High risk populations: Cancer
Surgeon General's Workshop on Deep Vein Thrombosis
Professor A K Kakkar
Probability of death within 183 days of initial hospital admission
Line chart showing data from large epidemiological databases indicate that patients who develop thromboembolic disease either at presentation with their cancer or during the course of their cancer have a poorer outcome when compared to patients with cancer who have never developed a thrombosis.
|Control (n = 72)||Cancer (n = 106)||p|
Factor VIIa, ng/mL
|Factor XIIa, ng/mL||2.0||3.0||0.02|
PF = prothrombin fragment; TAT = thrombin-antithrombin complex; TF = tissue factor.
|At risk||In-Hospital PE||After-discharge PE||Total PE||Overall incidence, %||95% CI||OR|
|Non surgical Cancer||815||5||1||6||0.73||0.27–1.60|
Major surgery in cancer patients
|Calf vein||40 – 80|
|Proximal vein||10 – 20|
|Clinical PE||4 – 10|
|Fatal PE||1 – 5|
ACCP, American College of Chest Physicians; PE, pulmonary embolism.
Line chart. Non-surgical cancer patients have been much less well investigated with regard to their risk for the development of venous thromboembolism. The best investigated population are women with breast cancer. In this population advancing stage of the disease, post menopausal status, and the combination of cytotoxic chemotherapy with hormonal therapy (Tamoxifen) was associated with an increasing risk for the development of venous thromboembolism.
|Incidence of VTE %|
|Glioma||7 - 24|
|Lymphoma||4 - 6|
|Anti-VEGF in colon||19|
Bar chart. With regard to preventing thromboembolic disease in cancer patients, the best investigated population are patients undergoing surgical intervention for their cancer. Low dose unfractionated heparin is effective in preventing both deep vein thrombosis and fatal pulmonary embolism in general and oncological surgical patients undergoing laparotomy. A landmark study published some 30 years ago, The International Multicentre Trial, 4121 patients undergoing surgical intervention 23% who underwent the operation for cancer were randomised to a control group or to perioperative low dose unfractionated heparin.
Bar chart. The frequency of autopsy proven fatal PE in the cancer sub population was reduced from 1.6% in the control group to 0.4% in the low dose unfractionated heparin group. However, low dose heparin therapy is associated with a small but significant increase in the frequency of wound haematoma.
(n = 6,124)
(n = 16,954)
|Re-operation because of bleeding|
|Patients, n (%)||68 (1.1%)||102 (0.6%)||< 0.001*|
|Transfusion of whole blood|
|Patients, n (%)||483 (7.9%)||890 (5.2%)||0.001*|
|Mean volume, mL (SD)||1,028 (862)||752 (507)||0.001†|
|Median volume, mL (range)||750 (120–8,000)||750 (600–4,000)|
|Post-operative wound bleeding||33||36|
*Calculated using Fisher’s Test. †Calculated using the Wilcoxon Test.
|All patients (low-dose UFH or LMWH)||Cancer (n=6124)||No cancer (n=16,954)||P value|
|Death (%)||192 (3.1)||120 (0.7)||0.0001|
|Fatal PE (%)||20 (0.33)||15 (0.09)||0.0001|
|Non-fatal PE (%)||5 (0.08)||4 (0.02)|
- 311 women with advanced breast cancer
- Low-dose warfarin INR 1.3–1.9
Bar chart. Prophylaxis in the ambulant cancer patient receiving chemotherapy out of hospital has not been well investigated. A single study in the literature evaluated low intensity oral anticoagulation with the vitamin-K antagonist Warfarin. This trial randomised woman with advanced breast cancer and demonstrated an 85% reduction in the frequency of symptomatic venous thromboembolism. However, the use of vitamin-K antagonists in patients with disseminated malignancy especially to the liver often causes concern because of the difficulty in achieving safe consistent anticoagulation.
Line chart. (Cumulative Proportion (%) Recurrent Thromboembolism) Once cancer patients develop a first episode of venous thromboembolism they are at three times the risk of developing subsequent episodes than non-cancer patients with thrombosis and twice as likely to develop bleeding complications on anticoagulant therapy as treatment for their thrombosis.
Line chart. (Cumulative Proportion (%) Major Bleeding) Once cancer patients develop a first episode of venous thromboembolism they are at three times the risk of developing subsequent episodes than non-cancer patients with thrombosis and twice as likely to develop bleeding complications on anticoagulant therapy as treatment for their thrombosis.
|Therapy||Median survival, months||p|
|Overall population||Good prognosis population|
6.6 (HR 1.0)
9.4 (HR 0.64)
|1-year survival, %|
61 (HR 1.0)
64 (HR 0.5)
HR = hazard ratio; OAC = oral anticoagulant.