CORRESPONDENCE

The bleeding edge

To the Editor: We read with great interest the study by Ebrahim et al.^[1] in the June SAMJ, titled 'Poor anticoagulation control in patients taking warfarin at a tertiary and district-level prothrombin clinic in Cape Town, South Africa. This was a retrospective review of anticoagulation control in patients taking warfarin at two international normalised ratio (INR) monitoring centres in Cape Town. The authors found that time in the therapeutic range (TTR), which reflects the time in which the patient's INR was within the desired range, was remarkably low, at a mean of 47%. For anticoagulation to be effective, the accepted TTR is >65%. A post hoc analysis of the multicentre ACTIVE-W trial that looked at patients with atrial fibrillation (AF) treated with either warfarin or dual antiplatelet therapy identified a threshold TTR range for therapeutic efficacy of oral anticoagulants (OACs) of 58 - 65%, below which OACs were no better than platelet blockade.^[2] Furthermore, an earlier subgroup analysis of combined data from the SPORTIF III and V trials looked at patients with AF randomised to warfarin. White et al.^[3] found that poor INR control, defined as TTR of <60%, with a median of 48% (similar to the local data), was associated with a significant risk of complications including myocardial infarction and ischaemic and haemorrhagic stroke,^[3] since time outside the therapeutic range includes both sub- and supratherapeutic levels.

Levels above the desired range are known to increase the risk of major bleeding, one of the complications of which is intracranial haemorrhage, a potentially devastating condition. At our neurosurgical centre, we see a steady number of patients every month with this complication. The most common presentations are intracerebral haematoma (ICH) and acute or chronic subdural haematomas. It is known that ICHs associated with warfarin anticoagulation are larger than spontaneous ICHs in non-warfarin users, tend to expand within 72 hours, and are associated with poorer prognosis in the form of either death or disability, with in-hospital mortality of up to 42%.^[4-6] Treatment of these haematomas is compounded by the fact that numerous studies have shown that surgery fails to change this prognostic outcome.^[7,8] Chronic subdural haematomas, which generally carry mortality between 1% and 3%, can be recurrent and when occurring in the elderly can have a mortality rate of up to 20 -32%.^[9] It is reassuring then that Ebrahim and his colleagues^[1] found a higher rate of TTR among older patients. Surgical treatment for these lesions is further hindered by the need to reverse what are sometimes remarkably high INRs, and there remains controversy over the best way to do this.

We have begun to look systematically at this patient population to better quantify this problem, and therefore wish to congratulate the authors on a very timely and appropriate study of relevance to multiple disciplines across a broad patient population. With the limited availability of alternative anticoagulants, a discussion on how to improve our anticoagulation monitoring to better protect our patients against life-threatening complications is overdue. And if we cannot improve our mean TTR, should we consider platelet inhibition instead for conditions such as AF, or should healthcare funders make alternatives like direct thrombin inhibitors more available to the state?

Ncedile Mankahla

Division of Neurosurgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa ncedilemankahla@yahoo.com

Reneiloe Lekoloane

Division of Neurosurgery, Groote Schuur Hospital, Cape Town, South Africa

Graham Fieggen

Division of Neurosurgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa; and Neurosciences Institute, University of Cape Town, South Africa

References

1. Ebrahim I, Bryer A, Cohen K, Mouton JP, Msemburi W, Blockman M. Poor anticoagulation control in patients taking warfarin at a tertiary and district-level prothrombin clinic in Cape Town, South Africa. S Afr Med J 2018;108(6):490-494. https://doi.org/10.7196/SAMJ.2018.v108i6.13062        [ Links ]

2. Connolly SJ, Pogue J, Eikelboom J, et al Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008;118(20):2029-2037. https://doi.org/10.1161/CIRCULATIONAHA.107.750000        [ Links ]

3. White H, Gruber M, Feyzi J, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: Results from SPORTIF III and V. Arch Intern Med 2007;167(3):239-245. https://doi.org/10.1001/archinte.167.3.239        [ Links ]

4. Flaherty M, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008;71(14):1084-1089. https://doi.org/10.1212/01.wnl.0000326895.58992.27        [ Links ]

5. Delcourt C, Huang Y, Chalmers J, et al. Hematoma growth and outcome in intracerebal hemorrhage: The INTERACT1 study. Neurology 2012;79(4):314-319. https://doi.org/10.1212/WNL.0b013e318260cbba        [ Links ]

6. Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008;39(11):2993-2996. https://doi.org/10.1161/STROKEAHA.108.520668        [ Links ]

7. Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): A randomised trial. Lancet 2013;382(9890):397-408. https://doi.org/10.1016/S0140-6736(13)60986-1        [ Links ]

8. Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): A randomised trial. Lancet 2005;365(9457):387-397. https://doi.org/10.1016/S0140-6736(05)17826-X        [ Links ]

9. Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic subdural hematoma: A historical and clinical perspective. World Neurosurg 2017;108(19):948-953. https://doi.org/10.1016/j.wneu.2017.09.064        [ Links ]