cancer associated thrombosis risk factors and management

1. Cancer
Associated
Thrombosis
When, How &
Why?
Dr/Marwa Mahmoud Khalifa
Internal Medicine & Hematology Specialist
Damanhour Oncology Center

2. Magnitude of the problem
 Venous thromboembolism (VTE) is a
common and life threatening condition in
cancer patients. (DVT&PE)
 Presence of cancer increased the risk for
VTE by 9-fold.
 Thrombosis is the leading cause of death
in cancer patients, second only to cancer
itself (higher mortality, reduced OS).
 Most common cause of death at 30-day
follow-up among cancer patients
underwent surgery.

3.  American Society of Hematology
 American Society of Clinical Oncology
 National Comprehensive Cancer
Network
 International Society of Thrombosis
and Hemostasis
 International Initiative on Thrombosis
in Cancer

4. VTE Risk Factors in Patients
With Cancer
Patient-Related
Cancer-Related
Treatment-Related

5. Patient-Related Risk
Factors
Older age
 Obesity (modifiable)
 Smoking, tobacco use (modifiable)
 Activity level/exercise (modifiable)
 Familial and/or acquired hypercoagulability
(including pregnancy)
 Medical comorbidities: infection, renal
disease, pulmonary disease, congestive
heart failure, arterial thromboembolism
 Prior VTE
 Hospitalization, prolonged immobilization
 Poor performance status

6. Cancer-Related Risk
Factors
 Active cancer
 Advanced stage of cancer
 Cancer types at higher risk:
◦ HEMATOLOGIC ( MPNs, MM, APL, high gradae
lymphoma)
◦ Brain
◦ Pancreas
◦ Stomach
◦ Bladder
◦ Gynecologic
◦ Lung
◦ Kidney
◦ Metastatic cancers

7. Treatment-Related Risk
Factors
 Major surgery
 Central venous catheter/intravenous
catheter
 Chemotherapy
 Protein kinase inhibitors
 Immunotherapy
 Exogenous hormonal therapies
 Antiangiogenic agents

8. Risk Assessment in Cancer
Patients
Khorana risk score
Vienna CATS risk assessment
Protecht model
CONKO score
ONKOTEV score
TicOnco score
COMPASS CAT model

9. VTE Prophylaxis in Patients With
Cancer
Inpatient VTE Prophylaxis
Who ??
◦ for all adults
◦ medical and surgical inpatients
◦ with a diagnosis of cancer or clinical
suspicion of cancer.
 For multiple myeloma patients receiving
lenalidomide, thalidomide, or
pomalidomide-based regimens, ASH
guideline panel suggests using low-dose
acetylsalicylic acid (ASA) or fixed low-
dose VKA or LMWH

10. Primary prophylaxis for patients
with cancer with central
venous catheter.
 ASH guideline suggests NOT using
parenteral / oral thromboprophylaxis.

11. Evaluation Prior To The Initiation
Of Thromboprophylaxis
 Comprehensive medical history and
physical examination
 CBC with platelet count and differential
 Prothrombin time, activated partial
thromboplastin time (aPTT)
 Liver and kidney function tests

13. 1- Medical Oncology Patients

14. 2- Surgical Oncology Patients

15. Contraindications to
Prophylactic Anticoagulation
• Active bleeding
• Thrombocytopenia (platelet count
<50,000/μL or clinical judgment)
• Underlying hemorrhagic coagulopathy
(eg, abnormal PT or aPTT excluding a
lupus inhibitor/anticoagulant) or known
bleeding disorder in the absence of
replacement therapy (eg, hemophilia, von
Willebrand disease)

16. Contraindications to
Prophylactic Anticoagulation
• Indwelling neuraxial catheters
(contraindication for apixaban,
dabigatran, edoxaban, fondaparinux,
rivaroxaban, or enoxaparin
dose exceeding 40 mg daily)
• Neuraxial anesthesia/lumbar
puncture
• Interventional spine and pain
procedures

17. Mechanical prophylaxis
 In case of contraindication to
anticoagulation
 Intermittent pneumatic compression
(IPC)
 Graduated compression stockings
(GCS)
 ??? efficacy

18. VTE Prophylaxis Following
Discharge For Medical
Oncology Patients /
Ambulatory
 Intermediate or high risk of VTE
(Khorana score ≤2)
 Anticoagulant prophylaxis for up to 6
months or longer, if risk persists.

