Cancer-Associated Venous Thromboembolic Disease

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Cancer-Associated Venous Thromboembolic Disease Version 1.2015 NCCN.org

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NCCN Guidelines Version 1.2015 Panel Members Cancer-Associated Venous Thromboembolic Disease * Michael B. Streiff, MD/Chair ‡ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bjorn Holmstrom, MD Þ/Vice-Chair Moffitt Cancer Center Aneel Ashrani, MD ‡ Mayo Clinic Cancer Center Paula L. Bockenstedt, MD ‡ University of Michigan Comprehensive Cancer Center Carolyn Chesney, MD St. Jude Children’s Research Hospital/ The University of Tennessee Health Science Center Charles Eby, MD ‡ Siteman Cancer Center at BarnesJewish Hospital and Washington University School of Medicine * John Fanikos, RPH, MBA Σ Dana-Farber/Brigham and Women’s Cancer Center Randolph B. Fenninger, JD ¥ National Blood Clot Alliance

NCCN Anita Engh, PhD Lauren Gallagher, RPh, PhD Nicole McMillian, MS Sarika Trikha, PharmD NCCN Guidelines Panel Disclosures

Annemarie E. Fogerty, MD ‡ Massachusetts General Hospital Cancer Center Shuwei Gao, MD Þ The University of Texas MD Anderson Cancer Center Samuel Z. Goldhaber, MD λ Dana-Farber/Brigham and Women’s Cancer Center Paul Hendrie, MD ‡ Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance Nicole Kuderer, MD, MS ‡ Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance Alfred Lee, MD, PhD ‡ Yale Cancer Center/Smilow Cancer Hospital Jason T. Lee, MD ¶ Stanford Cancer Institute Mirjana Lovrincevic, MD Roswell Park Cancer Institute Michael M. Millenson, MD ‡ Þ Fox Chase Cancer Center Anne T. Neff, MD ‡ Vanderbilt-Ingram Cancer Center

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NCCN Guidelines Index VTE Table of Contents Discussion

Thomas L. Ortel, MD, PhD ‡ Duke Cancer Institute Rita Paschal, MD University of Alabama at Birmingham Comprehensive Cancer Center Sanford Shattil, MD ‡ UC San Diego Moores Cancer Center Tanya Siddiqi, MD City of Hope Comprehensive Cancer Center Kristi J. Smock, MD ‡ ≠ Huntsman Cancer Institute at the University of Utah Gerald Soff, MD ‡ Memorial Sloan Kettering Cancer Center Tzu-Fei Wang, MD The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute Gary C. Yee, PharmD Σ Fred & Pamela Buffett Cancer Center Anaadriana Zakarija, MD ‡ Robert H. Lurie Comprehensive Cancer Center of Northwestern University ¶ Surgery/Surgical oncology ‡ Hematology/Hematology oncology Σ Pharmacology/Pharmacy † Medical oncology λ Cardiology Þ Internal medicine # Nursing ¥ Patient advocacy ≠ Pathology *Writing Committee Member

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NCCN Guidelines Version 1.2015 Table of Contents Cancer-Associated Venous Thromboembolic Disease NCCN Cancer-Associated Venous Thromboembolic Disease Panel Members Summary of the Guidelines Updates Inpatient-Venous Thromboembolism Prophylaxis (VTE-1) Deep or Superficial Vein Thrombosis (DVT-1) Pulmonary Embolism (PE-1) Heparin-Induced Thrombocytopenia (HIT-1) Splanchnic Vein Thrombosis (SPVT-1) VTE Risk Factors in Cancer Patients (VTE-A) Contraindications to Prophylactic or Therapeutic Anticoagulation Treatment and Contraindications to Mechanical Prophylaxis (VTE-B) Inpatient/Outpatient Prophylactic Anticoagulation Treatment (VTE-C) Therapeutic Anticoagulation Treatment for Venous Thromboembolism (VTE-D) Reversal of Anticoagulation (VTE-E) Elements for Consideration in Decision Not to Treat (VTE-F) Clinical Scenarios Warranting Consideration of Filter Placement (VTE-G) Therapeutic Anticoagulation Failure (VTE-H) Thrombolytic Agents (VTE-I) Contraindications to Thrombolysis (VTE-J) Perioperative Management of Anticoagulation and Antithrombotic Therapy (PMA-1)

