scholarly journals Marked Direct Hyperbilirubinemia due to Ceftriaxone in an Adult with Sickle Cell Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Daniyeh Khurram ◽  
Leonid Shamban ◽  
Robert Kornas ◽  
Maryann Paul
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Sickle Cell ◽  
Middle Lobe ◽  
Cell Disease ◽  
Drug Induced ◽  
Elevated Bilirubin ◽  
Chest X Ray ◽  
Conjugated Hyperbilirubinemia ◽  
Mixed Pattern

Drugs are a significant cause of liver injury. Drug-induced liver injury (DILI) can cause acute hepatitis, cholestasis, or a mixed pattern. Ceftriaxone is a commonly used antibiotic and has been associated with reversible biliary sludge, pseudolithiasis, and cholestasis. A 32-year-old male with sickle cell disease was admitted to the hospital for acute sickle cell crisis. On the second day of hospitalization, he developed cough and rhonchi with chest X-ray revealing right middle lobe infiltrates. Ceftriaxone and azithromycin were initiated. Subsequently, he developed conjugated hyperbilirubinemia and mild transaminitis. His total bilirubin trended upwards from 3.3 mg/dL on admission to 17 mg/dL. It was predominantly conjugated bilirubin, with preadmission bilirubin levels of 3-4 mg/dL. His transaminases were mildly elevated as well compared to previous levels. Extensive workup for bilirubin elevation was unremarkable. Ceftriaxone was switched to levofloxacin and the hyperbilirubinemia improved. On ambulatory follow-up, his bilirubin remained below 4 mg/dL. Ceftriaxone may be associated with marked direct hyperbilirubinemia particularly in sickle cell patients with chronic liver chemistry abnormalities. In the case of elevated bilirubin with concomitant ceftriaxone use, elimination of the offending agent should be considered.

scholarly journals Liver injury is associated with mortality in sickle cell disease

2015 ◽  
Vol 42 (7) ◽  
pp. 912-921 ◽  
Author(s):  
J. J. Feld ◽  
G. J. Kato ◽  
C. Koh ◽  
T. Shields ◽  
M. Hildesheim ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Sickle Cell ◽  
Cell Disease

Arterial Hypoxemia Syndrome in Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3801-3801
Author(s):  
Patricia Adams-Graves ◽  
M. Muthiah ◽  
G. Presbury ◽  
G. Somes ◽  
K. Lamar
Keyword(s):  
Mechanical Ventilation ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Normal Lung ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
X Ray ◽  
Arterial Hypoxemia ◽  
Arterial Blood ◽  
Chest X Ray

Abstract Acute chest syndrome (ACS) is the most common cause of death during hospitalization of adults with sickle cell disease (SCD). ACS includes symptoms referable to the chest and a new infiltrate on chest X-ray. Adults over age 20 years have more symptoms of the disease and are at increased risk of early death compared to children. ACS may be the presenting diagnosis for a patient with SCD, but equally as often, develops while the patient has a painful vascular occlusive crisis. Notably, 35% of SCD patients have a normal lung exam upon presentation to the hospital. Previous research studies indicate that nearly three-fourths of SCD patients who die present during painful crises in an extremity, and about 50% conclusively by autopsy died of massive fat embolism syndrome (FES). Unfortunately, definitive diagnostic tests with rapid turn-around for FES and other acute vascular occlusive lung events do not exist. Earlier identification of the danger that this event may be evolving can be life saving. Clinicians who adhere to the strict definition of ACS may prematurely dismiss the likelihood of a subsequent fatal event. This alarming rate of adverse events may represent a “pre-chest syndrome” prodromal phase of ACS. Arterial hypoxemia syndrome (AHS) or pre-chest syndrome is defined as any sign or symptom referable to the chest, an oxygen saturation (Sp02) of <94% by direct pulse oximeter or a Pa02 <80% by arterial blood gas on room air plus a clear chest X-ray with or without fever. AHS may be a warning sign of an ultimately fatal event if earlier interventions are not done in a timely manner. A secondary data analysis was performed utilizing 500 health records of SCD patients from 1960 to 2004. Prior to 2003, we averaged 2 to 3 ICU admissions per month for ACS with about 20% requiring mechanical ventilation. This study sought to gain insight on 45 years of experience in the treatment of SCD, particularly “pre-chest syndrome.” The primary aims of the study were to devise treatment protocols to reduce ICU admissions and the need for mechanical ventilation in SCD patients presenting with AHS. Retrospective analysis suggests that earlier blood exchanges for patients with SCD may substantially reduce ICU admissions and the need for mechanical ventilation in patients presenting with AHS, compared with patients receiving standard supportive care. Examination of computerized hospital records of 437 sickle cell hospital admissions from January 2003 to March 2005 revealed 3 ICU and 2 step-down unit admissions. During this time period, there were 101 chest syndrome occurrences, of which 2 died. Both patients required mechanical ventilation and underwent red cell apheresis to reduce hemoglobin S to <30%. One patient was admitted due to major trauma from a motor vehicle accident. Death was due to multi-organ failure. The medical condition of the second patient improved. This patient was discharged home in stable condition but died, unexpectedly, 48 hours at home of a massive pulmonary embolus. A protocol has been developed to prospectively evaluate our aims.

