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Review Article

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Blood Res 2021; 56(1):

Published online March 31, 2021

https://doi.org/10.5045/br.2021.2020083

© The Korean Society of Hematology

Updated recommendations for the treatment of venous thromboembolism

Junshik Hong1, Seo-Yeon Ahn2, Yoo Jin Lee3, Ji Hyun Lee4, Jung Woo Han5, Kyoung Ha Kim6, Ho-Young Yhim7, Seung-Hyun Nam8, Hee-Jin Kim9, Jaewoo Song10, Sung-Hyun Kim4, Soo-Mee Bang11, Jin Seok Kim12, Yeung-Chul Mun13, Sung Hwa Bae14, Hyun Kyung Kim15, Seongsoo Jang16, Rojin Park17, Hyoung Soo Choi18, Inho Kim1, Doyeun Oh19; on behalf of the Korean Society of Hematology Thrombosis and Hemostasis Working Party

Author Info. +

1Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Department of Hematology-Oncology, 2Chonnam National University Hwasun Hospital, Hwasun, 3Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 4Division of Hematology and Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Hospital, Busan, 5Division of Pediatric Hematology and Oncology, Department of Pediatrics, Yonsei University College of Medicine, Yonsei University Health System, 6Department of Oncology and Hematology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Department of Internal Medicine, 7Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, 8Veterans Health Service Medical Center, 9Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 10Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, 11Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, 12Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Department of Internal Medicine, 13Ewha Womans University College of Medicine, Seoul, 14Daegu Catholic University School of Medicine, Daegu Catholic University Hospital, Daegu, Department of Laboratory Medicine, 15Seoul National University College of Medicine, Seoul National University Hospital, 16University of Ulsan College of Medicine, Asan Medical Center, 17Soonchunhyang University Seoul Hospital, Seoul, 18Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 19Division of Hematology-Oncology, Department of Internal Medicine, CHA University School of Medicine, Seongnam, Korea

Correspondence to : Sung-Hyun Kim, M.D., Ph.D.
Division of Hematology and Oncology, Department of Internal Medicine, Dong-A University College of Medicine, 26 Daesingongwon-ro, Seo-gu, Busan 49201, Korea
E-mail: kshmoon@dau.ac.kr

Received: April 17, 2020; Revised: January 6, 2021; Accepted: January 6, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants. The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Keywords Venous thromboembolism, Deep vein thrombosis, Pulmonary embolism, Anticoagulants

Article

Review Article

Blood Res 2021; 56(1): 6-16

Published online March 31, 2021 https://doi.org/10.5045/br.2021.2020083

Copyright © The Korean Society of Hematology.

Updated recommendations for the treatment of venous thromboembolism

Junshik Hong1, Seo-Yeon Ahn2, Yoo Jin Lee3, Ji Hyun Lee4, Jung Woo Han5, Kyoung Ha Kim6, Ho-Young Yhim7, Seung-Hyun Nam8, Hee-Jin Kim9, Jaewoo Song10, Sung-Hyun Kim4, Soo-Mee Bang11, Jin Seok Kim12, Yeung-Chul Mun13, Sung Hwa Bae14, Hyun Kyung Kim15, Seongsoo Jang16, Rojin Park17, Hyoung Soo Choi18, Inho Kim1, Doyeun Oh19; on behalf of the Korean Society of Hematology Thrombosis and Hemostasis Working Party

1Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Department of Hematology-Oncology, 2Chonnam National University Hwasun Hospital, Hwasun, 3Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 4Division of Hematology and Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Hospital, Busan, 5Division of Pediatric Hematology and Oncology, Department of Pediatrics, Yonsei University College of Medicine, Yonsei University Health System, 6Department of Oncology and Hematology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Department of Internal Medicine, 7Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, 8Veterans Health Service Medical Center, 9Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 10Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, 11Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, 12Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Department of Internal Medicine, 13Ewha Womans University College of Medicine, Seoul, 14Daegu Catholic University School of Medicine, Daegu Catholic University Hospital, Daegu, Department of Laboratory Medicine, 15Seoul National University College of Medicine, Seoul National University Hospital, 16University of Ulsan College of Medicine, Asan Medical Center, 17Soonchunhyang University Seoul Hospital, Seoul, 18Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 19Division of Hematology-Oncology, Department of Internal Medicine, CHA University School of Medicine, Seongnam, Korea

