Questionable reversal of anticoagulation in the therapeutic management of cerebral haemorrhage associated with vitamin K antagonists

Maria Alonso de Leciñana; Nuria Huertas; Jose A. Egido; Alfonso Muriel; Ana García; Gerardo Ruiz-Ares; Exuperio Díez-Tejedor; Blanca Fuentes

doi:10.1160/TH13-04-0318

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(06): 1145-1151
DOI: 10.1160/TH13-04-0318

Blood coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Questionable reversal of anticoagulation in the therapeutic management of cerebral haemorrhage associated with vitamin K antagonists

Maria Alonso de Leciñana

¹Stroke Unit, Department of Neurology, University Hospital Ramón y Cajal, IRYCIS, Madrid, Spain

,

Nuria Huertas

²Department of Neurology, Hospital Severo Ochoa, Leganés, Spain

,

Jose A. Egido

³Stroke Unit, Department of Neurology, University Hospital San Carlos, IdISSC Madrid, Spain

,

Alfonso Muriel

⁴Department of Clinical Biostatistics, University Hospital Ramón y Cajal, IRYCIS, CIBERESP, Madrid, Spain

,

Ana García

³Stroke Unit, Department of Neurology, University Hospital San Carlos, IdISSC Madrid, Spain

,

Gerardo Ruiz-Ares

⁵Department of Neurology and Stroke Centre, University Hospital La Paz, Universidad Autonoma de Madrid, IdiPAZ Health Research Institute, Madrid, Spain

,

Exuperio Díez-Tejedor

⁵Department of Neurology and Stroke Centre, University Hospital La Paz, Universidad Autonoma de Madrid, IdiPAZ Health Research Institute, Madrid, Spain

,

Blanca Fuentes

⁵Department of Neurology and Stroke Centre, University Hospital La Paz, Universidad Autonoma de Madrid, IdiPAZ Health Research Institute, Madrid, Spain

› Author Affiliations

Abstract

Summary

Reversal of anticoagulation is recommended to correct the international normalised ratio (INR) for patients with intracranial haemorrhage (ICH) associated with vitamin K antagonists (VKA). However, the validity of such treatment is debated. We sought to identify, prospectively, the prognostic effect of VKA-ICH treatment in a cohort of patients (n=71; median age 78 years, range 20–89; 52% males). Data collated were: baseline characteristics, treatments, baseline and post-treatment INR, haematoma volume, and haematoma enlargement. Treatment effects and prognostic factor assessment were in relation to mortality and functional outcomes. On admission, the patients had a median score of 9 [p25; p75 of 5; 20] on the National Institute of Health Stroke Scale (NIHSS) and a mean INR of 2.7 (range: 0.9 – 10.8). Haematoma volume (34.6 cm³; SD: 24.9) correlated with NIHSS (r = 0.55; p<0.001) but not with INR. Anticoagulation reversal treatment was administered in 83% of patients. INR <1.5 was achieved in 60.7% of cases. Death or dependency at three months was 76%. Neither baseline INR, anticoagulation reversal nor haematoma enlargement were related to mortality or functional outcome. The only independent prognostic factor was clinical severity on admission. Baseline NIHSS predicted mortality (OR: 1.18; 95%CI: 1.09–1.27), independence (OR: 0.83; 95%CI: 0.74–0.94) and neurological recovery (NIHSS 0–1) (OR: 0.83; 95%CI: 0.73–0.95). The data indicate that VKA-ICH had a poor prognosis. Treatment and INR correction did not appear to affect outcomes.

Keywords

Intracerebral haemorrhage - oral anticoagulants - vitamin K antagonists - prothrombin complex concentrate

Full Text

References

References
1 Cucchiara B, Messe S, Sansing L. et al and the CHANT Investigators. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39: 2993-2996.
2 Cervera A, Amaro S, Chamorro A. Oral anticoagulant-associated intracerebral hemorrhage. J Neurol 2012; 259: 212-224.
3 Morgenstern LB, Hemphill 3rd JC, Anderson C. et al. and American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41: 2108-2129.
4 Rodríguez-Yáñez M, Castellanos M, Freijo MM. et al. And the Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN. Clinical practice guidelines in intracerebral haemorrhage. Neurologia 2013; 28: 238-249.
5 Dowlatshahi D, Butcher KS, Asdaghi N. et al. and the Canadian PCC Registry (CanPro) Investigators. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke 2012; 43: 1812-1817.
6 Kuwashiro T, Yasaka M, Itabashi R. et al. Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage. Cerebrovasc Dis 2011; 31: 170-176.
7 Selim MH, Molina CA. The role of hemostatic therapy in anticoagulation-associated intracerebral hemorrhage: intuition versus evidence. Stroke 2012; 43: 2539-2540.
8 van Swieten JC, Koudstaal PJ, Visser MC. et al. Inter-observer agreement for the assessment of handicap in stroke patients. Stroke 1988; 19: 604-607.
9 Masotti L, Di Napoli M, Godoy DA. et al. The practical management of intracerebral hemorrhage associated with anticoagulant therapy. Int J Stroke 2011; 6: 228-240.
10 Lyden PBT, Tilley B, Welch KMA. et al. Improved reliability of the NIH Stroke Scale using video training. Stroke 1994; 25: 2220-2226.
11 Kothari RU, Brott T, Broderick JP. et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996; 27: 1304-1305.
12 Zubkov AY, Mandrekar JN, Claassen DO. et al. Predictors of outcome in warfarin-related intracerebral hemorrhage. Arch Neurol 2008; 65: 1320-1325.
13 Sjöblom L, Hårdemark HG, Lindgren A. et al. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke 2001; 32: 2567-2574.
14 Davis SM, Broderick J, Hennerici M. et al. and the Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006; 66: 1175-1181.
15 Mayer SA, Davis SM, Skolnick BE. et al. and the FAST trial investigators. Can a subset of intracerebral hemorrhage patients benefit from hemostatic therapy with recombinant activated factor VII?. Stroke 2009; 40: 833-840.
16 Flibotte JJ, Hagan N, O'Donnell J. et al. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004; 63: 1059-1064.
17 Appelboam R, Thomas EO. Warfarin and intracranial haemorrhage. Blood Rev 2009; 23: 1-9.
18 Béjot Y, Aboa-Eboulé C, Hervieu M. et al. The deleterious effect of admission hyperglycemia on survival and functional outcome in patients with intracerebral hemorrhage. Stroke 2012; 43: 243-245.
19 Schulman S, Beyth RJ, Kearon C. et al and the American College of Chest Physicians. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 257S-298S.
20 Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005; 36: 1588-1593.
21 Kuwashiro T, Yasaka M, Itabashi R. et al. Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage. Cerebrovasc Dis 2011; 31: 170-176.
22 Liotta EM, Garg RK, Temes RE. et al. Warfarin-associated intracerebral hemorrhage is inadequately treated at community emergency departments. Stroke 2012; 43: 2503-2505.