This document describes a case study of a woman with cancer who developed deep vein thrombosis while undergoing chemotherapy. It provides details of her medical history and treatment. Ultrasound revealed she had a DVT in her left leg. Due to her thrombocytopenia from chemotherapy, proper anticoagulation treatment posed challenges around balancing risk of recurrent VTE and risk of bleeding. The document discusses options for anticoagulation including rivaroxaban and its efficacy and safety based on clinical trials. It recommends rivaroxaban as an effective option for treating cancer-associated VTE.

1. THE ROLE OF RIVAROXABAN IN DIFFERENT
CASE STUDIES

2. CHALLENGING ANTICOAGULATION CASES: CANCER-
ASSOCIATED VENOUS THROMBOEMBOLISM AND
CHEMOTHERAPY-INDUCED THROMBOCYTOPENIA

3. CASE STUDY
 A 54-year old women was recently diagnosed with biliary tract cancer and
hepatic metastasis. Due to the advanced stage of disease, palliative first-line
combination chemotherapy with cisplatin and gemcitabine was initiated.
 The first and second cycle of chemotherapy were well tolerated. At the eighth
day after the third cycle of chemotherapy, the patient reported swelling of the
left leg that had started two days ago.
https://doi.org/10.1016/j.thromres.2020.12.016

4. CASE STUDY
 Compression ultrasonography was performed and revealed proximal deep
vein thrombosis (DVT), extending into the common iliac vein.
 The patient reported no prior history of thrombotic or hemorrhagic events. In
routine blood count investigation mild anemia (hemoglobin count: 10.5 g/dl
[reference range in females: 11.6–15.0]) and decreased platelet counts (64 G/L
[reference range: 150–300 G/L]) were detected.
 What’s the proper management?
https://doi.org/10.1016/j.thromres.2020.12.016

5. WHAT’S THE PROPER MANAGEMENT
https://doi.org/10.1016/j.thromres.2020.12.016

6. WHAT’S THE PROPER MANAGEMENT
https://doi.org/10.1016/j.thromres.2020.12.016

7. ANTICOAGULATION IN PATIENTS WITH CANCER-
ASSOCIATED VTE
 Anticoagulation in patients with cancer-associated VTE is frequently
complicated by chemotherapy-induced thrombocytopenia.
 Due to the increased risk of bleeding in severely decreased platelet counts
and the recurrent course due to the necessity of ongoing anti-cancer
treatment, employing safe, effective, and feasible anticoagulation strategies is
important.
 The selection of an appropriate anticoagulation agent and dose must balance
risk of recurrent VTE and risk of bleeding, depending on platelet count and
risk factors for bleeding as well as type and time course of VTE.
https://doi.org/10.1016/j.thromres.2020.12.016

8. SELECT-D CLINICAL TRIAL

9. SELECT-D CLINICAL TRIAL
➢ Recurrent VTE at 6 months
57%
RRR
Young AM et al. J Clin Oncol. 2018 Jul 10;36(20):2017-2023. doi: 10.1200/JCO.2018.78.8034. Epub 2018 May 10. PMID: 29746227.

10. CONCLUSION
Rivaroxaban was associated with relatively low VTE recurrence
HR(95% CI) = 0.43 (0.19,0.99)
But higher clinically relevant non-major bleeding compared with dalteparin
HR(95% CI) = 3.76 (1.63,8.69).
The results provide evidence that rivaroxaban is an effective alternative to
LMWH for the treatment of VTE in cancer.
Oral administration is more convenient than daily subcutaneous injections.
It should be used with particular caution in patients with esophageal cancer.
Young AM et al. J Clin Oncol. 2018 Jul 10;36(20):2017-2023. doi: 10.1200/JCO.2018.78.8034. Epub 2018 May 10. PMID: 29746227.

11. AMERICAN SOCIETY OF HEMATOLOGY 2021 GUIDELINES FOR
MANAGEMENT OF VENOUS THROMBOEMBOLISM: PREVENTION
AND TREATMENT IN PATIENTS WITH CANCER
DOI 10.1182/bloodadvances.2020003442

12. CASE STUDY: THE SMART CHOICE FOR PREVENTION
OF RECURRENT VENOUS THROMBOEMBOLISM1

13. CASE STUDY
 A 34-year-old woman presents for follow-up after completion of
six months of therapeutic anticoagulation for a deep venous
thrombosis (DVT) of the right lower extremity complicated by
pulmonary embolism (PE).
 She initially presented six months prior to urgent care with severe
right lower extremity swelling and pain following immobilization
and casting for a right ankle fracture.

