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Cancer patients are at an increased risk of venous thromboembolism. There have been several guidelines published on the topic from the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Although they agree on some issues regarding prophylaxis and treatment there are several areas that vary. This presentation covers the varying recommendations and the areas of consensus (yellow boxes) among the guidelines while using a patient case to guide their interpretation.
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Venous Thromboembolism in the Cancer PatientMarti LarrivaPharmD Candidate 2014
December 5, 2013
OutlineGoals
Patient Case
Background
Guidelines
Conclusion of Patient Case
GoalsUnderstand risk of VTE associated with cancer
Take away where the consensus lies among guidelines
Identify gray areas regarding prophylaxis and treatment of VTE in cancer patients
Patient Case Ms. M is a 43 y/o female with cervical cancer
diagnosed 2 years ago Undergone 4 lines of chemotherapy with
progressive disease and painful lymphadenopathy TIL harvest surgery – L groin mass 2 months ago
Admitted for TIL therapy: Chemo -> T-cells -> IL-2 -> Supportive Care
PMH: Diabetes, HTN, PE (1 year ago)
Allergies: Aspirin
Relevant Labs
BMI 47.5 kg/m2
WBC 5.29 x 109/L
Hgb 10.3 g/dL
Platelets 306 x 109/L
BackgroundVTE
Cancer populationRisk Factors
Guidelines
Venous Thromboembolism
Armand Trousseau, 1860Trousseau’s sign of malignancy
What is the difference?
Cancer Patients Non-Cancer Patients
Ambulatory
8-19%
Ambulatory
1.4%
Path
ophysio
logy
Patient Related• Increased Age• Obesity• Co-morbidities• Performance Status
Treatment Related• Chemotherapy, antiangiogenesis
agents, hormonal therapy• Radiation therapy• Surgery• Indwelling venous access
Cancer Related• Primary Site• Stage• Histology• Time since diagnosis
Biomarkers• Platelets > 350 x 109/L• Leukocyte count > 11x 109/L• Hgb < 10 g/dL
Risk Factors
Treatment Options
Heparin, LMWH, Fondaparinux Warfarin
GuidelinesACCP 2012, ASCO 2013, NCCN 2013
Inpatient VTE Prophylaxis
ACCP NCCNNonsurgical:
High risk patients
Surgical:Depends upon
surgical site and patient risk
All cancer patients
*Note: These recommendations are all in the absence of contraindications to anticoagulation.
Active cancer PLUS
acute medical illness
OR reduced mobility
ASCO
Prophylactic doses UFH
LMWH Fondaparinux
Nonsurgical VTE Risk
Padua Prediction Score
Risk Factor PointsActive Cancer 3Previous VTE (excluding SVT) 3Reduced mobility* 2Already known thrombophilic condition 1Recent (≤ 1 mo.) trauma/surgery 1Elderly age (≥ 70y) 1Heart and/or respiratory failure 1Acute MI or ischemic stroke 1Obesity (BMI ≥ 30) 1Ongoing hormonal treatment 1
*Anticipated bed rest with bathroom privileges for at least 3 days
High Risk≥ 4 points
Surgical VTE Risk
Roger Operation type
Thoracic area highest risk
Cancer Disseminated cancer Chemo within 30 days
Caprini Recent Stroke (<1 mo.)
History of VTE
Age
Malignancy
BMI
Outpatient VTE Prophylaxis
ACCP NCCN
Solid tumor + “other risk factors”
Prophylaxis with LDUFH or LMWH
See consensus
*Note: These recommendations are all in the absence of contraindications to anticoagulation.
