Double bad luck: pulmonary embolism and vaginal bleeding - a case report

Double bad luck: pulmonary embolism and vaginal bleeding - a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Double bad luck: pulmonary embolism and vaginal bleeding - a case report Sarah Shiba, Jan Van Keer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3382374/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Pulmonary embolism is a common and potentially fatal condition. Exogenous estrogens in contraceptives are associated with an increased risk of venous thrombo-embolism. However, discontinuation of a combined oral contraceptive can lead to severe withdrawal bleeding in an anticoagulated patient. Case presentation: We report a case of a 47-year-old female who presented to the emergency room with a two-day history of worsening shortness of breath and chest pain. Her chronic medication included a combined oral contraceptive pill. Transthoracic echocardiogram showed pulmonary hypertension and right ventricular dilatation. Computerized tomography scan revealed bilateral pulmonary embolism. She received thrombolysis with alteplase and was started on rivaroxaban. Five days after discharge, however, she was readmitted with severe vaginal bleeding. Discussion and conclusion: We describe a case of submassive pulmonary embolism, treated with thrombolysis and anticoagulation, who developed severe vaginal bleeding after stopping the contraceptive pill. While discontinuation of combined contraceptive is important in reducing the risk of recurrent thrombosis, we argue that discontinuation can potentially be postponed until after the initial phase of high-intensity anticoagulation and until a safe alternative has been established. Figures Figure 1 Figure 2 Figure 3 Background Pulmonary embolism is a common and potentially fatal condition. Pulmonary embolism usually arises from a deep venous thrombosis of the lower extremities. Rarely it originates from the pelvic, renal, upper extremity veins or right heart. The risk factors for are summarized in Virchow's triad: hypercoagulability, stasis, and endothelial injury. Exogenous estrogens, either as contraceptives or as post-menopausal hormone replacement, induce a prothrombotic state and are thus associated with an increased risk of venous thrombo-embolism( 1 ). Case presentation A 47-year-old woman, non-smoker, with history of asthma and pollen allergy contacted the emergency services for subacute dyspnea, exercise intolerance and chest tightness. Her daily medication consisted of: desloratadine, a beclomethason/formoterol inhaler and an ethinylestradiol/levonorgestrel contraceptive. She had been feeling unwell for two days and thought her symptoms were due to an asthma attack. She had already tried increasing her inhaler, but without effect. Two days earlier she had returned from holiday after an 18-hour bus ride. She had taken the same bus on the outward journey 10 days earlier. On arrival, the first responders team found her sitting on the ground in respiratory distress, tachypneic, tachycardic, hypoxic, hypotensive, and afebrile. Her vital signs were: respiratory rate 36 breaths per minute, heart rate 142 beats per minute, oxygen saturation 72% on room air, blood pressure 64/43 mmHg and temperature 35.8°C. ECG showed sinus tachycardia, without Q waves or ischemic ST/T changes. The patient was given 12L/m of oxygen via face mask and 500 mL of normal saline and was brought to the hospital. Repeat ECG showed similar findings, lab (results of which were only available later) showed hemoglobin of 14.0 g/dL, troponin 330 ng/L, d-dimers 7509 mcg/L, C-reactive protein 30.4 mg/L and creatinine of 1.31 mg/dL, corresponding to estimated glomerular filtration rate of 48 mL/min/1.73m 2 . Quick-look echocardiogram showed a nondilated and normocontractile left ventricle, a dilated right ventricle with leftward shift of the interventricular septum and pulmonary hypertension with and estimated right ventricular systolic pressure of 64 mmHg + central venous pressure ( Fig. 1 ) . Inferior caval vein was plethoric without respiratory variation. There was no severe valvular pathology. Currently, blood pressure was 142/95 mmHg, heart rate 139 bpm and oxygen saturation 97% while breathing 12 L/m oxygen via face mask. Acute pulmonary embolism was suspected. The patient was given 80 mg of enoxaparin (weight = 83 kg) and an urgent computerized tomography scan with intravenous contrast was performed, which confirmed the diagnosis of bilateral pulmonary embolism ( Fig. 2 ). The Pulmonary Embolism Severity Index (PESI) score, calculated with the help of an online tool( 2 ), was 167: very high risk. Based on hemodynamic compromise, right ventricular dysfunction on echocardiogram and very high-risk PESI score, thrombolysis was administered. Alteplase was given as a 10 mg bolus and 90 mg infusion over 2 hours and the patient was admitted to the cardiac intensive care unit. Her condition gradually improved over the next few hours, with a decrease in heart rate from 130 bpm to 80 bpm and normalization of serum creatinine to 0.81 mg/dL (corresponding to eGFR of 85 mL/min/1.73 m 2 ) by the second day. Repeat echocardiography showed a marked decrease in right ventricular dimensions and lowering of estimated right ventricular pressure to 27 mmHg + central venous pressure. In addition to the pulmonary embolism, the patient was found to have extensive deep venous thrombosis of the right femoral vein. Thrombophilia screening revealed a Factor V Leiden mutation. After two days of continued therapeutic dose enoxaparin, she was switched to rivaroxaban, 15 mg twice daily and at day 6 she was discharged with this therapy for a total of 21 days, after which she should decrease the dose to 20 mg once daily. She was instructed to discontinue her combined oral contraceptive pill indefinitely. Five days later, however, the patient was re-admitted to the hospital with pre-syncope. She was looking pale. During the few days between hospital admissions, she had had severe vaginal bleeding, with need for hygienic pad change every few hours. Vital signs were: blood pressure 102/74 mmHg, heart rate 114 beats per minute, respiratory rate 18 per minute, saturation 99% on room air, temperature 36.7°C. There was no hematuria, melaena or hematochezia. Hemoglobin was 6.3 g/dL, ß-HCG negative, creatinine 0.96 mg/dL and C-reactive protein 2.1 mg/L. INR was 1.4 (12 hours after last intake of rivaroxaban). Figure 3 shows the evolution of anemia since the previous hospitalization. 500 mL of normal saline and two units of packed cells were infused. Rivaroxaban was withheld for 5 days and substituted for prophylactic dose enoxaparin, 40 mg once daily. Lynestrenol, an oral progestin, was administered at 5 mg twice daily for two weeks, and then switched to nomegestrol 5 mg once daily, to be taken continuously. An oral iron supplement was started to replete the iron stores. The patient was discharged on day 7. Discussion and conclusion We described a typical case of submassive pulmonary embolism, treated with thrombolysis and anticoagulation, in the context of immobilization and combined oral contraceptive use in a woman with Factor V Leiden, who developed severe vaginal bleeding after stopping the contraceptive pill. Submassive pulmonary embolism is characterized by the presence of right ventricular dysfunction and elevated biomarkers (troponin) in the absence of sustained hypotension. The role of thrombolysis in hemodynamically stable patients with submassive pulmonary embolism continues to be an area of debate. The risks and benefits of thrombolysis should be balanced on the case-by-case basis. Prognostic scores such as the PESI model can help clinicians with decision-making( 3 ). Combined oral contraceptive use is associated with an increased risk of venous thrombo-embolism. Therefore, women with a history of thrombosis should be advised to seek alternative (i.e. non-estrogen containing) methods of contraception. However, this case illustrates that timing of discontinuation of combined contraceptive pill should be chosen wisely, considering the risk of withdrawal bleeding. This patient had been taking a high dose second generation pill on a continuous basis (without pill-free days) because of severe pre-menopausal menometrorrhagia during the years before the current events. In hindsight, a severe withdrawal bleeding and/or recurrence of the previous menometrorrhagia could have been expected. In fact, continuation of a combined oral contraceptive pill in women with venous thromboembolism appears to be safe, as long as these women are taking anticoagulation. A subgroup analysis of women under 60 years treated with anticoagulants for acute venous thrombo-embolism included in the EINSTEIN DVT and PE trials, showed a similar rate of recurrent venous thrombo-embolism in those who did and did not receive hormonal therapy( 4 ). Therefore, discontinuation of a combined oral contraceptive pill can potentially be postponed until after the initial phase of high-intensity anticoagulation and