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Comprehensive Thrombosis Guidelines
Published CME
News Author: Lisa Nainggolan
CME Author: Laurie Barclay, MD
Disclosures

Release Date: July 1, 2008; Valid for credit through July 1, 2009

Credits Available




Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for
physicians;
Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians

To participate in this internet activity: (1) review the target audience, learning objectives, and
author disclosures; (2) study the education content; (3) take the post-test and/or complete the
evaluation; (4) view/print certificate View details.

Learning Objectives


Upon completion of this activity, participants will be able to:

   1. Describe new evidence-based American College of Chest Physicians recommendations to
      prevent and treat thrombosis in pregnant women and children.
   2. Describe American College of Chest Physicians recommendations to prevent and treat
      thrombosis during the perioperative and postoperative period.

Authors and Disclosures


Lisa Nainggolan
Disclosure: Lisa Nainggolan has disclosed no relevant financial relationships.

Laurie Barclay, MD
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Brande Nicole Martin
Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

From Heartwire — a professional news service of WebMD

July 1, 2008 — New recommendations on antithrombotic and thrombolytic therapy from the
American College of Chest Physicians (ACCP) have been published as a supplement to the
June issue of Chest [1]. Guidelines panel chair Dr Jack Hirsh (Henderson Research Centre,
Hamilton, ON) told heartwire that the 900-page document contains the most comprehensive
advice to date on the prevention, treatment, and long-term management of thrombotic disorders.

"We've markedly increased the number of non-North American participants, so the
recommendations are more international. The process of evaluation has improved dramatically —
it's much more rigorous, with panelists for each chapter developing questions sent out to an
evidenced-based center, which then performed a literature search. Tables of all the clinical trials
that have been done for every single clinical condition are included. The review process has
changed too, with each chapter and the manuscript as a whole reviewed by two independent
people," he explained.

Hirsh said it is impossible to cover all the subjects discussed in the new guidelines, which consist
of 22 chapters, but a good starting point is the almost 40-page-long executive summary. For
heartwire, he tried to pick out some of the most significant changes from previous guidelines
that are of relevance to cardiologists.

First-ever chapter on perioperative management

For the first time, the guidelines dedicate a full chapter (chapter 10) to the perioperative
management of patients on long-term antithrombotic therapy who require surgery or other
invasive procedures, Hirsh said.

Unfortunately, he explained, the previous recommendations for the most appropriate approach to
the pre- and perioperative management of such patients was "based on one randomized trial."
People might be taking warfarin, aspirin, or clopidogrel, and doctors need guidance on whether or
not to stop such therapies before surgery.

The recommendations offer a couple of options for warfarin: lowering the dose for simple
procedures, such as cataract surgery; or stopping therapy altogether around 5 days before
surgery and instead using low-molecular-weight heparins (LMWHs), or heparin, for coverage,
Hirsh said. In certain circumstances, warfarin can be continued until 48 hours before surgery,
when patients should be given a low dose of vitamin K. For aspirin, the recommendation is
normally to continue therapy, he said. For clopidogrel, it is usually stopped 5 to 7 days before
surgery.

Rather than going into too much detail, Hirsh said he wanted to stress that the guidelines provide
physicians with a rationale based on the likelihood of a thromboembolic event in any individual
person weighed against the risk of bleeding when antithrombotic therapy is stopped before
surgery.

HIT: Heparin can still be used for bypass surgery

Another chapter of relevance to cardiologists is the one on the treatment and prevention of
heparin-induced thrombocytopenia (HIT), Hirsh noted. "If someone has had an issue with HIT and
requires bypass surgery, what do you use as anticoagulation during bypass?"

He explained that any anticoagulant, apart from heparin, can be problematic for conventional on-
pump bypass surgery because the risk of bleeding is greater, experience is limited, and the
procedure is much riskier.

Hirsh said that in someone who has had HIT but who now has a negative HIT antibody level, "it's
safe to use heparin for bypass surgery because it is only used short-term and is cleared very
quickly. Physicians are uncomfortable with this because of medico-legal implications, but it is
perfectly rational."

Another important issue for physicians to understand is that the enzyme-linked immunosorbent
assay (ELIZA) test normally used to diagnose HIT "is commonly falsely positive after surgery,"
Hirsh explained. It is important for doctors to remember that falling platelet counts continue to
occur four to five days after heparin, he noted "and if you did this ELIZA test on all patients after
bypass surgery, 20% to 30% would be positive. It creates almost as much harm as good."

An alternative is to use another test — a serotonin-release test — "which is much more specific
but not always available," he said.

