Ethnopharmacological Survey and Antisickling Activity of Plants Used in the Management of Sickle Cell Disease in Kikwit City, DR Congo

Background. Sickle cell disease or drepanocytosis is the most known hemoglobin abnormality in the world. Recently, many medicinal plants used in the management of sickle cell disease in African traditional medicine have shown in vitro antisickling activity. Objective. This research study aims to document some Congolese plant species used in the management of sickle cell disease in Kikwit city and investigate their pharmacological property in vitro. Methods. A cross-sectional survey was done from June 2015 to March 2016 among 26 traditional healers in Kikwit city, Democratic Republic of Congo. Emmel test was used to assess in vitro antisickling activity. Habitat, morphological, biological types, phytogeographical distribution, local names, and used parts of these plant species were also determined. Results. Obtained results show that 23 plant species belonging to 16 families are used. The leaves represent the most used part (70%). Antisickling investigation showed that aqueous extracts of 18 plants (78%) exhibit a change in the shape of a sickle cell into a normal one with a normalized rate of at least 70%, confirming the in vivo effect observed by traditional healers when used as herbal medicine traditionally in the management of sickle cell disease. The evaluation of perimeter, surface, and radius of untreated and treated sickle red blood cells showed a significant difference ( p < 0.05 ) as modification indicators of the red blood cell shape. Alchornea cordifolia, Alternanthera bettzickiana, Annona senegalensis, Dissotis brazzae, Hypoxis angustifolia, and Justicia secunda presented a very high antisickling activity with normalization >70%. Otherwise, Dissotis brazzae was the most active plant with a minimal concentration of normalization (MCN) of 11 μg/mL and a maximal normalization rate (NRmax) of 86%. Conclusion. Almost 80% of the plants studied showed interesting antisickling activity and justified their use in traditional medicine. The isolation of the molecules responsible for the biological activity of the most active plants and the determination of their chemical structures is under investigation.

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Impact of Hydroxyurea on Thrombin Antithrombin Complex and Vaso-Occlusive Crisis in Pediatric Sickle Cell Disease.

Blood ◽

10.1182/blood.v108.11.5525.5525 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5525-5525

Author(s):

Mohsen Saleh Elalfy ◽

Ashraf M. Abdelmonem ◽

Soha Youssef ◽

Heba Ismail

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Coagulation System ◽

P Value ◽

Cell Disease ◽

Significant Difference ◽

Healthy Control ◽

Pain Crisis

Abstract Background: Several studies suggest that increased activity of the coagulation system may be important in the pathogenesis of vascular occlusion in sickle cell disease. Hydroxyurea (HU) has been shown to reduce the frequency of vaso-occlusive manifestations in both adults and children with sickle cell disease (SCD). Aim: To analyze the effect of HU on Thrombin-Antithrombin (TAT) as a marker of thrombin generation and hypercoagualbility in SCD and to find out the relation between TAT level and vaso-occusive crisis. Subjects and Method: we evaluated 37 child with sickle cell hemoglobinopathy (mean age 10.92±5.39 years) and 15 normal control children (mean age 9.75±6.34 years). Informed consent was obtained from patients and/or guardians and study approval by local IRB was obtained. Twenty-two patients (59.5%) were on HU, 15 (41.5%) patients did not receive HU, 7 (46.7%) of them were transfusion dependant. TAT assay was done in vitro using a sandwich enzyme immunoassay. Results: Mean patients’ age at institution of HU was 8.54± 3.85 years with median treatment duration of 4.5 years. Causes for initiating HU therapy were frequent blood transfusion in 11 patients (50%), frequent pain crisis (≥ 3/year) in 9 patients (41%), severe anemia and parents refusing blood transfusion in 1 patient (4.5%) and stroke in another patient (4.5%). HU dose was 20.82±4.95 mg/kg/day. We measured TAT in all patients and compared them to healthy control. There was significant difference in TAT level in sickle cell patients (198.86±185.7) compared to healthy control 2.91±0.94, [P value < 0.0001]. When the level of TAT was compared between the HU and non-HU groups we found that patients on HU had statistically significant lower TAT level (172.36 vs.225.37) [P=0.039]. There was also a significant negative correlation between HU dose and TAT level (p=0.03). A significant positive correlation between number of vaso-occlusive crisis/year [P=0.03], frequency of pain crisis/year [P=0.04], duration of pain crisis [P=0.03] and TAT level was observed. Conclusion: Hydroxyurea has significant inhibitory effect on thrombogenesis in sickle cell patients, which may be another mechanism for reducing vaso-occlusive crisis. Sickle cell children with higher TAT level had more frequent and severe vaso-occlusive crisis.

