Splenic sequestration associated with sickle cell trait and hereditary spherocytosis.

Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11-year span, while the other had two episodes of this complication during a 4-year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life-threatening complication should be considered in this condition.     

Pulmonary embolism and splenic infarction in a patient with sickle cell trait

A 43 year-old black man with sickle cell trait documented by hemoglobin electrophoresis presented with severe pleuritic chest pain and hypoxemia three weeks after discharge following abdominal surgery. A pulmonary embolus was diagnosed by angiography and he was treated with heparin; the minimum arterial pO2 was 55 torr while O2 was being administered at a rate of 3 L/min. During this therapy, he developed abdominal pain. Computerized tomography suggested splenic infarction, which was documented by radionuclide liver-spleen scan and magnetic resonance imaging (MRI); the patient's spleen had been normal at exploratory laparotomy three weeks previously. No source for emboli was identified in the deep venous system by MRI. Although splenic infarction has been reported in patients with sickle cell trait at high altitude, this is the first reported case of splenic infarction secondary to the hypoxemia of pulmonary embolism in a patient with sickle cell trait. The spleen is subject to infarction in sickle cell trait because blood flow is slow through a hypoxemic and acidemic environment. The additional hypoxemia due to pulmonary embolism is presumed, in our patient, to have created a local splenic environment which permitted infarction to occur.     

Sickle Cell Trait and Risk for Common Diseases: Evidence from the UK Biobank

BackgroundSickle cell trait is typically considered benign. Although evidence remains inconsistent, recent studies suggest that it is associated with several common diseases. We systematically assessed associations of sickle cell trait with reported diseases in a large population-based cohort.MethodsStudy subjects were self-reported Blacks from the UK Biobank (UKB), a United Kingdom population-based cohort of subjects aged 40-69 years at recruitment in the United Kingdom. Sickle cell status was based on the International Classification of Diseases, Tenth Revision (ICD-10) or mutations in the HBB gene. Diagnoses of diseases were obtained from ICD-10 and self-reports. Associations of sickle cell trait and diseases were tested using logistic regression, adjusting for age at recruitment, sex, and genetic background (top 10 principal components).ResultsAmong the 8019 Blacks in the UKB, 699 (8.72%) were sickle cell trait carriers; the rate was significantly higher in females (9.74%) than males (7.48%), P = .0005. Sickle cell trait was under-diagnosed; most heterozygous hemoglobin subunit beta (HBB) gene Glu6Val carriers did not have a sickle cell trait ICD-10 record. Compared with non-sickle cell trait, sickle cell trait carriers had significantly increased risk for type 2 diabetes; odds ratio 1.38; 95% confidence interval, 1.12-1.68; P = .002. Sickle cell trait was also significantly associated with increased risk for renal diseases (rhabdomyolysis, end-stage renal disease, chronic kidney disease, renal papillary necrosis) and vascular diseases (hypertension, retinopathy, non-ischemic stroke), P < .05. While most of these diseases are complications/comorbidities of diabetes, their associations with sickle cell trait remained significant after adjusting for diabetes. Association with end-stage renal disease was stronger in subjects without diabetes, odds ratio 6.45; 95% confidence interval, 1.93-19.61; P = .001.ConclusionsSickle cell trait is significantly associated with increased risk for diabetes and diabetes-related complications/comorbidities.     

Non hypoxia-related splenic infarct in a patient with sickle cell trait and infectious mononucleosis

Splenic infarction in patients with sickle cell trait is usually related to hypoxic conditions, while non-hypoxia-related infarcts are extremely rare. We report on a case of a 17-year-old male patient, living at sea level, who developed a severe left upper quadrant abdominal pain during the course of a febrile episode. On physical examination he had a mildly palpable but extremely painful spleen. A spleen scan revealed 2 areas of impaired radionucleide distribution. Hepatic enzymes were moderately increased and the IgM anti-EBV antibodies positive. Hemoglobin electrophoresis revealed the presence of 42% of hemoglobin S. A probable diagnosis of splenic infarction was established in a patient with sickle cell trait, during the course of infectious mononucleosis. The patient was treated symptomatically. The conditions of splenic congestion induced by the EBV infection and the high-grade fever may have contributed to splenic sequestration and subsequent infarcts.     

