Article Report: Warfarin vs. Other Anticoagulants in Hematoma Cases

This article report presents a systematic review investigating the association between warfarin and the risk of subdural hematoma compared to other anticoagulants. The review analyzes various studies, including cohort and longitudinal studies, focusing on the impact of warfarin on intracranial hemorrhage and subdural hemorrhage. The report examines the effects of warfarin on internalized normalized ratio (INR), clinical and functional outcomes, mortality, and the optimal timing for resuming anticoagulation. Key findings suggest that warfarin is associated with a significantly higher risk of subdural hematoma compared to other anticoagulants. The methodology employed a PRISMA framework to retrieve articles from databases such as CINAHL, MEDLINE, and PubMed. The study evaluates the effects of warfarin on patient outcomes, including length of hospitalization, quality of life, and recurrence of hematoma. The report also discusses the influence of INR levels and the timing of anticoagulation resumption on the risk of subdural hematoma and ischemic stroke. The findings highlight the importance of considering alternative anticoagulants and careful monitoring of patients undergoing warfarin therapy to minimize the risk of subdural hematoma.

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Nelson M. Oyesiku, MD, PhD, FACS,
Editor-in-Chief,
NEUROSURGERY® Publications.
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Does warfarin increase risk of subdural hematoma when compared to other anticoagulants?
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Abstract
Background- Localised circulation of blood in regions outside the blood vessels most often
results in a medical abnormality that is referred to as subdural haematoma. Inner layers of the
meninges namely, the dura mater and arachnoid generally get filled with this blood, as a
result of damage of the veins that are present in the subdural space. Millions of cases of
traumatic brain injury occur on an annual basis that often leads to death of the patients. Some
chemical agents, commonly known as blood thinners, or anticoagulants used for treatment of
cardiovascular abnormalities, lower the rate of blood clotting. There exists a perception that
warfarin, a blood thinner is associated with increasing risks of bleeding and deteriorating the
condition of subdural haematoma.
Objective- The article focuses on a systematic review that aimed to evaluate the effects of
warfarin on risks of intracranial hemorrhage or subdural haemorrhage among patients under
anticoagulation therapy.
Methods- A systematic review was conducted by retrieving quantitative articles, primarily
longitudinal ones that focused on the clinical or functional outcomes of patients under
warfarin administration, internalized normalised ratio and effects on subdural haematoma,
following resumption of warfarin.
Results- Warfarin has been associated with increased rates of mortality morbidity and poor
clinical and functional outcomes among haematoma patients. 5 days have been considered as
the optimal time for anticoagulant resumption.
Conclusion- Warfarin has been found associated with significantly high risk for subdural
haematoma among patients, when compared to those under the medication of other
anticoagulant.
Keywords- warfarin, subdural, haematoma, intracranial

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Introduction
Blood often gets accumulated in localised regions, outer the blood vessels, resulting in
a medical condition, commonly referred to as subdural hematoma. The inner layers of the
arachnoid ad the dura mater get filled with blood, and occur due to wear and tear of the veins
that span the subdural space. Subdural hematoma has been closely linked to an elevation in
the intracranial pressure that results in compression and damage of neuronal tissue that
subsequently develops in to life threatening conditions1. 1.7 million cases of traumatic brain
injuries occur annually in the United States, of which 275,000 cases result in patient
hospitalisation and 52,000 cases lead to death2. There are several chemical agents, referred to
as blood thinner or anticoagulants that lower blood clotting rates. Some of the most
commonly used blood thinners are warfarin, aspirin and heparin. There lies a perception that
anticoagulant therapies are associated with increased bleeding risks3. Although the
anticoagulants are commonly used for the treatment of myocardial infarction, coronary artery
disease, restenosis, and pulmonary embolism, they have been associated with greater risks of
intracranial haemorrhage, the most prevalent of which is subdural hematoma. This article
contains a systematic review that will discuss the association between warfarin and subdural
haemorrhage, in comparison to other anticoagulants.
Methodology
The evidence-based PRISMA (Preferred Reporting Items for Systematic Reviews and
Meta-Analyses) tool was employed for the systematic review, which in turn established
substantial transparency in the article selection. Several databases were used for retrieving the
articles that principally encompassed prospective and retrospective cohort studies. The
inclusion of articles was based on the PICO method that acted as a framework for
formulating the research question. The population under consideration comprised of adults
and older adults under anticoagulation therapy. Intervention of interest was warfarin as the
principle blood thinner. This was compared with to other antithrombotic agents. The
immediate and long lasting effects of warfarin and other anticoagulants such as aspirin and
heparin were evaluated on several aspects that encompassed clinical outcomes and quality of
life, internalised normalised ratio, and effect of resumption of anticoagulation agents on the
risks of subdural haemorrhage. The systematic review was based on a three step search
strategy. Specific key terms and phrases such as, anticoagulants, warfarin, intracranial
pressure, subdural hematoma, bleeding, and subdural haemorrhage were fed as input in the