NCCN Guidelines Index VTE Table of Contents Discussion

Clinical Trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. To find clinical trials online at NCCN Member Institutions, click here: nccn.org/clinical_trials/physician.html. NCCN Categories of Evidence and Consensus: All recommendations are category 2A unless otherwise specified. See NCCN Categories of Evidence and Consensus.

The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2015. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

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NCCN Guidelines Version 1.2015 Updates Cancer-Associated Venous Thromboembolic Disease

NCCN Guidelines Index VTE Table of Contents Discussion

Updates in Version 1.2015 of the NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease from Version 2.2014 include: Venous Thromboembolism VTE-1 • At Risk Population First bullet: Revised “Adult medical or surgical patient”. (Also for for VTE-2) New bullet added: “Providers are encouraged to discuss VTE risk factors, VTE prevention, and the importance of patient adherence to care programs.” (Also for VTE-2) • Initial Prophylaxis: Recommendation revised, “Prophylactic anticoagulation therapy (category 1) (Consider preoperative dosing with unfractionated heparin or low-molecular-weight heparin (LMWH) for high-risk surgery [eg, abdominal/pelvic] patients)...” • Footnote “c” revised: “Pharmacologic intervention. Discuss prevention and risks/benefits of VTE prophylactic anticoagulation by pharmacologic intervention.” • Footnote “d” revised: “IPC device is preferred over GCS. Patients should be...” VTE-2 • “Cancer surgery patient” revised to “Surgical oncology patient”. Deep or Superficial Vein Thrombosis DVT-2 Treatment • “Pelvic/iliac/inferior vena cava (IVC) or Femoral popliteal” pathway: After “IVC filter (retrievable filter preferred)” criteria revised, “Contraindication persists or is likely to recur.” • Footnote “h” revised: “Consider permanent filters only for rare patients with permanent contraindications to anticoagulation or with chronic comorbidities.” • Footnote “j” is new to the page: “Recommend IVC filter removal, if tolerating anticoagulation therapy.” Pulmonary Embolism PE-1 Diagnosis; Second bullet revised: “Unexplained shortness of breath, chest pain, tachycardia, apprehension, or tachynpnea.” PE-2 Treatment • Contradindication to anticoagulation; “No” pathway: Recommendation revised for clarity “Acute managment using anticoagulation therapy”. Change also made to first bullet in “Abnormal” pathway. “Normal” pathway: “Consider outpatient management” added. • Footnote “h” revised: “Consider permanent filters only for rare patients with permanent contraindications to anticoagulation or with chronic comorbidities.”