A sickle cell disease patient with dural venous sinus thrombosis: a case report and literature review

Abstract

Dural venous sinus thrombosis (DVST) is a rare disease associated with hypercoagulable states. Patients with sickle cell disease are known to be prothrombotic. We report a case of DVST presenting with anterior neck and facial pain in a 24-year-old female with sickle cell disease, found to have extensive thrombotic disease involving the internal jugular vein. A literature review of DVST in sickle cell disease consisting of 14 case reports was summarized. Headache was a presenting feature in two-thirds of patients. Nine cases were associated with vaso-occlusive crisis (VOC), transfusion, or acute respiratory illness. Most patients were treated with anticoagulation therapy. Over three-quarters either died or suffered from a serious neurological complication, including stroke, seizure, coma, or elevated intracranial pressure. Given its association with life-threatening complications, DVST should be considered when patients with sickle cell disease present with a VOC, especially in the context of headache or neurological deficits.     

Splenic function in persons with sickle cell trait at moderately high altitude

We investigated the possibility that persons with sickle cell trait who reside chronically at moderately high altitude might develop impaired splenic reticuloendothelial function. Seventeen healthy young black men with sickle trait who had lived at greater than or equal to 1,609 m for greater than or equal to 10 years participated in the study along with 25 matched control subjects with normal hemoglobin. Splenic function was assessed by radionuclide liver-spleen scanning and by red cell pit counts. No evidence of impaired splenic function was found in the sickle trait group. The data suggest that long-term residence at moderately high altitude does not place persons with sickle cell trait at risk for splenic dysfunction.     

AVASCULAR NECROSIS OF THE FEMORAL HEAD IN SICKLE CELL TRAIT

Avascular necrosis of the femoral head is known to occur insickle cell anaemia (Tanake, Clifford and Axelrod, 1956), andsome of the genetic variants of sickle cell disease (Chung andRalston, 1969). In sickle cell trait, only two cases of thisrare complication are reported, both in American negroes (Ratcliffand Wolf, 1962). We now report a third patient, a woman, withsickle cell trait and avascular necrosis. ^*Present address: Norfolk and Norwich Hospital, St. StephensRoad, Norwich.     

Splenic sepsis in sickle cell disease

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.     

Pulmonary function in sickle cell trait

Pulmonary function abnormalities, which have been reported to occur in persons with sickle cell trait (hemoglobin AS), could intensify the hypoxic stimulus for the systemic formation of sickle cells at high altitude. We sought to determine whether pulmonary function abnormalities occur as a result of exposure to high altitudes in persons with hemoglobin AS. In a prospective study, 13 men with hemoglobin AS ("cases") and 13 controls (hemoglobin AA) matched by age, sex, and race were exposed to five to seven altitude simulations (ranging from 1524 to 7620 m [5000 to 25,000 ft]) in a hypobaric chamber. Measurements of diffusing capacity for carbon monoxide (DLco), forced vital capacity, forced expiratory volume in one second, and forced midexpiratory flow were obtained before and after each exposure. Data before exposures did not differ statistically between cases and controls. Altitude had no systematic effect on DLco or spirometric values in cases compared with values in controls (p greater than 0.05). Individual declines in forced vital capacity or DLco of more than 10% occurred with similar frequency in both groups. Measurements made after the series of exposures showed no change from those made before. We conclude that short serial exposures to hypoxia at high altitudes does not acutely or cumulatively alter DLco or spirometric values in healthy, nonexercising persons with sickle cell trait.     

Safety of iodinated intravenous contrast medium administration in sickle cell disease

BackgroundIncreased sickling of erythrocytes following intravenous iodinated contrast has been described in patients with sickle cell disease. In vitro, the effect is correlated with the tonicity, viscosity, acidity, and ionic nature of contrast media. Less erythrocyte sickling is observed in vitro with second-generation low- and iso-osmolar contrast agents. Clinical impact of these newer intravenous contrast agents has not been investigated.PurposeTo review adverse outcomes following contrast administration in a cohort of patients with sickle cell disease.MethodsInpatients with sickle cell disease who received iodinated intravenous were identified. Medical records were reviewed for evidence of worsening crisis and occurrence of adverse events within 48 hours of contrast administration. Data points were further analyzed with the goal of identifying predictors of adverse outcome.ResultsThere were 132 imaging studies that met inclusion criteria in 79 patients, mostly with homozygous hemoglobin S. The low-osmolar contrast Optiray (Coviden Imaging Inc., Hazelwood, Mo) was used in 45%. Administration of fluids, Mucomyst (Bristol-Myers Squibb, New York, NY), oxygen, or blood transfusion preceded 58% of studies. Minor adverse events followed 16% of studies, with new or worsening pain being most common (12%). Contrast-induced nephropathy occurred in 1.5%, resolving in all cases. Prehydration was associated with a decreased incidence of adverse events (P = .02).ConclusionAdverse events related to intravenous contrast occur in sickle cell disease patients at a rate similar to the general population, without an increase in contrast-induced nephropathy. Subjective reports of new or worsening pain crisis do not translate to objective findings. Beneficial diagnostic imaging can be performed without increased risk of serious complication in this population.     

