Abstract
Our aim was to study the cause and describe the clinical features of pulmonary arterial hypertension (PHT) in splenectomized β-thalassemia (β-Thal) patients. Ten splenectomized β-Thal patients with systolic pulmonary artery (PA) pressure >30 mm Hg were evaluated by echocardiography, right-heart catheterization, and pulmonary angiography. Five of these patients later underwent hemodynamic studies. Echocardiography and pulmonary angiography on the 10 patients showed normal values of left ventricular systolic function and no findings of acute or chronic pulmonary embolism. Hemodynamic evaluation showed very high PA pressures associated with markedly increased pulmonary vascular resistance indices (PVRIs). Hematological evaluation of the 10 patients showed marked anemia, markedly increased numbers of nucleated red blood cells (nRBCs), and serum ferritin. Mean platelet count, plasma β2 thromboglobulin, and thrombin—antithrombin III complex levels were significantly increased. It was concluded that PHT can be found in splenectomized β-Thal patients. Features associated with PHT were female sex, hemoglobin E/β-Thal, status many years postsplenectomy, marked anemia, markedly increased nRBC count, thrombocytosis, and very high serum ferritin levels. PHT was not due to pulmonary emboli. Our findings suggested that severe PHT was due to increased PVRI from thrombotic pulmonary arteriopathy, likely from chronic low-grade hypercoagulability and platelet activation after splenectomy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Rich S. Pulmonary hypertension. In: Braunwald E, Zipes DP, Libby P, eds.Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia: WB Saunders; 2001:1908–1935.
Sonakul D, Pacharee P, Laohapand T, Fucharoen S, Wasi P. Pulmonary artery obstruction in thalassemia.Southeast Asian J Trop Med Public Health. 1980;11:516–523.
Sonakul D, Fucharoen S. Pulmonary thromboembolism in thalassemic patients.Southeast Asian J Trop Med Public Health. 1992;23(suppl 2):25–28.
Borgna-Pignatti C, Carnelli V, Caruso V, et al. Thromboembolic events in beta thalassemia major: an Italian multicenter study.Acta Haematol. 1998;99:76–79.
Cappellini MD, Robbiolo L, Bottasso BM, et al. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia.Br J Haematol. 2000;111:467–473.
Oh JK, Seward JB, Tajik AJ. Pulmonary hypertension. In: Oh JK, Seward JB, Tajik AJ, eds.The Echo Manual. Philadelphia: Lippincott Williams & Wilkins; 1999:215–222.
Oh JK, Seward JB, Tajik AJ. Assessment of ventricular systolic function. In: Oh JK, Seward JB, Tajik AJ, eds.The Echo Manual. Philadelphia: Lippincott Williams & Wilkins; 1999:37–44.
Peterson KL, Fred HL, Alexander JK. Pulmonary arterial web: a new angiographic sign of previous thromboembolism.N Engl J Med. 1967;277:33–35.
Grossman W. Blood flow measurement: the cardiac output and vascular resistance. In: Baim DS, Grossman W, eds.Grossman’s Cardiac Catheterization, Angiography and Intervention. Philadelphia: Lippincott Williams & Wilkins; 2000:159–178.
Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin III complex in plasma with an enzymelinked immunosorbent assay.Thromb Haemost. 1988;59:101–106.
Pelzer H, Schwarz A, Stuber W. Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against a synthetic peptide.Thromb Haemost. 1991;65:153–159.
Kaplan KL, Owen J. Plasma levels of β2-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo.Blood. 1981;57:199–202.
Ellis BC, Stransky A. A quick and accurate method for the determination of fibrinogen in plasma.J Lab Clin Med. 1961;58:477–488.
Kutlar A, Kutlar F, Wilson JB, Headlee MG, Huisman TH. Quantitation of hemoglobin components by high performance cationexchange liquid chromatography.Am J Hematol. 1984;17:39–53.
Forman DT, Parker SL. The measurement and interpretation of serum ferritin.Ann Clin Lab Sci. 1980;10:345–350.