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UPDATES 1 OF 3

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NCCN Guidelines Version 1.2015 Updates Cancer-Associated Venous Thromboembolic Disease Heparin-Induced Thrombocytopenia (HIT) HIT-1 Diagnosis and Treatment of HIT • “Low” pathway: Fourth bullet revised: “Consider sending HIT antibody test (enzyme-linked immunosorbent assay [ELISA]) for select patients” • “Moderate/high” pathway: First bullet revised, “Eliminate unfractionated and LMWH exposure from all sources, including treatment,...” HIT-2 • “HIT antibody negative” pathway: Second bullet revised, “Consider repeating HIT antibody test (ELISA) ± serotonin-release assay (SRA) if pre-test probability is moderate to high.” • “HIT antibody positive” pathway: Third bullet “Start warfarin when platelets ≥150,000/mcL or when platelets return to previous baseline” revised for clarity, “Start warfarin when platelets return to baseline or exceed 150,000/mcL.” • Pathway revised: “Pre-test probability score low, consider sending SRA.” • “Pre-test probability score moderate/high” pathway: The recommendation “Continue DTI or fondaparinux” was removed and this patient population is now treated the same as the “HIT antibody positive” pathway. HIT-B Therapeutic Options for HIT Page 1 of 2 • Footnote “1” is new: “The NCCN Guidelines Panel encourages the development of protocols or order sets for HIT treatment that includes DTI dosing, adjustment in renal or hepatic dysfunction, nursing instructions, and monitoring parameters.” Page 2 of 2 • Indirect Factor Xa Inhibitor; Fondaparinux: Recommendation revised, “For patients with CCr 30–50 mL/min (clearance reduced by ≥40% lower): Use caution.” • Footnote “5” is new: “Consider using a DTI.” Splanchnic Vein Thrombosis (SPVT) SPVT-1 • Clinical suspicion of SPVT: First bullet revised, “Abdominal or midabdominal colicky pain.” • Bullet “Colicky” deleted. • Footnote “a” revised: “Cancer” was removed from the risk factor list because it was redundant.

NCCN Guidelines Index VTE Table of Contents Discussion

VTE-C Inpatient/Outpatient Prophylactic Anticoagulation Treatment • This page was reformatted into a table that now includes obesity dosing for body mass index (BMI) ≥ 40 kg/m2 • Footnote “4” is new: “Given the impact of renal insufficiency on clearance of enoxaparin and fondaparinux, UFH or dalteparin are recommended for obese patients with severe renal impairment (CCr30 mL/min) prior” “Stop apixaban 2 3 days (CrCl ≥ >50 mL/min) or 4 days (CrCl 30–49 mL/min) prior”. Page 3 of 3 Table 2 for For “High” thromboembolic risk with “Low or Moderate” and “High or Very High” bleeding risk, the folllowing recommendations were revised: “Stop rivaroxaban 2 3 days (CrCl >30 mL/min) prior” “Stop apixaban 2 3 days (CrCl ≥ >50 mL/min) or 4 days (CrCl 30–49 mL/min) prior”.

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UPDATES 3 OF 3

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NCCN Guidelines Version 1.2015 Cancer-Associated Venous Thromboembolic Disease

NCCN Guidelines Index VTE Table of Contents Discussion

INPATIENT VENOUS THROMBOEMBOLISM PROPHYLAXIS AT-RISK POPULATION

• Adult medical or surgical patient • Diagnosis of cancer or clinical suspicion of cancera • Providers are encouraged to discuss VTE risk factors, VTE prevention, and the importance of patient adherence to care programs

WORKUP

Initial Workup: • History and physical • Complete blood count (CBC) with platelet count • Prothrombin time (PT) • Activated partial thromboplastin time (aPTT) • Liver and kidney function tests

INITIAL PROPHYLAXIS

No

Prophylactic anticoagulation therapyc (category 1) (Consider preoperative dosing with unfractionated heparin (UFH) or lowmolecular-weight heparin (LMWH) for highrisk surgery [eg, abdominal/pelvic] patients) ± Intermittent pneumatic compression (IPC) deviced,e ± Graduated compression stockings (GCS)d,e

Yes

Mechanical prophylaxise • IPC ± GCSd,e

Contraindication to anticoagulationb

VTE Prophylaxis following discharge (VTE-2)

aSee bSee

VTE Risk Factors in Cancer Patients (VTE-A). Contraindications to Prophylactic or Therapeutic Anticoagulation Treatment (VTE-B). cDiscuss prevention and risks/benefits of VTE prophylactic anticoagulation by pharmacologic intervention. See Inpatient/Outpatient Prophylactic Anticoagulation Treatment (VTE-C). dIPC device is preferred over GCS. Patients should be appropriately measured for stockings and monitored for adverse effects including skin ulcerations, especially in immobilized patients with peripheral neuropathy. See Contraindications to Mechanical Prophylaxis (VTE-B). (CLOTS Trial Collaboration. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet 2009. 373:1958-1965.) eMost data come from surgical patients; this is an extrapolation to the medical population. See Contraindications to Mechanical Prophylaxis (VTE-B). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