until a safe alternative has been established. Abbreviations ß-HCG ß- human chorionic gonadotrophin ECG electrocardiogram eGFR estimated glomerular filtration rate INR international normalized ratio PESI Pulmonary Embolism Severity Index Declarations Ethical Approval The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Ethical approval was obtained from the Ethical Committee: Ethische Commissie AZ Turnhout, Steenweg op Merksplas 44, 2300 Turnhout, accreditation number OG 192. Consent to participate Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analyzed for this case report. Competing interests The authors declare that they have no competing interests. Funding There was no financial support for this work. Authors’ contributions S.S. wrote the main manuscript. J.V.K. prepared Figures 1-3 and edited the manuscript. Both authors reviewed the manuscript. References Reitsma PH, Versteeg HH, Middeldorp S. Mechanistic view of risk factors for venous thromboembolism. Arterioscler Thromb Vasc Biol. 2012;32(3):563–8. https:// reference.medscape.com/calculator/86/pulmonary-embolism-severity-index-pesi . Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172(8):1041–6. Martinelli I, Lensing AWA, Middeldorp S, Levi M, Beyer-Westendorf J, Van Bellen B, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. 2016;127(11):1417–25. Available from: http://ashpublications.org/blood/article-pdf/127/11/1417/1391833/1417.pdf Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 15 Feb, 2024 Reviews received at journal 11 Jan, 2024 Reviewers agreed at journal 09 Jan, 2024 Reviewers invited by journal 30 Oct, 2023 Editor assigned by journal 06 Oct, 2023 Submission checks completed at journal 06 Oct, 2023 First submitted to journal 24 Sep, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3382374","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":238234908,"identity":"0b125df0-cff7-401e-8ae7-0f13a8fba018","order_by":0,"name":"Sarah Shiba","email":"","orcid":"","institution":"Erasmus Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Shiba","suffix":""},{"id":238234909,"identity":"2a34abcd-2ecc-4961-ac6b-50ff27603235","order_by":1,"name":"Jan Van Keer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYBACxgYIbQBiP4CwecBkAjFamA0gNA9YA04tMABSyiZBlBbm9rMHmHlq7hjzs/c+q/jx50/i9tm9Bx/z/mDI48flsJ68BGaeY8/MJHuOm93s4TFInHPnXLIxTwJDsWQDLr/kGDDOYDtsY3Ajje0Gj4RB4gyJHDNpoJbEDQdwaOl/A9Ty77CN/f1nbIV/DJC07MelZUaOAcPHtsNmBhJsbMw8Cci24PLLjDcGBz72HTaWOJPGLC1zwNgYqMXYcE6aRLEEDlsM+3MMHyR8O2zY336M8eObP3KyQC2GD97Y2OTx4/C+IVAcq2kSOJzFwCCPU2YUjIJRMApGAQwAAOzUVxgjzoo1AAAAAElFTkSuQmCC","orcid":"","institution":"AZ Turnhout","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jan","middleName":"Van","lastName":"Keer","suffix":""}],"badges":[],"createdAt":"2023-09-24 22:14:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3382374/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3382374/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":44456895,"identity":"12c9fab7-03dc-4067-af58-fe735389e5f7","added_by":"auto","created_at":"2023-10-11 17:22:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":443333,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eTransthoracic echocardiogram: \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eA.\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Parasternal short axis image, showing dilated right ventricle with systolic D-shaping of the interventricular septum (arrow); \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eB.\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eContinuous wave doppler in apical four chamber view, showing estimated pulmonary artery systolic pressure of 64 mmHg + central venous pressure, as measured by tricuspid regurgitation jet velocity (arrow).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3382374/v1/f01e23e3459e2004de1e3921.png"},{"id":44456907,"identity":"bcb41b0d-4b27-431b-8dc3-d3437e89d493","added_by":"auto","created_at":"2023-10-11 17:22:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":175954,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eComputerized tomography scan with intravenous contrast, showing pulmonary embolism (arrows) in right and left pulmonary artery\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3382374/v1/8c29af542b6df96d7ee3ac04.png"},{"id":44456908,"identity":"e130deff-3e4d-45f5-8530-91633d3f2bb5","added_by":"auto","created_at":"2023-10-11 17:22:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51685,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eGraph showing evolution of Hemoglobin (y-axis, in g/dL) over Time (x-axis, in days). First hospitalization is, from day 0 to 6, second hospitalization is from day 11 to 18.