Sickle cell trait in a white Jewish family presenting as splenic infarction at high altitude

We report the presence of sickle cell trait in several members of a white Jewish family. The trait was discovered when the propositus developed massive splenic infarction at high altitude. No erythrocyte markers characteristic of African ancestry were detected in any of the family members. This is the first bona fide documentation of sickle trait among white Jews.     

A Cross-Sectional Survey of Plasmodium falciparum pfcrt Mutant Haplotypes in the Democratic Republic of Congo

Splenic infarction is a rare complication of malaria. We report two recent cases of splenic infarction after Plasmodium vivax infection. No systematic review of malaria-induced splenic infarction was available, therefore we conducted a systematic review of the English, French, and Spanish literature in PubMed and KoreaMed for reports of malaria-associated splenic infarction from 1960 to 2012. Of the 40 cases collected on splenic infarction by Plasmodium species, 23 involved P. vivax, 11 Plasmodium falciparum, one Plasmodium ovale, and five a mixed infection of P. vivax and P. falciparum. Of the 40 cases, 2 (5.0%) involved splenectomy and 5 (12.5%) were accompanied by splenic rupture. The median time from symptom onset to diagnosis was 8.5 days (range, 3–90 days). Improved findings after treatment were observed in 8 (88.9%) of 9 patients with splenic infarction on follow-up by computed tomography or ultrasonography. All patients survived after treatment with the exception of one patient with cerebral malaria. Clinicians should consider the possibility of splenic infarction when malaria-infected patients have left upper quadrant pain.     

Haemoglobin F,A2, and S levels in subjects with or without sickle cell trait in south-eastern Gabon

Background: Infant mortality due to sickle cell disease in sub-Saharan Africa is high, necessitating a better understanding of the modulating factors of the disease in this region.

Methods: We assessed the hereditary persistence of foetal haemoglobin and α-thalassemia. We diagnosed 787 subjects, with or without sickle cell trait, by capillary electrophoresis in the Medical Diagnostic Laboratory of the CIRMF (Franceville, Gabon).

Results: Heterocellular and pancellular forms of hereditary persistence of foetal haemoglobin occurred at low rates of 10.9 and 2.3%, respectively. The distribution of HbS levels in individuals with sickle cell trait was trimodal, showing a high percentage (52.4%) of heterozygous subjects with α-thalassemia. The distribution of HbA2 levels was bimodal in individuals without sickle cell trait, estimated to be comprised of 12 and 15% of α and β-thalassemic heterozygous subjects, respectively.

Conclusions: In sub-Saharan Africa, α-thalassemia is a far more prevalent modulating factor than hereditary persistence of foetal haemoglobin. Our study highlights the need for further investigation of thalassemia, haemoglobinopathies that are neglected in sub-Saharan Africa.     

Exertion-Induced rhabdomyolysis with acute renal failure and disseminated intravascular coagulation in sickle cell trait

From 1970 to 1974, among thousands of trainees seen at two large military installations who were subjected to the same physical and environmental stresses, only four recruits were hospitalized because of acute exertional rhabdomyolysis, renal failure and coagulopathy. The illness followed the performance of vigorous exercise. These four patients had sickle cell trait. In an attempt to explain this association, the data in these four cases are summarized. The hypothesis is then developed that rhabdomyolysis and endothelial damage, terminating in severe coagulopathy, may more likely occur in patients with sickle cell trait who are subjected to vigorous physical exertion.     

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases

Abstract

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients’ charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.     

Obstructive sleep apnoea predicted by the STOP-BANG questionnaire is not associated with higher rates of post-operative complications among a high-risk surgical cohort

Purpose

The purpose of this study is to establish if obstructive sleep apnoea (OSA) predicted by the STOP-BANG questionnaire would be associated with higher rates of post-operative cardiac, respiratory or neurological complications among a selected high-risk population with established major comorbidities undergoing major surgery. We hypothesise that a cohort selected for major comorbidities will show a higher post-operative complication rate that may power any potential association with co-existent OSA and identify an important target group for OSA screening and treatment pathways in preparation for major surgery.

Methods

Patients attending a high-risk preadmission clinic prior to major surgery from May 2015 to November 2015 were prospectively screened for OSA using the STOP-BANG questionnaire. Patients with treated OSA were excluded. Patient data and complications were attained from the pre-admission clinic and subsequent inpatient medical record at discharge.