VTE-1

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NCCN Guidelines Version 1.2015 Cancer-Associated Venous Thromboembolic Disease AT-RISK POPULATION • Adult medical or surgical patient • Diagnosis of cancer • Patient received VTE prophylaxis during hospitalization • Cancer inpatient intended for discharge • Outpatients at risk • Providers are encouraged to discuss VTE risk factors, VTE prevention, and the importance of patient adherence to care programs

NCCN Guidelines Index VTE Table of Contents Discussion

VTE PROPHYLAXIS FOLLOWING DISCHARGE AND FOR AMBULATORY CANCER PATIENTS AT RISKa

Surgical oncology patient

Out-of-hospital primary VTE prophylaxis is recommended for up to four weeks post-operation (particularly for high-risk abdominal or pelvic cancer surgery patientsf) See Inpatient/Outpatient Prophylactic Anticoagulation Treatment (VTE-C) Multiple myeloma patients receiving thalidomide or lenalidomide: • High risk: Recommend anticoagulant VTE prophylaxisg • Low risk: Recommend aspiring

Medical oncology patient Other outpatient settingsh • No routine VTE prophylaxis recommended outside of a clinical trial setting

aSee VTE Risk Factors in Cancer Patients (VTE-A). fHigh-risk abdominal/pelvic cancer surgery patients include

patients undergoing surgery for gastrointestinal malignancies, patients with a previous history of VTE, anesthesia time greater than 2 hours, bed rest >4 days, advanced-stage disease, and patient age greater than 60 years. gMultiple myeloma patients receiving thalidomide/lenalidomide: in combination with high-dose dexamethasone (≥480 mg per month) or doxorubicin or multi-agent chemotherapy or for myeloma patients with two or more individual or myeloma risk factors (See VTE Risk Factors in Cancer Patients [VTE-A 2 of 3]), recommended prophylaxis is LMWH (enoxaparin 40 mg subcutaneous every 24 hours or its equivalent) or warfarin (adjusted to INR 2-3). For low-risk myeloma patients with one or fewer individual or myeloma risk factors, aspirin 81–325 mg daily may be used. Aspirin should not be used in non-myeloma patients for VTE prevention. hConsider patient conversation about risks and benefits of VTE prophylaxis in patients with a Khorana score ≥3. (See Khorana Predictive Model [VTE-A 3 of 3]) Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

VTE-2

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NCCN Guidelines Version 1.2015 Deep or Superficial Vein Thrombosis (DVT/SVT) DIAGNOSIS

Clinical suspicion of DVT or SVT: • Swelling of unilateral extremity • Heaviness in extremity • Pain in extremity • Unexplained persistent calf cramping • Swelling in face, neck, or supraclavicular space • Incidental DVT/SVT • Catheter dysfunction (If catheter is present See Catheter-Related DVT [DVT-3])

WORKUP/IMAGINGa

IMAGING FINDINGS

SVT TREATMENT

ADDITIONAL IMAGING

Peripheral catheter related

• Symptomatic treatment, including warm compresses, anti-inflammatory medications, and elevation • Re-evaluate if there are progressive symptoms

Remove catheter

SVT

• Comprehensive medical history and physical examination • CBC with platelet count • PT, aPTT • Liver and kidney function tests • Venous ultrasound (US)a,b

NCCN Guidelines Index VTE Table of Contents Discussion

Non-catheter related

Not close proximity to deep venous system

• Recommend anticoagulationc for at least 6 weeks (category 2B) Consider treating up to 12 weeks for close proximity to the common femoral vein See Treatment (DVT-2)

Close proximity to deep venous system

Positive for DVT

Negative or indeterminate Continued clinical suspicion of DVT

Yes

Venous imaging: • Repeat venous US • CT scan • Magnetic resonance venogram (MRV) • Venogram

Positive for DVT Negative

No

aImaging recommendations reflect initial diagnostic workup of an individual who has not previously been diagnosed with DVT. bIn cases with high suspicion of DVT and no contraindications, consider initiating early anticoagulation while waiting for imaging cSee Therapeutic Anticoagulation Treatment for Venous Thromboembolism (VTE-D).