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Hoslundia opposita and other Nigerian plants inhibit sickle hemoglobin polymerization and prevent erythrocyte sickling: a virtual screening-guided identification of bioactive plants.

10.1101/2021.07.25.453693 ◽

2021 ◽

Author(s):

Eric O. Olori ◽

Olujide Oludayo Olubiyi ◽

Chinedum Peace Babalola

Keyword(s):

Natural Products ◽

Sickle Cell Disease ◽

Plant Species ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Traditional Healers ◽

Sub Saharan Africa ◽

Cell Disease ◽

Sickle Hemoglobin ◽

Methanolic Extracts

In sickle cell disease, a hereditary hemoglobinopathy, clinically observed disease presentations are the endpoint of a point mutation involving the substitution of glutamic acid with valine at the position 6 of the beta globin chain. With about 4.4 million people globally being affected, and another 43 million people bearing the sickle cell trait, several research efforts have been made to discover new and affordable treatment and possibly cure for the disease. Africa is endowed with a large flora population and traditional healers and citizens have over time depended on the use of herbs in folkloric medicine for different ailments including sickle cell disease (SCD). Such native knowledge has often formed the basis for different research exploration into the anti-sickling activities of selected African plants. These plants that have been so far investigated for their anti-sickling properties represent about 0.05 % of the 45,000 plant species enriching the flora landscape in Sub-Saharan Africa. Some of these have yielded potent anti-sickling profiles. In the current work we seek to achieve a more extensive search of the African plant diversity with anti-sickling properties: for this we have adopted a hybrid computational-cum-experimental protocol that employed computer-aided drug design (CADD) means for identifying plants with at least one constituent capable of interacting with the sickle hemoglobin, followed by extractive procedures and anti-sickling experiments for validating the predictions. Over two thousand (or 2,000) African natural products, representing over 200 plant species, were first virtually screened against the crystal structure of the dimerized human sickle hemoglobin. The natural products with the best computed sickle hemoglobin interaction energetics were found to belong to five plant species including Catharanthus roseus, Rauvolfia vomitoria, Hoslundia opposita, Lantana camara and Euphorbia hirta. The leaves of these plants were each collected subsequently and subjected to standard processing and extraction procedures. Using both HbSS polymerization inhibition and sickling reversal tests significant reductions in polymerization of erythrocyte hemolysate of the HbSS genotype were observed with the methanolic extracts of the plants, as well as sickling reversal levels of up to 68.50 % (H. opposita) was observed.

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Hypoxia Enhanced Red Cell Adhesion in Vitro May Identify Patients at Risk for Vasculopathy

Blood ◽

10.1182/blood-2018-99-120207 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3672-3672

Author(s):

Charlotte Yuan ◽

Erina Quinn ◽

Sargam Kapoor ◽

Myeongseop Kim ◽

Erdem Kucukal ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Cell Disease ◽

