High risk populations: Cancer
Surgeon General's Workshop on Deep Vein Thrombosis
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SLIDE 1: High risk populations: Cancer
Professor A K Kakkar
SLIDE 2: Concurrent VTE and cancer increases the risk of death
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.
SLIDE 3: Activation of coagulation in cancer patients
| Control (n = 72) | Cancer (n = 106) | p | |
|---|---|---|---|
| TF, pg/mL Factor VIIa, ng/mL | 349 69 | 582 100 | 0.0006 0.0002 |
| TAT, g/L PF1+2, ng/mL | 2.0 1.0 | 8.0 3.0 | 0.0001 0.0001 |
| Factor XIIa, ng/mL | 2.0 | 3.0 | 0.02 |
PF = prothrombin fragment; TAT = thrombin-antithrombin complex; TF = tissue factor.
| Number | |||||||
|---|---|---|---|---|---|---|---|
| At risk | In-Hospital PE | After-discharge PE | Total PE | Overall incidence, % | 95% CI | OR | |
| Surgical Cancer | 1,796 | 40 | 2 | 42 | 2.34 | 1.69–3.15 | |
| 6.7 | |||||||
| No cancer | 17,365 | 40 | 22 | 62 | 0.36 | 0.27–0.46 | |
| Non surgical Cancer | 815 | 5 | 1 | 6 | 0.73 | 0.27–1.60 | |
| 7.3 | |||||||
| No cancer | 8,977 | 5 | 4 | 9 | 0.10 | 0.50–019 | |
SLIDE 5: ACCP Consensus conference on antithrombotic therapy
Major surgery in cancer patients
| % 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.
SLIDE 6: Incidence of VTE in malignancy: non-surgical breast cancer
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.
SLIDE 7: Incidence of VTE in malignancy: non-surgical other cancers (limited data)
| Incidence of VTE % | |
|---|---|
| Ovarian | 10 |
| Glioma | 7 - 24 |
| Lymphoma | 4 - 6 |
| Germ cell | 8 |
| Anti-VEGF in colon | 19 |
SLIDE 8: Prophylaxis against Fatal Post-operative PE with Low-dose UFH
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.
SLIDE 9: Prevention of Fatal Pulmonary Embolism
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.
SLIDE 10: Bleeding driven by pathology
| Cancer surgery (n = 6,124) | Non-cancer surgery (n = 16,954) | p | |
|---|---|---|---|
| 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) | |
| Bleeding complications | |||
| Wound haematoma | 198 | 293 | 0.001* |
| Post-operative wound bleeding | 33 | 36 | |
| Gastric bleeding | 7 | 2 | |
| Intestinal bleeding | 5 | 2 |
*Calculated using Fisher’s Test. †Calculated using the Wilcoxon Test.
SLIDE 11: PE and Death: Cancer vs. No Cancer
| 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) |
SLIDE 12: Prophylaxis: ambulant patient
- 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.
SLIDE 13: Cumulative Incidence of Recurrent VTE During Anticoagulant Therapy
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.
SLIDE 14: Cumulative Incidence of Clinically Important Bleeding During Anticoagulant Therapy
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 | |||
| FAMOUS1 (2002) | Daltaparin Placebo | 10.80 9.14 | 43.5 24.3 | 0.03 |
| SCLC study2 (2003) | Daltaparin Placebo | 13.0 8.0 | 16.0 10.0 | 0.007 |
| MALT3 (2003) | Daltaparin Placebo | 8.0 6.6 (HR 1.0) | 15.4 9.4 (HR 0.64) | 0.01 |
| 1-year survival, % | ||||
| CLOT4 (2003) | Dalteparin OAC | 62 61 (HR 1.0) | 80 64 (HR 0.5) | 0.03 |
HR = hazard ratio; OAC = oral anticoagulant.