• Reassurance • Evaluate for other causes

results.

Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

DVT-1

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NCCN Guidelines Version 1.2015 Deep or Superficial Vein Thrombosis (DVT/SVT) DVT LOCATION

• Pelvic/iliac/ inferior vena cava (IVC) • Femoral/popliteal

No Contraindication to anticoagulationd Yes

No Calf

Contraindication to anticoagulationd Yes

• Upper extremity • Superior vena cava (SVC)

DVT: TREATMENT • Anticoagulation therapyc,e • Consider catheter-directed pharmacomechanical thrombolysis in appropriate candidatesf • Consider GCSg IVC filterh (retrievable filter preferred)

No

• Anticoagulation therapyc,e • Recommend filter removalj

Yes

Re-evaluate as clinically indicated

Anticoagulation therapyc,e

Follow-up for DVT progression initially at one week

Progression

See Pelvic/iliac/IVC and Femoral/popliteal pathway above

No progression

Continue to follow as clinically indicated

No

• Anticoagulation therapyc,e • Consider catheter-directed pharmacomechanical thrombolysis in appropriate candidatesf,i

Yes

Follow until contraindication is resolved or progression of DVT

Contraindication to anticoagulationd

cSee Therapeutic Anticoagulation Treatment for Venous Thromboembolism (VTE-D). dSee Contraindications to Prophylactic or Therapeutic Anticoagulation Treatment

(VTE-B). Therapeutic Anticoagulation Failure (VTE-H), if extension of VTE or new VTE while on recommended anticoagulation therapy. fChoice of regimen should be made based on institutional expertise/preferences in conjunction with interventional radiology or vascular surgery colleagues. (See Thrombolytic Agents [VTE-I]) eSee

Contraindicationd persists or is likely to recur

NCCN Guidelines Index VTE Table of Contents Discussion

gThe

Re-evaluate for risk/benefit of anticoagulationk

SOX trial was unable to demonstrate that GCS reduced the rate of post thrombotic syndrome. (Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2014;383:880-888) hConsider permanent filters only for rare patients with permanent contraindications to anticoagulation. iSee Contraindications to Thrombolysis (VTE-J). jRecommend IVC filter removal, if tolerating anticoagulation therapy. kSee Elements for Consideration in Decision Not To Treat (VTE-F).

Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

DVT-2

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NCCN Guidelines Version 1.2015 Deep or Superficial Vein Thrombosis (DVT/SVT)

NCCN Guidelines Index VTE Table of Contents Discussion

CATHETER-RELATED DVT: DIAGNOSIS AND TREATMENT DIAGNOSIS

WORKUP/IMAGING

TREATMENT

No contraindication to anticoagulationd

• Anticoagulate for as long as catheter is in place;c,e if catheter removed, total duration of therapy is at least 3 months • Consider catheter removal if symptoms persist or if the catheter is infected or dysfunctional or no longer necessary • Consider catheter-directed pharmacomechanical thrombolysis in appropriate candidatesf,i

DVT Clinical suspicion of catheter-related DVT • Unilateral arm/leg swelling • Pain in supraclavicular space or neck • Dysfunctional catheter