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databases CINAHL, MEDLINE, Embase, Cochrane Library, PubMed, Joanna Briggs
Institute EBP database, and Scopus, among many others. The user guidelines published by
the Joanna Briggs Institute was used for appraising the quantitative evidences. Use of the
critical appraisal tool helped to establish validity of the systematic review. Only articles that
met the criteria specified in the critical appraisal tool were included in the review. Certain
factors that were taken into consideration during the appraisal of the articles include the fact
whether all participants were equal at the beginning of the study, use of reliable and valid
tools for outcome measurements, mention about elimination of confounding variables and use
of reliable exposure tools.
The schematic diagram given below depicts the steps that were undertaken for
retrieval of articles that have been included in the systematic review. 340 articles were
obtained in the initial hits after searching the databases mentioned above with the pre-decided
key phrases. Following extraction of these 340 articles, several duplicates were removed that
resulted in 101 articles, all of which were screened for their titles and abstracts. 58 articles
were not relevant to the research and were excluded. Of the 43 articles that were reviewed for
their full text eligibility, only 9 could be retrieved for inclusion in the review. Quantitative
cohort studies that contained information on patients under pre-operative and post-operative
antiplatelet or antithrombotic medications, with intracranial haemorrhage or subdural
haematoma were selected. The population of patuents that was taken into consideration for
the review included adults and older adults, under anticoagulation therapy. This approach of
systematic review helped in summarising the results of the extracted healthcare cohort studies
and presented high level of evidence regarding the effectiveness of the intervention
(anticoagulation).

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Figure 1- PRISMA chart showing number of articles included in the review
Results
The PRISMA, commonly referred to as Preferred Reporting Item for Systematic
Review and Meta-Analysis, helped in including quantitative articles and the systematic
review. Most of the articles that were included in the systematic review were of a cohort or
longitudinal nature, which were performed in cross sections at intervals, over time. All the
studies included in the systematic review were found to illustrate the occurrence of acute
subdural hemorrhage, and intracranial hemorrhage, following anticoagulation therapy

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treatment that encompassed administration of warfarin or other anticoagulant. Inclusion of
the studies helped in achieving the research objective of investigating the link or association
between administration of anticoagulant among patients and their susceptibility of facing
high intracranial pressure that subsequently lead to subdural haematoma. Oral administration
of Vitamin K antagonist leads to various health complications. All the studies were based on
previous findings that had established close associations with intracranial haemorrhage and
Vitamin K antagonist therapy. Uses of all the studies helped in identification of several
themes that are mentioned below:
Internalized normalised ratio
The internalised normalised ratio is most often used for calculating prothrombin time
with respect to subdural haematoma that is associated with usage of anticoagulant.
Retrospective study that focused on 69 patients suffering from subdural hematoma linked
with warfarin administration, and 197 patients suffering from the condition not under
warfarin medication focused on assessing expansion of the haematoma. Radiology reports
were analysed for noting the enlargement among patients in the warfarin group, and they
failed in remembering history of their trauma4. The group corresponding to HD1 INR 0.8-1.3
demonstrated an increased rate in the mean internalized normalised ratio along with
radiographic expansions, in an estimated 22.5% patients. 20% patients in the other group
HD1 INR 1.31-1.69, showed radiographic expansions. The effects of time to INR were also
evaluated in another study that focused on haemorrhage among patients having undergone
traumatic brain injury, under anticoagulant therapy5. Initial INR was demonstrated to be more
than 2.0 among the patients who showed positive CT scan tests for subdural haemorrhage.
Mean INR was found to take approximately 13.3 ± 10.5 hours reversal time below 1.5. While
49 patients could reach this mean INR in less than 10 hours, only 14 could do so in less than
5 hours. Reversal of INR in the group less than 5 hours also did not show any significant
association with intracranial haemorrhage evolution. Differences for objects observed in
mean INR among patients with good or poor outcomes by as much as 0.07, in a study that
measured effects of preoperative anticoagulation on subdural hemorrhage. Values of INR
versus among patients with mRS ≤ 1, in comparison to those having suffered subdural
haemorrhage and with mRS > 16. INR values <1.5 also found among intracranial
haemorrhage patient had received prothrombin complex concentrates after an hour of its
infusion7. These findings help in establishing the differences that exist in rates of INR among