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3382374/v1/3f8a7731f190b0d6c03c907b.png"},{"id":44456915,"identity":"be5354b5-0d21-4469-a7af-f182051be860","added_by":"auto","created_at":"2023-10-11 17:22:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":926375,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3382374/v1/564d1b3f-8bc5-4398-b1f1-7878754beab2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Double bad luck: pulmonary embolism and vaginal bleeding - a case report","fulltext":[{"header":"Background","content":"\u003cp\u003ePulmonary embolism is a common and potentially fatal condition. Pulmonary embolism usually arises from a deep venous thrombosis of the lower extremities. Rarely it originates from the pelvic, renal, upper extremity veins or right heart. The risk factors for are summarized in Virchow's triad: hypercoagulability, stasis, and endothelial injury. Exogenous estrogens, either as contraceptives or as post-menopausal hormone replacement, induce a prothrombotic state and are thus associated with an increased risk of venous thrombo-embolism(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 47-year-old woman, non-smoker, with history of asthma and pollen allergy contacted the emergency services for subacute dyspnea, exercise intolerance and chest tightness. Her daily medication consisted of: desloratadine, a beclomethason/formoterol inhaler and an ethinylestradiol/levonorgestrel contraceptive. She had been feeling unwell for two days and thought her symptoms were due to an asthma attack. She had already tried increasing her inhaler, but without effect. Two days earlier she had returned from holiday after an 18-hour bus ride. She had taken the same bus on the outward journey 10 days earlier.\u003c/p\u003e \u003cp\u003eOn arrival, the first responders team found her sitting on the ground in respiratory distress, tachypneic, tachycardic, hypoxic, hypotensive, and afebrile. Her vital signs were: respiratory rate 36 breaths per minute, heart rate 142 beats per minute, oxygen saturation 72% on room air, blood pressure 64/43 mmHg and temperature 35.8\u0026deg;C. ECG showed sinus tachycardia, without Q waves or ischemic ST/T changes. The patient was given 12L/m of oxygen via face mask and 500 mL of normal saline and was brought to the hospital. Repeat ECG showed similar findings, lab (results of which were only available later) showed hemoglobin of 14.0 g/dL, troponin 330 ng/L, d-dimers 7509 mcg/L, C-reactive protein 30.4 mg/L and creatinine of 1.31 mg/dL, corresponding to estimated glomerular filtration rate of 48 mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e. Quick-look echocardiogram showed a nondilated and normocontractile left ventricle, a dilated right ventricle with leftward shift of the interventricular septum and pulmonary hypertension with and estimated right ventricular systolic pressure of 64 mmHg\u0026thinsp;+\u0026thinsp;central venous pressure \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Inferior caval vein was plethoric without respiratory variation. There was no severe valvular pathology. Currently, blood pressure was 142/95 mmHg, heart rate 139 bpm and oxygen saturation 97% while breathing 12 L/m oxygen via face mask.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAcute pulmonary embolism was suspected. The patient was given 80 mg of enoxaparin (weight\u0026thinsp;=\u0026thinsp;83 kg) and an urgent computerized tomography scan with intravenous contrast was performed, which confirmed the diagnosis of bilateral pulmonary embolism \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe Pulmonary Embolism Severity Index (PESI) score, calculated with the help of an online tool(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), was 167: very high risk. Based on hemodynamic compromise, right ventricular dysfunction on echocardiogram and very high-risk PESI score, thrombolysis was administered. Alteplase was given as a 10 mg bolus and 90 mg infusion over 2 hours and the patient was admitted to the cardiac intensive care unit. Her condition gradually improved over the next few hours, with a decrease in heart rate from 130 bpm to 80 bpm and normalization of serum creatinine to 0.81 mg/dL (corresponding to eGFR of 85 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e) by the second day. Repeat echocardiography showed a marked decrease in right ventricular dimensions and lowering of estimated right ventricular pressure to 27 mmHg\u0026thinsp;+\u0026thinsp;central venous pressure. In addition to the pulmonary embolism, the patient was found to have extensive deep venous thrombosis of the right femoral vein. Thrombophilia screening revealed a Factor V Leiden mutation. After two days of continued therapeutic dose enoxaparin, she was switched to rivaroxaban, 15 mg twice daily and at day 6 she was discharged with this therapy for a total of 21 days, after which she should decrease the dose to 20 mg once daily. She was instructed to discontinue her combined oral contraceptive pill indefinitely.