Infusion of Pegylated Bovine Carboxyhemoglobin (PEG-COHb) Is Associated with Rapid Reversal of Progressive Acute Chest Syndrome in a Jehovah's Witness Patient with Hemoglobin SC Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4541-4541 ◽  
Author(s):  
Roberta Miyeko Kato ◽  
Thomas Hofstra ◽  
Herbert J. Meiselman ◽  
Henry Jay Forman ◽  
Abe Abuchowski ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lower Lobe ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
X Ray ◽  
Rapid Reversal ◽  
Chest X Ray ◽  
The Right

Abstract Acute chest syndrome (ACS) is a potentially fatal complication of sickle cell disease (SCD) and is characterized by opacification of the chest x-ray (CXR) and progressive pulmonary failure due, in part, to intra-pulmonary sickling. The ACS process can proceed very rapidly from a small area of lung involvement in one lobe to total opacification of the lung and pulmonary failure within 12 to 24 hours. In the early phases of this process, oxygenation and pulmonary function may be preserved. In the face of rapidly progressing CXR changes, the ACS process may be reversed if diagnosed early and managed by emergent transfusion to decrease the percent of sickle red blood cells (SRBC). A 10 years old African American child with hemoglobin SC type SCD was transferred to our institution with fever and right upper lobe consolidation. Her respiratory rate was 23 breaths/min, SpO2 was 95% breathing room air. Serial CXR showed opacification of the entire right lung and part of the left lower lobe over a 12-hour period (Panel A). Because of the rapid progression, transfusion was recommended. However, because of the family's Jehovah's Witness religious faith, transfusion was refused. PEG-COHb is in clinical development for the treatment of SCD and is designed to deliver preloaded carbon monoxide (CO), pick up O2, and deliver O2 to hypoxic tissue. PEG-COHb serves as a vasodilator and anti-inflammatory agent. It has been shown to have anti-sickling properties in vitro (ASH Abstract 1372, 2014). The agent was obtained from Prolong Pharmaceuticals via an emergency IND (16432) from the FDA. The agent was acceptable to the family and church elders. After written consent was obtained, 500 cc were infused according to dosing information obtained from Prolong Pharma. The CXR (Panel A) 3 hours before infusion shows opacification of the right lung and the left lower lobe. A CXR obtained one hour after infusion showed no worsening, and the CXR (Panel B) obtained 29 hours after Panel A shows significant improvement in the opacification of the lower lobes. The right upper lobe consolidation was likely bacterial pneumonia, and would not be expected to clear rapidly. The patient was mildly hypertensive for age (138/72 mmHg) prior to PEG-COHb infusion. Her blood pressure rose to 153/85 mmHg during infusion; the infusion was stopped and anti-hypertensives were administered. The infusion was restarted at a lower infusion rate and completed in 6 hours instead of the planned 4 with no untoward effects. She was discharged 4 days after the infusion. There were no other serious adverse events clearly related to the drug. There were significant laboratory abnormalities and transaminases that were most likely falsely elevated due to interference of the PEG-COHb with the laboratory methods. Continuous non-invasive monitoring of carboxyhemoglobin showed basal levels of 7% rose to 24% during infusions and returned to normal prior to discharge. Continual recording of SpO2, methemoglobin, heart-rate variability and blood rheological measures showed no significant abnormalities. The rapid reversal of radiographic features consistent with progressive "pure ACS" secondary to the right upper lobe infectious process suggests that PEG-COHb may be an effective treatment for sickle cell related ACS. SHAPE Figure 1. Panel A demonstrates the chest x-ray 3 hours prior to PEG-COHb with right upper lobe consolidation and evolving bilateral lower lobe consolidation and Panel B 29 hours following administration of PEG-COHb demonstrating improvement in the lower lobes. Figure 1. Panel A demonstrates the chest x-ray 3 hours prior to PEG-COHb with right upper lobe consolidation and evolving bilateral lower lobe consolidation and Panel B 29 hours following administration of PEG-COHb demonstrating improvement in the lower lobes. Disclosures Off Label Use: SANGUINATE (pegylated carboxyhemoglobin bovine) is 40 mg/mL of purified bovine hemoglobin that has been pegylated, saturated with carbon monoxide, and dissolved in a buffered saline solution.. Abuchowski:Prolong Pharmaceuticals: Employment. Parmar:Prolong Pharmaceuticals: Employment.