Prevention of venous thromboembolism; not much new in AF

Hirsh said that research has revealed that certain high-risk medical patients and nonorthopedic
surgical patients are not getting venous thromboembolism (VTE) prophylaxis, "when there is good
evidence that it works. Often it's not been given because people just don't think about it."

Thus, the guidelines recommend that hospitals adopt an opt-out policy when it comes to VTE
prevention, in which all relevant patients are routinely given it unless doctors remove it because
they think it is not warranted.

The recommendations also add more about the surgical management of VTE, he noted, and
advice on the duration of anticoagulant therapy following VTE.

For atrial fibrillation (AF), there is "not a lot that is new," Hirsh said. The guidelines make
treatment recommendations on the basis of low-, moderate-, and-high risk AF. Hirsh said that one
of the problems with AF is that, despite "an enormous amount of evidence" indicating the benefits
of warfarin, it is "grossly underutilized" for those at moderate or high risk, particularly by family
practitioners.

On a related note, he said that there are "more and more randomized clinical trials that have been
published that demonstrate the benefits of computer-assisted INR [international normalized ratio]
monitoring for warfarin therapy, showing it is superior to physician monitoring, with various
nomograms for dose adjustment being more effective than decisions made 'off-the-cuff'."

Other chapters of relevance

Other chapters in the guidelines of relevance to cardiologists include antithrombotic therapy for
non-ST-segment elevation acute coronary syndrome, acute ST-segment elevation myocardial
infarction, primary and secondary prevention of coronary artery disease, and valvular and
structural heart disease.

There are also chapters on antithrombotic therapy for peripheral artery occlusive disease, on
antithrombotic and thrombolytic therapy for ischemic stroke, and on pregnancy. The information
on the use of antithrombotics in children and neonates has been expanded.

"Care for children with major cardiac problems has improved dramatically," Hirsh said. "But
thrombosis remains a major cause of secondary complications for these children, so effective
antithrombotic therapy is critical."

Source

   1. Hirsh J, Guyatt G, Albers GW, et al. American College of Chest Physicians evidence-based
      clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):110S-968S. Available
      at: http://www.chestnet.org/education/hsp/guidelinesAT8.php.

The complete contents of Heartwire, a professional news service of WebMD, can be found at
www.theheart.org, a Web site for cardiovascular healthcare professionals.
Clinical Context

Antithrombotic and thrombolytic treatments are in widespread use for prophylaxis and therapeutic
intervention for arterial, venous, and cardiac thrombosis. Despite the long-term experience in use
of these therapies, certain clinical situations in thrombosis treatment present unique challenges,
such as during pregnancy, in childhood, or in the perioperative period.

Therefore, the ACCP issued new evidence-based guidelines for thrombosis prevention and
treatment, supporting previous recommendations regarding routine use of preventive therapies
and highlighting management in children, pregnant women, and other specific patient subgroups.

Study Highlights

   •   An international panel of 90 experts developed this 8th Edition of the ACCP Antithrombotic
       and Thrombolytic Therapy Guidelines.
   •   The revised guidelines include more than 700 comprehensive recommendations concerning
       prophylaxis, therapy, and long-term management of thrombotic disorders in pregnant
       women and children and in perioperative and postoperative patients.
   •   The revised recommendations also support previous guidelines concerning the routine use
       of aspirin and other therapies to prevent thrombosis.
   •   Because warfarin and other vitamin K antagonists (VKA) increase the risk for birth defects
       and miscarriage, pregnant women should ideally stop taking VKAs before 6 weeks of fetal
       gestation.
   •   Some pregnant women with certain types of mechanical heart valves should continue
       VKAs, because alternative anticoagulants may be less effective in preventing stroke and
       valve thrombosis.
   •   For other pregnant women, LMWH or unfractionated heparin (UFH) should be substituted
       for VKAs.
   •   2 options for implementing this recommendation are to continue VKA while conducting
       frequent pregnancy tests, then substituting LMWH or UFH when pregnancy is confirmed; or
       substituting VKAs with LMWH or UFH before conception.
   •   The latter option prevents fetal exposure to VKA but presents additional challenges. LMWH
       and UFH are more expensive than VKAs; they must be administered via once- or twice-
       daily injection; and long-term use of LMWH or UFH has been linked to osteoporosis.
   •   Recommendations on pediatric management and prevention of thrombosis have been
       significantly expanded since the previous guideline.
   •   Childhood stroke is one of the 10 leading causes of death in children. Embolism or
       thrombosis usually causes arterial ischemic stroke (AIS).
   •   Diagnosis of AIS is difficult in children because predisposing health conditions are markedly
       different from those in adult stroke and because nearly 15% of children with AIS have no
       clear risk factors.
   •   Until the underlying causes are determined, children with AIS should initially receive
       antithrombotic treatment, followed by maintenance therapy to prevent long-term
       recurrence.
   •   The revised recommendations regarding prevention and treatment of thrombosis after
       interventions for congenital heart disease highlight appropriate treatment options for
       children with ventricular assist devices and prosthetic heart valves.
   •   The revised guidelines emphasize the perioperative management of patients receiving
       long-term antithrombotic treatment who must undergo surgery or other invasive
       procedures.
   •   To minimize surgical bleeding, most patients must temporarily discontinue antithrombotic
       treatment immediately before and during surgery.
•   Because discontinuing antithrombosis can increase the risk for a thromboembolic event;
       however, this risk must be weighed against the risk for bleeding when deciding whether or
       not to interrupt antithrombotic therapy just before surgery.
   •   Routine thromboprophylaxis use is recommended for patients undergoing major general,
       gynecologic, or orthopaedic surgery as well as bariatric and coronary artery bypass
       surgery.
   •   Most patients who are hospitalized should receive thromboprophylaxis, but routine
       thromboprophylaxis use is not recommended for patient groups with a very low risk for
       VTE.
   •   Patients undergoing laparoscopic surgery, knee arthroscopy, or those who take long
       airplane flights are considered to be at low risk. In these cases, decisions about
       thromboprophylaxis should be based on individual patient risk.
   •   Aspirin alone is not recommended to prevent VTE in any patient population because there
       are more effective methods.