Buri PS, Hathirat S, Watthanakaset S, Na Ranong W. Weight and height in normal Thai adult.Thai Med Counc Bull. 1983;12:409–414.
Weatherall DJ. The thalassemias. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds.Hematology. New York: McGraw-Hill; 2001:547–580.
Pattanapanyasat K, Thepthai C, Lamchiagdhase P, et al. Lymphocyte subsets and specific T-cell immune response in thalassemia.Cytometry. 2000;42:11–17.
Pootrakul P, Kitcharoen K, Yansukon P, Anuwatanakulchai M, Thuvassethakul P, Wasi P. The effect of erythroid hyperplasia on iron balance.Blood. 1988;71:1124–1129.
Rich S, Brundage BH. Pulmonary hypertension: a cellular basis for understanding the pathophysiology and treatment.J Am Coll Cardiol. 1989;14:545–550.
Stone RM, Bridges KR, Libby P. Hematological-oncological disorders and cardiovascular disease. In: Braunwald E, Zipes DP, Libby P, eds.Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia: WB Saunders; 2001:2223–2243.
Andrews NC. Disorders of iron metabolism.N Engl J Med. 1999;341:1986–1995.
Lau KC, Li AMC, Hui PW, Yeung CY. Left ventricular function in β-thalassaemia major.Arch Dis Child. 1989;64:1046–1051.
Gibbs JSR, Higenbottam TW. Recommendations on the management of pulmonary hypertension in clinical practice.Heart. 2001;86(suppl I): i1-i13.
Kay JM. Vascular disease. In: Thurlbeck WM, Churg AM, eds.Pathology of the Lung. New York:Thieme Medical Publishers; 1995:931–1066.
Eldor A, Durst R, Hy-Am E, et al. A chronic hypercoagulable state in patients with β-thalassemia major is already present in childhood.Br J Haematol. 1999;107:739–746.
Zwaal RFA, Schroit AJ. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells.Blood. 1997;89:1121–1132.
Borenstain-Ben Yashar V, Barenholz Y, Hy-Am E, Rachmilewitz EA, Eldor A. Phosphatidylserine in the outer leaflet of red blood cells from beta-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes.Am J Hematol. 1993;44:63–65.
Helley D, Eldor A, Girot R, Ducrocq R, Guillin MC, Bezeaud A. Increased procoagulant activity of red blood cells from patients with homozygous sickle cell disease and β-thalassemia.Thromb Haemost. 1996;76:322–327.
Srinivasan PT, Basu J. Altered membrane phospholipid organization and erythrophagocytosis in E β-thalassemia.Biochim Biophys Acta. 1996;1285:65–70.
Atichartakarn V, Angchaisuksiri P, Aryurachai K, et al. Relationship between hypercoagulable state and erythrocyte phosphatidylserine exposure in splenectomized haemoglobin E/β-thalassaemic patients.Br J Haematol. 2002;118:893–898.
Rodriguez-Erdman F, Naimi S. Studies on the pathogenesis of the generalized Shwartzman reaction.Thromb Diath Haemor. 1967;17:156–164.
Lee L. Reticuloendothelial clearance of circulating fibrin in the pathogenesis of the generalized Shwartzman reaction.J Exp Med. 1962;15:1065–1082.
Shirahata A, Funahara Y, Opartkiattikul N, Fucharoen S, Laosombat V, Yamada K. Protein C and protein S deficiency in thalassemic patients.Southeast Asian J Trop Med Public Health. 1992;23(suppl 2):65–73.
O’Driscoll A, Mackie IJ, Porter JB, Marchin SJ. Low plasma heparin cofactor II levels in thalassaemia syndromes are corrected by chronic blood transfusion.Br J Haematol. 1995;90:65–70.
Brass LF,Ahuja M, Belmonte E, Pizarro S,Tarver A, Hoxie JA. The human platelet thrombin receptor: turning it on, turning it off.Ann N Y Acad Sci. 1994;714:1–12.
