LETTERS TO THE EDITOR
|Year : 2022 | Volume
| Issue : 6 | Page : 1236-1238
A short course of tranexamic acid to continue anticoagulation and control bleed in cerebral venous thrombosis with abnormal uterine bleeding and anemia
Shreyashi Jha, AV R. Taallapalli, Pratik Kishore, Saraswati Nashi, Girish Baburao Kulkarni
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru, Karnataka, India
|Date of Submission||17-Jul-2022|
|Date of Decision||01-Sep-2022|
|Date of Acceptance||11-Sep-2022|
|Date of Web Publication||3-Dec-2022|
Girish Baburao Kulkarni
Department of Neurology, NIMHANS, Bengaluru
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jha S, R. Taallapalli A V, Kishore P, Nashi S, Kulkarni GB. A short course of tranexamic acid to continue anticoagulation and control bleed in cerebral venous thrombosis with abnormal uterine bleeding and anemia. Ann Indian Acad Neurol 2022;25:1236-8
|How to cite this URL:|
Jha S, R. Taallapalli A V, Kishore P, Nashi S, Kulkarni GB. A short course of tranexamic acid to continue anticoagulation and control bleed in cerebral venous thrombosis with abnormal uterine bleeding and anemia. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Feb 6];25:1236-8. Available from: https://www.annalsofian.org/text.asp?2022/25/6/1236/361569
Cerebral venous thrombosis (CVT) comprises <1% of all strokes, frequent in adults, mainly in women, with an annual incidence of three to four cases per million and a mortality rate of 8%.,
Abnormal uterine bleeding (AUB) is defined by the International Federation of Obstetrics and Gynecology (FIGO) as any departure from a normal menstrual cycle pattern, severe enough to impact the quality of life. Hormonal preparations (HPs) are prescribed for the management of AUB, which increases the risk of CVT by sevenfold., Evidence is lacking in the management of emergent vaginal bleeding while on anticoagulation during the acute phase of CVT, long-term treatment of the CVT, and concurrent management of AUB. We present a series of four cases presented to our hospital with CVT coexisting with AUB complicated by HP, anemia, and breakthrough vaginal bleeding on the initiation of anticoagulation. A short course of tranexamic acid (TXA) controlled the vaginal bleeding and enabled the continuation of anticoagulation. Patients were followed up for 3 months and were continued on anticoagulation without exacerbation of the AUB or progression of the CVT.
A 39-year-old lady presented with acute headache and left focal motor seizures with generalization and left hemiparesis for 5 days. She had AUB for the past 1 year secondary to a fundal fibroid. Her magnetic resonance imaging (MRI) showed thrombosis of the anterior and middle one-third of the superior sagittal sinus and left transverse sinus with extension into bilateral frontal veins. Blood investigations revealed anemia (Hemoglobin: 7.2 gram%). On day 3 of anticoagulation, she had vaginal bleeding. Oral TXA was given at the dose of 500 mg thrice a day for 5 days. Her vaginal bleeding stopped. Anticoagulation was continued, and anemia was corrected with blood transfusion and iron supplementation. She was discharged on oral anticoagulation with mRS 0 and planned on a hysterectomy after the completion of 6 months of oral anticoagulation.
A 48-year-old lady presented with acute headache, left focal motor seizures, and left hemiparesis for 6 days. She had AUB for the past 4 years for which she was on combined HPs for past 1 month. Her computerized tomography (CT) brain showed a right temporoparietal and occipital infarct with a midline shift of 8 mm and uncal herniation. She was taken up for urgent decompression (DC) in view of poor sensorium and impeding herniation. On postoperative day 2, she developed vaginal bleeding and was given intravenous TXA 500 mg thrice a day for 3 days. Her vaginal bleed stopped and anticoagulation was continued. She was discharged on oral anticoagulation with mRS 0.
A 35-year-old lady presented with headache and seizures for 3 days. Her MRI showed thrombosis of the right transverse and sigmoid sinus. She had AUB for 2 years secondary to multiple fundal and intramural fibroids, for which she was on depot preparation of medroxy progesterone acetate (MDPA) for 1 month. On day 3 of anticoagulation, she had vaginal bleeding. Oral TXA was given at the dose of 500 mg twice a day for 5 days. Her vaginal bleed stopped and anticoagulation was continued. She was discharged on oral anticoagulation with mRS 0 and planned on hysterectomy after completion of 6 months of oral anticoagulation.
A 45-year-old lady presented with headache and vomiting. Her CT brain with contrast showed left transverse sinus thrombosis. She had AUB for 6 months and was on HPs. On day 3 of anticoagulation, she had vaginal bleeding. Oral TXA was given at the dose of 500 mg thrice a day for 5 days. Her vaginal bleeding stopped and anticoagulation was continued. She was discharged on oral anticoagulation with mRS 0.
