Early-onset indicators of a hypercoagulable state and clinical complications in a cohort of children with sickle cell trait.

Adults with sickle cell trait (SCT) have a procoagulant state with increased risk of thromboembolism, but limited data are available for children. We compared the coagulation profile of children with SCT, different sickle cell disease (SCD) genotypes, and healthy controls. Compared to controls and similarly to HbSC patients, 41 SCT children (mean age 6.85 years; 20 males; 88% Africans) had a characteristic procoagulant profile: higher levels of factor VIII, von Willebrand factor (VWF) Ag and CBA, D-dimer; lower levels of ADAMTS 13 activity, ADAMTS13 activity: VWFAg, plasminogen activator inhibitor, tissue plasminogen activator. Moreover, 13/41 had clinical complications of SCD, five requiring hospitalization.

Occlusive Retinal Vasculitis in a Pediatric Patient With Kikuchi-Fujimoto Disease and Sickle Cell Trait.

A 13-year-old Black male patient with a history of Kikuchi-Fujimoto disease (KFD) and sickle cell trait presented with acute painless vision loss and no light perception vision (NLP) in his left eye. The examination was indicative of occlusive retinal vasculitis with near total central retinal artery occlusion (CRAO). He was started on oral steroids with dramatic reperfusion and improvement of the retinal hemorrhages. However, his vision remained at NLP. Oral steroids were tapered, and rituximab infusion was initiated. While ocular involvement is uncommon in KFD, vision-limiting complications, such as occlusive retinal vasculitis, ophthalmic artery occlusion, and CRAO can occur. Early systemic immunosuppression is key in achieving rapid remission. [Ophthalmic Surg Lasers Imaging Retina 2024;55:235-239.].

Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.

Unusual coexistence of Stewart-Treves syndrome and sickle cell anaemia: a case of dual pathology.

Chronic lymphoedema can rarely be complicated by an angiosarcoma. This combination called Stewart-Treves syndrome usually observed in upper limb in patients of post-mastectomy with axillary lymph node resection. Here, we report a male patient who had a 10-year history of right leg elephantiasis. Later on, he developed two large ulceronodular masses in the same leg with few satellite nodules in the surrounding skin. With the clinical suspicion of malignancy, a wedge biopsy was performed which revealed histological features of angiosarcoma with sickled red cells. The above knee amputation specimen received further confirmed the histological diagnosis. The investigation for haemoglobinopathy also suggested the presence of sickle cell trait. This report describes a multifocal tumour as a rare manifestation of Stewart-Treves syndrome in a post-filariasis case with sickle cell trait, which is an extremely uncommon combination.

HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.

INTRODUCTION: Sickle cell disease (SCD), an inherited hemoglobinopathy, affects primarily African Americans in the U.S.A. In addition, about 15% African Americans carry sickle cell trait (SCT). Despite the risk associated with blood transfusions, SCD patients have lower risk of acquiring HIV-1 infection. SCT individuals might also have some protection from HIV-1 infection. AREAS COVERED: Here, we will review recent and previous studies with the focus on molecular mechanisms that might underlie and contribute to the protection of individuals with SCD and SCT from HIV-1 infection. As both of these conditions predispose to hemolysis, we will focus our discussion on the effects of systemic and intracellular iron on HIV-1 infection and progression. We will also review changes in iron metabolism and activation of innate antiviral responses in SCD and SCT and their effects on HIV-1 infection. EXPERT OPINION: Previous studies, including ours, showed that SCD might protect from HIV-1 infection. This protection is likely due to the upregulation of complex protein network in response to hemolysis, hypoxia and interferon signaling. These findings are important not only for HIV-1 field but also for SCD cure efforts as antiviral state of SCD patients may adversely affect lentivirus-based gene therapy efforts.

Sickle Cell Trait and SARS-CoV-2-Induced Rhabdomyolysis: A Case Report.