Hypoxic Conditions ◽

Significant Difference ◽

History Of ◽

Male Subjects

Abstract Background: Priapism is a serious complication associated with Sickle Cell Disease (SCD) that may be a manifestation of underlying vasculopathy. The Centers for the Study of Complex Diseases of Childhood (CSCCD), comprising independent Comprehensive Sickle Cell Centers, demonstrated an association of priapism with hemolysis.1 Previously, we identified two groups of people with SCD based on red blood cell (RBC) adhesion under hypoxic conditions: those patients whose RBCs showed hypoxia-enhanced adhesion (HEA) and those whose did not (non-HEA).2 Patients with HEA had evidence for more hemolysis in vivo. Here, we aimed to examine (1) the association of HEA with hypoxia in vivo, and (2) RBC adhesion in normoxic and hypoxic conditions in male patients with or without a history of priapism. Methods: This retrospective study was conducted at the Adult Sickle Cell Disease Clinic at the University Hospitals Seidman Cancer Center, in Cleveland, OH between 2015 to 2018. Blood samples were obtained from 26 male subjects (29 samples, 25 HbSS and 1 HbSS HPFH). Adhesion experiments were performed as previously reported by passing surplus whole blood through LN-immobilized microchannels at physiological conditions under both normoxic and hypoxic conditions.2,3 Adherent RBCs were then quantified with microscope after a wash step. The median value was used for data analyses from multiple samples obtained from an individual. Chart review was conducted to examine results of hypoxia testing obtained in vivo as part of routine clinical care. Results: Male subjects with HbSS and a history of priapism had higher HEA in comparison to subjects without a history of priapism (3268 ± 5647 vs. 122 ± 1218, p=0.016). However, there was no significant difference between RBC adhesion of the two groups under normoxic conditions (529 ± 1528 vs. 402 ± 280). More male subjects with priapism had hypoxia in vivo (10 out of 14) than subjects without priapism (5 out of 12). Compared to male subjects with a history of priapism, those without a history of priapism had lower lactate dehydrogenase levels (474 ± 267 vs. 290 ± 215, p=0.008). Conclusions: Our data showed that subjects with a history of priapism had a higher HEA and tended to have more evidence for hypoxia in vivo than did subjects without a history of priapism. Further, male subjects with hypoxia in vivo had more HEA than did those without hypoxia in vivo (not shown). Hypoxia in vivo may cause increased RBC damage (reflected by HEA), hemolysis, nitric oxide depletion, and consequent vasculopathy, resulting in priapism. Hypoxia may be treatable, when identified in subjects with a history priapism in vivo or possibly with HEA in vitro. This could plausibly modify disease severity in some cases. References: Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Blood. 20015 Nov;106(9):3264-7. doi: 10.1182/blood-2005-04-1594 Kim M, Alapan Y, Adhikari A, Little JA, Gurkan Microcirculation. 2017 Jul;24(5). doi: 10.1111/micc.12374. Alapan Y, Kim C, Adhikari A, Gray KE, Gurkan-Cavusoglu E, Little JA, Gurkan Transl Res. 2016 Jul;173:74-91.e8. doi: 10.1016/j.trsl.2016.03.008. Epub 2016 Mar 19. Disclosures Little: NHLBI: Research Funding; PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding.

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Hypoxia-induced acute lung injury in murine models of sickle cell disease

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00288.2002 ◽

2004 ◽

Vol 286 (4) ◽

pp. L705-L714 ◽

Cited By ~ 57

Author(s):

Kirkwood A. Pritchard ◽

Jingsong Ou ◽

Zhijun Ou ◽

Yang Shi ◽

James P. Franciosi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Lung Injury ◽

Sickle Cell ◽

Globin Gene ◽

Heat Shock Protein 90 ◽

Cell Disease ◽

Vascular Congestion ◽

Nitrite Nitrate ◽

Endothelial Nitric Oxide

Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, the pathogenic mechanisms driving these events remain unclear. Using hypoxia to induce pulmonary injury, we investigated mechanisms by which sickle hemoglobin increases susceptibility to lung injury in a murine model of SCD, where mice either exclusively express the human α/sickle β-globin (hαβS) transgene (SCD mice) or are heterozygous for the normal murine β-globin gene and express the hαβStransgene (mβ+/-, hαβS+/-; heterozygote SCD mice). Under normoxia, lungs from the SCD mice contained higher levels of xanthine oxidase (XO), nitrotyrosine, and cGMP than controls (C57BL/6 mice). Hypoxia increased XO and nitrotyrosine and decreased cGMP content in the lungs of all mice. After hypoxia, vascular congestion was increased in lungs with a greater content of XO and nitrotyrosine. Under normoxia, the association of heat shock protein 90 (HSP90) with endothelial nitric oxide synthase (eNOS) in lungs of SCD and heterozygote SCD mice was decreased compared with the levels of association in lungs of controls. Hypoxia further decreased association of HSP90 with eNOS in lungs of SCD and heterozygote SCD mice, but not in the control lungs. Pretreatment of rat pulmonary microvascular endothelial cells in vitro with xanthine/XO decreased A-23187-stimulated nitrite + nitrate production and HSP90 interactions with eNOS. These data support the hypotheses that hypoxia increases XO release from ischemic tissues and that the local increase in XO-induced oxidative stress can then inhibit HSP90 interactions with eNOS, decreasing ·NO generation and predisposing the lung to vaso-occlusion.

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Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients

Frontiers in Immunology ◽

10.3389/fimmu.2020.535147 ◽

2020 ◽

Vol 11 ◽

Author(s):

Vanessa Araujo Gomes Santaterra ◽

Maiara Marx Luz Fiusa ◽

Bidossessi Wilfried Hounkpe ◽

Francine Chenou ◽

Wouitchekpo Vincent Tonasse ◽

...

