Hypercoagulability in Sickle Cell Disease: New Approaches to an Old Problem

Hematology. American Society of Hematology. Education Program - Tập 2007 Số 1 - Trang 91-96 - 2007
Kenneth I. Ataga1, Nigel S. Key
1Division of Hematology/Oncology, University of North Carolina at Chapel Hill, CB# 7305, 3009 Old Clinic Bldg, Chapel Hill, NC 27599-7305, USA. [email protected]

Tóm tắt

AbstractPatients with sickle cell disease (SCD) exhibit high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis steady state. In addition, platelets and other cellular elements are chronically activated in the non-crisis state. Despite an abundance of evidence for coagulation and platelet activation, it remains uncertain whether these changes contribute to the pathophysiology of SCD or are, rather, simple epiphenomena. With the occurrence of macrovascular thrombotic complications in SCD, as well as the recognition that soluble CD40 ligand is biologically active in SCD, coagulation and platelet activation may indeed play a role in SCD pathophysiology. Defining a role for hypercoagulability in SCD requires further understanding of its pathogenesis. Furthermore, the conduct of well-controlled clinical trials using anticoagulants and antiplatelet agents and using a variety of clinical endpoints is warranted.

Từ khóa


Tài liệu tham khảo

Prengler M, Pavlakis SG, Prohovnik I, Adams RJ. Sickle cell disease: the neurological complications. Ann Neurol. 2002;51:543–552.

Adedeji MO, Cespedes J, Allen K, Subramony C, Hughson MD. Pulmonary thrombotic arteriopathy in patients with sickle cell disease. Arch Pathol Lab Med. 2001;125:1436–1441.

Stein PD, Beemath A, Meyers FA, Skaf E, Olson RE. Deep venous thrombosis and pulmonary embolism in hospitalized patients with sickle cell disease. Am J Med. 2006;119:897.e7–e11.

James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors and mortality. Am J Obst Gynecol. 2006;194:1311–1315.

Austin H, Key NS, Benson JM, et al. Sickle-cell trait and the risk of venous thromboembolism among African Americans. Blood. 2007;110:908–912.

Francis RB. Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role in vascular occlusion. Blood Coagul Fibrinolysis. 1991;2:341–353.

Kuypers F, Lewis RA, Ernst JD, et al. Detection of altered membrane phospholipid asymmetry in subpopulations of human red blood cells using fluorescently labeled annexin V. Blood. 1996;87:1179–1187.

Wood BL, Gibson DF, Tait JF. Increased erythrocyte phosphatidylserine exposure in sickle cell disease: flow-cytometric measurement and clinical associations. Blood. 1996;88:1873–1880.

Devaux PF, Zachowski A. Maintenance and consequences of membrane phospholipid asymmetry. Chem Phys Lipids. 1994;73:107–120.

Zwaal RFA, Schroit AJ. Pathophysiologic implications of membrane phospholipids asymmetry in blood cells: a review. Blood. 1997;89:1121–1132.

Allan D, Limbrick AR, Thomas P, Westerman MP. Release of spectrin-free spicules on reoxygenation of sickled erythrocytes. Nature. 1982;295:612–613.

De Jong K, Gerdwerth D, Kuypers FA. Oxidative damage does not alter membrane phospholipid asymmetry in human erythrocytes. Biochemistry. 1997;36:6768–6776.

De Jong K, Kuypers FA. Sulphydryl modifications alter scramblase activity in murine sickle cell disease. Br J Haematol. 2006;133:427–432.

Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148:2207–2216.

Setty BN, Kulkani S, Stuart MJ. Role of erythrocyte phosphatidylserine in sickle red cell-endothelial adhesion. Blood. 2002;99:1564–1571.

Setty BN, Rao AK, Stuart MJ. Thrombophilia in sickle cell disease: the red cell connection. Blood. 2001;98:3228–3233.

Setty BN, Kulkani S, Rao AK, Stuart MJ. Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation. Blood. 2000; 96:1119–24.

Styles L, de Jong K, Vichinsky E, Lubin B, Adams R, Kuypers F. Increased RBC phosphatidylserine exposure in sickle cell disease patients at risk for stroke by transcranial Doppler screening [abstract]. Blood. 1997;90:604a.

Setty BNY, Zhang J, Kulkarni S, et al. Pathologic implications of type-II phosphatidyserine (PS)-positive erythrocytes in patients with sickle cell disease. 29th Annual Meeting of the National Sickle Cell Disease Program: Memphis, TN; April 8–12, 2006: Abstract 53.

Westerman MP, Green D, Gilman-Sachs, et al. Coagulation changes in individual with sickle cell trait. Am J Hematol. 2002;69:89–94.

Solovey A, Kollander R, Shet A, et al. Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin. Blood. 2004;104:840–846.

Nemersom Y. The tissue factor pathway of blood coagulation. Semin Haematol. 1992,29:170–176.

Solovey A, Gui L, Key NS, Hebbel RP. Tissue factor expression by endothelial cells in sickle cell anemia. J Clin Invest. 1998;101:1899–1904.

Key NS, Slungaard A, Dandelet L, et al. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood. 1998;91:4216–4223.

Mohan JS, Lip GYH, Wright J, et al. Plasma levels of tissue factor and soluble E-selectin in sickle cell disease: relationship to genotype and to inflammation. Blood Coagul Fibrinolysis. 2005;16:209–214.