Tracy PB. Role of platelets and leukocytes in coagulation. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, eds.Hemostasis and Thrombosis: Basic Principles & Clinical Practice. Philadelphia: Lippincott Williams & Wilkins; 2001:575–596.
Rostagno C, Prisco D, Abbate R, Poggesi L. Pulmonary hypertension associated with long-standing thrombocytosis.Chest. 1991;99:1303–1305.
Kisanuki A, Kietthubthew S, Asada Y, Marutsuka K, Funahara Y, Sumiyoshi A. Intravenous injection of sonicated blood induces pulmonary microthromboembolism in rabbits with ligation of the splenic artery.Thromb Res. 1997;85:95–103.
Hoeper MM, Niedermeyer J, Hoffmeyer F, Flemming P, Fabel H. Pulmonary hypertension after splenectomy?Ann Intern Med. 1999;130:506–509.
Hovav T, Goldfarb A, Artmann G, Yedgar S, Barshtein G. Enhanced adherence of beta-thalassaemic erythrocytes to endothelial cells.Br J Haematol. 1999;106:178–181.
Closse C, Dachary-Prigent J, Boisseau MR. Phosphatidylserinerelated adhesion of human erythrocytes to vascular endothelium.Br J Haematol. 1999;107:300–302.
Vordermeier S, Singh S, Biggerstaff J, et al. Red blood cells from patients with sickle cell disease exhibit an increased adherence to cultured endothelium pretreated with tumor necrosis factor.Br J Haematol. 1992;81:591–597.
Wanachiwanawin W. Infections in thalassemia. In: Pansatiankul B, ed.Proceedings of the 7th International Conference on Thalassemia and the Haemoglobinopathies, Bangkok, Thailand, 31 May-4 June 1999. 1999:162, S1104.
Aswapokee P, Aswapokee N, Fucharoen S, Sukroongreung S, Wasi P. Severe infection in thalassemia: a prospective study.Birth Defects. 1988;23:521–526.
Rich S, Levitsky S, Brundage BH. Pulmonary hypertension from chronic pulmonary thromboembolism.Ann Intern Med. 1988;108:425–434.
Butthep P, Bunyaratvej A, Funahara Y, et al. Alterations in vascular endothelial cell-related plasma proteins in thalassaemic patients and their correlation with clinical symptoms.Thromb Haemost. 1995;74:1045–1049.
Aessopos A, Stamatelos G, Skoumas V, Vassilopoulos G, Mantzourani M, Loukopoulos D. Pulmonary hypertension and right heart failure in patients with β-thalassemia intermedia.Chest. 1995;107:50–53.
Aessopos A, Farmakis D, Karagiorga M, et al. Cardiac involvement in thalassemia intermedia: a multicenter study.Blood. 2001;97:3411–3416.
Du ZD, Roguin N, Milgram E, Saab K, Koren A. Pulmonary hypertension in patients with thalassemia major.Am Heart J. 1997;134:532–537.
Sonakul D, Pacharee P, Wasi P, Fucharoen S. Cardiac pathology in 47 patients with beta thalassemia/haemoglobin E.Southeast Asian J Trop Med Public Health. 1984;15:554–563.
Wasi P. Hemoglobinopathies including thalassemia.Clin Haematol. 1981;10:707–729.
Schrier SL. Pathophysiology of the thalassemias.West J Med. 1997;167:82–89.
Morse JH, Barst RJ, Itescu S, et al. Primary pulmonary hypertension in HIV infection: an outcome determined by particular HLA class II alleles.Am J Respir Crit Care Med. 1996;53:1299–1301.
Voelkel NF, Tuder RM. Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension.Eur Respir J. 1995;8:2129–2138.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Atichartakarn, V., Likittanasombat, K., Chuncharunee, S. et al. Pulmonary Arterial Hypertension in Previously Splenectomized Patients with β-Thalassemic Disorders. Int J Hematol 78, 139–145 (2003). https://doi.org/10.1007/BF02983382
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02983382