Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P
Source: Blood - Category: Hematology Authors: Tags: Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis Source Type: research

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Conclusion: Intermittent blood transfusion remains a common practice for the management of children with acute SCD complications. Main indications were acute anemic crises, severe pain crises, ACS, and stroke. In limited resource settings, such as Yemen, conservative transfusion policy appears to be appropriate. PMID: 32908695 [PubMed]
Source: Anemia - Category: Hematology Tags: Anemia Source Type: research
Abstract Sickle cell disease (SCD) is associated with chronic hemolytic anemia and a heightened inflammatory state. The causal role of inflammatory pathways in stroke associated with SCD is unclear. Therefore, the hypothesis that deletion of the non-hematopoietic interleukin-1 receptor (IL-1R) pool may be beneficial in SCD was pursued. Since potential deleterious effects of IL-1R signaling in SCD could be mediated via downstream production of interleukin-6 (IL-6), the role of the non-hematopoietic IL-6 pool was also addressed. Bone marrow transplantation (BMT) from SCD to wild-type (WT) recipient mice was used to ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
CONCLUSIONS: There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is lo...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
CONCLUSIONS: We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves of sickle mice. PMID: 32573897 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
Sickle cell disease (SCD) is a hemoglobin disorder leading to chronic hemolysis and multi-organ morbidity. Increasing evidence suggests that activation of coagulation contributes to its complications such as stroke, pulmonary hypertension, venous thromboembolism and avascular necrosis [1]. The effects are most profound in homozygous state Hemoglobin SS (HbSS) and Hemoglobin S-Beta zero thalassemia referred together as sickle cell anemia (SCA). With improved survival of patients with SCA in the current era, early recognition of long-term complications is a priority, but there is a paucity of biomarkers to identify SCA hypercoagulability.
Source: Transfusion and Apheresis Science - Category: Hematology Authors: Source Type: research
This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of common and rare blood cell disorders. recent findings A growing number of preventive treatment options are available for stroke in sickle cell disease. Paroxysmal nocturnal hemoglobinuria and immune thrombocytopenia can lead to stroke. Thrombotic thrombocytopenic purpura frequently causes neurologic symptoms and should be considered in the differential diagnosis of a patient with neurologic symptoms, thrombocytopenia, and hemolytic anemia. Polycythemia vera and essential thrombocythemia are rare causes of stroke....
Source: CONTINUUM: Lifelong Learning in Neurology - Category: Neurology Tags: REVIEW ARTICLES Source Type: research
Overt stroke in adults with sickle cell anemia (SCA) continues to be a major cause of morbidity and mortality, while no evidence-based strategy for prevention has been reached so far. Although transcranial Doppler ultrasonography represents the most important tool for identifying young patients with SCA at risk of primary stroke, strategies for stroke prediction in adulthood remain challenging. Emerging data suggest that oxidative stress may exert a pivotal role in the pathogenesis of ischemic brain injury.
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Source Type: research
This study is par for the course, looking at Japanese Olympic participants. Interestingly, it hints at the upper end of the dose-response curve for physical activity, in that a longer career as a professional athlete may be detrimental in comparison to lesser degrees of exercise and training. From this large, retrospective cohort study targeting 3546 Japanese Olympic athletes, we observed significant lower mortality among Olympians compared with the Japanese general population. The overall standardised mortality ratio (SMR) was 0.29. The results were consistent with previous studies conducted in other non-Asian co...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 12 March 2020Source: Hematology/Oncology and Stem Cell TherapyAuthor(s): Lori C. Jordan, Adetola A. Kassim, Karina L. Wilkerson, Chelsea A. Lee, Spencer L. Waddle, Manus J. Donahue
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Arterial remodeling due to SCA is mediated by JNK signaling, cathepsin proteolytic upregulation, and degradation of elastin and collagen. Demonstration in Townes mice establishes their utility for mechanistic studies of arterial vasculopathy, related complications, and therapeutic interventions for large artery damage due to SCA. PMID: 32160775 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
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