Contraindication to anticoagulationd • US • CT/MRI • Venogram

No DVT

Remove catheter

Follow for change in contraindication as clinically indicated

Contraindication resolved

Anticoagulate;c,e recommended total duration of therapy is at least 3 months

Contraindication persists

Re-evaluate for risk/ benefit of anticoagulationk

Evaluate for other causes • Consider further imaging/testing with another modality if clinical suspicion is high and initial imaging failed to show DVT

cSee Therapeutic Anticoagulation Treatment for Venous Thromboembolism (VTE-D). dSee Contraindications to Prophylactic or Therapeutic Anticoagulation Treatment (VTE-B). eSee Therapeutic Anticoagulation Failure (VTE-H), if extension of VTE or new VTE while on recommended anticoagulation therapy. fChoice of regimen should be made based on institutional expertise/preferences in conjunction with interventional radiology or vascular

(See Thrombolytic Agents [VTE-I]). iSee Contraindications to Thrombolysis (VTE-J). kSee Elements for Consideration in Decision Not To Treat (VTE-F).

surgery colleagues

Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

DVT-3

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NCCN Guidelines Version 1.2015 Pulmonary Embolism (PE)

NCCN Guidelines Index VTE Table of Contents Discussion

PE: DIAGNOSIS DIAGNOSIS

WORKUPb

Clinical suspicion of PE: • Current DVT or recent history of DVT • Unexplained shortness of breath, chest pain, tachycardia, apprehension, or tachypnea • Syncope • O2 desaturation • Incidental PEa

• Comprehensive medical history and physical examination • CBC with platelet count • PT, aPTT • Liver and kidney function tests • Chest x-rayc • EKG

IMAGING

• CT angiography (CTA) • Pulmonary angiography (rarely used unless coupled with clot extraction or thrombolytic therapy) • Ventilation/perfusion (VQ) scan (lung scan) (if patient has renal insufficiency or uncorrectable allergy to contrast)

aRepeat imaging is not routinely needed in patients with incidental PE. Consider outpatient management for these bD-dimer has limited utility in cancer patients. cIn cases with high suspicion of PE and no contraindications, consider initiating early anticoagulation while waiting

Negative

Evaluate for other causes

Positive

See PE Treatment (PE-2)

Nondiagnostic

Clinical judgment See DVT/SVT (DVT-1)

Negative

Evaluate for other causes

patients. for imaging results.

Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

PE-1

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NCCN Guidelines Version 1.2015 Pulmonary Embolism (PE)

NCCN Guidelines Index VTE Table of Contents Discussion

PE: TREATMENT

No

Acute management using anticoagulation therapye,f

Contraindication to anticoagulationd

Yes

dSee

Consider IVC filter (retrievable filter preferred)g,h ± embolectomyi

Upon diagnosis, PE patients should be considered for risk stratification j with: • Transthoracic echocardiogram or CTA to assess for right ventricular enlargement or dysfunction • Troponin

Follow frequently for change in clinical status

Contraindications to Prophylactic or Therapeutic Anticoagulation Treatment (VTE-B). eSee Therapeutic Anticoagulation Treatment for Venous Thromboembolism (VTE-D). fSee Therapeutic Anticoagulation Failure (VTE-H), if extension of VTE or new VTE while on recommended anticoagulation therapy. gIt is unclear if IVC filter placement is beneficial in the absence of lower extremity, IVC, or pelvic DVT. See Clinical Scenarios Warranting Consideration of Filter Placement (VTE-G). hConsider permanent filters only for rare patients with permanent contraindications to anticoagulation. iConsider embolectomy for treatment of massive PE (category 2B).