14. CASE STUDY
 She was promptly diagnosed with a large proximal DVT of the right
lower extremity via lower extremity doppler ultrasound and, given
shortness of breath and tachycardia at the time of presentation, PE
protocol computerized tomography (CT) was performed that
demonstrated multiple bilateral pulmonary emboli. She was initiated
on therapeutic anticoagulation with rivaroxaban.
 She has no other known medical problems and no prior personal or
family history of venous thromboembolism (VTE).
Case Study: The Smart Choice for Prevention of Recurrent Venous Thromboembolism - Hematology.org

15.  She takes no medications aside from rivaroxaban, does not use
exogenous hormonal birth control, and takes no nutritional
supplements. Her body mass index (BMI) is 22.
 She had no complications whatsoever from the rivaroxaban and is
interested in any evidence-based intervention to minimize her risk
of recurrent VTE, given the size of her first clot and the negative
impact it has had on her life.
Case Study: The Smart Choice for Prevention of Recurrent Venous Thromboembolism - Hematology.org
CASE STUDY

16.  A) Obtain thrombophilia workup (antiphospholipid antibody testing
and testing for factor V Leiden, prothrombin gene mutation, protein C
deficiency, protein S deficiency, and antithrombin deficiency)
 B) Discontinue rivaroxaban and initiate aspirin 81 mg daily for one year
 C) Reduce rivaroxaban dose to 10 mg daily and continue indefinitely
 D) Reduce rivaroxaban dose to 10 mg daily and continue this dose for
one year
 E) Continue rivaroxaban 20 mg daily indefinitely
Case Study: The Smart Choice for Prevention of Recurrent Venous Thromboembolism - Hematology.org
WHAT’S THE PROPER MANAGEMENT

17. BASED ON THE RESULTS OF THE EINSTEIN CHOICE STUDY
D) Reduce rivaroxaban dose to 10 mg daily and continue this dose for one year
Case Study: The Smart Choice for Prevention of Recurrent Venous Thromboembolism - Hematology.org
The patient is an otherwise young, healthy woman who suffered a provoked VTE following
immobilization of her leg in a cast.
She has a normal weight, does not use exogenous hormones for birth control, and has no
known underlying thrombophilia.
She was appropriately treated with therapeutic anticoagulation for six months, and now
presents for the next step in her management.
Continuation of rivaroxaban for one year at a dose of either 10 mg daily or 20 mg daily for
one year is the most appropriate evidence-based risk reduction strategy, making reducing
rivaroxaban dose to 10mg daily and continuing this dose for one year, the correct answer.

18. THE EINSTEIN CHOICE STUDY
PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE IN MARCH 2017
Rivaroxaban or aspirin for extended treatment of venous
thromboembolism
Randomized, double blind, active comparator, event driven, superiority study.
March 30, 2017 N Engl J Med 2017; 376:1211-1222DOI: 10.1056/NEJMoa1700518

19. THE EINSTEIN CHOICE STUDY
PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE IN MARCH 2017
March 30, 2017 N Engl J Med 2017; 376:1211-1222DOI: 10.1056/NEJMoa1700518
➢ Primary efficacy outcome: symptomatic recurrent fatal or nonfatal VTE.
➢ Hazard ratio for 20 mg of
rivaroxaban vs. aspirin, 0.34;
95% confidence interval
[CI], 0.20 to 0.59.
➢ Hazard ratio for 10 mg of
rivaroxaban vs. aspirin, 0.26;
95% CI, 0.14 to 0.47.
➢ P<0.001 for both
comparisons.

20. THE EINSTEIN CHOICE STUDY
PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE IN MARCH 2017
➢ Principal safety outcome: Major bleeding - ISTH.
➢ the rates of clinically relevant non major bleeding were 2.7%, 2.0%, and 1.8%, respectively. The
incidence of adverse events was similar in all three groups.
March 30, 2017 N Engl J Med 2017; 376:1211-1222DOI: 10.1056/NEJMoa1700518

21. THE EINSTEIN CHOICE STUDY
PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE IN MARCH 2017
CONCLUSIONS
Among patients with venous thromboembolism in equipoise for continued
anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban
at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin,
without a significant increase in bleeding rates.
March 30, 2017 N Engl J Med 2017; 376:1211-1222DOI: 10.1056/NEJMoa1700518

22. AMERICAN SOCIETY OF HEMATOLOGY 2020 GUIDELINES FOR
MANAGEMENT OF VENOUS THROMBOEMBOLISM
TREATMENT OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
For patients with DVT and/or PE who have completed primary treatment and will
continue to receive secondary prevention, the ASH guideline panel suggests using
anticoagulation over aspirin.
For patients with DVT and/or PE who have completed primary treatment and will
continue with a DOAC for secondary prevention, the ASH guideline panel suggests
using a standard-dose DOAC or a lower-dose DOAC.
DOI 10.1182/bloodadvances.2020001830.

23. RIVAROXABAN IN PATIENTS WITH
VTE AND RENAL INSUFFICIENCY

24. CASE STUDY
1. 2017, American Society of Health-System Pharmacist www.ashpadvantage.com/go/vteseries
A 78‐year‐old man with chronic kidney disease is admitted
for pulmonary embolism. He is stabilized on heparin and is
ready to be transitioned to an oral anticoagulant. His CrCl
is 42 mL/min. What is the appropriate Rivroxaban dose?

25. ➢ Mild: CrCL 50-80 ml/min
○ No dose adjustment
➢ Moderate: CrCL 30-49 ml/min, and Severe: CrCL 15-29
○ Any Dose of 20 mg OD should be reduced to 15 mg OD
○ VTE treatment dose is 15 mg BID followed by 15 mg OD.
➢ End stage renal disease (ESRD): CrCL < 15 ml/min:
○ NOT RECOMMENDED.
RENAL IMPAIRMENT

27. THANK YOU