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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Review

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events

Authors: Tim Jang, Maria Poplawska, Emanuela Cimpeanu, George Mo, Dibyendu Dutta, Seah H. Lim

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Painful vaso-occlusive crisis (VOC) remains the most common reason for presenting to the Emergency Department and hospitalization in patients with sickle cell disease (SCD). Although two new agents have been approved by the Food and Drug Administration for treating SCD, they both target to reduce the frequency of VOC. Results from studies investigating various approaches to treat and shorten VOC have so far been generally disappointing. In this paper, we will summarize the complex pathophysiology and downstream events of VOC and discuss the likely reasons for the disappointing results using monotherapy. We will put forward the rationale for exploring some of the currently available agents to either protect erythrocytes un-involved in the hemoglobin polymerization process from sickling induced by the secondary events, or a multipronged combination approach that targets the complex downstream pathways of VOC.
Literature
1.
2.
Steiner CA, Miller JL. Sickle Cell Disease Patients in U.S. Hospitals, 2004: Statistical Brief #21. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville (MD); 2006.
3.
Brousseau DC, Owens PL, Mosso AL, Panepinto JA, Steiner CA. Acute care utilization and rehospitalizations for sickle cell disease. JAMA. 2010;303:1288–94.CrossRefPubMed
4.
Brousseau DC, Steiner CA, Owens P, Mosso A, Panepinto JA. Emergency department treat-and-release visits for sickle cell disease: a sign of acute events to come. Blood. 2011;118:169.CrossRef
5.
Ballas SK, Smith ED. Red blood cell changes during the evolution of the sickle cell painful crisis. Blood. 1992;79:2154–63.CrossRefPubMed
6.
Ballas SK. The sickle cell painful crisis in adults: phases and objective signs. Hemoglobin. 1995;19:323–33.CrossRefPubMed
7.
Dutta D, Aujla A, Knoll BM, Lim SH. Intestinal pathophysiological and microbial changes in sickle cell disease: potential targets for therapeutic intervention. Br J Haematol. 2020;188:488–93.CrossRefPubMed
8.
Fingar KR, Owens PL, Reid LD, Mistry KB, and Barrett ML. Characteristics of inpatient hospital stays involving sickle cell disease, 2000–2016. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb. 2019 Sep 3.
9.
Jang T, Mo G, Stewart C, Egini O, Dutta D, Muthu J, Lim SH. Antibiotic use in adults during sickle cell vaso-occlusive crisis: is it time for a controlled trial? Br J Haematol. 2021;193:1281–3.CrossRefPubMed
10.
Anyaegbu CC, Okpala IE, Akren’Ova YA, Salimonu LS. Peripheral blood neutrophil count and candidacidal activity correlate with the clinical severity of sickle cell anaemia (SCA). Eur J Haematol. 1998;60:267–8.CrossRefPubMed
11.
12.
Lard LR, Mul FP, de Haas M, Roos D, Duits AJ. Neutrophil activation in sickle cell disease. J Leukoc Biol. 1999;66:411–5.CrossRefPubMed
13.
Lum AF, Wun T, Staunton D, Simon SI. Inflammatory potential of neutrophils detected in sickle cell disease. Am J Hematol. 2004;76:126–33.CrossRefPubMed
14.
Belcher JD, Marker PH, Weber JP, Hebbel RP, Vercellotti GM. Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion. Blood. 2000;96:2451–9.CrossRefPubMed
15.
Sparkenbaugh E, Pawlinski R. Interplay between coagulation and vascular inflammation in sickle cell disease. Br J Haematol. 2013;162:3–14.CrossRefPubMed
16.
Browne P, Shalev O, Hebbel RP. The molecular pathobiology of cell membrane iron: the sickle red cell as a model. Free Radic Biol Med. 1998;24:1040–8.CrossRefPubMed
17.
Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci USA. 2002;99:3047–51.PubMedCentralCrossRefPubMed
18.
Merle NS, Grunenwald A, Rajaratnam H, Gnemmi V, Frimat M, Figueres ML, Knockaert S, Bouzekri S, Charue D, Noe R, Robe-Rybkine T, Le-Hoang M, Brinkman N, Gentinetta T, Edler M, Petrillo S, Tolosano E, Miescher S, Le Jeune S, Houillier P, Chauvet S, Rabant M, Dimitrov JD, Fremeaux-Bacchi V, Blanc-Brude OP, Roumenina LT. Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles. JCI Insight. 2018;3:e96910.PubMedCentralCrossRef
19.
Pradhan P, Vijayan V, Gueler F, Immenschuh S. Interplay of heme with macrophages in homeostasis and inflammation. Int J Mol Sci. 2020;21:740.PubMedCentralCrossRef
20.
Chen G, Zhang D, Fuchs TA, Manwani D, Wagner DD, Frenette PS. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood. 2014;123:3818–27.PubMedCentralCrossRefPubMed
21.
