ArticleBlood2012
Hydroxyurea and a cGMP-amplifying agent have immediate benefits on acute vaso-occlusive events in sickle cell disease mice.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02824471 (Sickle Cell Disease), which is not on this map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sickle Cell Disease (SCD) Biochip': Towards a Simple and Reliable Way to Monitor Sickle Cell Disease
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.Expert review of hematology · 2015Pooled it
- PF-04447943, a Phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase Ib Randomized, Placebo-Controlled Study.Clinical and translational science · 2019Trial
- Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial.American journal of hematology · 2015Trial
- Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis.American journal of hematology · 2015Trial
- Hydroxyurea reduces hyperadhesion measured by a VLA-4-targeting PET tracer in sickle transgenic Townes mice.Blood advances · 2026Article
- Beneficial effects of SGLT1/2 and SGLT2 inhibitors on vaso-occlusive events and organ damage in sickle cell disease mice.Cardiovascular research · 2026Article
- Review
- Higher aged neutrophils and differential inflammatory profiles in sickle cell disease patients on chronic transfusion therapy versus those on hydroxyurea.Frontiers in immunology · 2025Article
- sGC stimulator (BAY 41-8543) combined with PDE9 inhibitor (BAY 73-6691) reduces renal fibrosis in 5/6 nephrectomized rats.Basic & clinical pharmacology & toxicology · 2025Article
- Arterial Stiffness as a New Predictor of Clinical Outcome in Patients with Polycythemia Vera.Journal of clinical medicine · 2024Article
- The Current Role of Hydroxyurea in the Treatment of Sickle Cell Anemia.Journal of clinical medicine · 2024Review
- Renal and cardiac effects of the PDE9 inhibitor BAY 73-6691 in 5/6 nephrectomized rats.Pflugers Archiv : European journal of physiology · 2024Article
- Impact of hydroxyurea on lymphocyte subsets in children with sickle cell anemia.Pediatric research · 2023Article
- Neutrophils as drivers of vascular injury in sickle cell disease.Immunological reviews · 2023Review
- Persistence of chronic inflammation after regular blood transfusion therapy in sickle cell anemia.Blood advances · 2023Article
- TGF-β1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice.Cells · 2022Article
- Impact of Abnormal Leukocyte Count in the Pathophysiology of Sickle Cell Anemia.Journal of blood medicine · 2022Article
- Effects of Hydroxyurea on Skeletal Muscle Energetics and Function in a Mildly Anemic Mouse Model.Frontiers in physiology · 2022Article
- Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites' Inhibition of Erythroid Progenitor Growth.Biomolecules · 2021Article
- Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso-occlusion and nephropathy in mouse models of sickle cell disease.British journal of pharmacology · 2021Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Inhibition of leukocyte adhesion to the vascular endothelium represents a novel and important approach for decreasing sickle cell disease (SCD) vaso-occlusion. Using a humanized SCD-mouse-model of tumor necrosis factor-α-induced acute vaso-occlusion, we herein present data demonstrating that short-term administration of either hydroxyurea or the phosphodiesterase 9 (PDE9) inhibitor, BAY73-6691, significantly altered leukocyte recruitment to the microvasculature. Notably, the administration of both agents led to marked improvements in leukocyte rolling and adhesion and decreased heterotypic red blood cell-leukocyte interactions, coupled with prolonged animal survival. Mechanistically, these rheologic benefits were associated with decreased endothelial adhesion molecule expression, as well as diminished leukocyte Mac-1-integrin activation and cyclic guanosine monophosphate (cGMP)-signaling, leading to reduced leukocyte recruitment. Our findings indicate that hydroxyurea has immediate beneficial effects on the microvasculature in acute sickle-cell crises that are independent of the drug's fetal hemoglobin-elevating properties and probably involve the formation of intravascular nitric oxide. In addition, inhibition of PDE9, an enzyme highly expressed in hematopoietic cells, amplified the cGMP-elevating effects of hydroxyurea and may represent a promising and more tissue-specific adjuvant therapy for this disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.