Venous ThromboembolismIn Cancer Patients

VTE

Nabeel Rajeh, MD

VTE IN CANCER PATIENTS

• First described by Trousseau 1865

• Hypercoagulability related to cancer• Procoagulant, vessel wall damage,

stasis and immobilization, chemotherapy, surgery, radiation,

• Underlying intrinsic hypercoagulability• Factor V leiden, antiphospholipid

syndrome

• 2-6 fold increase in risk of death

VENOUS THROMBOSIS IN CANCER PATIENTS FRONTLINE SURVEY

• first comprehensive global survey of thrombosis and cancer

• 3,891 completed responses were analyzed

• Brain and pancreatic tumors were a high risk for VTE

• 50% surgeons used thromboprophylaxis routinely

• 5% oncologists used thromboprophylaxis routinely

• Low molecular weight heparin (LMWH) was the most popular Aspirin for prophylaxis used in 20%

• LMWH use by as initial treatment for VTE as outpatient followed by VKA

• The results of the FRONTLINE survey demonstrate a need for guidelines to direct clinical practice in line with evidence-based data concerning cancer and VTE

Risk may be 1-35%

PREDICTORS OF VTE IN CANCER

• Anemia , Leukocytosis, Thrombocytosis

• History of VTE

• Hospitalization

• Infections

• Immobilization

• D-Dimer and P- Selectin

PREDICTORS OF VTE IN CANCER

• Adenoca compared to squamous cell ca

• Solid tumors as well as liquid tumors

• Certain treatment• Thalidomid, lenalidomide, doxorubicin, tamoxifen,

oral contraceptive, Dexamethasone erythropoietin, Bevacizumab

WHY CANCER PATIENT

• Patient with solid tumor and distant metastases has 20 fold increase VTE

• VTE second leading cause of cancer deaths

• Risk of bleeding is 13% compared with 4% in none cancer

• Significant early mortality if VTE

DIAGNOSIS OF VTE• Clinical prediction of risk

• Symptoms and signs

• D-Dimer testing to diagnose VTE is not recommended

• Duplex venous ultrasonography with compressibility and flow

• Indirect CT Venography

• MRI

• CTA for PE

• Invasive venography may be outdated

SUPERFICIAL VEIN THROMBOSIS

• Clinical diagnosis

• Must rule out DVT

• Trouseau Syndrome migratory SVT require UFH, or LMWH

• Treatment with 4 weeks LMWH if central catheter related

• NSAID

LMWH

• Dalteparin, Enoxaparin, Tinzaparin

• All inhibit Xa

• Therapeutically equivalent and Interchangeable

• RCT Tinzaparin compared to Dalteparin prove equality

• Immediate therapy and prophylaxis is FDA

• Continuation therapy require dose reduction?

• Concern in renal, obese, elderly, HIT,

FONDAPARINUX

• Specific Xa inhibitor

• No cross reaction with HIT

• Value in renal failure, obese, underweight, elderly is questionable

• Dosing once daily

UNFRACTIONATED HEPARIN

• Do we remember!

• SQ prophylaxis may be better than LMWH

• Bid or tid dosing

• Treatment based on weight 80u/kg/h

• Can be used with renal failure (liver metabolism)

• Risk of HIT

• Resistance

WARFARIN

• The advisable chronic therapy

• Concomitant with UFH or LMWH for 5 days

• PT INR monitoring

• Labile INR result

• Resistance to therapeutic INR (genetically interaction and none compliance)

INPATIENT PROPHYLACTIC THERAPY

• To all patients hospitalized with active cancer

• Or suspicious cancer

• Encourage ambulation although it is not enough prophylaxis

• LMWH, UFH, Fondaparinux are effective

• Low dose warfarin and adjusted to INR1.5-2 for port catheter or chemotherapy catheter are not recommended

• May extend for 4 week post discharge in very high risk patient

PROPHYLAXIS

• SHOULD AMBULATORY PATIENTS WITH CANCER RECEIVE ANTICOAGULATION FOR VTE PROPHYLAXIS DURING SYSTEMIC CHEMOTHERAPY

• Not at this time

TREATMENT OF VTE• Immediate LMWH, UFH, Fondaparinux for 5-10 days

• Followed by LMWH for 6 m in patient with active cancer

• LMWH beyond 6 m is not recommended

• Warfarin with close monitoring

• Meta-analysis LMWH reduce 3 m mortality comapred to UFH

• Recurrence VTE and major bleeding are higher with chronic warfarin compared to LMWH

WHAT IS THE BEST TREATMENT FOR PATIENTS WITH CANCER WITH ESTABLISHED VTE TO

PREVENT RECURRENT VTE?

• LMWH is the preferred approach for the initial 5 to 10 days of anticoagulant treatment of the cancer patient with established VTE.

• LMWH given for at least 6 months is also the preferred approach for long-term anticoagulant therapy. Vitamin K antagonists with a targeted INR of 2 to 3 are acceptable for long-term therapy when LMWH is not available

SHOULD PATIENTS WITH CANCER RECEIVE ANTICOAGULANTS IN THE ABSENCE OF

ESTABLISHED VTE TO IMPROVE SURVIVAL?

• Anticoagulants are not recommended to improve survival in patients with cancer without VTE.

HEPARIN INDUCED THROMBOCYTOPENIA

HIT

• Thrombocytopenia Timeing, Thrombosis, oThers

• PF4/antibodies detection and serotonin release assay

• Stop warfarin stop heparin no platelets

• Direct thrombin inhibitors lepirudin argatroban

• Fondaparinux

Thank You

Nabeel Rajeh, MDwww.syriaoncology.com