ASH's comprehensive guidelines aim to improve management of venous thromboembolism

ASH, in collaboration with the McMaster University GRADE Centre, published the first six chapters of the ASH Clinical Practice Guidelines on Venous Thromboembolism to improve the diagnosis, treatment and management of blood clots, the society announced in a press event.

The six guideline chapters — published in Blood Advances represented the culmination of efforts by more than 100 VTE experts, including hematologists, other clinicians, guideline development specialists and patient representatives.

“The patients took on a role as full guideline panel members — they were participating in discussions, they were involved in any voting that took place and they were fully engaged in the process,” Holger Schünemann, MD, PhD, ASH VTE Guidelines coordination panel co-chair and professor and chair in the department of health research methods, evidence, and impact at McMaster University, said during the webcast. “We are now working with the patient representatives to translate these guidelines, which are already available in different versions for our various stakeholders, into patient-friendly material.”

Although VTE is a serious condition, causing up to 100,000 deaths each year in the U.S. alone, it remains relatively underestimated by the general population. VTE — which includes deep vein thrombosis and pulmonary embolism — affects patients of all ages and in various health care settings. For this reason, the prevention and treatment of VTE is the responsibility of a wide range of physicians.

The six published chapters of the guidelines address prevention of VTE in hospital and outpatient settings, diagnosis of VTE, optimizing anticoagulation therapy, management of heparin-induced thrombocytopenia (HIT), how to effectively address VTE during pregnancy and treatment of pediatric VTE.

VTE prophylaxis

The guidelines included 19 recommendations for VTE prophylaxis.

Strong recommendations included pharmacological VTE prophylaxis for acutely or critically ill inpatients at acceptable bleeding risk and mechanical prophylaxis when bleeding risk is unacceptable. The guidelines strongly recommended against direct oral anticoagulants during hospitalization and extending pharmacological prophylaxis after hospital discharge.

The panel conditionally recommended against routine VTE prophylaxis for long-term care patients or outpatients with minor VTE risk factors. Graduated compression stockings or low-molecular-weight heparin (LMWH) for long-distance travelers at high risk for VTE received a conditional recommendation.

Acknowledging the prevalence of VTE among hospitalized or ambulatory patients is important when determining a patient’s risk factors, panel chair Mary Cushman, MD, medical director of the thrombosis and hemostasis program, hematologist and professor of medicine and pathology at Lerner College of Medicine, said during the webcast.

“Prevention is very tricky, because anticoagulants have serious bleeding risks, so risk assessment for thrombosis and bleeding is needed whenever we’re considering options for prevention,” Cushman said. “What we covered in this chapter was defining who should receive an intervention and what that intervention should be, and then considering the benefits and risks of different kinds of medications.”

Diagnosis, treatment

The guidelines include 10 recommendations for VTE diagnosis, according to diagnosis panel chair Wendy Lim, MD, program director of the adult hematology residency training program and professor in the department of hematology and thromboembolism at McMaster University.

“Specifically, it aims to provide guidance in establishing a diagnosis in not only an accurate, but also an efficient manner, by utilizing the minimum number of diagnostic tests in the pathway and trying to avoid more invasive tests,” Lim said. “Accurate diagnosis is important because it avoids the potential complications of misdiagnosis — it avoids exposing those patients to the unnecessary risks, potential side effects and financial costs of anticoagulant medication.”

The diagnosis recommendations include use of D-dimer as the initial test for low-risk VTE patients, and imaging for high-risk VTE patients.

The panel noted ventilation-perfusion scanning and CT pulmonary angiography are the most validated tests for PE diagnosis, whereas ultrasonography is appropriate for lower or upper extremity DVT diagnosis.

To monitor anticoagulation therapy, the guidelines strongly recommended patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy. They strongly recommended against using periprocedural LMWH bridging therapy.

Conditional recommendations included basing treatment dosing of LMWH on body weight, not using antifactor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding.

Balancing the risks and benefits of anticoagulants is key to optimal use of anticoagulation therapy, according to panel chair Daniel M. Witt, PharmD, of the department of pharmacotherapy at The University of Utah.

“There is an inevitable tradeoff between the benefits of anticoagulant therapy, which reduces the coagulability of blood so that healing can occur, but the tradeoff is that any bleeding that develops can potentially be more severe,” Witt said. “So, navigating that very delicate balance between preventing further clotting and also minimizing the risk of bleeding is largely what this chapter is all about.”

Heparin-induced thrombocytopenia

The guidelines include 33 recommendations for HIT to address screening of asymptomatic patients, diagnosis and initial management of suspected HIT, treatment of acute cases, and special situations in patients with acute HIT or a history of HIT.

Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT. The panel also recommended avoiding HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score.

The panel conditionally recommended non-heparin anticoagulants — such as argatroban, bivalirudin, danaparoid (Orgaran, Aspen Global), fondaparinux and direct oral anticoagulants — for treatment of acute HIT.