Highly select patients with solid tumors undergoing
chemotherapyConsider LMWH
ASCO
Cancer Surgery patients
4 weeks post-operation
Multiple Myeloma patients
Multiple Myeloma Low Risk High Risk
Thalidomide or Lenalidomide therapy
PLUS
0-1 risk factor for VTE
Thalidomide or Lenalidomide therapy in combination with: High dose dexamethasone Doxorubicin Multiagent chemo
Thalidomide or Lenalidomide therapy
PLUS
≥ 2 risk factors for VTE
Aspirin 81-325 mg once daily LMWH
OR
Full dose warfarin (INR 2-3)
Khorana ScorePatient Characteristic Risk Score
Site of Primary Cancer Very High Risk (stomach, pancreas) High Risk (lung, lymphoma, gynecologic, bladder,
testicular)
21
Prechemotherapy platelet count ≥ 350 x 109/L 1
Hgb < 10 g/dL 1
Prechemotherapy leukocyte count ≥ 11 x 109/L 1
BMI 35 kg/m2 1
Total Score0
1-23 or higher
Risk of Symptomatic VTE
Low (0.8-3%)Intermediate (1.8-8.4%)
High (7.1-41%)
DVT/PE
ACCP NCCNVKA(INR 2-3) bridged with LMWH Provoked: 3 monthsUnprovoked: ≥ 3 months
LMWH for a minimum of 3 months, indefinite if active cancer/persistent risk factors
*Note: These recommendations are all in the absence of contraindications to anticoagulation.
LMWH for at least 6 months, perhaps longer if active
cancer
ASCO
LMWH preferred to Warfarin
Cochrane Collaboration:LMWH vs. Warfarin
ConclusionsConsensus summary
Gray areasFuture Research
Consensus Summary Inpatient prophylaxis should consist of
prophylactic doses of LMWH, UFH, or Fondaparinux
Outpatient prophylaxis should be done: In multiple myeloma patients undergoing
therapy with thalidomide or lenalidomide As an extension of inpatient surgical prophylaxis
for high risk abdominal or pelvic surgeries
Treatment of DVT/PE should be done using LMWH rather than Warfarin
Gray AreasWho should receive prophylaxis as an
inpatient?
Should outpatients at high risk for VTE receive prophylaxis based upon the Khorana score?
What is the appropriate length of therapy for VTE/PE in the cancer patient? What factors impact extension of therapy beyond
3-6 months?
Future Directions for ResearchDetermine which cancer patients benefit most
from thromboprophylaxis: Risk stratification tools Specific cancer types Identify better biomarkers
Determine ideal duration of anticoagulation: Prophylaxis - Risk related to time from diagnosis Treatment - Need for extended therapy
Patient Case Ms. M is a 43 y/o female with cervical cancer
diagnosed 2 years ago Undergone 4 lines of chemotherapy with
progressive disease and painful lymphadenopathy TIL harvest surgery – L groin mass 2 months ago
Admitted for TIL therapy: Chemo -> T-cells -> IL-2 -> Supportive Care
PMH: Diabetes, HTN, PE (1 year ago)
Allergies: Aspirin
Relevant Labs
BMI 47.5 kg/m2
WBC 5.29 x 109/L
Hgb 10.3 g/dL
Platelets 306 x 109/L
Patient CaseMs. M has a Padua score of 7 indicating she is
at high risk for VTE According to ACCP and NCCN she should receive
prophylaxis as an inpatient: Enoxaparin 40mg SQ Qday UFH 5,000 units SQ Q8H Fondaparinux 2.5 mg SQ Qday
Upon discharge, should she continue prophylaxis? Intermediate Khorana Risk
References1. Akl EA, Labedi N, Barba M et al. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev. 2011;(6):CD006650. doi(6):CD006650.
2. Gould MK, Garcia DA, Wren SM et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e227S-77S.
3. Kahn SR, Lim W, Dunn AS et al. Prevention of VTE in nonsurgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e195S-226S.
4. Khorana AA. Cancer-associated thrombosis: Updates and controversies. Hematology Am Soc Hematol Educ Program. 2012;2012:626-30.
5. Lyman GH, Khorana AA, Kuderer NM et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2013;31(17):2189-204.
6. Palumbo A, Rajkumar SV, Dimopoulos MA et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414-23.
7. Semchuk WM, Sperlich C. Prevention and treatment of venous thromboembolism in patients with cancer. Can Pharm J (Ott). 2012;145(1):24,29.e1.
8. Streiff MB, Bockenstedt PL, Cataland SR et al. Venous thromboembolic disease. J Natl Compr Canc Netw. 2013;11(11):1402-29.
Questions?
