|Year : 2015 | Volume
| Issue : 2 | Page : 106-108
Recurrent cerebral/cerebellar infarcts and hemorrhages in a patient with oral anticoagulants for prosthetic valve
Chirra Bhakthavatsala Reddy1, Kishor V Hegde2, Umamaheswara Reddy Venati3, Suneetha Pentyala2, Amit Agrawal4
1 Department of Cardiology, Narayana Medical College Hospital, Nellore, Andhra Pradesh, India
2 Department of Radiology, Narayana Medical College Hospital, Nellore, Andhra Pradesh, India
3 Department of Radiology, Narayana Medical College Hospital, Chinthareddypalem, Nellore - 524 003, Andhra Pradesh, India
4 Department of Neurosurgery, Narayana Medical College Hospital, Nellore, Andhra Pradesh, India
|Date of Web Publication||20-Aug-2015|
Umamaheswara Reddy Venati
Department of Radiology, Narayana Medical College Hospital, Chinthareddypalem, Nellore - 524 003, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Patients on long-term oral anticoagulant therapy (OAT) for prosthetic valves require close monitoring of their international normalized ratio (INR) levels to prevent deleterious effects. We present a case of a 35-year-old male with a known case of rheumatic heart disease who underwent mitral valve replacement and aortic valve replacement. In our patient, there was an undulation of coagulation parameters between low (INR-2.1) and high (INR-6.0) target levels, which eventually lead to ischemic strokes and fatal intracranial hemorrhage (ICH). Repeat INR was 6.0, which was much beyond the therapeutic range. Attempts to correct the coagulation abnormalities did not succeed and the patient succumbed to ICHs. All patients with valve replacement require chronic OAT. Judicious monitoring of the INR levels with dose adjustments can reduce morbidity and mortality from OAT-related complications like hemorrhage and infarction.
Keywords: Anticoagulant, Prosthetic valve, Stroke, Thromboembolic event
|How to cite this article:|
Reddy CB, Hegde KV, Venati UR, Pentyala S, Agrawal A. Recurrent cerebral/cerebellar infarcts and hemorrhages in a patient with oral anticoagulants for prosthetic valve. J Med Soc 2015;29:106-8
|How to cite this URL:|
Reddy CB, Hegde KV, Venati UR, Pentyala S, Agrawal A. Recurrent cerebral/cerebellar infarcts and hemorrhages in a patient with oral anticoagulants for prosthetic valve. J Med Soc [serial online] 2015 [cited 2020 Oct 27];29:106-8. Available from: https://www.jmedsoc.org/text.asp?2015/29/2/106/163201
| Introduction|| |
All patients with mechanical valve replacement require long-term anticoagulation.  Patients on long-term oral anticoagulant therapy (OAT) for prosthetic valves require close monitoring of their international normalized ratio (INR) levels to prevent deleterious effects. The INR levels should always be maintained within the therapeutic range. Recommended therapeutic range depends upon the type and the location of mechanical valves. ,, Depending on the patient's clinical status, anticoagulant treatment must be individualized while taking into consideration risk factors like atrial fibrillation, left ventricular dysfunction, previous thromboembolism, and hypercoagulable condition.  Patients with mechanical prosthetic heart valves and on oral anticoagulants with previous thromboembolic episode, and with INR target of 3.0 (range: 2.5-3.5) are recommended additional aspirin therapy. , During OAT if the INR levels are below the recommended therapeutic range, the patient can have thromboembolic event, whereas when they are above the therapeutic range, the patient can have intracranial hemorrhage (ICH).  In our patient, there was an undulation of coagulation parameters between low (INR of 2.1) and high (INR of 6.0) target levels, which eventually lead to ischemic strokes and fatal ICH.
| Case report|| |
A 35-year-old male, with a known case of rheumatic heart disease underwent mitral valve replacement and aortic valve replacement 5 years ago. He was on oral anticoagulants, along with low dose of aspirin since 5 years; he presented to the emergency room with sudden onset altered sensorium. The patient had a past history of cerebrovascular accident 3 years ago from which he recovered completely and had a symptom-free period until the present episode. His vitals were stable on admission. He was febrile (102°F); the Glasgow Coma Scale (GCS) gave the following data: eye opening to pain (E4), verbal response groaning to pain (V2), and motor response localizing to pain (M5). Neurological examination was unremarkable except for extensor plantars. Investigation revealed that the patient had anemia, his prothrombin time (PT) and INR levels were below the recommended therapeutic range, and there was no evidence of atrial fibrillation. Echocardiogram did not show any vegetation or thrombus on the prosthetic valves/left atrium. Three consecutive blood cultures were negative, ruling out infective endocarditis. The magnetic resonance imaging (MRI) performed showed embolic shower of acute infarcts in the thalamus, bilateral parietal cortices, chronic infarcts in the cerebellum and left insular cortex, gliotic area in the left caudate, and lentiform nucleus with hemosiderin rim. MRI also showed punctate microhemorrhages in the midbrain and the bilateral frontotemporal lobes [Figure 1] and [Figure 2]. With symptomatic treatment, the patient recovered well, and his INR was corrected to the therapeutic range before discharge. After 1 month, the patient was presented in coma to the emergency department. He was intubated and emergency computed tomography (CT) was performed, which showed recent onset hemorrhages in the right frontal and temporal lobes, and a large cerebellar hematoma with fluid-fluid levels. Repeat INR was 6.0, which was much beyond the therapeutic range. Attempts to correct the coagulation abnormalities were not successful and the patient succumbed to ICHs.