Results

Three-hundred-and-ten patients were included in the study (age 68.6?±?13.1 years, body mass index [BMI] 30.6?±?7.4 kg/m²; 52.9% female). Sixty-four patients (20.6%) experienced 82 post-operative complications. Seventy-five percent of the cohort had a STOP-BANG?≥?3. There was no association between the STOP-BANG score (unadjusted and adjusted for comorbidity) with the development of post-operative complications.

Conclusions

OSA predicted by the STOP-BANG score was not associated with higher rates of post-operative complications in patients with major comorbidities undergoing high-risk surgery. As the findings from this cohort contrast with other observational studies, more definitive studies are required to establish a causative link between OSA and post-operative complications and determine whether treating OSA reduces this complication rate.

     

rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients

Aims: Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia (SCA) by inhibiting deoxy sickle hemoglobin (HbS) polymerization. HbF genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Herein, we aimed to determine whether two functional polymorphisms of BCL11A are implicated in the variation of HbF and clinical events in SCA Tunisian patients.

Material and methods: The studied population consisted of 148 SCA patients with SS phenotype. The group of patients was divided into two subgroups according to the threshold point of %HbF which is 15%. Genotyping of rs11886868 and rs4671393 was performed using PCR/Sequencing. To test for trait association with the candidate SNPs, genotype and allele frequencies between ‘group who had %HbF?<?15’ and ‘group who had %HbF >15’ (controls) were compared using Pearson's chi-square test (compare 2, version 1.02). The association of each genotype and the combined genotype with complications was performed by logistic regression test.

Results: Our findings showed that the majority of patients carried genotype CT of rs11886868 and genotypes AG and GG of rs4671393 present HbF level?<?15%. RR?=?0.08, RR?=?0.176, and RR?=?0.189, respectively. The results showed a significant association between the alleles T of rs11886868 and G of rs4671393 and %HbF?<?15% with P?=?0.016; RR?=?0.39 and P?=?8.9?×?10^?3: RR?=?0.567, respectively. Interestingly, the C allele of the rs11886868 and the A allele of the rs46713939 were associated with an ameliorated phenotype in patient's SCA. The combination of the genotypes GG and CT explains more phenotypic variance than the sum of the two BCL11A SNPs taken individually.     

Prevalence of other diabetes-associated complications and comorbidities and its impact on health care charges among patients with diabetic neuropathy

IntroductionDiabetic neuropathy (DN) is a common complication associated with diabetes. This study assesses the prevalence of other diabetes-related complications or comorbidities among DN patients and its marginal contribution to health care charges.MethodsUsing administrative claims database, we studied commercially insured patients below 65 years old with at least one claim of DN anytime from July 2004 through June 2005 (Year 1). Using propensity scoring, a 10:1 ratio of demographically matched controls with diabetes but no DN was constructed. Both DN patients and controls had 12 months of continuous enrollment in Year 1 and Year 2 (July 2005–June 2006). We compared the Year 1 prevalence of other diabetes-associated complications or comorbidities between DN patients and diabetic controls. Controlling for comorbidities, we used multivariate regressions to examine the incremental impact of DN or any other diabetes-related complication or comorbidity on Year 2 health care charges.ResultsA higher percentage of DN patients had at least one other diabetes-related complication or comorbidity than diabetic controls. Individuals with DN had a higher prevalence of each individual other diabetes-related complication or comorbidity. Controlling for comorbidities, the presence of any other diabetes-related complication or comorbidity was statistically associated with higher outpatient pharmacy and total charges for both DN patients and controls. Total and outpatient pharmacy charges were also significantly higher for DN patients than for controls, among those with or without any other diabetes-related complications or comorbidities.ConclusionsDN can occur in the absence of other diabetes-related complications or comorbidities. The presence of DN and any other diabetes-related complications or comorbidities significantly increases health care charges.     

Is the Medical Home for Adult Patients with Sickle Cell Disease a Reality or an Illusion?

Abstract

Recently, the patient-centered medical home (PCMH) emerged as a viable method to improve delivery of medical care. Due to all the promotion about the effectiveness of the PCMH, patients with sickle cell disease, their families and the community hoped that this could be a possible solution to the problems that arise in the treatment of adult patients with sickle cell disease. Review of the literature and review of the criteria for the establishment of a PCMH show that the PCMH is not an ideal model for patients with sickle cell disease because finding a personal physician, which is the first criteria of a functional PCMH, is a major problem in the process of transitioning the care of patients with sickle cell disease from pediatrics to adult care. Moreover, garnering hospital support to defray the initial costs to establish a PCMH for adults with sickle cell disease is unlikely given the already high costs of care for patients with sickle cell disease. Moreover, recent studies have shown insufficient evidence to determine the presumed beneficial effects of the PCMH, especially in patients with chronic disease.