Pearls for Practice

   •   Pregnant women should ideally stop taking VKAs before 6 weeks of fetal gestation, but
       some pregnant women with certain types of mechanical heart valves should continue VKAs
       because alternative anticoagulants may be less effective to prevent stroke and valve
       thrombosis. For other pregnant women, LMWH or UFH should be substituted for VKAs.
       Until the underlying causes are determined, children with AIS should initially receive
       antithrombotic treatment, followed by maintenance therapy to prevent long-term
       recurrence.
   •   To minimize surgical bleeding, most patients must temporarily discontinue antithrombotic
       treatment immediately before and during surgery. Because discontinuing antithrombotic
       treatment can increase the risk for a thromboembolic event, however, this risk must be
       weighed against the risk for bleeding when deciding whether to interrupt antithrombotic
       therapy just before surgery. Routine use of thromboprophylaxis is recommended for
       patients undergoing major general, gynecologic, or orthopaedic surgery as well as bariatric
       and coronary artery bypass surgery.

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Comprehensive Thrombosis Guidelines P...

  • 1. Comprehensive Thrombosis Guidelines Published CME News Author: Lisa Nainggolan CME Author: Laurie Barclay, MD Disclosures Release Date: July 1, 2008; Valid for credit through July 1, 2009 Credits Available Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians; Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians To participate in this internet activity: (1) review the target audience, learning objectives, and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation; (4) view/print certificate View details. Learning Objectives Upon completion of this activity, participants will be able to: 1. Describe new evidence-based American College of Chest Physicians recommendations to prevent and treat thrombosis in pregnant women and children. 2. Describe American College of Chest Physicians recommendations to prevent and treat thrombosis during the perioperative and postoperative period. Authors and Disclosures Lisa Nainggolan Disclosure: Lisa Nainggolan has disclosed no relevant financial relationships. Laurie Barclay, MD Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships. Brande Nicole Martin Disclosure: Brande Nicole Martin has disclosed no relevant financial information. From Heartwire — a professional news service of WebMD July 1, 2008 — New recommendations on antithrombotic and thrombolytic therapy from the American College of Chest Physicians (ACCP) have been published as a supplement to the June issue of Chest [1]. Guidelines panel chair Dr Jack Hirsh (Henderson Research Centre, Hamilton, ON) told heartwire that the 900-page document contains the most comprehensive advice to date on the prevention, treatment, and long-term management of thrombotic disorders. "We've markedly increased the number of non-North American participants, so the recommendations are more international. The process of evaluation has improved dramatically —
  • 2. it's much more rigorous, with panelists for each chapter developing questions sent out to an evidenced-based center, which then performed a literature search. Tables of all the clinical trials that have been done for every single clinical condition are included. The review process has changed too, with each chapter and the manuscript as a whole reviewed by two independent people," he explained. Hirsh said it is impossible to cover all the subjects discussed in the new guidelines, which consist of 22 chapters, but a good starting point is the almost 40-page-long executive summary. For heartwire, he tried to pick out some of the most significant changes from previous guidelines that are of relevance to cardiologists. First-ever chapter on perioperative management For the first time, the guidelines dedicate a full chapter (chapter 10) to the perioperative management of patients on long-term antithrombotic therapy who require surgery or other invasive procedures, Hirsh said. Unfortunately, he explained, the previous recommendations for the most appropriate approach to the pre- and perioperative management of such patients was "based on one randomized trial." People might be taking warfarin, aspirin, or clopidogrel, and doctors need guidance on whether or not to stop such therapies before surgery. The recommendations offer a couple of options for warfarin: lowering the dose for simple procedures, such as cataract surgery; or stopping therapy altogether around 5 days before surgery and instead using low-molecular-weight heparins (LMWHs), or heparin, for coverage, Hirsh said. In certain circumstances, warfarin can be continued until 48 hours before surgery, when patients should be given a low dose of vitamin K. For aspirin, the