Panel co-chair Adam Cuker, MD, MS, clinical director of Penn Blood Disorders Center, director of Penn Comprehensive Thrombosis Program, and assistant professor of medicine and of pathology and laboratory medicine at University of Pennsylvania, described the need for these guidelines, as HIT is a potentially limb/life-threatening complication.

“HIT is very uncommon, but suspicion for HIT is very frequent,” he said.

“All of these suspected cases of HIT and consideration of HIT can lead to misdiagnosis,” he added. “This can result in poor management decisions and adverse outcomes for patients.”

Specific patient subgroups

Pregnancy is another situation in which risk factors should be considered carefully. According to panel chair Shannon Bates, MDCM, MSc, FRCPC, pregnancy-associated blood clots are a leading cause of maternal morbidity and death in Western countries.

“We suspect these risks will continue to increase as the pregnant population changes and becomes more likely to have additional factors that predispose them to blood clots, such as increased age, overweight and comorbid medical conditions,” Bates said. “We hope this document will make it easier for obstetricians, gynecologists, maternal fetal medicine specialists, and even thrombosis specialists to provide evidence-based care to women with or at risk for developing blood clots.”

The 31 recommendations related to VTE in pregnancy included a strong recommendation for LWMH over unfractionated heparin for acute VTE. They also strongly recommended antepartum anticoagulant prophylaxis for those with a history of unprovoked or hormonally associated VTE, but they conditionally recommended against antepartum anticoagulant prophylaxis for those with prior VTE associated with a resolved nonhormonal-provoking risk factor.

The panel noted the other recommendations were mostly conditional, and included twice-per-day or once-per-day LMWH dosing for the treatment of acute VTE and initial outpatient therapy over hospital admission for low-risk acute VTE, as well as guidance against routine antifactor Xa monitoring to guide dosing with LMWH.

The pediatric guidelines included 30 recommendations but stressed the need for additional research on the natural history of asymptomatic thrombosis, determination of subgroup boundaries that enable risk stratification for treatment escalation, and appropriate study of newer anticoagulant agents in children.

Panel chair Paul Monagle, MD, professor of pediatrics at University of Melbourne and a pediatric hematologist at Royal Children’s Hospital, discussed the importance of effectively treating VTE in these patients.

“While the incidence of VTE in children at a population level is very low, it really is a disease of hospitalized children, and is one of the most common complications we see in children who have underlying major illness,” he said. “There’s nothing more devastating than having a child who has survived such an illness to then have long-term effects from a complicating thrombosis.” – by Jennifer Byrne

For more information:

The guidelines are available at http://www.bloodadvances.org/.

Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.

ASH, in collaboration with the McMaster University GRADE Centre, published the first six chapters of the ASH Clinical Practice Guidelines on Venous Thromboembolism to improve the diagnosis, treatment and management of blood clots, the society announced in a press event.

The six guideline chapters — published in Blood Advances represented the culmination of efforts by more than 100 VTE experts, including hematologists, other clinicians, guideline development specialists and patient representatives.

“The patients took on a role as full guideline panel members — they were participating in discussions, they were involved in any voting that took place and they were fully engaged in the process,” Holger Schünemann, MD, PhD, ASH VTE Guidelines coordination panel co-chair and professor and chair in the department of health research methods, evidence, and impact at McMaster University, said during the webcast. “We are now working with the patient representatives to translate these guidelines, which are already available in different versions for our various stakeholders, into patient-friendly material.”

Although VTE is a serious condition, causing up to 100,000 deaths each year in the U.S. alone, it remains relatively underestimated by the general population. VTE — which includes deep vein thrombosis and pulmonary embolism — affects patients of all ages and in various health care settings. For this reason, the prevention and treatment of VTE is the responsibility of a wide range of physicians.

The six published chapters of the guidelines address prevention of VTE in hospital and outpatient settings, diagnosis of VTE, optimizing anticoagulation therapy, management of heparin-induced thrombocytopenia (HIT), how to effectively address VTE during pregnancy and treatment of pediatric VTE.

VTE prophylaxis

The guidelines included 19 recommendations for VTE prophylaxis.

Strong recommendations included pharmacological VTE prophylaxis for acutely or critically ill inpatients at acceptable bleeding risk and mechanical prophylaxis when bleeding risk is unacceptable. The guidelines strongly recommended against direct oral anticoagulants during hospitalization and extending pharmacological prophylaxis after hospital discharge.

The panel conditionally recommended against routine VTE prophylaxis for long-term care patients or outpatients with minor VTE risk factors. Graduated compression stockings or low-molecular-weight heparin (LMWH) for long-distance travelers at high risk for VTE received a conditional recommendation.

Acknowledging the prevalence of VTE among hospitalized or ambulatory patients is important when determining a patient’s risk factors, panel chair Mary Cushman, MD, medical director of the thrombosis and hemostasis program, hematologist and professor of medicine and pathology at Lerner College of Medicine, said during the webcast.

PAGE BREAK

“Prevention is very tricky, because anticoagulants have serious bleeding risks, so risk assessment for thrombosis and bleeding is needed whenever we’re considering options for prevention,” Cushman said. “What we covered in this chapter was defining who should receive an intervention and what that intervention should be, and then considering the benefits and risks of different kinds of medications.”

