Disease ◽  
Cell Counts

Abstract Hydroxyurea (HU) is now widely used in the treatment of sickle cell disease (SCD). The effect of this agent on T-lymphocytes in this disease has not been extensively studied. In other diseases such as human immunodeficiency virus (HIV) disease, HU was found to have a variable effect on T-cell subsets. We previously reported (Blood2002; 100: 363) a case of a sickle cell disease patient who was HIV- negative who was found to have low CD4 count on HU that normalized after stopping this agent. We have since conducted a case-controlled study in our sickle cell disease clinic in an attempt to analyze the effects of HU on CD4 count and other T-lymphocyte subsets. Written informed consent was obtained from 15 SCD patients. All patients had SCD as confirmed by hemoglobin electrophoresis. We placed patients into 2 cohorts: the treatment group consisted of patients already receiving HU therapy and the control group consisted of patients not taking HU. Among 15 patients, 8 patients were in treatment group and 7 patients were in the control group. In control group, 5 patients were female and 2 patients were male with mean age of 38 years. In treatment group, 7 patients were female and 1 was male with mean age of 35 years. In the treatment group, the mean duration of HU therapy was 4 years. We collected venous blood from all patients and tested for the following blood cell counts: total white blood cell (WBC), total neutrophil, total lymphocyte, CD4, CD8, CD3 cells and CD4/CD8 ratio. We also tested and found that there was no significant difference between the 2 cohorts for the presence of alloantibodies, cytomegalovirus virus and hepatitis C viral status. All patients were found to be HIV- negative. The lymphocyte assay was done using Coulter MAXAM hematology analyzer and using a combination of white blood cell counts and differential count in the same laboratory for all patients. We compared the mean value of total T-lymphocyte counts, T-cell subgroups CD4, CD8, CD3 levels and CD4/CD8 ratios between the 2 groups by performing the t-test (Table 1). Our study showed that the treatment group had a statistically significant increase in total T- lymphocyte count and in levels of the CD4, CD8 and CD3 levels compared to the control group. There was no difference in the CD4/CD8 ratio between the 2 groups. These results provide additional information to our previous observation of a lowered CD4 count in a SCD patient on HU. These results are consistent with findings in HIV positive patients where changes in T- lymphocytes subsets have been observed in patients treated with HU (AIDS2002; 14:619–621 and J Acquir Immune Defic Syndr2000; 25: 329–336). We conclude that in SCD patients HU can affect T-lymphocyte subset counts. The mechanism and clinical significance of the effect, if any, is unknown and requires further investigation. Table 1: Effects of HU on T-lymphocytes Blood test Control group treatment group P value * P-value significant below 0.05 Total WBC th/mm3 15.36 12.28 0.23 Neutrophil ct/mm3 7.87 4.92 0.12 Total lymphocyte ct/mm3 2458.83 3739.4 0.01* Absolute CD4, mm3 1621.7 2284.8 0.05* Absolute CD8, mm3 701.42 1340.33 0.01* Absolute CD3, mm3 2520 3723 0.01* CD4/CD8 Ratio 2.321 2.32 0.99

Severe Sickle Cell Disease Is Characterized by Low ADAMTS13/VWF: Ag Ratio

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3235-3235
Author(s):  
Despoina Adamidou ◽  
Erasmia Rouka ◽  
Despoina Kyriakou ◽  
Stamatia Theodoridou ◽  
E Vetsiou ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Normal Values ◽  
Clinical Phenotype ◽  
Severe Disease ◽  
Control Group ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Significant Difference ◽  
Lower Ratio

