Venous thromboembolic events during warm autoimmune hemolytic anemia

Sylvain Audia, Benoit Bach, Maxime Samson, Daniela Lakomy, Jean-Baptiste Bour, Bénédicte Burlet, Julien Guy, Laurence Duvillard, Marine Branger, Vanessa Leguy-Seguin, Sabine Berthier, Marc Michel, Bernard Bonnotte, Sylvain Audia, Benoit Bach, Maxime Samson, Daniela Lakomy, Jean-Baptiste Bour, Bénédicte Burlet, Julien Guy, Laurence Duvillard, Marine Branger, Vanessa Leguy-Seguin, Sabine Berthier, Marc Michel, Bernard Bonnotte

Abstract

Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ≥ 40 μmol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x10(9)/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined.

Trial registration: ClinicalTrials.gov NCT02158195.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart of patients.
Fig 1. Flowchart of patients.
Fig 2. Comparison of serum levels of…
Fig 2. Comparison of serum levels of soluble CD163, ferritin, free hemoglobin and nitrates between patients with venous thromboembolism (VTE+) and those without (VTE-).
Results are given by medians [interquartile range (IQR)]. NS: non-significant.

References

    1. Zoller B, Li X, Sundquist J, Sundquist K (2012) Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 379: 244–249. 10.1016/S0140-6736(11)61306-8
    1. Ramagopalan SV, Wotton CJ, Handel AE, Yeates D, Goldacre MJ (2011) Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study. BMC Med 9: 1 10.1186/1741-7015-9-1
    1. Johannesdottir SA, Schmidt M, Horvath-Puho E, Sorensen HT (2012) Autoimmune skin and connective tissue diseases and risk of venous thromboembolism: a population-based case-control study. J Thromb Haemost 10: 815–821. 10.1111/j.1538-7836.2012.04666.x
    1. Yusuf HR, Hooper WC, Grosse SD, Parker CS, Boulet SL, Ortel TL (2015) Risk of venous thromboembolism occurrence among adults with selected autoimmune diseases: A study among a U.S. cohort of commercial insurance enrollees. Thromb Res 135: 50–57. 10.1016/j.thromres.2014.10.012
    1. Zoller B, Li X, Sundquist J, Sundquist K (2012) Autoimmune diseases and venous thromboembolism: a review of the literature. Am J Cardiovasc Dis 2: 171–183.
    1. Pullarkat V, Ngo M, Iqbal S, Espina B, Liebman HA (2002) Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism. Br J Haematol 118: 1166–1169.
    1. van Zaane B, Nur E, Squizzato A, Gerdes VE, Buller HR, Dekkers OM, et al. (2010) Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors. J Thromb Haemost 8: 2483–2493. 10.1111/j.1538-7836.2010.04034.x
    1. Allgood JW, Chaplin H, Jr. (1967) Idiopathic acquired autoimmune hemolytic anemia. A review of forty-seven cases treated from 1955 through 1965. Am J Med 43: 254–273.
    1. Ataga KI (2009) Hypercoagulability and thrombotic complications in hemolytic anemias. Haematologica 94: 1481–1484. 10.3324/haematol.2009.013672
    1. L'Acqua C, Hod E (2015) New perspectives on the thrombotic complications of haemolysis. Br J Haematol 168: 175–185. 10.1111/bjh.13183
    1. Cappellini MD (2007) Coagulation in the pathophysiology of hemolytic anemias. Hematology Am Soc Hematol Educ Program: 74–78. 10.1182/asheducation-2007.1.74
    1. Ungprasert P, Tanratana P, Srivali N (2015) Autoimmune hemolytic anemia and venous thromboembolism: A systematic review and meta-analysis. Thromb Res 136: 1013–1017. 10.1016/j.thromres.2015.09.004
    1. Barcellini W, Fattizzo B, Zaninoni A, Radice T, Nichele I, Di Bona E, et al. (2014) Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood 124: 2930–2936. 10.1182/blood-2014-06-583021
    1. Lecouffe-Desprets M, Neel A, Graveleau J, Leux C, Perrin F, Visomblain B, et al. (2015) Venous thromboembolism related to warm autoimmune hemolytic anemia: a case-control study. Autoimmun Rev 14: 1023–1028. 10.1016/j.autrev.2015.07.001
    1. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40: 1725.
    1. Lundberg IE, Tjarnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. (2017) 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups. Arthritis Rheumatol 69: 2271–2282. 10.1002/art.40320
    1. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127: 2375–2390. 10.1182/blood-2016-01-643569
    1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127: 2391–2405. 10.1182/blood-2016-03-643544
    1. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15: e538–548. 10.1016/S1470-2045(14)70442-5
    1. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. (2010) A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 8: 2450–2457. 10.1111/j.1538-7836.2010.04044.x
    1. Vardi M, Ghanem-Zoubi NO, Zidan R, Yurin V, Bitterman H (2013) Venous thromboembolism and the utility of the Padua Prediction Score in patients with sepsis admitted to internal medicine departments. J Thromb Haemost 11: 467–473. 10.1111/jth.12108
    1. Crosby WH, Furth FW (1956) A modification of the benzidine method for measurement of hemoglobin in plasma and urine. Blood 11: 380–383.
    1. Moestrup SK, Moller HJ (2004) CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. Ann Med 36: 347–354.
    1. Peacock-Young B, Macrae FL, Newton DJ, Hill A, Ariens RAS (2018) The prothrombotic state in paroxysmal nocturnal hemoglobinuria: a multifaceted source. Haematologica 103: 9–17. 10.3324/haematol.2017.177618
    1. Hill A, Kelly RJ, Hillmen P (2013) Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 121: 4985–4996; quiz 5105. 10.1182/blood-2012-09-311381
    1. Bongarzoni V, Annino L, Roveda A, Amendolea MA, Tirindelli MC, Avvisati G (2005) Risk of thromboembolism in patients with idiopathic autoimmune hemolytic disease and antiphospholipid antibodies: results from a prospective, case-control study. Haematologica 90: 711–713.
    1. Kokori SI, Ioannidis JP, Voulgarelis M, Tzioufas AG, Moutsopoulos HM (2000) Autoimmune hemolytic anemia in patients with systemic lupus erythematosus. Am J Med 108: 198–204.
    1. Roumier M, Loustau V, Guillaud C, Languille L, Mahevas M, Khellaf M, et al. (2014) Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single-center experience with 60 patients. Am J Hematol 89: E150–155. 10.1002/ajh.23767
    1. Baek SW, Lee MW, Ryu HW, Lee KS, Song IC, Lee HJ, et al. (2011) Clinical features and outcomes of autoimmune hemolytic anemia: a retrospective analysis of 32 cases. Korean J Hematol 46: 111–117. 10.5045/kjh.2011.46.2.111
    1. Hendrick AM (2003) Auto-immune haemolytic anaemia—a high-risk disorder for thromboembolism? Hematology 8: 53–56. 10.1080/1024533021000059474
    1. Chen G, Zhang D, Fuchs TA, Manwani D, Wagner DD, Frenette PS (2014) Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood 123: 3818–3827. 10.1182/blood-2013-10-529982
    1. Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN (2005) Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993–2002). J Am Vet Med Assoc 226: 1869–1880.

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