Schaer DJ, Buehler PW. Cell-free hemoglobin and its scavenger proteins: new disease models leading the way to targeted therapies. Cold Spring Harb Perspect Med. 2013;3:013433.CrossRef
22.
Nagano S, Otsuka T, Niiro H, Yamaoka K, Arinobu Y, Ogami E, Akahoshi M, Inoue Y, Miyake K, Nakashima H, Niho Y, Harada M. Molecular mechanisms of lipopolysaccharide-induced cyclooxygenase-2 expression in human neutrophils: involvement of the mitogen-activated protein kinase pathway and regulation by anti-inflammatory cytokines. Intern Immunol. 2002;14:733–40.CrossRef
23.
Bryant CE, Spring DR, Gangloff M, Gay NJ. The molecular basis of the host response to lipopolysaccharide. Nat Rev Microbiol. 2010;8:8–14.CrossRefPubMed
24.
Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, Burk RD, Kunisaki Y, Jang JE, Scheiermann C, Merad M, Frenette PS. Neutrophil ageing is regulated by the microbiome. Nature. 2015;525:528–32.PubMedCentralCrossRefPubMed
25.
Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP. Investigators of the phase 3 trial of l-glutamine in sickle cell disease. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018;379:226–35.CrossRefPubMed
26.
Lim SH, Morris A, Li K, Fitch AC, Fast L, Goldberg L, Quesenberry M, Sprinz P, Methé B. Intestinal microbiome analysis revealed dysbiosis in sickle cell disease. Am J Hematol. 2018;93:E91–3.CrossRefPubMed
27.
28.
Dutta D, Li K, Methe B, Lim SH. Rifaximin on intestinally-related pathologic changes in sickle cell disease. Am J Hematol. 2020;95:E83–6.CrossRefPubMed
29.
30.
Hidalgo A, Chang J, Jang JE, Peired AJ, Chiang EY, Frenette PS. Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nat Med. 2009;15:384–91.PubMedCentralCrossRefPubMed
31.
Wallace KL, Marshall MA, Ramos SI, Lannigan JA, Field JJ, Strieter RM, Linden J. NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-gamma and CXCR3 chemokines. Blood. 2009;114:667–76.PubMedCentralCrossRefPubMed
32.
Sparkenbaugh E, Pawlinski R. Prothrombotic aspects of sickle cell disease. J Thromb Haemost. 2017;15:1307–16.CrossRefPubMed
33.
Mitchell MJ, Kawchak DA, Stark LJ, Zemel BS, Ohene-Frempong K, Stallings VA. Brief report: parent perspectives of nutritional status and mealtime behaviors in children with sickle cell disease. J Pediatr Psychol. 2004;29:315–20.CrossRefPubMed
34.
35.
Liu SC, Zhai S, Palek J. Detection of hemin release during hemoglobin S denaturation. Blood. 1988;71:1755–8.CrossRefPubMed
36.
Carvalho MOS, Rocha LC, Reis JHO, de Araújo Santos T, do Nascimento VML, Carvalho MB, Luz NF, de Matos Borges V, Goncalves MS. Heme concentration as a biomarker of sickle cell disease severity: its role in steady-state and in crisis patients. Blood. 2015;126:975.CrossRef
37.
Silva M, Videira PA, Sackstein R. E-Selectin ligands in the human mononuclear phagocyte system: implications for infection, inflammation, and immunotherapy. Front Immunol. 2017;8:1878.CrossRefPubMed
38.
Schimmel M, Nur E, Biemond BJ, van Mierlo GJ, Solati S, Brandjes DP, Otten HM, Schnog JJ, Zeerleder S. Nucleosomes and neutrophil activation in sickle cell disease painful crisis. Haematologica. 2013;98:1797–803.PubMedCentralCrossRefPubMed
39.
Kruger P, Saffarzadeh M, Weber ANR, Rieber N, Radsak M, von Bernuth H, Benarafa C, Roos D, Skokowa J, Hartl D. Neutrophils: between host defence, immune modulation, and tissue injury. PLoS Pathog. 2015;11:e1004651.PubMedCentralCrossRefPubMed
40.
Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA. 2010;107:15880–5.PubMedCentralCrossRefPubMed
41.
Huang YM, Wang H, Wang C, Chen M, Zhao MH. Promotion of hypercoagulability in antineutrophil cytoplasmic antibody-associated vasculitis by C5a-induced tissue factor-expressing microparticles and neutrophil extracellular traps. Arthritis Rheumatol. 2015;67:2780–90.CrossRefPubMed
42.
