The Role of Platelets in Sickle Cell Disease

Brzóska, Tomasz; Kato, Gregory J.; Sundd, Prithu

doi:10.1016/b978-0-12-813456-6.00031-x

Cited by 4 publications

(5 citation statements)

References 339 publications

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“…The preclinical data for increased platelet activation in patients with SCD are referred to in the “Introduction.” In addition, there is growing evidence of von Willebrand factor interaction via GPIbα, tissue factor, and thrombin to promote neutrophil–platelet aggregation. 37 The lack of effect of ticagrelor on the incidence of vaso-occlusive crises in this study may further implicate the primacy of neutrophil involvement. 9-11 It may be that the propagation of cellular aggregation and initiation of vaso-occlusive crises is more dependent on endothelial interaction via von Willebrand factor, selectins, GPIbα, and/or GPIIb/IIIa.…”

Section: Discussionmentioning

confidence: 66%

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Ticagrelor vs placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: the HESTIA3 study

Heeney

Abboud

Githanga

et al. 2022

Blood

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The phase 3 HESTIA3 study assessed the efficacy and safety of the reversible P2Y12 inhibitor ticagrelor versus placebo in preventing vaso-occlusive crises in pediatric patients with sickle cell disease (SCD). Patients aged 2 to 17 years were randomly assigned 1:1 to weight-based doses of ticagrelor or matching placebo. The primary endpoint was the rate of vaso-occlusive crises, a composite of painful crises and/or acute chest syndrome (ACS). Key secondary endpoints included number and duration of painful crises, number of ACS events, and number of vaso-occlusive crises requiring hospitalization or emergency department visits. Exploratory endpoints included the effect of ticagrelor on platelet activation. In total, 193 patients (ticagrelor: N = 101; placebo: N = 92) underwent randomization at 53 sites across 16 countries. The study was terminated 4 months before planned completion for lack of efficacy. Median ticagrelor exposure duration was 296.5 days. The primary endpoint was not met: estimated yearly incidence of vaso-occlusive crises was 2.74 in the ticagrelor group and 2.60 in the placebo group (rate ratio: 1.06; 95% confidence interval: 0.75-1.50; P =.7597). There was no evidence of efficacy for ticagrelor versus placebo across secondary endpoints. Median platelet inhibition with ticagrelor at 6 months was 34.9% at pre-dose and 55.7% at 2 hours post-dose. Nine patients (9%) in the ticagrelor group and eight patients (9%) in the placebo group had at least one bleeding event. In conclusion, no reduction of vaso-occlusive crises was seen with ticagrelor versus placebo in these pediatric patients with SCD. Trial registration: ClinicalTrials.gov NCT03615924.

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Section: Discussionmentioning

confidence: 66%

“… 9-11 It may be that the propagation of cellular aggregation and initiation of vaso-occlusive crises is more dependent on endothelial interaction via von Willebrand factor, selectins, GPIbα, and/or GPIIb/IIIa. 37 …”

Section: Discussionmentioning

confidence: 99%

Ticagrelor vs placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: the HESTIA3 study

Heeney

Abboud

Githanga

et al. 2022

Blood

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“…Indeed, platelet interaction with VWF has been shown to play a crucial role in the pathophysiology of multiple hemolytic disorders including TTP (7,8,20,58). Fourth, nitric oxide (NO) depletion and ROS generation by cell-free hemoglobin may also contribute to hemolysis-induced platelet activation and pulmonary thrombosis (3,17,27,55). Fifth, although thrombin did not seem to play a direct role in our study, thrombin generation may still contribute to acute hemolysis-triggered pulmonary thrombosis by unknown mechanisms.…”