\u003c/p\u003e \u003cp\u003eFive days later, however, the patient was re-admitted to the hospital with pre-syncope. She was looking pale. During the few days between hospital admissions, she had had severe vaginal bleeding, with need for hygienic pad change every few hours. Vital signs were: blood pressure 102/74 mmHg, heart rate 114 beats per minute, respiratory rate 18 per minute, saturation 99% on room air, temperature 36.7\u0026deg;C. There was no hematuria, melaena or hematochezia. Hemoglobin was 6.3 g/dL, \u0026szlig;-HCG negative, creatinine 0.96 mg/dL and C-reactive protein 2.1 mg/L. INR was 1.4 (12 hours after last intake of rivaroxaban).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the evolution of anemia since the previous hospitalization. 500 mL of normal saline and two units of packed cells were infused. Rivaroxaban was withheld for 5 days and substituted for prophylactic dose enoxaparin, 40 mg once daily. Lynestrenol, an oral progestin, was administered at 5 mg twice daily for two weeks, and then switched to nomegestrol 5 mg once daily, to be taken continuously. An oral iron supplement was started to replete the iron stores. The patient was discharged on day 7.\u003c/p\u003e"},{"header":"Discussion and conclusion","content":"\u003cp\u003eWe described a typical case of submassive pulmonary embolism, treated with thrombolysis and anticoagulation, in the context of immobilization and combined oral contraceptive use in a woman with Factor V Leiden, who developed severe vaginal bleeding after stopping the contraceptive pill.\u003c/p\u003e \u003cp\u003eSubmassive pulmonary embolism is characterized by the presence of right ventricular dysfunction and elevated biomarkers (troponin) in the absence of sustained hypotension. The role of thrombolysis in hemodynamically stable patients with submassive pulmonary embolism continues to be an area of debate. The risks and benefits of thrombolysis should be balanced on the case-by-case basis. Prognostic scores such as the PESI model can help clinicians with decision-making(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCombined oral contraceptive use is associated with an increased risk of venous thrombo-embolism. Therefore, women with a history of thrombosis should be advised to seek alternative (i.e. non-estrogen containing) methods of contraception. However, this case illustrates that timing of discontinuation of combined contraceptive pill should be chosen wisely, considering the risk of withdrawal bleeding. This patient had been taking a high dose second generation pill on a continuous basis (without pill-free days) because of severe pre-menopausal menometrorrhagia during the years before the current events. In hindsight, a severe withdrawal bleeding and/or recurrence of the previous menometrorrhagia could have been expected.\u003c/p\u003e \u003cp\u003eIn fact, continuation of a combined oral contraceptive pill in women with venous thromboembolism appears to be safe, as long as these women are taking anticoagulation. A subgroup analysis of women under 60 years treated with anticoagulants for acute venous thrombo-embolism included in the EINSTEIN DVT and PE trials, showed a similar rate of recurrent venous thrombo-embolism in those who did and did not receive hormonal therapy(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Therefore, discontinuation of a combined oral contraceptive pill can potentially be postponed until after the initial phase of high-intensity anticoagulation and until a safe alternative has been established.