Cameron SJ, Mix DS, Ture SK, Schmidt RA, Mohan A, Pariser D, Stoner MC, Shah P, Chen L, Zhang H, Field DJ, Modjeski KL, Toth S, Morrell CN. Hypoxia and ischemia promote a maladaptive platelet phenotype. Arterioscler Thromb Vasc Biol. 2018;38:1594–606.PubMedCentralCrossRefPubMed
43.
Riboldi E, Porta C, Morlacchi S, Viola A, Mantovani A, Sica A. Hypoxia-mediated regulation of macrophage functions in pathophysiology. Int Immunol. 2013;25:67–75.CrossRefPubMed
44.
Hoenderdos K, Lodge KM, Hirst RA, Chen C, Palazzo SGC, Emerenciana A, Summers C, Angyal A, Porter L, Juss JK, O’Callaghan C, Chilvers ER, Condliffe AM. Hypoxia upregulates neutrophil degranulation and potential for tissue injury. Thorax. 2016;71:1030–8.CrossRefPubMed
45.
Zennadi R, Moeller BJ, Whalen EJ, Batchvarova M, Xu K, Shan S, Delahunty M, Dewhirst MW, Telen MJ. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007;110:2708–17.PubMedCentralCrossRefPubMed
46.
Porter LS, Gil KM, Carson JW, Anthony KK, Ready J. The role of stress and mood in sickle cell disease pain: an analysis of daily diary data. J Health Psychol. 2000;5:53–63.CrossRefPubMed
47.
48.
Charache S, Barton FB, Moore RD, Terrin ML, Steinberg MH, Dover GJ, Ballas SK, McMahon RP, Castro O, Orringer EP. Hydroxyurea and sickle cell anemia Clinical utility of a myelosuppressive “switching” agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore). 1996;75:300–26.CrossRef
49.
Saunthararajah Y, Hillery CA, Lavelle D, Molokie R, Dorn L, Bressler L, Gavazova S, Chen Y-H, Hoffman R, DeSimone J. Effects of 5-aza-2-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood. 2003;102:3865–70.CrossRefPubMed
50.
McArthur JG, Svenstrup N, Chen C, Fricot A, Carvalho C, Nguyen J, Nguyen P, Parachikova A, Abdulla F, Vercellotti GM, Hermine O, Edwards D, Ribeil JA, Belcher JD, Maciel TT. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020;105:623–31.PubMedCentralCrossRefPubMed
51.
Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381:509–19.CrossRefPubMed
52.
Hutchaleelaha A, Patel M, Washington C, Siu V, Allen E, Oksenberg D, Gretler DD, Mant T, Lehrer-Graiwer J. Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Br J Clin Pharmacol. 2019;85:1290–302.PubMedCentralCrossRefPubMed
53.
Nur E, Brandjes DP, Teerlink T, Otten HM, Oude Elferink RP, Muskiet F, Evers LM, ten Cate H, Biemond BJ, Duits AJ, Schnog JJ. N-acetylcysteine reduces oxidative stress in sickle cell patients. Ann Hematol. 2012;91:1097–105.PubMedCentralCrossRefPubMed
54.
Sins JWR, Fijnvandraat K, Rijneveld AW, Boom MB, Kerkhoffs JH, van Meurs AH, de Groot MR, Heijboer H, Dresse MF, Lê PQ, Hermans P, Vanderfaeillie A, Van Den Neste EW, Benghiat FS, Kesse-Adu R, Delannoy A, Efira A, Azerad MA, de Borgie CA, Biemond BJ. Effect of N-acetylcysteine on pain in daily life in patients with sickle cell disease: a randomised clinical trial. Br J Haematol. 2018;182:444–8.CrossRefPubMed
55.
56.
Kharalkar SS, Joshi GS, Musayev FN, Fornabaio M, Abraham DJ, Safo MK. Identification of novel allosteric regulators of human-erythrocyte pyruvate kinase. Chem Biodivers. 2007;4:2603–17.CrossRefPubMed
57.
Rab MAE, Bos J, van Oirschot BA, van Straaten S, Kosinski PA, Chubukov V, Kim H, Mangus H, Schutgens REG, Pasterkamp G, Dang L, Kung C, van Beers EJ, van Wijk R. Decreased activity and stability of pyruvate kinase in sickle cell disease: a novel target for mitapivat therapy. Blood. 2021;137:2997–3001.PubMedCentralCrossRefPubMed
58.
59.
Penkert RR, Hurwitz JL, Thomas P, Rosch J, Dowdy J, Sun Y, Tang L, Hankins JS. Inflammatory molecule reduction with hydroxyurea therapy in children with sickle cell anemia. Haematologica. 2018;103:e50–4.PubMedCentralCrossRefPubMed
60.
Lanaro C, Franco-Penteado CF, Albuqueque DM, Saad ST, Conran N, Costa FF. Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy. J Leukoc Biol. 2009;85:235–42.CrossRefPubMed
61.