Correspondence to:Sung-Hyun Kim, M.D., Ph.D.
Division of Hematology and Oncology, Department of Internal Medicine, Dong-A University College of Medicine, 26 Daesingongwon-ro, Seo-gu, Busan 49201, Korea
E-mail: kshmoon@dau.ac.kr

Received: April 17, 2020; Revised: January 6, 2021; Accepted: January 6, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants. The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Keywords: Venous thromboembolism, Deep vein thrombosis, Pulmonary embolism, Anticoagulants

Fig 1.

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Figure 1.Overview of anticoagulant therapy for venous thromboembolism. a)Doses can be modified according to organ function, body weight, or concomitant medications. Abbreviations: INR, international normalized ratio; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin.
Abbreviations: INR, international normalized ratio; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin.
Blood Research 2021; 56: 6-16https://doi.org/10.5045/br.2021.2020083

Fig 2.

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Figure 2.Pregnancy-adapted YEARS algorithm for suspected acute pulmonary embolism in pregnant patients. a)If a woman has clinical sign of DVT, check compression ultrasonography of the symptomatic leg and initiate anticoagulant if DVT is confirmed. b)Initiate ant-icoagulant if chest CTPA indicates PE.
Abbreviations: CTPA, computed pulmonary angiography; DVT, deep vein thrombosis; PE, pulmonary embolism.
Blood Research 2021; 56: 6-16https://doi.org/10.5045/br.2021.2020083

Table 1 . Use of anticoagulants for the treatment of venous thromboembolism in patients with renal insufficiency..

AnticoagulantRecommendationa)
Unfractionated heparinCrCl ≥30 mL/min: no adjustment
CrCl <30 mL/min: no adjustment, use with caution
LMWHCrCl ≥30–80 mL/min: no adjustment, use with caution
CrCl <30 mL/min: enoxaparin - 1 mg/kg subcutaneously once a day, use with caution, anti-Xa monitoring is recommended if applicable; dalteparin - dose adjustment according to anti-Xa activity, use with caution
WarfarinNo adjustment recommended
EdoxabanCrCl ≥50 mL/min: no adjustment
CrCl 15–49 mL/min: 30 mg once daily
CrCl <15 mL/min: not recommended
DabigatranCrCl ≥50 mL/min: no adjustment
CrCl 30–49 mL/min: 110 mg twice daily
CrCl <30 mL/min: not recommended
Rivaroxaban/ApixabanCrCl ≥30 mL/min: no adjustment
CrCl 15–29 mL/min: no adjustment, use with caution
CrCl <15 mL/min: not recommended

a)Detailed recommendations may differ slightly according to guidelines and in the context of clinical trials. The list above is based on the approval package of each drug from the Korean Food and Drug Safety (KFDS) for the treatment of venous thromboembolism..

Abbreviations: CrCl, creatinine clearance; LMWH, low-molecular-weight heparin..

Table 2 . Characteristics of common anticoagulants and its approved or potential antidotes..

AnticoagulantsMetabolism and excretionPlasma half-lifeAntidotes
UFHRapid endothelial internalization40–90 minutesProtamine sulfate
Slow renal clearance
LMWHRenal excretion4 hoursProtamine sulfate (ciraparantaga))
VKAHepatic metabolism40 hoursOral or IV Vitamin K
Fresh frozen plasma
Dabigatran80% renal, 20% hepatic13 hoursIdarucizumab (ciraparantaga))
Apixaban27% renal, 73% hepatic12 hoursAndexanet alfa (ciraparantaga))
Edoxaban50% renal, 50% hepatic10–14 hours(andexanet alfa, ciraparantaga))
Rivaroxaban35% renal, 65% hepatic5–9 hoursAndexanet alfa (ciraparantaga))

a)Under investigation..

Abbreviations: IV, intravenous; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin; VKA, vitamin K antagonist..
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