BACKGROUND Rhabdomyolysis is a syndrome characterized by muscle necrosis and the subsequent release of intracellular muscle constituents into the bloodstream. Although the specific cause is frequently evident from the history or from the immediate events, such as a trauma, extraordinary physical exertion, or a recent infection, sometimes there are hidden risk factors that have to be identified. For instance, individuals with sickle cell trait (SCT) have been reported to be at increased risk for rare conditions, including rhabdomyolysis. Moreover, there have been a few case reports of SARS-CoV-2 infection-related rhabdomyolysis. CASE REPORT We present a case of a patient affected by unknown SCT and admitted with SARS-CoV-2 pneumonia, who suffered non-traumatic non-exertional rhabdomyolysis leading to acute kidney injury (AKI), requiring acute hemodialysis (HD). The patients underwent 13 dialysis session, of which 12 were carried out using an HFR-Supra H dialyzer. He underwent kidney biopsy, where rhabdomyolysis injury was ascertained. No viral traces were found on kidney biopsy samples. The muscle biopsy showed the presence of an "open nucleolus" in the muscle cell, which was consistent with virus-infected cells. After 40 days in the hospital, his serum creatinine was 1.62 mg/dL and CPK and Myoglobin were 188 U/L and 168 ng/mL, respectively; therefore, the patient was discharged. CONCLUSIONS SARS-CoV-2 infection resulted in severe rhabdomyolysis with AKI requiring acute HD. Since SARS-CoV-2 infection can trigger sickle-related complications like rhabdomyolysis, the presence of SCT needs to be ascertained in African patients.

Longitudinal study of glomerular hyperfiltration and normalization of estimated glomerular filtration in adults with sickle cell disease.

Glomerular hyperfiltration is common in sickle cell disease (SCD) and precedes proteinuria and declining kidney function. We evaluated hyperfiltration in SCD patients and its "normalization." Routine visit data were collected retrospectively from adult SCD patients in a single centre from 2004 to 2013. Baseline was defined as first available serum creatinine and hyperfiltration as estimated glomerular filtration rates (eGFR) >130 ml/min/1·73 m2 for women and >140 ml/min/1·73 m2 for men. Normalization of hyperfiltration was eGFR reduction to 90-130 ml/min/1·73 m2 for women or 90-140 ml/min/1·73 m2 for men. Among 292 patients, median age was 27 years [interquartile range (IQR):20·0-38·0], and 56·8% had baseline hyperfiltration. Baseline hyperfiltration was inversely associated with age [odds ratio (OR):0·86, 95% confidence interval (CI): 0·82-0·90; P < 0·0001], male sex (OR:0·16, 95% CI: 0·07-0·41; P = 0·0001), haemoglobin (OR:0·76, 95% CI 0·61-0·94; P = 0·01), weight (OR:0·96, 95% CI: 0·93-0·99; P = 0·004), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use (OR:0·08, 95% CI: 0·01-0·75; P = 0·03), and positively with hydroxycarbamide use (OR:2·99, 95% CI: 1·18-7·56; P = 0·02). Of 89 hyperfiltration patients without baseline proteinuria, 10 (11·2%) developed new-onset proteinuria [median 1·05 years (IQR:0·63-2·09)]. Normalization of hyperfiltration was less likely with higher baseline eGFR [hazard ratio (HR):0·90, 95% CI: 0·86-0·95; P < 0·0001] and more likely in males (HR:6·35, 95% CI:2·71-14·86, <0·0001). Hyperfiltration is common in adult SCD patients, particularly when younger. Decline to normal values is more likely in males, possibly representing kidney function loss rather than improvement in hyperfiltration.

Malaria is a cause of iron deficiency in African children.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

Haematogenous osteoarticular infections in paediatric sickle cell trait patients: A reality in a tertiary centre in West Africa.