Beiter JL Jr, Simon HK, Chambliss CR, Adamkiewicz T, Sullivan K. Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness. Arch Pediatr Adolesc Med. 2001;155:496–500.CrossRefPubMed
62.
Griffin TC, McIntire D, Buchanan GR. High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease. N Engl J Med. 1994;330:733–7.CrossRefPubMed
63.
Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376:429–39.CrossRefPubMed
64.
Telen MJ, Wun T, McCavit TL, De Castro LM, Krishnamurti L, Lanzkron S, Hsu LL, Smith WR, Rhee S, Magnani JL, Thackray H. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood. 2015;125:2656–64.PubMedCentralCrossRefPubMed
65.
Field JJ, Majerus E, Gordeuk VR, Gowhari M, Hoppe C, Heeney MM, Achebe M, George A, Chu H, Sheehan B, Puligandla M, Neuberg D, Lin G, Linden J, Nathan DG. Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease. Blood Adv. 2017;1:1645–9.PubMedCentralCrossRefPubMed
66.
Turhan A, Jenab P, Bruhns P, Ravetch JV, Coller BS, Frenette PS. Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes. Blood. 2004;103:2397–400.CrossRefPubMed
67.
Chang J, Shi PA, Chiang EY, Frenette PS. Intravenous immunoglobulins reverse acute vaso-occlusive crises in sickle cell mice through rapid inhibition of neutrophil adhesion. Blood. 2008;111:915–23.PubMedCentralCrossRefPubMed
68.
Manwani D, Xu C, Lee SK, Amatuni G, Cohen HW, Carullo V, Morrone K, Davila J, Shi PA, Ireland K, Keenan J, Frenette PS. Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: lessons learned from the midpoint analysis. Complement Ther Med. 2020;52:102481.CrossRefPubMed
69.
Wang B, Wu G, Zhou Z, Dai Z, Sun Y, Ji Y, Li W, Wang W, Liu C, Han F, Wu Z. Glutamine and intestinal barrier function. Amino Acids. 2015;47:2143–54.CrossRefPubMed
70.
De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012;5:437–44.PubMedCentralCrossRefPubMed
71.
Payne J, Aban I, Hilliard LM, Madison J, Bemrich-Stolz C, Howard TH, Brandow A, Waite E, Lebensburger JD. Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis. Pediatr Blood Cancer. 2018;65:e27420.PubMedCentralCrossRefPubMed
72.
Waugh WH, Daeschner CW 3rd, Files BA, McConnell ME, Strandjord SE. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. J Natl Med Assoc. 2001;93:363–71.PubMedCentralPubMed
73.
Jaja SI, Ogungbemi SO, Kehinde MO, Anigbogu CN. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia. Pathophysiology. 2016;23:81–5.CrossRefPubMed
74.
Gladwin MT, Kato GJ, Weiner D, Onyekwere OC, Dampier C, Hsu L, Hagar RW, Howard T, Nuss R, Okam MM, Tremonti CK, Berman B, Villella A, Krishnamurti L, Lanzkron S, Castro O, Gordeuk VR, Coles WA, Peters-Lawrence M, Nichols J, Hall MK, Hildesheim M, Blackwelder WC, Baldassarre J, Casella JF. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011;305:893–902.PubMedCentralCrossRefPubMed
75.
Aboursheid T, Albaroudi O, Alahdab F. Inhaled nitric oxide for treating pain crises in people with sickle cell disease. Cochrane Database Syst Rev. 2019;11(10):CD011808.
76.
77.
78.
Wun T, Soulieres D, Frelinger AL, Krishnamurti L, Novelli EM, Kutlar A, Ataga KI, Knupp CL, McMahon LE, Strouse JJ, Zhou C, Heath LE, Nwachuku CE, Jakubowski JA, Riesmeyer JS, Winters KJ. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease. J Hematol Oncol. 2013;6:17.PubMedCentralCrossRefPubMed
79.
Lee SP, Ataga KI, Zayed M, Manganello JM, Orringer EP, Phillips DR, Parise LV. Phase I study of eptifibatide in patients with sickle cell anaemia. Br J Haematol. 2007;139:612–20.CrossRefPubMed
80.
Qari MH, Aljaouni SK, Alardawi MS, Fatani H, Alsayes FM, Zografos P, Alsaigh M, Alalfi A, Alamin M, Gadi A, Mousa SA. Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial. Thromb Haemost. 2007;98:392–6.CrossRefPubMed
81.
Biemond BJ, Tombak A, Kilinc Y, Al-Khabori M, Abboud M, Nafea M, Inati A, Wali Y, Kristensen J, Kowalski J, Donnelly E, Ohd J. Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2021;8:e334–43.CrossRefPubMed
Metadata
Title
Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events
Authors
Tim Jang
Maria Poplawska
Emanuela Cimpeanu
George Mo
Dibyendu Dutta
Seah H. Lim
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-03074-z

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