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u0026szlig;-HCG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e\u0026szlig;- human chorionic gonadotrophin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eelectrocardiogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eestimated glomerular filtration rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einternational normalized ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePESI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePulmonary Embolism Severity Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthical Approval\u003c/h2\u003e\n\u003cp\u003eThe study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.\u0026nbsp;Ethical approval was obtained from the Ethical Committee: Ethische Commissie AZ Turnhout, Steenweg op Merksplas 44, 2300 Turnhout, accreditation number OG 192.\u003c/p\u003e\n\u003ch2\u003eConsent to participate\u003c/h2\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analyzed for this case report.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThere was no financial support for this work.\u003c/p\u003e\n\u003ch2\u003eAuthors’ contributions\u003c/h2\u003e\n\u003cp\u003eS.S. wrote the main manuscript. J.V.K. prepared Figures 1-3 and edited the manuscript. Both authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eReitsma PH, Versteeg HH, Middeldorp S. Mechanistic view of risk factors for venous thromboembolism. Arterioscler Thromb Vasc Biol. 2012;32(3):563\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ehttps://\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ereference.medscape.com/calculator/86/pulmonary-embolism-severity-index-pesi\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172(8):1041\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMartinelli I, Lensing AWA, Middeldorp S, Levi M, Beyer-Westendorf J, Van Bellen B, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. 2016;127(11):1417\u0026ndash;25. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ashpublications.org/blood/article-pdf/127/11/1417/1391833/1417.pdf\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3382374/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3382374/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Pulmonary embolism is a common and potentially fatal condition. Exogenous estrogens in contraceptives are associated with an increased risk of venous thrombo-embolism. However, discontinuation of a combined oral contraceptive can lead to severe withdrawal bleeding in an anticoagulated patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e We report a case of a 47-year-old female who presented to the emergency room with a two-day history of worsening shortness of breath and chest pain. Her chronic medication included a combined oral contraceptive pill. Transthoracic echocardiogram showed pulmonary hypertension and right ventricular dilatation. Computerized tomography scan revealed bilateral pulmonary embolism. She received thrombolysis with alteplase and was started on rivaroxaban. Five days after discharge, however, she was readmitted with severe vaginal bleeding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion and conclusion:\u003c/strong\u003e We describe a case of submassive pulmonary embolism, treated with thrombolysis and anticoagulation, who developed severe vaginal bleeding after stopping the contraceptive pill. While discontinuation of combined contraceptive is important in reducing the risk of recurrent thrombosis, we argue that discontinuation can potentially be postponed until after the initial phase of high-intensity anticoagulation and until a safe alternative has been established.\u003c/p\u003e","manuscriptTitle":"Double bad luck: pulmonary embolism and vaginal bleeding - a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-11 17:22:20","doi":"10.21203/rs.3.rs-3382374/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-15T12:19:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-11T15:28:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"44b6406c-b38a-49b1-9fe2-f0bcfd844423","date":"2024-01-09T16:58:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-10-30T08:39:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-10-06T06:17:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-10-06T06:17:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Emergency Medicine","date":"2023-09-24T22:03:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fa826aa1-389b-4222-9e07-d7143641b7c7","owner":[],"postedDate":"October 11th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-04T03:54:51+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-11 17:22:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3382374","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3382374","identity":"rs-3382374","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}