Patients with Essential Thrombocythaemia have an Increased Prevalence of Antiphospholipid Antibodies which may be associated with Thrombosis

C.N. Harrison; S. Donohoe; P. Carr; M. Dave; I. Mackie; S.J. Machin

doi:10.1055/s-0037-1613087

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(05): 802-807
DOI: 10.1055/s-0037-1613087

Review Article

Schattauer GmbH

Patients with Essential Thrombocythaemia have an Increased Prevalence of Antiphospholipid Antibodies which may be associated with Thrombosis

C.N. Harrison

¹Department of Haematology, University College London Hospital, UK

,

S. Donohoe

¹Department of Haematology, University College London Hospital, UK

,

P. Carr

¹Department of Haematology, University College London Hospital, UK

,

M. Dave

¹Department of Haematology, University College London Hospital, UK

,

I. Mackie

¹Department of Haematology, University College London Hospital, UK

,

S.J. Machin

¹Department of Haematology, University College London Hospital, UK

› Author Affiliations

Abstract

Summary

A significant proportion of patients with Essential Thrombocythaemia (ET) have thrombotic complications which have an important impact upon the quality, and duration of their life. We performed a retrospective cross sectional study of the prevalence of antiphospholipid antibodies (APA) in 68 ET patients. Compared to 200 “elderly” controls (> 50 years) there was a significant increase in anticardiolipin IgM (p < 0.0001) and anti β₂ glycoprotein I (anti-β₂GPI) IgM (p < 0.0001) antibodies in ET. Thrombosis occurred in 10/20 with APA and 12/48 without, p = 0.04, relative risk 2.0 (95% confidence intervals 1.03–3.86); these patients did not differ in terms of other clinical features. The prevalence of thrombosis in patients with dual APA (6/7) was significant when compared to those with single APA (p = 0.02) and the remaining patients (p < 0.0002). Also anti-β₂GP1 IgM antibodies either alone, or in combination with another APA, were associated with thrombosis (p = 0.02). These results suggest that the prevalence of APA in ET and their influence upon thrombotic risk merit investigation in a larger study.