recommendation is normally to continue therapy, he said. For clopidogrel, it is usually stopped 5 to 7 days before surgery. Rather than going into too much detail, Hirsh said he wanted to stress that the guidelines provide physicians with a rationale based on the likelihood of a thromboembolic event in any individual person weighed against the risk of bleeding when antithrombotic therapy is stopped before surgery. HIT: Heparin can still be used for bypass surgery Another chapter of relevance to cardiologists is the one on the treatment and prevention of heparin-induced thrombocytopenia (HIT), Hirsh noted. "If someone has had an issue with HIT and requires bypass surgery, what do you use as anticoagulation during bypass?" He explained that any anticoagulant, apart from heparin, can be problematic for conventional on- pump bypass surgery because the risk of bleeding is greater, experience is limited, and the procedure is much riskier. Hirsh said that in someone who has had HIT but who now has a negative HIT antibody level, "it's safe to use heparin for bypass surgery because it is only used short-term and is cleared very quickly. Physicians are uncomfortable with this because of medico-legal implications, but it is perfectly rational." Another important issue for physicians to understand is that the enzyme-linked immunosorbent assay (ELIZA) test normally used to diagnose HIT "is commonly falsely positive after surgery," Hirsh explained. It is important for doctors to remember that falling platelet counts continue to
  • 3. occur four to five days after heparin, he noted "and if you did this ELIZA test on all patients after bypass surgery, 20% to 30% would be positive. It creates almost as much harm as good." An alternative is to use another test — a serotonin-release test — "which is much more specific but not always available," he said. Prevention of venous thromboembolism; not much new in AF Hirsh said that research has revealed that certain high-risk medical patients and nonorthopedic surgical patients are not getting venous thromboembolism (VTE) prophylaxis, "when there is good evidence that it works. Often it's not been given because people just don't think about it." Thus, the guidelines recommend that hospitals adopt an opt-out policy when it comes to VTE prevention, in which all relevant patients are routinely given it unless doctors remove it because they think it is not warranted. The recommendations also add more about the surgical management of VTE, he noted, and advice on the duration of anticoagulant therapy following VTE. For atrial fibrillation (AF), there is "not a lot that is new," Hirsh said. The guidelines make treatment recommendations on the basis of low-, moderate-, and-high risk AF. Hirsh said that one of the problems with AF is that, despite "an enormous amount of evidence" indicating the benefits of warfarin, it is "grossly underutilized" for those at moderate or high risk, particularly by family practitioners. On a related note, he said that there are "more and more randomized clinical trials that have been published that demonstrate the benefits of computer-assisted INR [international normalized ratio] monitoring for warfarin therapy, showing it is superior to physician monitoring, with various nomograms for dose adjustment being more effective than decisions made 'off-the-cuff'." Other chapters of relevance Other chapters in the guidelines of relevance to cardiologists include antithrombotic therapy for non-ST-segment elevation acute coronary syndrome, acute ST-segment elevation myocardial infarction, primary and secondary prevention of coronary artery disease, and valvular and structural heart disease. There are also chapters on antithrombotic therapy for peripheral artery occlusive disease, on antithrombotic and thrombolytic therapy for ischemic stroke, and on pregnancy. The information on the use of antithrombotics in children and neonates has been expanded. "Care for children with major cardiac problems has improved dramatically," Hirsh said. "But thrombosis remains a major cause of secondary complications for these children, so effective antithrombotic therapy is critical." Source 1. Hirsh J, Guyatt G, Albers GW, et al. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):110S-968S. Available at: http://www.chestnet.org/education/hsp/guidelinesAT8.php. The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