Keyword(s):

Sickle Cell Disease ◽

Healthy Volunteers ◽

Sickle Cell ◽

Endothelial Barrier ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Experimental Conditions ◽

Cell Monolayers ◽

Junction Protein

Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions.

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Mineral Content and Antisickling Activity of Annona senegalensis, Alchornea cordifolia and Vigna unguiculata Used in the Management of Sickle Cell Disease in the Kwilu Province (Congo, DR)

International Blood Research & Reviews ◽

10.9734/ibrr/2020/v11i330131 ◽

2020 ◽

pp. 18-27

Author(s):

Jules M. Kitadi ◽

Clément L. Inkoto ◽

Emmanuel M. Lengbiye ◽

Damien S. T. Tshibangu ◽

Dorothée D. Tshilanda ◽

...

Keyword(s):

Sickle Cell Disease ◽

Mineral Composition ◽

Sickle Cell ◽

Mineral Elements ◽

Spectrometric Method ◽

Spectrometric Analysis ◽

Composition Analysis ◽

Cell Disease ◽

Republic Of The Congo

Aims: To determine the mineral composition of some plants (Annona senegalensis Pers., Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. and Vigna unguiculate (L.) Walp.) used in the management of sickle cell disease by traditional practitioners in Kwilu province and to evaluate their antisickling activity in vitro. Study Design: Plant collection in the Kwilu province, sample preparation, antisickling tests and fluorescence spectrometric analysis. Place and Duration of Study: This work was performed at the Faculty of Science, University of Kinshasa, Congo DR, from October 2016 to January 2018. Methodology: These three plants were harvested in the province of Kwilu in Democratic Republic of the Congo. The mineral composition analysis was carried out using the fluorescence spectrometric method while the in vitro antisickling activity was evaluate using Emmel and hemolysis tests. Results: Twenty three mineral elements were identified in each of these three plants: Potassium (K), Phosphorus (P), Calcium (Ca), Sodium (Na), Magnesium (Mg), Sulphur (S), Chlorine (Cl) and trace elements as: Aluminum (Al), Silicon (Si), Vanadium (V), Chromium (Cr), Manganese (Mn), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Selenium (Se), Brome (Br), Molybdenum (Mo), Tin (Sn), Iodine (I), Barium (Ba) and Lead (Pb). Annona senegalensis Pers., Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg. and Vigna unguiculate (L.) Walp. aqueous extracts showed the capacity to prevent the sickling and the hemolysis of red blood cells. Conclusion: The obtained results confirm the antisickling activity thus justifying the use of these plants in Traditional Medicine for the management of sickle cell disease. The presence of some mineral elements like Fe, Zn, Mg and Se are useful for sickle cell disease patients.

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Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

Journal of Personalized Medicine ◽

10.3390/jpm11090870 ◽

2021 ◽

Vol 11 (9) ◽

pp. 870

Author(s):

Pia Proske ◽

Laura Distelmaier ◽

Carmen Aramayo-Singelmann ◽

Nikolaos Koliastas ◽

Antonella Iannaccone ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Neonatal Outcomes ◽

University Hospital ◽

High Rate ◽

Successful Outcome ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

Tract Infections

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

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Survey of Medicinal Plants Used in the Management of Sickle Cell Disease by Traditional Medical Practitioners of Gbonyin Local Government Area of Ekiti State, Nigeria

Nigerian Journal of Natural Products and Medicine ◽

10.4314/njnpm.v19i0.8 ◽

2015 ◽

Vol 19 ◽

pp. 78-84

Author(s):

TI Famojuro ◽

JO Moody

Keyword(s):