Keywords

ET - antiphospholipid antibodies - thrombosis

Full Text

References

References
1 Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995; 332: 1132-6.
2 Lengfelder E, Hochhaus A, Kronawitter U, Hoche D, Queisser W, Jahn-Eder M, Burkhardt R, Reiter A, Ansari H, Hehlmann R. Should a platelet limit of 600 X 10(9)/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages. Br J Haematol 1998; 100: 15-23.
3 Sterkers Y, Preudhomme C, Lai JL, Demory JL, Caulier MT, Wattel E, Bordessoule D, Bauters F, Fenaux P. Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998; 91: 616-22.
4 Cortelazzo S, Viero P, Finazzi G, D’Emilio A, Rodeghiero F, Barbui T. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 1990; 08: 556-62.
5 Harrison CN, Gale RE, Machin SJ, Linch DC. A large proportion of patients with a diagnosis of essential thrombocythaemia do not have a clonal disorder and may be at lower risk of thrombotic complications. Blood 1999; 93: 417-24.
6 Chiusolo P, La Barbera EO, Laurenti L, Piccirillo N, Sora F, Giordano G, Urbano R, Mazzucconi MG, De Stefano V, Leone G, Sica S. Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia. Exp Hematol 2001; 29: 670-6.
7 Juvonen E, Ikkala E, Oksanen K, Ruutu T. Megakaryocyte and erythroid colony formation in essential thrombocythaemia and reactive thrombocytosis: diagnostic value and correlation to complications. Br J Haematol 1993; 83: 192-7.
8 Harrison CN, Machin SJ. Essential thrombocythaemia and antiphospholipid antibodies. Am J Med 1997; 102: 317-8.
9 Murphy S, Peterson P, Iland H, Laszlo J. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol 1997; 34: 29-39.
10 Petri M. Epidemiology of the antiphospholipid antibody. Journal of Autoimmunity 2000; 15: 145-51.
11 Scurr JH, Machin SJ, Bailey-Kig S, Mackie IJ, McDonald S, Smith PD. Frequency and prevention of symptomless deep-vein thrombosis in longhaul flights: a randomised trial. Lancet 2001; 357: 1485-9.
12 Loizou S, McCrea JD, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp Immunol 1985; 62: 738-45.
13 Harris EN, Hughes GR. Standardising the anti-cardiolipin antibody test. Lancet 1987; 01: 77.
14 McNally T, Mackie IJ, Machin SJ, Isenberg DA. Increased levels of beta 2-glycoprotein-I antigen and beta 2-glycoprotein-I binding antibodies are associated with a history of thromboembolic complications in patients with SLE and primary antiphospholipid syndrome. Br J Rheumatol 1995; 34: 1031-6.
15 Donohoe S, Mackie IJ, Isenberg D, Machin SJ. Anti-prothrombin antibodies: assay conditions and clinical associations in the anti-phospholipid syndrome. Br J Haematol 2001; 113: 544-9.
16 Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome?. Journal of Autoimmunity 2000; 15: 163-72.
17 Horbach DA, Oort EV, Donders RCJM, Derksen RHWM, deGroot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with SLE. Thromb Haemost 1996; 76: 916-24.
18 Varaala O, Puurunen M, Manttari M, Manien V, Aho K, Palosuo T. Antibodies to prothrombin imply a risk of myocardial infarction in middle aged men. Thromb Haemost 1996; 75: 456-9.
19 Finazzi G, Brancaccio V, Moia M, Ciaverella N, Mazzucconi MG, Schinco PC, Ruggeri M, Pogliani EM, Gamba G, Rossi E, Baudo F, Manotti C, D’Angelo A, Palareti G, De Stefano V, Berrettini M, Barbui T. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 1996; 100: 530-6.
20 Stasi R, Stipa E, Masi M, Oliva F, Sciarra A, Perrotti A, Zaccari G, Papa G. Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin’s lymphoma. Thromb Haemost 1993; 70: 568-72.
21 Stasi R, Stipa E, Masi M, Oliva F, Olivieri M, Perrotti A, Zaccari G, Amadori S, Papa G. Antiphospholipid antibodies: their prevalence, clinical significance and correlation with cytokine levels in acute myeloid leukemia and non-Hodgkin’s lymphoma. Recenti Prog Med 1995; 86: 57-62.
22 Crook M, Machin S, Crawford N. Electrokinetic behaviour and surface sialic acid status of blood platelets in essential thrombocythaemia (ET). Eur J Haematol 1992; 49: 128-32.
23 Joseph JE, Harrison P, Mackie IJ, Isenberg DA, Machin SJ. Increased circulating platelet-leukocyte complexes and platelet activation in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Br J Haematol 2001; 115: 451-9.
24 Griesshammer M, Beneke H, Nussbaumer B, Grunewald M, Bangerter M, Bergmann L. Increased platelet surface expression of P-selectin and thrombospondin as markers of platelet activation in essential thrombocythaemia. Thromb Res 1999; 96: 191-6.
25 Jensen MK, de Nully Brown P, Lund BV, Nielsen OJ, Hasselbalch HC. Increased circulating platelet-leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count. Eur J Haematol 2001; 66: 143-51.
26 van Genderen PJ, Prins FJ, Michiels JJ, Schror K. Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent. Br J Haematol 1999; 104: 438-41.
27 Falanga A, Marchetti M, Evangelista V, Vignoli A, Licini M, Balicco M, Manarini S, Finazzi G, Cerletti C, Barbui T. Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythaemia and polycythemia vera. Blood 2000; 96: 4261-6.
28 Hill MB, Phipps JL, Hughes P, Greaves M. Anti-endothelial cell antibodies in primary antiphospholipid syndrome and SLE: patterns of reactivity with membrane antigens on microvascular and umbilical venous cell membranes. Br J Haematol 1998; 103: 416-21.
29 Gharavi AE, Pierangeli SS. Infections and Antiphospholipid Antibodies. In: Khamashta M. (ed) 2000. Hughes Syndrome Antiphospholipid Syndrome. London: Springer-Verlag Limited; 135-43.
30 Greaves M, Cohen H, MacHin SJ, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol 2000; 109: 704-15.