Abstract Abstract 3235 Endothelial damage is one of the major mechanisms causing most of the manifestations in sickle cell disease (SCD). We hypothesized that a possible defect in the cleavage of large vWF multimers through the protease ADAMTS13 could add further to the well established chronic activation of the endothelium and consequently to the severity of the disease. For this purpose we measured the activity of the enzyme and looked for any correlations with regard to the clinical phenotype of patients with SCD. We studied 22 steady state patients (9 men/13 women) with a median age of 35(22–74) years. Of them, 3 were in homozygous state(HbSS) and 19 were compound heterozygous for thalassamia β(HbS/β+, HbS/β0). The clinical phenotype was mild in 12 patients, moderate in 3 and 7 were suffering from severe symptoms (history of frequent vaso-occlusive and acute chest crises and need for regular exchange transfusion). We applied FRET (fluorescence resonance energy transfer) technique to measure ADAMTS13 activity (normal values>65%). Factor VIII and vWF: Ag was measured using 1-stage clotting assay and immunoassay respectively (normal values 50–150%). We considered all relevant clinical parameters (spleen size, transfusion frequency, comorbidities, and medications with special regard to iron chelation, hydroxyurea and antiplatelet agents) together with laboratory readings (markers of haemolysis, proportion of haemoglobin fractions using high-performance liquid chromatography HPLC).We used as control group 22 healthy volunteers blood donors with their written consent matched for age, sex, body mass index and ABO blood group. All samples were taken at least 30 days post last transfusion. We found higher levels of both vWF: Ag [189(33–345)] and ADAMTS13 [164(75–310)] in the patients compared to the control group [87(44–152) και 126(55–171) (p<0.001/p<0.025)] respectively. When we analyzed the ratio ADAMTS13/vWF: Ag we found significant difference between the two groups: 1,041(0.3–4.6) vs 1.56(0.5–2.6) (p<0.020). Furthermore, patients with severe disease experienced significantly lower ratio ADAMTS/vWF 0.7(0.5–1.2) compared to both control group (p<0.001) as well as patients with milder clinical phenotype [1.30(0.3–4.6)].Of note, in patients with severe SCD despite the fact that vWF: Ag levels were found considerably higher and in significant difference with the control group [196(130–345) vs 87(44–152)p<0.001], we could not find the same pattern for ADAMTS13 [140(75–210) vs 126(55–171)].The lower ratio found in patients with SCD and in particular in those with severe disease might indicate the need for higher protease levels in comparison to healthy controls. It looks like in this group of patients ADAMTS13, although normal, is not sufficient enough to manage the reasonably high vWF levels that characterize the chronic endothelial activation. This relevant deficiency of the metaloprotease might be caused by either biggest consumption due to large and constant release of its substrate-vWF or by an acquired inhibition of its action as the free intravascular hemoglobin might exhibit an antagonistic role for the binding site of vWF. In conclusion, the low ADAMTS13/vWF: Ag ratio seems to detect patients with severe SCD and would be of interest to prospectively investigate its role both as a prognostic tool as well as a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Vascular endothelial dysfunction in sickle cell disease by brachial artery flow mediated dilatation

2014 ◽  
Vol 5 (3) ◽  
pp. 105-107 ◽  
Author(s):  
Pranav Kumar Raghuwanshi ◽  
Somnath Singh Raghuvanshi
Keyword(s):  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Control Group ◽  
Cell Disease ◽  
Significant Difference ◽  
Flow Mediated Dilatation ◽  
Artery Flow ◽  
And Control

Objective: The present study was conducted aiming to assess endothelial function in sickle cell disease (SS), sickle cell trait(SA) and compare to endothelial dysfunction between sickle cell anemia (SS), sickle cell trait (SA) cases and control (AA) patients to evaluate correlation of endothelial dysfunction. Methods: The study population comprised of, total 25 cases having sickle cell disease and sickle cell trait and 25 age and sex matched normal control. Endothelial dysfunction as assessed by brachial artery flow mediated dilatation by colour Doppler (non-invasive method)by using Siemens Sonoline 500. Statistical analysis was performed using Software Statistical Package for Social Sciences (SPSS) version 20, and P value of less than 0.05 was considered as statistically significant at 95% confidence intervals. Results: Significant difference were observed in FMD (flow mediated vasodilatation) in case and control group (p<0.05), also significant difference was demonstrated between AS and SS group. Conclusion: The percentage of flow mediated dilatation of vessel is a marker of endothelial function was significantly lower in cases as compared to controls and was also lower in AS & SS when compared to control group & significantly lower in SS group than AS group. Asian Journal of Medical Science, Volume-5(3) 2014: 105-107 http://dx.doi.org/10.3126/ajms.v5i3.9445