Sickle Cell Disease ◽

Local Government ◽

Medicinal Plants ◽

Plant Species ◽

Sickle Cell ◽

Mangifera Indica ◽

Local Government Area ◽

Herbal Remedies ◽

Cell Disease ◽

Ethnobotanical Survey

Ethnobotanical survey was conducted on plants used traditionally for the management of sickle cell disease (SCD) in Gbonyin Local Government Area (LGA) of Ekiti State, South Western Nigeria. The study was conducted to document some of the medicinal plants used in the management of SCD with the aim of identifying possible drug leads from the phytomedicine of the area. A semi-structured questionnaire was used to obtain information on the use of herbal remedies for the management of SCD. A total of 32 respondents were interviewed in this study. twenty of them were males while twelve were females with the age range of 25 to 70 years. A total of 44 plant species belonging to 44 genera and 30 families were identified to be useful for the management of SCD. The most prominent among these plant families (genera) are Anacardiaceae (Anacardium occidentalis, Mangifera indica, Spondias mombin), Euphorbiaceae (Croton lobatus, Jatropha gossypifolia, Plukeneta conophora) and Fabaceae (Cajanus cajan, Pterocarpus osun, Cassia siamea) with three species each. Eighty percent (80%) of the 32 respondents interviewed said that their clients did not report any side effect and that the herbs were either collected from the forest (where available) or purchased from the herb markets. In all, the commonest plant species among the recipes given by the respondents according to their Use Mention Index (UMI) include: Elaeis guineense Jacq., Arecaceae (0.124); Khaya grandifoliola C.DC., Meliaceae (0.094); Carica papaya L., Caricaceae(0.094); Hymenocardia acida Tul., Phyllanthaceae (0.094); Mangifera indica L., Anacardiaceae (0.094); Parquetina nigrescens (Afzel.) Bullock, Asclepiadaceae (0.094) and Xylopia aethiopica (Dunal) A. Rich., Annonaceae (0.094).The main method of preparation is by decoction and in most cases, the preparation is taken orally twice to thrice daily. All the plants identified in this work have been used by most of the herbalists and adjudged to be efficacious in SCD management. The study concluded that the medicinal folklore of the Ekiti State LGA covered by this survey indicated high potential for drug discovery for the management of sickle cell disease.Keywords: Ethnobotany, Sickle Cell Disease, Traditional Medicine, Gbonyin LGA, Medicinal Plants

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In vivo survival studies of 51Cr-labeled methyl acetimidate treated erythrocytes in patients with sickle cell disease

Blood ◽

10.1182/blood.v56.6.1041.1041 ◽

1980 ◽

Vol 56 (6) ◽

pp. 1041-1047 ◽

Cited By ~ 5

Author(s):

TG Gabuzda ◽

TL Chao ◽

MR Berenfeld ◽

T Gelbart

Keyword(s):

Sickle Cell Disease ◽

Survival Time ◽

Sickle Cell ◽

Clinical Testing ◽

Cell Disease ◽

Show Evidence ◽

Survival Studies ◽

Circulating Antibody

Abstract Studies of the survival time of 51Cr labeled erythrocytes treated in vitro with methyl acetimidate (MAI) were conducted in 13 patients with sickle cell disease in order to assess the suitability of this antisickling agent for more extensive clinical testing. In comparison with previously measured control values (average t1/2 8.4 +/- 1.1 days a), the survival time of the treated erythrocytes in 10 of the patients who were not transfused was initially prolonged (average t1/2 24.4 +/- 4.6 days). However, 5 of the 13 patients studied developed circulating antibody against the MAI treated erythrocytes, markedly reducing the survival time of MAI treated erythrocytes in subsequent studies. Two patients, each challenged 3 times with infused MAI treated erythrocytes, failed to show evidence of antibody production, suggesting that not all subjects become immunized even after repeated exposure. In spite of many other promising properties of MAI as an antisickling agent of potential value, consideration of its use in further clinical testing must depend on successful avoidance of immunization in patients receiving infusions of treated erythrocytes.

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Placenta growth factor in sickle cell disease: association with hemolysis and inflammation

Blood ◽

10.1182/blood-2009-04-217950 ◽

2010 ◽

Vol 115 (10) ◽

pp. 2014-2020 ◽

Cited By ~ 35

Author(s):

Julia E. Brittain ◽

Ben Hulkower ◽

Susan K. Jones ◽

Dell Strayhorn ◽

Laura De Castro ◽

...

Keyword(s):

Growth Factor ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Predictive Accuracy ◽

Cross Sectional Study ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Placenta Growth Factor ◽

Cross Sectional

Abstract Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute chest syndrome. The observed correlation between PlGF and various measures of red cell destruction suggests that hemolysis, and the resultant erythropoietic response, results in the up-regulation of PlGF. Although relatively specific, PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular cell adhesion molecule, has low predictive accuracy for the presence of PHT. Prospective studies are required to conclusively define the contribution of PlGF to the pathogenesis of PHT and other hemolytic complications in SCD.

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