Normal

Abnormal

Contraindication resolvedk

• Continue anticoagulation therapye,f • Consider outpatient management • Acute management using anticoagulation therapye,f • Assess cancer statusl and Consider: Thrombolytic therapym,n for massive PE or submassive PE with moderate or severe right ventricular enlargement or dysfunction Embolectomyi (catheter or surgical) IVC filter (retrievable filter preferred)g,h

Contraindication persists

jThe

Pulmonary Embolism Severity Index (PESI) clinical prediction rule can also be considered, but should not be substituted for the risk stratification procedures indicated above. (Donze J, Le Gal G, Fine MJ, et al. Prospective validation of the Pulmonary Embolism Severity Scale. Throm Haemost 2008;100:943-948). Consideration can also be given to the RIETE Cancer Score (den Exter P, Gómez V, Jiménez D, et al. A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer. Chest 2013;143:138-145.) kRecommend IVC filter removal, if tolerating anticoagulation therapy. lSee Elements for Consideration in Decision Not To Treat (VTE-F). mSee Thrombolytic Agents (VTE-I). nSee Contraindications to Thrombolysis (VTE-J).

Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

PE-2

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NCCN Guidelines Version 1.2015 Heparin-Induced Thrombocytopenia (HIT)

NCCN Guidelines Index VTE Table of Contents Discussion

DIAGNOSIS AND TREATMENT OF HIT

HIT Suspected

Low (4 T Score 50% platelet fall

Nadir 10,000–19,000/mcL or 30%–50% platelet fall

Nadir 3.6 mg/dL or AST/ALT >600 IU/L): Use bivalirudin or fondaparinux • Bivalirudin (half-life 25 minutes with normal renal function; aPTT ratio 1.5–2.5)3 Consider strongly for patients with combined hepatic and renal dysfunction Dosing: ◊◊Estimated creatinine clearance (CCr) >60 mL/min): 0.15 mg/kg/h –adjust to aPTT (first check 2 hours) ◊◊Estimated CCr 45–60 mL/min: 0.1 mg/kg/h ◊◊Estimated CCr 31–44 mL/min: 0.075 mg/kg/h ◊◊Estimated CCr 8 weeks or Cavernous transformation/collaterals noted or Signs of portal hypertension

Yes

• Anticoagulationd,e • Surgery (if bowel infarction) • Consider catheter-directed thrombolysisf • Gastrointestinal/surgery evaluation • Surgery (if bowel infarction) • Re-assess contraindications to anticoagulation regularly • Gastrointestinal evaluation • Beta blockade • Consider variceal banding or sclerosis • Consider anticoagulationd,e

cSee Contraindications to Prophylactic or Therapeutic Anticoagulation Treatment (VTE-B). dWeigh risks/benefits of anticoagulation, particularly for chronic thromboses. Duration of anticoagulation

should be at least 6 months for triggered events (eg, postsurgical) and indefinite if active cancer, thrombophilic state, or idiopathic thrombosis. eSee Therapeutic Anticoagulation Treatment for Venous Thromboembolism (VTE-D). fDecision to offer thrombolysis should be based on local availability/expertise, location of thrombus, and risk of bleeding. Choice of regimen should be made based on institutional expertise/preferences in conjunction with interventional radiology or vascular surgery colleagues. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 1.2015, 08/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

SPVT-2

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NCCN Guidelines Version 1.2015 Cancer-Associated Venous Thromboembolic Disease

NCCN Guidelines Index VTE Table of Contents Discussion

VTE RISK FACTORS IN CANCER PATIENTS General patient risk factors • Active cancer • Advanced stage of cancer • Cancer types at higher risk: Brain Pancreas Stomach Bladder Gynecologic Lung Lymphoma Myeloproliferative neoplasms Kidney Metastatic cancers • Regional bulky lymphadenopathy with extrinsic vascular compression • Familial and/or acquired hypercoagulability (including pregnancy) • Medical comorbidities: Infection, renal disease, pulmonary disease, congestive heart failure, arterial thromboembolism • Poor performance status • Older age High-risk outpatients on chemotherapy, based on combinations of the following risk factors1 • Active cancers associated with high incidence of VTE: Stomach, pancreas, lung, lymphoma, gynecologic, bladder, and testicular • Prechemotherapy platelet count >300,000/mcL • Prechemotherapy white blood cell (WBC) >11,000/mcL • Hemoglobin 48 hours • Thrombocytopenia (platelets