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subdural haemorrhage patients underwater in medication when compared to other
anticoagulants.
Outcomes and quality of life
The length of hospitalization, clinical outcome, functional outcome, mortality rates
and quality of life of patients undergoing anticoagulant therapy, after subdural haematoma,
were investigated by various studies. Effects of oral anticoagulation or warfarin were
investigated in a retrospective cohort study that encompassed 94 cases. 22 patients under
warfarin administration had been found to report low mean discharge Glasgow Outcome
Scale scores (2.3 ± 0.3 versus 3.0 ± 0.2), when compared to the controls subjects. Sizes of the
subdural haematoma world larger among patients underwater in administration, who also
reported higher rates of mortality (55%), in comparison to haematoma patients without
anticoagulation therapy (29%)8. Recurrent haematoma was found among patients after 25
days, who were under antiplatelet therapy that comprised of heparin, clopidogrel and aspirin9.
Preoperative mortality rates for around 0.5% were much less than other studies with that
focused on subdural haematoma patients under warfarin medication. No associated
comorbidities of heart failure, pulmonary embolism, or aortic valve disease were found to
create any impact on clinical outcome of these patients. Impacts of preoperative
anticoagulation were also evaluated on the outcomes of subdural haematoma patients in
another study that focused on utilisation of the Barthel Index (BI), Rankin Scale (mRS) score
and quality of life (QoL) scales. 21 patients reported a BI scor <100, while 53 had mRS score
>16. High rates of in-hospital mortality (42.3%) also found in another prospective cohort
study that had taken into account patients treated with warfarin, following acute intracranial
hemorrhage7. Rankin scale measures for degrees of disability of dependents were found to be
approximately 5 for these patients under warfarin medication.
Resumption of anticoagulation agents
Several studies evaluated impacts of anticoagulation resumption on acute subdural
hemorrhage. A retrospective study was conducted among 140 patients under low dose
medication of acetylsalicylic acid after burr-hole drainage of subdural haematoma. No
significant associations were found between the low dose of the anticoagulation resumption
and recurrence of subdural haematoma among the patients (95% CI, 1.001-1.022; P =.06)10.
Optimal timings of resumption of warfarin after subdural haemorrhage were investigated by
another study that calculated the cardiac indications for anticoagulation or previous stroke
with the help of Cox model. While 177 patients under warfarin-induced subdural

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haemorrhage were found to survive the first week, 59 patients received the medication after
5.6 median weeks (IQR 2.6 –17). While warfarin resumption was found to produce recurrent
haemorrhage and had a hazard ratio 5.6, when compared to that of 0.11 hazard ratio for
stroke. Optimal water in reception time was an estimated 10 to 30 weeks, which was found to
increase risks of subdural haemorrhage and ischemic stroke11. In another retrospective cohort
study 71 patients were found to report major haemorrhage symptoms and 110 of them
experience symptoms of minor haemorrhage. Thromboembolism was also found among eight
patients. Kinds of antithrombotic agents did not create any significant impact on haemorrhage
frequency when compared to patients without the history of any anticoagulant medication.
Risks of rebleeding were also found among patients who had resumed the anticoagulation
therapy, after the operation for subdural haematoma OR 0.06; 95% CI 0.02–0.2; p < 0.01).
Early resumption of antithrombotic agent within 3 days, post operation was considered safe
for subdural haematoma patients12.
Discussion
Significantly high subdural haematoma associated risks are observed among patients
who are underwater in medication in comparison to other antiplatelets. Intracellular
haemorrhage exists in less frequency in combination with the use of other oral anticoagulant.
Upon comparison with other forms of antiplatelet therapy, warfarin has been found to
increase risks of subdural haematoma by three times. This shows consistency with previous
findings of a systematic review that included 9 trials focusing on antiplatelet therapy, in that
was conducted among 11000 participants13. Upon comparison of warfarin with direct oral
thrombin inhibitors such as dabigatran, subdural haematoma was found at an increased risk of
80% with warfarin medication. Similarities for also found with another study that
demonstrated risks of subdural haematoma with antiplatelet and warfarin therapy (OR, 3.0;
95% CI, 1.5, 6.1), compared to factor Xa inhibitors (OR, 2.9; 95% CI, 2.1, 4.1)14. Fewer
evidences exist in cases of atrial fibrillation or myocardial infarction, whether INR elevation
in absence of warfarin therapy, will indicate traumatic coagulopathy. There exist a range of
outcomes with preoperative use of warfarin, when compared to without its use. Warfarin has
been found to result in deterioration of the functional and clinical outcome of patience, than
other anticoagulants15.
No functional improvements were also seen among the patients, despite enhancement
of the neurological function. Surgical evaluation plays an essential role in elderly patients
under anticoagulation therapy, who have undergone burr-hole drainage for subdural