|Figure 1 : Axial T2-weighted (T2W) image showing normal cerebellum (a), Diffusion weighted imaging ( DWI) image at the level of third ventricle showing acute infarct in the right thalamus (b), DWI image at the level of Sylvian fissure showing infarcts (lacunar infarcts) in both parietal lobes (c), Susceptibility-weighted images showing gliotic area with hemosiderin rim|
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|Figure 2 : Axial NECT showing new onset in right cerebellar hematoma with fluid-fluid levels and no perihematomal edema (a and b) Axial NECT image at the level of third ventricle showing hypodense areas suggestive of gliosis in the head of the caudate, lentiform nucleus, thalamus, and left frontal cortex (c) acute bleeding with minimal perihematomal edema in the right frontal cortex (d)|
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| Discussion|| |
In developing countries, patients with rheumatic fever who undergo valve replacement therapy early in their lives are put on chronic anticoagulation. In such patients, mechanical prosthetic valves are a prime site for thrombus formation.  The risk of thrombotic recurrences, even during anticoagulation, is 1-2%. ,,,, Maintaining a desired level of anticoagulation is difficult due to many factors including drug absorption, drug interaction with foods, medicines, and variations in liver function.  In practice, the patient is maintained within a certain therapeutic range. In our case, the patient, being on indigent INR monitoring, had an ischemic episode followed by OAT-ICH. The erratic fluctuation of his INR levels could be attributed to his pharmacodynamics. It was supported by the indirect evidence that his INR levels were not in the patient recommended therapeutic range of 2.5-3.5. , The patient's INR was 2.1 when he had a thromboembolic event and 6.0 when he had ICH. ICH is the most feared and life threatening complication of OAT. ,, Current understanding of OAT-ICH remains limited as compared to spontaneous intracerebral hemorrhage (SICH). The mean age of presentation of OAT-ICH is 70 years.  In our patient, OAT-ICH had occurred at a very early age, which was unusual. OAT-ICH is more fatal than SICH, with mortality greater than 50%. , In our case, cerebellar hematoma showed classical fluid-fluid levels. ,, Similar findings were described by Jung et al.  Consumption of clotting factors with the separation of plasma or serum from the blood cells result in two components, creating a fluid-level. , All the hematomas had a decreased amount of perilesional edema, correlated to a study on OAT-induced ICH by Geber et al.  We also observed the microhemorrhages in the susceptibility imaging, which were hypothesized to be predictors of anticoagulant induced hematoma.  According to the guidelines, for a patient who has an embolic episode while on adequate OAT, the dose of anticoagulant therapy should be increased and low dose aspirin should be initiated. , In patients with INR above the therapeutic range, excessive anticoagulation is managed by withholding warfarin and with timely INR determinations. , Over- and undercorrection of INR have their own undesirable effects. Excessive anticoagulation (INR >5) highly increases the risk of hemorrhage, whereas a rapid attempt to decrease it can lead to INR falling below the therapeutic level, thereby increasing the risk of thromboembolism. ,, Patients with prosthetic heart valves with an INR between 5 and 10 and who are asymptomatic can be managed by the cessation of warfarin and administration oral vitamin K. , Warfarin therapy with dose adjustment can be started to maintain the INR in the therapeutic range, and the INR needs to be determined after 24 h and a serial monitoring is recommended. Fresh frozen plasma may be preferred to high-dose vitamin K1 in emergency situations, as the parenteral vitamin K1 increases the danger of overcorrection with a higher incidence of hypercoagulable states.
| Conclusion|| |
Every patient with valve replacement requires chronic OAT. Judicious monitoring of the INR levels with dose adjustments can reduce morbidity and mortality from OAT-related complications. The guidelines for long-term anticoagulation and management of their complications are unclear as there is a lack of evidence from randomized controlled trials. In case of anticoagulant-induced complications, especially oral anticoagulation therapy-induced hemorrhage being an alarming situation, early diagnosis is of utmost importance. Brain CT scan showing fluid-fluid level with least amount of perihematomal edema is moderately specific of oral anticoagulation therapy-induced hemorrhage. Mortality associated with OAT-ICH can only be avoided with rigorous medical management, including reversal of anticoagulation. Newer anticoagulants like dabigatran, currently approved by the Food and Drug Administration (FDA) approved for the treatment of atrial fibrillation, give hope to patients with valve replacement as they do not require monitoring, the absorption is independent of food intake, and they have better safety profile with lesser chances of OAT-induced bleeding.
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[Figure 1], [Figure 2]