BACKGROUND: Sickle cell trait (SCT) affects at least 5.2% of the world population, and it is considered asymptomatic by medical practitioners. There is a paucity of data regarding SCT paediatric patients and haematogenous osteoarticular infections (HOAIs). In our practice, some children with SCT presented HOAIs. This study aims to describe the pattern of HOAIs in children with SCT admitted in our unit. MATERIALS AND METHODS: A single-centre retrospective study of medical records of SCT paediatric patients treated for HOAIs between January 2012 and June 2019 was performed. The data extracted were epidemiologic (gender, age at diagnosis, history of haemoglobinopathy and ethnic group), diagnostic (time to diagnosis, type of infection and fraction of haemoglobin S [HbS] at standard electrophoresis of Hb), germs and complications. RESULTS: Among 149 patients with haemoglobinopathy treated for HOAIs, 52 have SCT. The prevalence of SCT patients was 34.9%. Thirty-nine (n = 39) records were retained for the study. The average age at diagnosis was 7.18 ± 4.59 years (7 months-15 years). The Malinké ethnic group was found in 22 (56.4%) cases. The mean HbS fraction was 37.2% ± 4.3% (30%-46%). Septic arthritis and osteoarthritis involved the hip in 11 cases, the shoulder in 4 and the knee in 2. Osteomyelitis was acute in 5 cases (11.1%) and chronic in 16 (35.5%). None of the patients has multifocal involvements. Bacterial identification was positive in 17 cases (37.8%). Staphylococcus aureus was involved in 9 cases (52.9%), and in one case, it was Mycobacterium tuberculosis. This patient has abscess of the psoas. No patient was infected by human immunodeficiency virus. The sequelae were joint destruction (n = 2), epiphysiodesis (n = 5) and retractile scars (n = 2). CONCLUSION: Relatively infrequent in our daily practice, SCT patients present with HOAIs. These infections had characteristics that are not very different from the series of the literature.

Summit on Exercise Collapse Associated with Sickle Cell Trait: Finding the "Way Ahead".

ABSTRACT: Although largely benign, sickle cell trait (SCT) has been associated with exertion-related events, to include sudden death. In 2011, a summit on SCT introduced the term exercise collapse associated with SCT (ECAST). A series of ECAST deaths in military personnel in 2019 prompted reevaluation of current efforts and led to a second summit in October 2019 hosted by the Consortium for Health and Military Performance of the Uniformed Services University in Bethesda, MD. The goals were to (1) review current service policies on SCT screening, (2) develop draft procedural instructions for executing current policy on SCT within the Department of Defense, (3) develop draft clinical practice guidelines for management of ECAST, (4) establish a framework for education on SCT and ECAST, and (5) prepare a research agenda to address identified gaps.

Spontaneous splenic rupture, mesenteric ischemia and spinal infarction after aortic repair for acute type A dissection in a patient with sickle cell trait.

Sickle cell trait (SCT), a benign hematological condition affecting approximately 300 million individuals globally, is associated with an increased risk of vaso-occlusive disease. However, the risks related to surgery employing cardiopulmonary bypass in patients with SCT are not well established. Herein, we report the case of a 27-year-old African American man with SCT who underwent an emergency aortic repair for acute Stanford type A aortic dissection using hypothermic circulatory arrest. The patient developed a sickle cell crisis, which was followed by spontaneous splenic infarction and rupture, nonocclusive mesenteric ischemia, and spinal infarction.

Fatal sickling-associated microvascular occlusive crisis in a young with sickle cell trait

Sickle cell trait (SCT), a heterozygous state characterized by hemoglobin AS, occurs commonly in sub-Saharan Africa, South America, Central America, India, and the Mediterranean countries. SCT is compatible with a normal lifespan and is not commonly regarded as a cause of morbid illness or death compared to its homozygous counterpart. We describe a case of fatal sickling-associated microvascular crisis, identified on post mortem evaluation in a previously undiagnosed 21-year-old military recruit with sickle cell trait. The individual presented with repeated syncope episodes during his training and was autopsied in the pursuit of cardiac anomalies and heat syncope. During the terminal episode, he collapsed and died of severe metabolic complications as he struggled to complete an organized run during routine training activities. To our knowledge, this is the first report of fatal sickling-associated crisis in a military recruit with sickle cell trait from India. This case serves to remind all armed forces and sports physicians of the importance of screening a recruit who is unable to complete exertional physical training for the presence of sickle cell trait.