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haematoma. Apart from thromboembolism and atrial fibrillation, falls are also associated
with increased rates of injury among patients. Older people under anticoagulation therapy
have been found to demonstrate increase rates of mortality. This identifies the potential for
increasing incidence of intracranial haemorrhage and subdural haematoma among such
people. Warfarin use an abnormal INR, when compared to other anticoagulants have
independently predicted increased risks of ICH in cases of ground level falls, among
patients16. New model anticoagulants such as, factor Xa inhibitor has been found to lack
reversal agents on comparison to warfarin17.
Implications for research
Emerging evidence exists for reduced risks of subdural haemorrhage, with the use of
new oral anticoagulants, in place of warfarin. Taking into consideration elderly patients with
more incidence rates of chronic subdural haematoma, novel oral anticoagulant therapy should
be considered as the mainstay treatment. Lower risks of intracranial haemorrhage have also
been observed during NOAC medication, when compared to warfarin18.
Implications to health
Greater emphasis must also be put to patient education. Efforts must be taken by
nursing professionals to create awareness among patients about the risk factors and lifestyle
modifications that are associated with effects of anticoagulant. Potential risks and benefits of
anticoagulant therapy must also be discussed with the patients18.
Recommendations
Lack of clarity exists regarding the efficacy and safety of resuming warfarin treatment
among adult patients, following an intracranial haemorrhage or subdural haematoma. Further
randomised control trials should be conducted for data mining risks of recurrent intracranial
hemorrhage after resumption of anticoagulation therapy. New oral anticoagulants have been
identified safe, with lower incidence of intracranial haemorrhage and can be restarted,
whenever necessary20. However, several challenges exist due to lack of optimal reversing
agent. More trials should be conducted for developing reversal agents that are normal and
safe for new generation oral anticoagulants.
Limitations
The systematic review has several limitations in terms of careful interpretation of
data, which prevents for the recommendations for patient care. However, quality of the
review has not been compromised, since data has been collected from heterogeneous patient

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groups, regardless of their ethnicity and background, from prospective and retrospective
cohort studies. The studies provide high quality evidence for the same. One major limitation
can be associated with the fact that the observational studies included non-binding methods,
which might have added to bias in the results. Studies published over a long period have also
been used for data collection. Reporting bias is restricted, since case reports are not included
in the review. It might be effective to conduct prospective trials, for drawing a firm
conclusion14.
Conclusion
Warfarin administration has been associated with development of high intracranial
pressure that subsequently leads to subdural haematoma, among adults under anticoagulant
therapy. Major findings of the study suggest that administration of warfarin medication
results in a deterioration of clinical and functional outcomes, upon comparison to other
anticoagulants and also elevates the mortality rate. Thus, it can be concluded that resumption
of anticoagulants as early as 5 days, post operation is considered safe for patients, having
suffered intracranial haemorrhage, more commonly subdural haematoma. Future research
must be targeted to reduced incidence of mortality and morbidity in elderly patients and
anticoagulation therapy. This calls for the need of an effective collaboration between
emergency department personnel, transfusion medicine, hematology, neurosurgery services,
and critical care specialists.