Abdominal Manifestations of Sickle Cell Disease

Kinger, Nikhar; Moreno, Courtney C.; Miller, Frank H.; Mittal, Pardeep

doi:10.1067/j.cpradiol.2020.05.012

Cited by 9 publications

(6 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47,48 Differentiation of memory B cells into plasma cells was not affected by heme, although it remains to be determined whether hemolysis affects differentiation of naïve B cells to memory B cells, thus contributing to their low circulating levels in SCD, which have been ascribed to asplenia. [49][50][51] Our finding that heme inhibits human plasma B-cell differentiation in vitro differs from mouse data showing increased plasma B-cell differentiation through Bach2. 25 We found very low levels of Bach2 in human B cells before and after stimulation, with no significant change even in the presence of heme (data not shown), suggesting that Bach2 response to heme differs between human and mouse B cells.…”

Section: Discussioncontrasting

confidence: 63%

Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease

Pal¹,

Bao²,

Wang

et al. 2021

Blood

View full text Add to dashboard Cite

Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B cell plasmablast/plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas non-alloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group were non-responsive to heme inhibition and readily differentiated into plasma cells. Consistent with a differential B cell response to hemolysis, we found elevated B cell basal levels of DOCK8 and higher HO-1-mediated inhibition of activated B cells in non-alloimmunized compared to alloimmunized SCD patients. To overcome the alloimmunized B cell heme insensitivity, we screened several heme-binding molecules and identified quinine as a potent inhibitor of B cell activity, reversing the resistance to heme suppression in alloimmunized patients. B cell inhibition by quinine only occurred in the presence of heme and through HO-1 induction. Altogether, these data suggest that hemolysis can dampen the humoral B cell response and that B cell heme responsiveness maybe a determinant of alloimmunization risk in SCD. Quinine by restoring B cell heme sensitivity may have therapeutic potential to prevent and inhibit alloimmunization in SCD patients.

show abstract

Section: Discussioncontrasting

confidence: 63%

Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease

Pal¹,

Bao²,

Wang

et al. 2021

Blood

View full text Add to dashboard Cite

show abstract

“…However, despite the high risk of developing acute pancreatitis, it is a rare cause of acute abdomen in SCD 5 – 8 It appears to be more prevalent in the younger population with several cases being reported in this age group 9 , 10 But only a few cases have been reported in adults 2 , 11 We found no single report of RAP in the adult population with SCD, however, we came across one case of recurrence in chronic calcific pancreatitis with pseudocyst in a male child 12 …”

Section: Introductionmentioning

confidence: 99%

Recurrent acute pancreatitis in an adult female with sickle cell disease: A case report

Sharma

Khadka

Sharma

et al. 2023

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

Introduction and Importance: Although risk factors such as cholelithiasis and vaso-occlusive crises exist in sickle cell disease, acute pancreatitis and its recurrence are considered rare complications manifesting as acute abdomen. Case Presentation: A 33-year-old female with sickle cell disease and established cholelithiasis presented to the center with acute abdomen. After examination, investigation, and contrast enhanced computed tomography, acute pancreatitis was diagnosed. Conservative management was done and cholecystectomy was planned but delayed due to low hemoglobin. In the interval she presented again with similar features and diagnosed with of recurrence. After conservative management and after optimization of patient’s hemodynamic status, laparoscopic cholecystectomy was finally performed. Postoperative period and follow-up visit after 2 months were uneventful. Clinical Discussion: As the features of pancreatitis and vaso-occlusive crisis are similar, the former should be considered as a differential diagnosis of acute abdomen in sickle cell patients. Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis in these patients. However, some issues related to management such as preoperative transfusion and prophylactic cholecystectomy are still debated. This uncertainty caused delay in surgery which may have contributed to the recurrence of pancreatitis in our patient. As the risk of recurrence is possible after the first attack, standard guidelines are required for the definite management of the cause. Conclusion: This case report adds to the limited literature on recurrent acute pancreatitis in sickle cell patients and points out the need for studies on developing management guidelines in such patients and need for prophylactic treatment.

show abstract

“…This ultimately leads to a progressive fibrosis and atrophy of the spleen, a process known as functional asplenia or auto-splenectomy that is usually completed by three to five years of age in almost all patients with SCA. 1,2 However, this may not always be the case, as sometimes the spleen increases in size during the course of the disease requesting its surgical removal for a variety of reasons such as acute splenic sequestration crisis, hypersplenism and massive splenic infarction. 3,4 To date, much remains unknown about the fate of spleen in patients with SCA, especially when it is still structurally and functionally preserved.…”

Section: Introductionmentioning

confidence: 99%

Impact of splenectomy on circulating microparticles in patients with sickle cell anemia

Boulassel,

Al‐Rubkhi,

Al‐Qasabi

et al. 2023

Int J Lab Hematology

View full text Add to dashboard Cite

IntroductionCirculating microparticles (MP) are being described as potential biomarkers for disease activity in a variety of conditions including sickle cell anemia (SCA). However, relatively little is known about the influence of spleen status on MP levels in patients with SCA.MethodsUsing a prospective study design we characterize circulating MP in 144 patients with SCA in steady state by assessing their cellular origin and their relationships to spleen status defined by clinical and imaging findings. In addition, MP levels were studied according to demographic characteristics, clinical status, treatment modalities, and other hematological and biochemical parameters. Absolute plasma concentrations of MP were determined by flow cytometry.ResultsPatients with SCA displayed a 10‐fold increase in levels of MP derived from red blood cell (RBC) and platelets (PLT) when compared to their healthy counterparts (p < 0.0001). Splenectomized patients with SCA have more pronounced levels of MPRBC and MPPLT, and remained elevated after several weeks of follow‐up. Levels of MP were not significantly associated with spleen removal procedures, age, gender, clinical severity score, hydroxyurea therapy, hemoglobin F, and co‐existence of glucose‐6‐phosphate dehydrogenase deficiency.ConclusionCollectively, these results suggest that splenectomy affects circulating levels of MP regardless of the known SCA modifiers and correlates.

show abstract

Abdominal Manifestations of Sickle Cell Disease

Cited by 9 publications

References 79 publications

Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease

Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease

Recurrent acute pancreatitis in an adult female with sickle cell disease: A case report

Impact of splenectomy on circulating microparticles in patients with sickle cell anemia

Contact Info

Product

Resources

About