Evidence-Based Mini-Review: Are Systemic Corticosteroids an Effective Treatment for Acute Pain in Sickle Cell Disease?

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 416-417 ◽  
Author(s):  
L. Vandy Black ◽  
Wally R. Smith
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Adjunctive Treatment ◽  
Cell Disease ◽  
X Ray ◽  
Systemic Corticosteroids ◽  
Potential Efficacy ◽  
History Of ◽  
Chest X Ray ◽  
Pain Crisis

Abstract An 18-year-old African-American male with sickle cell disease (SCD) is admitted to the hospital with a vaso-occlusive pain crisis affecting his chest and right upper extremity. He has a history of asthma but does not have a fever or respiratory symptoms, and a chest X-ray is negative for an infiltrate. He is treated with intravenous fluids and morphine. You are asked about the potential efficacy of systemic corticosteroids as an adjunctive treatment for pain control.

Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Paul Harmatz ◽  
Ellen Butensky ◽  
Keith Quirolo ◽  
Roger Williams ◽  
Linda Ferrell ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Liver Iron ◽  
Transfusion Therapy

Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in children with sickle cell disease who receive chronic red blood cell transfusions. A poor correlation was observed between serum ferritin and the quantitative iron on liver biopsy (mean 13.68 ± 6.64 mg/g dry weight;R = 0.350, P = .142). Quantitative iron was highly correlated with the months of transfusion (R = 0.795, P < .001), but serum ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P = .200). Sixteen patients had abnormal biopsies showing mild to moderate changes on evaluation of inflammation or fibrosis. Liver iron was correlated with fibrosis score (R = 0.50, P = .042). No complications were associated with the liver biopsy. Our data suggest that, in patients with sickle cell disease, ferritin is a poor marker for accurately assessing iron overload and should not be used to direct long-term chelation therapy. Despite high levels of liver iron, the associated liver injury was not severe.

scholarly journals Senicapoc trial results support the existence of different sub-phenotypes of sickle cell disease with possible drug-induced phenotypic shifts

