Microparticle profile during painful crisis and steady state in children with sickle cell anemia
Year 2024,
Volume: 49 Issue: 3, 592 - 599, 30.09.2024
Anıl Atmış
,
Hatice İlgen Şaşmaz
,
İlknur Kozanoğlu
,
Bahriye Atmış
,
Barbaros Karagün
,
İbrahım Boğa
,
Bülent Antmen
,
Yurdanur Kılınç
Abstract
Purpose: Sickle cell anemia is a disease characterized by hemolytic anemia, hypercoagulopathy, and painful crises. Microparticles are 0.1-1 µm sized membrane particles derived during cellular activation or apoptotic phases of the cell cycle. In this study, we investigated the role of microparticles on clinical state and prognosis during painful crisis and steady state in children with sickle cell anemia.
Materials and Methods: Patients with sickle cell anemia who were followed up in Çukurova University Pediatric Hematology Department and presented with a painful crisis were included in the study. Children without any systemic disease were included in the control group. Total microparticle levels, erythrocyte (CD235a), endothelial (CD106), and monocyte (CD14) microparticle levels, and tissue factor expressing (CD142) microparticle levels were analyzed.
Results: A total of 29 patients with sickle cell anemia who presented with a painful crisis were included in the study. In addition, blood samples were collected from 26 of these patients in a steady state. Blood samples were obtained from 18 healthy children as the control group. Total microparticle levels were significantly higher in sickle cell anemia patients in painful crises than in control group. Erythrocyte and monocyte microparticle levels were significantly higher in patients with a painful crisis than in a steady state. Endothelial and tissue factor expressing microparticle levels were higher during a painful crisis than steady state, although not at statistically significant levels. Microparticle levels were lower in patients with hydroxyurea treatment than those without, although it was not a statistically significant difference.
Conclusion: Total microparticles as well as erythrocyte and monocyte microparticles were high in sickle cell anemia patients during a painful crisis. Studies involving larger numbers of patients are needed to better understand the role of microparticles in the pathophysiology of sickle cell anemia and their association with painful crises.
References
- Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med.1910;6:517.
- Hebbel RP. Pathobiology of sickle cell disease. In: Hematology Basic Principles and Practice, 5th ed. (Eds Hoffman R, Benz EJ, Shattil SJ):565-76. Philadelphia, Elsevier Churchill Livingstone, 2009.
- Ingram VM. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature. 1957;180:326-8.
- Shet AS, Aras O, Gupta K, Hass MJ, Rausch DJ, Saba N et al. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood. 2003;102:2678-83.
- Burnier L, Fontana P, Kwak BR, Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost. 2009;101:439-51.
- Cognasse F, Hamzeh-Cognasse H, Laradi S, Chou ML, Seghatchian J, Burnouf T et al. The role of microparticles in inflammation and transfusion: A concise review. Transfus Apher Sci. 2015;53:159-67.
- Nieuwland R, Berckmans RJ, McGregor S, Böing AN, Romijn FP, Westendorp RG et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood. 2000;95:930-5.
- Sabatier F, Roux V, Anfosso F, Camoin L, Sampol J, Dignat-George F. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood. 2002;99:3962-70.
- van Beers EJ, Schaap MC, Berckmans RJ, Nieuwland R, Sturk A, van Doormaal FF et al. Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease. Haematologica. 2009;94:1513-9.
- Tantawy AA, Adly AA, Ismail EA, Habeeb NM, Farouk A. Circulating platelet and erythrocyte microparticles in young children and adolescents with sickle cell disease: Relation to cardiovascular complications. Platelets. 2013;24:605-14.
- Nébor D, Romana M, Santiago R, Vachiery N, Picot J, Broquere C et al. Fetal hemoglobin and hydroxycarbamide moduate both plasma concentration and cellular origin of circulating microparticles in sickle cell anemia children. Haematologica. 2013;98:862-7.
- Marsh A, Schiffelers R, Kuypers F, Larkin S, Gildengorin G, van Solinge W, Hoppe C. Microparticles as biomarkers of osteonecrosis of the hip in sickle cell disease. Br J Haematol. 2015;168:135-8.
- Kasar M, Boğa C, Yeral M, Asma S, Kozanoglu I, Ozdogu H. Clinical significance of circulating blood and endothelial cell microparticles in sickle-cell disease. J Thromb Thrombolysis. 2014;38:167-75.
- Boulassel MR, Al-Rubkhi K, Al-Qasabi J, El-Ghamry I, Khan H, Panjwani V et al. Impact of splenectomy on circulating microparticles in patients with sickle cell anemia. Int J Lab Hematol. 2024;46:141-7.
- Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med. 1997;337:1584-90.
- Solovey A, Gui L, Key NS, Hebbel RP. Tissue factor expression by endothelial cells in sickle cell anemia. J Clin Invest. 1998;101:1899-904.
- Brunetta DM, De Santis GC, Silva-Pinto AC, Oliveira de Oliveira LC, Covas DT. Hydroxyurea increases plasma concentrations of microparticles and reduces coagulation activation and fibrinolysis in patients with sickle cell anemia. Acta Haematol. 2015;133:287-94.
- Piccin A, Murphy C, Eakins E, Kunde J, Corvetta D, Di Pierro A et al. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia. J Extracell Vesicles. 2015;4:28414.
- Westerman M, Pizzey A, Hirschman J, Cerino M, Weil-Weiner Y, Ramotar P et al. Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy. Br J Haematol. 2008;142:126-35.
- Zahran AM, Elsayh KI, Saad K, Embaby MM, Youssef MAM, Abdel-Raheem YF et al. Circulating microparticles in children with sickle cell anemia in a tertiary center in upper Egypt. Clin Appl Thromb Hemost. 2019;25:1076029619828839.
- Garnier Y, Ferdinand S, Etienne-Julan M, Elana G, Petras M, Doumdo L et al. Differences of microparticle patterns between sickle cell anemia and hemoglobin SC patients. PLoS One. 2017;12:e0177397.
- Falanga A, Trinchero A. Circulating microparticles in children with sickle cell anemia: a heterogeneous procoagulant storm directed by hemolysis and fetal hemoglobin. Haematologica. 2013;98:995-7.
- Garnier Y, Ferdinand S, Garnier M, Cita KC, Hierso R, Claes A et al. Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties. Blood. 2020;136:247-56.
Orak hücreli anemili çocuklarda ağrılı kriz ve kriz dışı dönemde mikropartikül profili
Year 2024,
Volume: 49 Issue: 3, 592 - 599, 30.09.2024
Anıl Atmış
,
Hatice İlgen Şaşmaz
,
İlknur Kozanoğlu
,
Bahriye Atmış
,
Barbaros Karagün
,
İbrahım Boğa
,
Bülent Antmen
,
Yurdanur Kılınç
Abstract
Amaç: Orak hücreli anemi, hemolitik anemi, hiperkoagülopati ve ağrılı krizlerle karakterize bir hastalıktır. Mikropartiküller, hücre döngüsünün hücresel aktivasyonu veya apoptotik fazları sırasında hücrelerden dökülen 0.1-1 µm boyutlarında membran parçacıklarıdır. Bu çalışmada, orak hücreli anemisi olan çocuklarda kriz ve kriz dışı durumda mikropartiküllerin klinik durum ve prognoz üzerindeki rolünü araştırdık.
Gereç ve Yöntem: Çukurova Üniversitesi Pediatrik Hematoloji Bölümünde takipli ve ağrılı kriz ile başvuran orak hücreli anemi tanılı hastalar çalışmaya dahil edildi. Herhangi bir sistemik hastalığı olmayan çocuklar kontrol grubuna dahil edildi. Hastaların ve kontrol grubunun total mikropartikül düzeyleri, eritrosit (CD235a), endotel (CD106), monosit (CD14) mikropartikül düzeyleri ve doku faktörü eksprese eden (CD142) mikropartikül düzeyleri analiz edildi.
Bulgular: Orak hücreli anemi tanısı olan ve ağrılı kriz ile başvuran toplam 29 hasta çalışmaya dahil edildi. Ayrıca bu hastaların 26'sının ağrılı kriz dışı durumda kan örnekleri alındı. Kontrol grubu olan 18 sağlıklı çocuktan kan örnekleri alındı. Total mikropartikül düzeyleri ağrılı krizdeki orak hücreli anemi hastalarında kontrol grubuna göre anlamlı olarak yüksek bulundu. Eritrosit ve monosit mikropartikül düzeyleri ağrılı krizde kriz dışı döneme göre anlamlı olarak yüksekti. Endotelyal ve doku faktörü eksprese eden mikropartikül seviyeleri, istatistiksel olarak anlamlı olmasa da ağrılı krizde kriz dışı döneme göre daha yüksekti. Mikropartikül seviyeleri hidroksiüre tedavisi alan hastalarda almayanlara göre daha düşüktü, ancak istatistiksel olarak anlamlı bulunmadı.