scholarly journals Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease

2021 ◽  
Author(s):  
Ho Chi Hsien ◽  
Dulce Elena Casarini ◽  
João Tomas de Abreu Carvalhaes ◽  
Fernanda Aparecida Ronchi ◽  
Lilian Caroline Gonçalves de Oliveira ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Angiotensin Converting Enzyme ◽  
Glomerular Filtration ◽  
Sickle Cell ◽  
Control Group ◽  
Healthy Children ◽  
Converting Enzyme ◽  
Cell Disease ◽  
Significant Difference ◽  
Ace Activity

Abstract Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Methods: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. Results: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. Conclusion: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

Dominant Role for SDF-1 in the Vasculo-Angiogenesis Phenotype in Children with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1432-1432
Author(s):  
Beatrice E Gee ◽  
Jerry M Manlove-Simmons ◽  
Yao Huang ◽  
Nana Wilson ◽  
Jonathan Stiles ◽  
...  
Keyword(s):  
Growth Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Injury ◽  
Peripheral Blood ◽  
Plasma Concentrations ◽  
Control Group ◽  
Cell Disease ◽  
Angiogenic Growth Factors ◽  
Colony Number

Abstract BACKGROUND: Vasculogenesis is critically important to restoring and maintaining vascular homeostasis in patients who have sickle cell disease. Emerging evidence indicates vasculo-angiogenesis is a complex process involving recruitment of endothelial progenitor cells (EPCs) from the bone marrow and homing of EPCs to sites of vascular injury. Both recruitment and homing of EPCs are intimately regulated by cytokines and growth factors that are released in response to vascular insult. Hitherto, the phenotype of growth factors and cytokines intimately involved in EPC recruitment and homing in patients who have sickle cell disease remains poorly understood. METHODS: A total of 50 children aged 6–18 years were studied, 30 with Hemoglobin SS, including 11 on chronic red blood cell transfusions, and 20 with normal hemoglobin. We measured plasma concentrations of angiogenesis growth factors/cytokines using a multiplex assay, which permitted analysis of nine factors concurrently, and determined the number and phenotype of EPC colonies derived from peripheral blood samples. RESULTS: Plasma concentrations of stromal derived growth factor (SDF-1, 1.7-fold), angiopoietin-2 (Ang-2, 2-fold) and erythropoietin (7-fold) were significantly elevated (p&lt;0.001) in children with sickle cell disease compared to control subjects. On the contrary, plasma leptin was significantly lower (2-fold, p&lt;0.001) in the sickle cell disease group, while no significant differences were found for several other angiogenic growth factors including VEGF, HGF, IL-8, PGF and PDGF between children with sickle cell disease and the control group. Peripheral blood-derived EPC colonies were significantly higher (almost 3-fold) in patients who have sickle cell disease compared to the control group. Interestingly, EPC colony number was lower in sickle cell patients on chronic transfusion therapy compared to those who were not on chronic transfusion. There were significant correlations between EPC colony number and plasma concentrations of SDF-1 (r=0.65, p&lt;0.001) and Ang-2 (r=0.36, p&lt;0.05), but no correlation between EPC colony number and plasma erythropoietin and leptin. CONCLUSION: These data demonstrate for the first time enhanced vasculogenic potential in patients with sickle cell disease at steady-state. SDF-1 enhances the homing of EPCs and is highly expressed in ischemic tissues. The association of elevated SDF-1 and Ang-2 levels with EPC colony number is consistent with the hypothesis that sickle cell disease causes ongoing ischemic vascular injury. SDF-1 may be potentially used as a marker for vascular injury and a therapeutic target that can be developed to augment vascular repair in sickle cell disease.

scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

scholarly journals Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

2021 ◽  
Vol 11 (9) ◽  
pp. 870
Author(s):  
Pia Proske ◽  
Laura Distelmaier ◽  
Carmen Aramayo-Singelmann ◽  
Nikolaos Koliastas ◽  
Antonella Iannaccone ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Neonatal Outcomes ◽  
University Hospital ◽  
High Rate ◽  
Successful Outcome ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Significant Difference ◽  
Tract Infections

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

scholarly journals Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Deepali K. Bhat ◽  
Purevdorj B. Olkhanud ◽  
Arunakumar Gangaplara ◽  
Fayaz Seifuddin ◽  
Mehdi Pirooznia ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Graft Rejection ◽  
Immune Cell ◽  
Plasma Concentrations ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Post Transplant

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection rates. Here, we aimed to evaluate immune reconstitution following haplo-HSCT and identify cytokines and cells associated with graft rejection/engraftment. 50 cytokines and 10 immune cell subsets were screened using multiplex-ELISA and flow cytometry, respectively, at baseline and PT-Days 30, 60, 100, and 180. We observed the most significant differences in cytokine levels between the engrafted and rejected groups at PT-Day 60, corresponding with clinical findings of secondary graft rejection. Of the 44 cytokines evaluated, plasma concentrations of 19 cytokines were different between the two groups at PT-Day 60. Factor analysis suggested two independent factors. The first factor (IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, and TGFb1 contributed significantly) was strongly associated with engraftment with OR = 2.7 (95%CI of 1.4 to 5.4), whereas the second factor (GROa and IL-18 contributed significantly) was not significantly associated with engraftment. Sufficient donor myeloid chimerism (DMC) is critical for the success of HSCT; here, we evaluated immune cells among high (H) DMC (DMC≥20%) and low (L) DMC (DMC&lt;20%) groups along with engrafted and rejected groups. We found that early myeloid-derived suppressor cell (eMDSC) frequencies were elevated in engrafted patients and patients with HDMC at PT-Day 30 (P&lt; 0.04 &amp; P&lt; 0.003, respectively). 9 of 20 patients were evaluated for the source of eMDSCs. The HDMC group had high mixed chimeric eMDSCs as compared to the LDMC group (P&lt; 0.00001). We found a positive correlation between the frequencies of eMDSCs and Tregs at PT-Day 100 (r=0.72, P &lt;0.0007); eMDSCs at BSL and Tregs at PT-Day 100 (r=0.63, P &lt;0.004). Of 10 immune regulatory cells and 50 cytokines, we observed mixed chimeric eMDSCs and IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, TGFb1 as potential hits which could serve as prognostic markers in predicting allograft outcome towards engraftment following haploidentical HSCT employing post-transplant cyclophosphamide. The current findings need to be replicated and further explored in a larger cohort.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis

2020 ◽  
pp. 001857872095417
Author(s):  
Katherine Rector ◽  
Shelby Merchant ◽  
Rachel Crawford ◽  
Justin R. Arnall ◽  
James Symanowski ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Cell Disease ◽  
Median Length ◽  
Significant Difference ◽  
Oral Group ◽  
Icd 10 ◽  
Secondary Endpoints ◽  
Group 2

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Whole Blood Tissue Factor Procoagulant Activity Is Elevated in Patients With Sickle Cell Disease

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4216-4223 ◽  
Author(s):  
Nigel S. Key ◽  
Arne Slungaard ◽  
Luke Dandelet ◽  
Stephen C. Nelson ◽  
Christopher Moertel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Tissue Factor ◽  
Mononuclear Cell ◽  
Sickle Cell ◽  
Whole Blood ◽  
Procoagulant Activity ◽  
Cell Disease ◽  
Blood Samples ◽  
Significant Difference ◽  
Whole Blood Samples

Abstract We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood TF levels were significantly (P &lt; .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels.

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