2011 ◽  
Vol 155 (5) ◽  
pp. 636-638 ◽  
Author(s):  
Oswaldo L. Castro ◽  
Victor R. Gordeuk ◽  
Mark T. Gladwin ◽  
Martin H. Steinberg
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Drug Induced

scholarly journals Evidence for Transient Acute Liver Injury in Mouse Models of Sickle Cell Disease during Steady State Health

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1373-1373 ◽  
Author(s):  
Nancy J. Wandersee ◽  
Sandra L. Holzhauer ◽  
Dawn M. Retherford ◽  
Thomas D. Foster ◽  
Cheryl A. Hillery
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Liver Injury ◽  
Mouse Models ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Organ Injury ◽  
State Health ◽  
Cell Disease ◽  
Over Time

Abstract Individuals with sickle cell disease experience episodes of acute vaso-occlusive complications interspersed by periods of feeling well and apparent health during “steady state”. It is likely that episodic and subclinical sickling and vaso-occlusion occur on an ongoing basis even during periods of steady state. In order to determine whether mice with sickle disease have acute vaso-occlusion sufficient for organ injury at apparent steady state health, we chose to study 2 mouse models of severe sickle cell disease with serial blood draws over time. Since we have shown in previous studies that the liver is highly susceptible to acute sickling/vaso-occlusion induced by hypoxia, we first examined serial ALT measurements in a total of 13 Berkeley sickle cell (BERK-SS) mice, initially from week-to-week and month-to-month, and then day-to-day time frames. Individual BERK-SS mice showed week-to-week and month-to-month variations of up to 5-fold over baseline ALT levels, followed by return to baseline levels in most mice. This suggests that BERK-SS mice, during steady state health, experience acute, yet transient, liver injury. Surprisingly, we also found day-to-day variations of up to 3-fold in ALT levels in BERK-SS mice. To determine if these changes in ALT levels were mirrored by changes in other biomarkers, we measured serum amyloid P (SAP) as a marker of acute inflammation (similar to CRP in humans) in the same plasma samples. We found up to 1.6-fold variation in SAP over baseline plasma levels over time. However, there was less overall variation in SAP levels in individual mice compared to the striking changes in ALT. In addition, we found that variations in SAP did not consistently precede, follow, or coincide with variations in ALT levels, suggesting that SAP is a marker of sickle cell-induced inflammation or vaso-occlusion independent of liver injury. We next sought to confirm our findings with daily serial ALT and SAP measurements from Townes sickle cell (TOWNES-SS) mice (n=8), a second commonly used mouse model of severe sickle cell disease. Our data showed that baseline ALT levels are higher and SAP levels are lower in TOWNES-SS as compared to BERK-SS mice, likely reflecting differences in strain background between the two models. However, we again found daily fluctuations in ALT and SAP levels in individual TOWNES-SS mice, similar to those seen in individual BERK-SS mice. We propose that these temporal variations indicate that both the Berkeley and Townes mouse models of sickle cell disease exhibit fluctuations in steady state health, similar to those seen in human individuals with sickle cell disease. In addition, the results suggest that studies in these mouse models should be designed and interpreted with these temporal fluctuations in mind. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hot Off the Press: Which Febrile Children With Sickle Cell Disease Need a Chest X-Ray?

2017 ◽  
Vol 24 (5) ◽  
pp. 641-643
Author(s):  
Justin Morgenstern ◽  
Corey Heitz ◽  
William K. Milne
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
X Ray ◽  
The Press ◽  
Chest X Ray

scholarly journals Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury

Blood ◽  
2009 ◽  
Vol 114 (21) ◽  
pp. 4632-4638 ◽  
Author(s):  
Thomas V. Adamkiewicz ◽  
Miguel R. Abboud ◽  
Carole Paley ◽  
Nancy Olivieri ◽  
Melanie Kirby-Allen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Blood Transfusion ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Ferritin Level ◽  
Liver Weight ◽  
Cell Disease ◽  
Iron Load

AbstractChronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% ± 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% ± 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% ± 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% ± 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.

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