Section: R E S E R C H a R T I C L Ementioning

confidence: 62%

“…Hemolysis is associated with hemostatic abnormalities such as enhanced platelet activation and thrombin generation, elevated circulating tissue factor, and endothelial injury (1,3,5,9,15,(27)(28)(29)(30)(31)(32). Thrombocytopenia, which is suggestive of intravascular platelet sequestration, is a risk factor for acute systemic and pulmonary complications of hemolytic disorders (8,(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in precapillary pulmonary arterioles

et al. 2020

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“…The current study further reinforces finding by demonstrating a stronger positive correlation demonstrated between WBC and PDW (platelet distribution width). PDW can be defined as a coefficient of variation of platelet size and it is considered a marker of platelet function and activation (Brzoska et al, 2019, Hoffbrand et al, 2016. Increased PDW in this case could be explained by pre-existing anisocytosis and continuous thrombocytosis which results in the release of micro-and macro-platelets into peripheral circulation as a compensatory response in sickle cell anaemia.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum Infection Modulates Platelet Count than Leucocyte Parameters in Carriage of Different Haemoglobin Beta Subunit (HBB) Genotypes

2023

JNSR

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Background: Sickle cell disease is a prime genetic disorder due to a single nucleotide mutation resulting in haemoglobin gene (HbS) occurring in the regions where malaria is endemic. Though it primarily a disease of erythrocytes, non-erythrocytic cells are equally affected just like in malaria infection. Furthermore, leucocytes and thrombocytes have equally been hypothesized to be the driving force for sickle cell crisis. However, the modulatory trends and magnitude of Plasmodium falciparum infection on platelet and leucocyte parameters in sickle cell disease is not entirely explored.Objectives: The current study therefore determined the modulatory effects of P. falciparum infection on platelet and leucocyte parameters in carriage of different haemoglobin beta subunit (HBB) genotypes.Methodology: This cross-sectional study evaluated leucocytes and thrombocytes parameters in P. falciparuminfected and non-infected children (n=217, aged 1-192 months) with different HBB genotypes. Children with acute febrile conditions were randomly selected and enrolled at Jaramogi Oginga Odinga Teaching and Referral Hospital for a period of ten months at outpatient clinic. Haematological parameters were determined using Beckman Coulter counter ACTdiff2 TM while HBB genotyping was done using TaqMan ® SNP genotyping assay. Chi-square (χ 2 ) analysis was used to determine differences between proportions. Mann-Whitney U test and Kruskal Wallis test were used for comparisons of demographic and laboratory characteristics wherever applicable. Partial correlation test was used to determine relationship between leucocytes and thrombocyte parameters in carriage of different HBB genotypes while adjusting for age and sex as covariates.Results: Generally, there were no differences in WBC (p=0.746), lymphocytes (p=0.103), monocyte (p=0.084) and granulocytes (p=0.354) between the infected and non-infected children. Platelet count [median (IQR); 236 (129.5), p=0.001] and PCT, [median (IQR); 0.13 (0.1), p=0.001] were markedly reduced in infected children. Specifically, monocytes had a positive correlation with platelet count (r= 0.742, p=0.002) in non-infected children with HbSS genotype. WBC revealed a positive correlation with platelet count in both infected and non-infected children (r =0.358, r 2 =0.128, p =0.047 and r = -0.638, r 2 =0.407, p= 0.047) in carriage of HbSS respectively WBC and RDW in children infected with falciparum in carriage of HbSS genotypes (r =0.818, r 2 =0.669, p =0.004). Monocyte count revealed a positive correlation with platelet count in non-infected children and no correlation in children infected with malaria (r= -0.742, P=0.022 and r= -0.245, P=0.525, respectively). Conclusion: P. falciparum infection is responsible for a decrease the platelet count as WBC count increases in children with HbSS. Therefore, a decrease in platelet count against leukocytosis in carriage of HbSS should warrant a test for P. falciparum infection.

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The Role of Platelets in Sickle Cell Disease

Cited by 4 publications

References 339 publications

Ticagrelor vs placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: the HESTIA3 study

Ticagrelor vs placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: the HESTIA3 study

Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in precapillary pulmonary arterioles

Plasmodium falciparum Infection Modulates Platelet Count than Leucocyte Parameters in Carriage of Different Haemoglobin Beta Subunit (HBB) Genotypes

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