Vitamin K Antagonists–Associated Cerebral Hemorrhages

Abstract

Background and Purpose-The high prevalence of atrial fibrillation in aging populations leads to an increasing incidence of vitamin K antagonists-associated intracerebral hemorrhages (VKAs-ICH

Antithrombotic medications and the etiology of intracerebral hemorrhage

“…17,18 In addition, evidence supporting a link between CAA and OAC-ICH includes the demonstration that the APOE e2 allele, a known genetic risk factor of CAA-related lobar ICH, 19,20 is more common in warfarin-associated ICH than in control patients on warfarin without ICH, 8 and that individual cases of ICH following anticoagulation or coronary thrombolysis revealed advanced CAA on autopsy. 21,22 Our findings are in apparent disagreement with those derived from the PITCH study by DequatrePonchelle et al 12 who found no influence of OACs on the anatomical distribution of ICH but a significant effect of these compounds on the volume of deep brain hematomas. This would support the conclusion that deep perforating arteries are more sensitive to anticoagulation than cortical-subcortical vessels.…”

“…[7][8][9][10] However, data on the impact of specific small-vessel arteriopathies on OAC-related ICH are scarce, mainly derived from studies including small case series, sometimes recording individual history of OAC use without taking into consideration the intensity of anticoagulation, 7 including patients receiving heparin at the time of stroke, 8,11 or aimed at addressing different issues, 8,9,11 with only a few notable exceptions. 10,12 In this regard, a novel finding from our data is the evidence of a direct dose-response relationship between OAC treatment and lobar ICH, as illustrated by the increasing number of patients in this subgroup as the INR values increase. We speculate that OACs affect CAA and hypertensive arteriolosclerosis equally when INR values are within the therapeutic range, but that they exert a differential impact on the 2 cerebral microangiopathies, with a greater effect on cortical-subcortical vessels, in case of excessive anticoagulation.…”

“…Such a discrepancy might be explained by the slightly different definition of deep and lobar ICH in the 2 studies, as well as by the potential biases in the measurement of hematoma volumes, as pointed out by the authors themselves, and, even more important, by the fact that regression models in the PITCH study did not include adjustment for hypertension. 12 …”

“…In this regard, sparse reports have suggested that cerebral amyloid angiopathy (CAA) may be a stronger predictor of antithrombotic-associated ICH than hypertensive microangiopathy, [7][8][9][10] but some recent observations have questioned this assumption. 11,12 Thus, any specific relation has not yet been established. The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) provides the opportunity to investigate this issue owing to its large sample size, the homogeneous demographic characteristics and clinical phenotype of the subjects included, and the standard diagnostic workup.…”

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

“…Patient registration years ranged from 1993 to 2014, with 90% of patients from 2004 to 2013. Registry methods are summarized in Supplementary Table I, with further details previously published 2, 3, 4, 14, 15, 16, 17, 18, 19, 20…”