Lee SP, Ataga KI, Orringer EP, Parise LV. Biologically active CD40 ligand is elevated in sickle cell disease: potential role for platelet-mediated inflammation. Arterioscler Thromb Vasc. 2006;26:1626–1631.

Tomer A, Harker LA, Kasey S, Eckman JR. Thrombogenesis in sickle cell disease. J Lab Clin Med. 2001;137:398–407.

Westerman MP, Green D, Gilman-Sachs A, et al. Antiphospholipid antibodies, protein C and S, and coagulation changes in sickle cell disease. J Lab Clin Med. 1999;134:352–362.

Wright JG, Malia R, Cooper P, Thomas P, Preston FE, Serjeant GR. Protein C and S in homozygous sickle cell disease: does hepatic dysfunction contribute to low levels? Br J Haematol. 1997;98:627–631.

El-Hazmi MAF, Warsy AS, Bahakim H. Blood proteins C and S in sickle cell disease. Acta Haematol. 1993;90:114–119.

Lane PA, O’Connell JL, Marler RA. Erythrocyte membrane vesicles and irreversibly sickled cells bind protein S. Am J Hematol. 1994;47:295–300.

Stuart MJ, Setty BNY. Hemostatic alterations in sickle cell disease: relationship to disease pathophysiology. Pediatr Pathol Mol Med. 2001;20:27–46.

Tam DA. Protein C and S activity in sickle cell disease and stroke. J Child Neurol. 1997;12:19–21.

Porter JB, Young L, Mackie IJ, Marshall L, Machin SJ. Sickle cell disorders and chronic intravascular haemolysis are associated with low plasma heparin cofactor II. Br J Haematol. 1993;83:459–465.

Haut MJ, Cowan DH, Harris JW. Platelet function and survival in sickle cell disease. J Lab Clin Med. 1973;82: 44–53.

Semple MJ, Al-Hasani SF, Kioy P, Savidge GF. A double-blind trial of ticlopidine in sickle cell disease. Thromb Haemost. 1984;51:303–306.

Westwick J, Watson-Williams EJ, Krishnamurthi S, et al. Platelet activation during steady state sickle cell disease. J Med. 1983;14:17–36.

Inwald DP, Kirkham FJ, Peters MJ, et al. Platelet and leucocyte activation in childhood sickle cell disease: association with nocturnal hypoxaemia. Br J Haematol. 2000;111:474–481

Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle cell disease, hemolysis-associated pulmonary hypertension and nitric oxide scavenging by cell-free hemoglobin. Blood. First Edition Paper, prepublished online May 29, 2007, as DOI 10.1182/blood-2006-12-061697.

Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP. Circulating activated endothelial cells in sickle cell anaemia. N Engl J Med. 1997;337:1584–1590.

Shet AS, Aras O, Gupta K, et al. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood. 2003;102:2678–2683.

Adams RJ, Mckie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anaemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339:5–11.

Liesner R, Mackie I, Cookson J, et al. Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion. Br J Haematol. 1998;103:1037–1044.

Orringer EP, Jones S, Strayhorn D, Hoffman E, Parker J, Greenberg CS. The effect of hydroxyurea (HU) administration on circulating D-dimer levels in patients with sickle cell anemia [abstract]. Blood. 1996;88:496a.

Saunthararajah Y, Hillery CA, Lavelle D, et al. Effects of 5-aza-2′-deoxycytidine on fetal haemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood. 2003;102:3865–3870.

Greenberg J, Ohene-Frempong K, Halus J, Way C, Schwartz E. Trial of low doses of aspirin as prophylaxis in sickle cell disease. J Pediatr. 1983;102:781–784.

Chaplin H, Alkjaersig N, Fletcher AP, Michael JM, Joist JH. Aspirin-dipyridamole prophylaxis of sickle cell pain crises. Thromb Haemost. 1980;43:218–221.

Osamo NO, Photiades DP, Famodu AA. Therapeutic effect of aspirin in sickle cell anaemia. Acta Haemat. 1981;66:102–107.

Zago MA, Costa FF, Ismael SJ, Tone LG, Bottura C. Treatment of sickle cell diseases with aspirin. Acta Haemat. 1984;72:61–64.

Cabannes, R, Lonsdorfer J, Castaigne JP, Ondo A, Plassard A, Zohoun I. Clinical and biological double-blind study of ticlopidine in preventive treatment of sickle-cell disease crises. Agents Actions Suppl. 1984;15:213–221.

Salvaggio JE, Arnold CA, Banov CH. Long-term anticoagulation in sickle cell disease. N Eng J Med. 1963;269:182–186.

Wolters HJ, Ten Cate H, Thomas LLM, et al. Low-intensity oral anticoagulation in sickle-cell disease reverses the prethrombotic state: promises for treatment? Br J Haematol. 1995;90:715–717.

Schnog JB, Kater AP, MacGillavry MR, et al. Low adjusted dose acenocoumarol therapy in sickle cell disease: a pilot study. Am J Haematol. 2001;68:179–183.

Chaplin H Jr, Monroe MC, Malecek AC, Morgan LK, Michael J, Murphy WA. Preliminary trial of minidose heparin prophylaxis for painful sickle cell crises. East Afri Med J. 1989;66:574–584.

Matsui NM, Varki A, Embury SH. Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin. Blood. 2002;100:3790–3796.