  • 4. Clinical Context Antithrombotic and thrombolytic treatments are in widespread use for prophylaxis and therapeutic intervention for arterial, venous, and cardiac thrombosis. Despite the long-term experience in use of these therapies, certain clinical situations in thrombosis treatment present unique challenges, such as during pregnancy, in childhood, or in the perioperative period. Therefore, the ACCP issued new evidence-based guidelines for thrombosis prevention and treatment, supporting previous recommendations regarding routine use of preventive therapies and highlighting management in children, pregnant women, and other specific patient subgroups. Study Highlights • An international panel of 90 experts developed this 8th Edition of the ACCP Antithrombotic and Thrombolytic Therapy Guidelines. • The revised guidelines include more than 700 comprehensive recommendations concerning prophylaxis, therapy, and long-term management of thrombotic disorders in pregnant women and children and in perioperative and postoperative patients. • The revised recommendations also support previous guidelines concerning the routine use of aspirin and other therapies to prevent thrombosis. • Because warfarin and other vitamin K antagonists (VKA) increase the risk for birth defects and miscarriage, pregnant women should ideally stop taking VKAs before 6 weeks of fetal gestation. • Some pregnant women with certain types of mechanical heart valves should continue VKAs, because alternative anticoagulants may be less effective in preventing stroke and valve thrombosis. • For other pregnant women, LMWH or unfractionated heparin (UFH) should be substituted for VKAs. • 2 options for implementing this recommendation are to continue VKA while conducting frequent pregnancy tests, then substituting LMWH or UFH when pregnancy is confirmed; or substituting VKAs with LMWH or UFH before conception. • The latter option prevents fetal exposure to VKA but presents additional challenges. LMWH and UFH are more expensive than VKAs; they must be administered via once- or twice- daily injection; and long-term use of LMWH or UFH has been linked to osteoporosis. • Recommendations on pediatric management and prevention of thrombosis have been significantly expanded since the previous guideline. • Childhood stroke is one of the 10 leading causes of death in children. Embolism or thrombosis usually causes arterial ischemic stroke (AIS). • Diagnosis of AIS is difficult in children because predisposing health conditions are markedly different from those in adult stroke and because nearly 15% of children with AIS have no clear risk factors. • Until the underlying causes are determined, children with AIS should initially receive antithrombotic treatment, followed by maintenance therapy to prevent long-term recurrence. • The revised recommendations regarding prevention and treatment of thrombosis after interventions for congenital heart disease highlight appropriate treatment options for children with ventricular assist devices and prosthetic heart valves. • The revised guidelines emphasize the perioperative management of patients receiving long-term antithrombotic treatment who must undergo surgery or other invasive procedures. • To minimize surgical bleeding, most patients must temporarily discontinue antithrombotic treatment immediately before and during surgery.
  • 5. Because discontinuing antithrombosis can increase the risk for a thromboembolic event; however, this risk must be weighed against the risk for bleeding when deciding whether or not to interrupt antithrombotic therapy just before surgery. • Routine thromboprophylaxis use is recommended for patients undergoing major general, gynecologic, or orthopaedic surgery as well as bariatric and coronary artery bypass surgery. • Most patients who are hospitalized should receive thromboprophylaxis, but routine thromboprophylaxis use is not recommended for patient groups with a very low risk for VTE. • Patients undergoing laparoscopic surgery, knee arthroscopy, or those who take long airplane flights are considered to be at low risk. In these cases, decisions about thromboprophylaxis should be based on individual patient risk. • Aspirin alone is not recommended to prevent VTE in any patient population because there are more effective methods. Pearls for Practice • Pregnant women should ideally stop taking VKAs before 6 weeks of fetal gestation, but some pregnant women with certain types of mechanical heart valves should continue VKAs because alternative anticoagulants may be less effective to prevent stroke and valve thrombosis. For other pregnant women, LMWH or UFH should be substituted for VKAs. Until the underlying causes are determined, children with AIS should initially receive antithrombotic treatment, followed by maintenance therapy to prevent long-term recurrence. • To minimize surgical bleeding, most patients must temporarily discontinue antithrombotic treatment immediately before and during surgery. Because discontinuing antithrombotic treatment can increase the risk for a thromboembolic event, however, this risk must be weighed against the risk for bleeding when deciding whether to interrupt antithrombotic therapy just before surgery. Routine use of thromboprophylaxis is recommended for patients undergoing major general, gynecologic, or orthopaedic surgery as well as bariatric and coronary artery bypass surgery. CME/CE Test