Microsurgery in the sickle cell trait population: is it actually safe?

Although sickle cell disease has long been viewed as a contraindication to free flap transfer, little data exist evaluating complications of microsurgical procedures in the sickle cell trait patient. Reported is the case of a 55-year-old woman with sickle cell trait who underwent a deep inferior epigastric perforator microvascular free flap following mastectomy. The flap developed signs of venous congestion on postoperative day 2 but was found to have patent arterial and venous anastomoses on exploration in the operating room. On near-infrared indocyanine green angiography, poor vascular flow was noted despite patent anastomoses and strong cutaneous arterial Doppler signals. Intrinsic microvascular compromise or sickling remains a risk in the sickle cell trait population as it does for the sickle cell disease population. Just like in sickle cell disease patients, special care should be taken to optimise anticoagulation and minimise ischaemia-induced sickling for patients with sickle cell trait undergoing microsurgery.

Renal medullary carcinoma and its association with sickle cell trait: a case report and literature review.

Renal medullary carcinoma (rmc) is a rare and aggressive renal malignancy that usually presents at an advanced stage, has a poor prognosis, and is associated with sickle cell trait. We present a case of rmc including radiologic and pathology findings, treatment, and outcome. A review of the literature is also presented, with an emphasis on the association of rmc with sickle cell trait, which was an unknown diagnosis in our patient preoperatively.

Serious adverse events in African-American cancer patients with sickle cell trait and inherited haemoglobinopathies in a SEER-Medicare claims cohort.

African-American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA-; 144,863 NHW-). AA+ patients had significantly increased risk for ≥1 AEs compared to AA- (RR = 1.19; 95% CI 1.11-1.27) and NHW- (RR = 1.23; 95% CI 1.15-1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.

Renal Medullary Carcinoma.

Renal medullary carcinoma, also referred to as the seventh sickle cell nephropathy, typically affects young African Americans with sickle cell trait, or, less frequently, patients with sickle cell disease. The existence of renal medullary carcinoma without a concomitant hemoglobinopathy is a topic of controversy. The typical patient is a young male of African or Mediterranean descent, with hematuria and/or flank pain. Most patients have metastatic disease at the time of presentation. The tumor is characteristically a poorly circumscribed mass in the medullary region, commonly showing variable amounts of hemorrhage and necrosis. Microscopically, a characteristic reticular or cribriform pattern with a striking desmoplastic stromal response and a robust mixed inflammatory infiltrate is observed. Collecting duct carcinoma, malignant rhabdoid tumor, urothelial carcinoma, and other subtypes of renal cell carcinoma are in the differential diagnosis. Because of the advanced stage of disease at presentation and the aggressive nature of this malignant neoplasm, survival is poor even with chemotherapy; however, isolated reports of prolonged survival have been documented.

RETINAL AND CHOROIDAL VASCULAR OCCLUSION FOLLOWING AQUEOUS MISDIRECTION SYNDROME IN A PATIENT WITH SICKLE CELL TRAIT.

PURPOSE: To report a patient with retinal and choroidal vascular occlusion as a presenting sign of sickle cell trait following the development of aqueous misdirection syndrome. METHODS: Retrospective chart review. RESULTS: A patient treated for bilateral chronic angle-closure glaucoma with sequential EX-PRESS glaucoma filtration device surgery developed sequential bilateral aqueous misdirection syndrome. The left eye developed retinal arterial and localized choroidal vascular occlusions subsequent to an acute elevation in intraocular pressure and possibly the use of oral acetazolamide. The patient was subsequently found to have sickle cell trait. The right eye developed aqueous misdirection with acute elevation of intraocular pressure as well, but the patient was not treated with oral acetazolamide and did not develop vascular occlusion. CONCLUSION: Retinal and choroidal vascular occlusions can be the presenting sign of a patient with sickle cell trait. Sickle cell screening may be beneficial in African American or Middle Eastern patients after an acute rise in intraocular pressure, particularly before initiation of treatment with oral carbonic anhydrase inhibitors.