All patients were started on unfractionated heparin 5000 i.u. subcutaneous, 6th hourly at admission, and overlapped with Acecnocoumarol (4 mg on day 1, 3 mg on day 2, 2 mg on day 3, and continued based on INR). Target INR was 1.5–2.5. Patients were discharged on acenocoumarol at discharge and had mRS 0 at discharge and after 3 months. None of them had a recurrence of severe vaginal bleeding subsequently and two patients were advised surgical excision of fibroid, and two were on progestin preparations, which were daily oral pills in one patient and monthly depot preparations in the other. The TXA was stopped after the complete cessation of bleeding. No adverse effects were observed. It was thus reliably concluded that a short course of TXA at a relatively lower dose is effective at controlling breakthrough vaginal bleeding without causing any major adverse effects.
A normal menstrual cycle has a frequency of 24 to 38 days, and lasts 7 to 9 days with 5 to 80 mL of blood loss. Variations in any of these parameters constitute abnormal uterine bleeding. The FIGO divides the causes of AUB into structural (polyp, adenomyosis, leiomyoma, malignancy, and hyperplasia), nonstructural (ovulatory dysfunction, coagulopathy, endometrial disorders, and iatrogenic), and not otherwise classified. Therapeutic options to manage thrombotic episodes with AUB include intrauterine hormonal implant, endometrial ablation, hysteroscopic resection of fibroids, embolization, and tranexamic acid.
Tranexamic acid is a trans-stereoisomer of 4-(aminomethyl) cyclohexane-carboxylic acid, which prevents plasmin activation, reduces fibrinolysis, and stabilizes clots, without enhancing new clot formation. The TXA 1 g three times daily for 5 days significantly reduced tissue plasminogen activator and plasmin activity in the menstrual and peripheral blood of menorrhagic women, compared with pretreatment values., Although active thromboembolism is a relative contraindication, other treatment options were limited in our cases, so TXA was used after discussion with the gynecologist, and close neurological monitoring was done to look for worsening.
There are only single case reports of AUB with CVT in which the coexisting AUB was managed with hormonal intrauterine devices, and a short course of TXA. Out of all the options available to control emergent vaginal bleeding, TXA was the safest as hormonal preparations were contraindicated. However, since some studies conclude on the evidence of TXA being thrombogenic in a few case reports, it was used at a small dose and only for a few days during breakthrough bleeding alone in our case series so as not to increase the risk of thrombosis. We did not find any neurological worsening with the dose and duration of TXA used.
Our study is one of its own that has seen a cohort of four patients as compared with previous isolated case reports, who responded to the uniform treatment protocol of TXA with anticoagulation. The limitations of our study were a small number, nonexclusion of prothrombotic disorders, and only a short course of TXA.
In conclusion, this case series attempts to highlight the importance of AUB and the intake of HPs as a common cause of CVT in young women, which might create challenges in treatment. The low-dose TXA is effective in mitigating breakthrough vaginal bleeding while the patient is on anticoagulants. This observation needs larger prospective studies to further confirm.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Diacinti D, Cartocci G, Colonnese C. Cerebral venous thrombosis: A case series and a neuroimaging review of the literature. J Clin Neurosci 2018;58:142-7.
Danwang C, Mazou TN, Tochie JN, Tankeu R, Bigna JJ. Global epidemiology and patterns of cerebral venous thrombosis: A systematic review and meta-analysis protocol. BMJ Open 2018;8:e019939.
Fraser IS, Critchley HOD, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med 2011;29:383-90.
Amoozegar F, Ronksley PE, Sauve R, Menon BK. Hormonal contraceptives and cerebral venous thrombosis risk: A systematic review and meta-analysis. Front Neurol 2015;6:1-11.
Kulkarni GB, Mustare V, Abbas MM. Profile of patients with cerebral venous sinus thrombosis with cerebellar involvement. J Stroke Cerebrovasc Dis 2014;23:1106-11.
Pisoni CN, Cuadrado MJ, Khamashta MA, Hunt BJ. Treatment of menorrhagia associated with oral anticoagulation: Efficacy and safety of the levonorgestrel releasing intrauterine device (Mirena coil). Lupus 2006;15:877-80.
Chaplin S. The use of tranexamic acid in reducing bleeding complications. J Haemoph Pract 2018;3:62-70.
Leminen H, Hurskainen R. Tranexamic acid for the treatment of heavy menstrual bleeding: Efficacy and safety. Int J Womens Health 2012;4:413-21.
Mehta P, Naga VG, Pushpalatha B. Cerebral venous thrombosis following oral contraceptive pill use for menorrhagia: Management dilemma. J South Asian Feder Menopause Soc 2015;3:27-8.