21. Surgical Oncology Patients
VTE Prophylaxis Following
Discharge
 Prophylaxis for up to 4 weeks
 Surgery for gastrointestinal
malignancies or pelvic cancer surgery
patients
 Previous episode of VTE
 Anesthesia time 2 hours
 Perioperative bed rest ≤4 days
 Advanced stage disease
 Age ≤60 years.

23. Treatment for Patients with
Active Cancer and VTE
 The decision of treatment should be
made based on the risk-benefit
ratio
 The selection among
anticoagulants should be made
based on efficacy, bleeding risk
assessment, renal or hepatic
function, drug-drug interactions,
clinical setting, convenience of
use, cost, drug availability and
patient preference.

24. Initial Treatment (First Week)
 DOAC (apixaban or rivaroxaban) or
LMWH be used for initial treatment
 LMWH over UFH
 LMWH over fondaparinux

25. Short-term Treatment (Initial 3-
6 Months).
 DOAC (apixaban, edoxaban, or
rivaroxaban) over LMWH
 DOAC (apixaban, edoxaban, or
rivaroxaban) over VKA
 LMWH over VKA

26. Long-term treatment (>6
months)
 Continuing indefinitely
anticoagulation over stopping after
completion of a definitive period of
anticoagulation
 using DOACs or LMWH

27. CVC-related VTE
 Start anticoagulant treatment
 keep the CVC rather than removal

28. Recurrent VTE despite receiving
therapeutic LMWH
 Increasing the LMWH dose to a
supratherapeutic level or continuing
with a therapeutic dose
 NOT using an inferior vena cava (IVC)
filter over using a filter

30. Treatment of Cancer-associated
VTE in special situations
1- Intracranial malignancy
 Patients with intracranial malignancy
are at increased risk of thrombotic
complications and intracranial
hemorrhage (ICH) simultaneously

31. A retrospective comparative cohort
study compared the cumulative
incidence of ICH between the use of
DOACs and LMWH for 12 months in
172 patients with brain tumors and
VTE.
Primary
brain tumor
0% in the
DOACs
group
36.8% in
the LMWH
group
Brain Mets
11.1% in
the DOACs
group
17.8% in
the LMWH
group

32. 2-Renal impairment and Patients
on Hemodialysis
 Bleeding risk is high in cancer patients
with concurrent renal impairment
 LMWH should be used with caution &
avoided for those on hemodialysis.
 DOACs should generally be avoided.
 Apixaban NO dosing adjustment for
patients with end-stage renal disease
on dialysis. (insufficient data)
 Warfarin may be preferred

33.  In the CATCH trial, between patients
with and without renal impairment,
recurrent VTE rates were 14 and 8%,
major bleeding rates were 6.1 and
2.0%
mortality rates were 40 and 34%.

34. 3- Liver Disease
 DOACs are to be avoided in active,
and clinically significant liver disease.
 LMWH is preferred with warfarin as an
alternative anticoagulant option.

35. 4- Altered Gastrointestinal
Anatomy or Feeding Tubes
 The DOACs are absorbed at various
locations in the gastrointestinal tract,
largely in the stomach and small
intestine,
 Only apixaban, which is also absorbed in
the distal small bowel and ascending
colon.
 LMWH may be preferred warfarin as an
alternative option.
 Dabigatran and edoxaban are not
recommended for administration by
enteral tubes.
 Rivaroxaban and apixaban can be
administered via nasogastric feeding

36. Treatment of Cancer-associated
VTE with COVID-19
Thrombosis is one of the sequences
due to COVID-19 putting cancer
patients at higher VTE risk.
Parenteral anticoagulation (e.g.
LMWH) is preferred over oral
anticoagulation in the treatment of
established VTE in cancer patients
with COVID-19

37. Conclusions
 Cancer-associated venous thromboembolism
is a concerning issue that increases both
morbidity and mortality for patients with cancer.
 the decision of treatment should be made
based case by case
 LMWH, DOACs have shown a predominant
role in the treatment of cancer-associated VTE
 A minimum of 6 months of treatment should be
offered to patients with cancer associated VTE
 Continuation or discontinuation of treatment
should be made on a risk-benefit ratio of
anticoagulation

38. References
1. NCCN clinical practice guidelines in oncology
Version 2.2021
2. American Society of Hematology 2021 guidelines
for management of venous thromboembolism
3. How to Choose An Appropriate Anticoagulant for
Cancer-Associated Thrombosis (J Natl Compr
Canc Netw 2021;19(10):1203–1210)
4. Update on Guidelines for the Management of
Cancer-AssociatedThrombosis (The Oncologist
2021;26:e24–e40)
5. Current status of treatment of cancer associated
venous thromboembolism (Thrombosis Journal
2021)