Diagnosis, treatment

The guidelines include 10 recommendations for VTE diagnosis, according to diagnosis panel chair Wendy Lim, MD, program director of the adult hematology residency training program and professor in the department of hematology and thromboembolism at McMaster University.

“Specifically, it aims to provide guidance in establishing a diagnosis in not only an accurate, but also an efficient manner, by utilizing the minimum number of diagnostic tests in the pathway and trying to avoid more invasive tests,” Lim said. “Accurate diagnosis is important because it avoids the potential complications of misdiagnosis — it avoids exposing those patients to the unnecessary risks, potential side effects and financial costs of anticoagulant medication.”

The diagnosis recommendations include use of D-dimer as the initial test for low-risk VTE patients, and imaging for high-risk VTE patients.

The panel noted ventilation-perfusion scanning and CT pulmonary angiography are the most validated tests for PE diagnosis, whereas ultrasonography is appropriate for lower or upper extremity DVT diagnosis.

To monitor anticoagulation therapy, the guidelines strongly recommended patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy. They strongly recommended against using periprocedural LMWH bridging therapy.

Conditional recommendations included basing treatment dosing of LMWH on body weight, not using antifactor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding.

Balancing the risks and benefits of anticoagulants is key to optimal use of anticoagulation therapy, according to panel chair Daniel M. Witt, PharmD, of the department of pharmacotherapy at The University of Utah.

“There is an inevitable tradeoff between the benefits of anticoagulant therapy, which reduces the coagulability of blood so that healing can occur, but the tradeoff is that any bleeding that develops can potentially be more severe,” Witt said. “So, navigating that very delicate balance between preventing further clotting and also minimizing the risk of bleeding is largely what this chapter is all about.”

Heparin-induced thrombocytopenia

The guidelines include 33 recommendations for HIT to address screening of asymptomatic patients, diagnosis and initial management of suspected HIT, treatment of acute cases, and special situations in patients with acute HIT or a history of HIT.

PAGE BREAK

Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT. The panel also recommended avoiding HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score.

The panel conditionally recommended non-heparin anticoagulants — such as argatroban, bivalirudin, danaparoid (Orgaran, Aspen Global), fondaparinux and direct oral anticoagulants — for treatment of acute HIT.

Panel co-chair Adam Cuker, MD, MS, clinical director of Penn Blood Disorders Center, director of Penn Comprehensive Thrombosis Program, and assistant professor of medicine and of pathology and laboratory medicine at University of Pennsylvania, described the need for these guidelines, as HIT is a potentially limb/life-threatening complication.

“HIT is very uncommon, but suspicion for HIT is very frequent,” he said.

“All of these suspected cases of HIT and consideration of HIT can lead to misdiagnosis,” he added. “This can result in poor management decisions and adverse outcomes for patients.”

Specific patient subgroups

Pregnancy is another situation in which risk factors should be considered carefully. According to panel chair Shannon Bates, MDCM, MSc, FRCPC, pregnancy-associated blood clots are a leading cause of maternal morbidity and death in Western countries.

“We suspect these risks will continue to increase as the pregnant population changes and becomes more likely to have additional factors that predispose them to blood clots, such as increased age, overweight and comorbid medical conditions,” Bates said. “We hope this document will make it easier for obstetricians, gynecologists, maternal fetal medicine specialists, and even thrombosis specialists to provide evidence-based care to women with or at risk for developing blood clots.”

The 31 recommendations related to VTE in pregnancy included a strong recommendation for LWMH over unfractionated heparin for acute VTE. They also strongly recommended antepartum anticoagulant prophylaxis for those with a history of unprovoked or hormonally associated VTE, but they conditionally recommended against antepartum anticoagulant prophylaxis for those with prior VTE associated with a resolved nonhormonal-provoking risk factor.

The panel noted the other recommendations were mostly conditional, and included twice-per-day or once-per-day LMWH dosing for the treatment of acute VTE and initial outpatient therapy over hospital admission for low-risk acute VTE, as well as guidance against routine antifactor Xa monitoring to guide dosing with LMWH.

The pediatric guidelines included 30 recommendations but stressed the need for additional research on the natural history of asymptomatic thrombosis, determination of subgroup boundaries that enable risk stratification for treatment escalation, and appropriate study of newer anticoagulant agents in children.

PAGE BREAK

Panel chair Paul Monagle, MD, professor of pediatrics at University of Melbourne and a pediatric hematologist at Royal Children’s Hospital, discussed the importance of effectively treating VTE in these patients.

“While the incidence of VTE in children at a population level is very low, it really is a disease of hospitalized children, and is one of the most common complications we see in children who have underlying major illness,” he said. “There’s nothing more devastating than having a child who has survived such an illness to then have long-term effects from a complicating thrombosis.” – by Jennifer Byrne

For more information:

The guidelines are available at http://www.bloodadvances.org/.

Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.