Sonuç: Orak hücreli anemi hastalarında ağrılı kriz sırasında total mikropartiküller, eritrosit ve monosit mikropartikülleri yüksek bulunmuştur. Mikropartiküllerin orak hücreli aneminin patofizyolojisindeki rolünü ve ağrılı krizlerle ilişkisini daha iyi anlamak için daha fazla sayıda hastayı içeren çalışmalara ihtiyaç vardır
References
- Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med.1910;6:517.
- Hebbel RP. Pathobiology of sickle cell disease. In: Hematology Basic Principles and Practice, 5th ed. (Eds Hoffman R, Benz EJ, Shattil SJ):565-76. Philadelphia, Elsevier Churchill Livingstone, 2009.
- Ingram VM. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature. 1957;180:326-8.
- Shet AS, Aras O, Gupta K, Hass MJ, Rausch DJ, Saba N et al. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood. 2003;102:2678-83.
- Burnier L, Fontana P, Kwak BR, Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost. 2009;101:439-51.
- Cognasse F, Hamzeh-Cognasse H, Laradi S, Chou ML, Seghatchian J, Burnouf T et al. The role of microparticles in inflammation and transfusion: A concise review. Transfus Apher Sci. 2015;53:159-67.
- Nieuwland R, Berckmans RJ, McGregor S, Böing AN, Romijn FP, Westendorp RG et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood. 2000;95:930-5.
- Sabatier F, Roux V, Anfosso F, Camoin L, Sampol J, Dignat-George F. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood. 2002;99:3962-70.
- van Beers EJ, Schaap MC, Berckmans RJ, Nieuwland R, Sturk A, van Doormaal FF et al. Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease. Haematologica. 2009;94:1513-9.
- Tantawy AA, Adly AA, Ismail EA, Habeeb NM, Farouk A. Circulating platelet and erythrocyte microparticles in young children and adolescents with sickle cell disease: Relation to cardiovascular complications. Platelets. 2013;24:605-14.
- Nébor D, Romana M, Santiago R, Vachiery N, Picot J, Broquere C et al. Fetal hemoglobin and hydroxycarbamide moduate both plasma concentration and cellular origin of circulating microparticles in sickle cell anemia children. Haematologica. 2013;98:862-7.
- Marsh A, Schiffelers R, Kuypers F, Larkin S, Gildengorin G, van Solinge W, Hoppe C. Microparticles as biomarkers of osteonecrosis of the hip in sickle cell disease. Br J Haematol. 2015;168:135-8.
- Kasar M, Boğa C, Yeral M, Asma S, Kozanoglu I, Ozdogu H. Clinical significance of circulating blood and endothelial cell microparticles in sickle-cell disease. J Thromb Thrombolysis. 2014;38:167-75.
- Boulassel MR, Al-Rubkhi K, Al-Qasabi J, El-Ghamry I, Khan H, Panjwani V et al. Impact of splenectomy on circulating microparticles in patients with sickle cell anemia. Int J Lab Hematol. 2024;46:141-7.
- Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med. 1997;337:1584-90.
- Solovey A, Gui L, Key NS, Hebbel RP. Tissue factor expression by endothelial cells in sickle cell anemia. J Clin Invest. 1998;101:1899-904.
- Brunetta DM, De Santis GC, Silva-Pinto AC, Oliveira de Oliveira LC, Covas DT. Hydroxyurea increases plasma concentrations of microparticles and reduces coagulation activation and fibrinolysis in patients with sickle cell anemia. Acta Haematol. 2015;133:287-94.
- Piccin A, Murphy C, Eakins E, Kunde J, Corvetta D, Di Pierro A et al. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia. J Extracell Vesicles. 2015;4:28414.
- Westerman M, Pizzey A, Hirschman J, Cerino M, Weil-Weiner Y, Ramotar P et al. Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy. Br J Haematol. 2008;142:126-35.
- Zahran AM, Elsayh KI, Saad K, Embaby MM, Youssef MAM, Abdel-Raheem YF et al. Circulating microparticles in children with sickle cell anemia in a tertiary center in upper Egypt. Clin Appl Thromb Hemost. 2019;25:1076029619828839.
- Garnier Y, Ferdinand S, Etienne-Julan M, Elana G, Petras M, Doumdo L et al. Differences of microparticle patterns between sickle cell anemia and hemoglobin SC patients. PLoS One. 2017;12:e0177397.
- Falanga A, Trinchero A. Circulating microparticles in children with sickle cell anemia: a heterogeneous procoagulant storm directed by hemolysis and fetal hemoglobin. Haematologica. 2013;98:995-7.
- Garnier Y, Ferdinand S, Garnier M, Cita KC, Hierso R, Claes A et al. Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties. Blood. 2020;136:247-56.