# Presentation: 368336

## High risk populations: Cancer

**Professor A K Kakkar**

## Concurrent VTE and cancer                   increases the risk of death

**Probability of death within 183 days of initial hospital admission**

**Probability of death**

**1.00**
**0.80**
**0.60**
**0.40**
**0.20**
**0.00**

**0****	****40****	****80****	****120****	****180**
**Number of days**

**Malignant disease alone**

**DVT/PE and ****malignant disease**

- Levitan N, et al.  “Rates of thromboembolic disease among patients with malignancy versus those without malignancy: Risk analysis using Medicare claims data.”  Medicine 1999; 78:285-291

## Activation of coagulation in cancer patients

**Activation of coagulation**** in cancer patients**

- 	Control	Cancer	p
- 	(n = 72)	(n = 106)
- TF, pg/mL	349	582	0.0006
- Factor VIIa, ng/mL	69	100	0.0002
- TAT, g/L	2.0	8.0	0.0001
- PF1+2, ng/mL	1.0	3.0	0.0001
- Factor XIIa, ng/mL	2.0	3.0	0.02

- PF = prothrombin fragment; TAT = thrombin-antithrombin complex; TF = tissue factor.

## Cancer and PE

|  | 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 |  |
|  |  |  |  |  |  |  |  |
|  |  |  |  |  |  |  |  |

**Huber O, et al. Arch Surg. 1992;127:310-3. **

## ACCP Consensus conference on antithrombotic therapy

|  | % 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.

**ACCP Consensus conference on antithrombotic therapy**

- Geerts et al
- Chest 2004

## Incidence of VTE in malignancy: non-surgical breast cancer

- Prevention

- Node -ve

- Node +ve

- Advanced

**0.2%**
**0.1%**

**0.2%**

**0.9%**

**1.6%**

**9.6%**

**17.6%**

**VTE incidence**

## Incidence of VTE in malignancy: non-surgical other cancers

|  | Incidence of VTE % |
| --- | --- |
| Ovarian | 10 |
| Glioma | 7 - 24 |
| Lymphoma | 4 - 6 |
| Germ cell | 8 |
| Anti-VEGF in colon | 19 |

**Incidence of VTE in malignancy: ****non-surgical other cancers**

- LIMITED DATA

## Prophylaxis against Fatal Post-operative PE with Low-dose UFH 

*P*<0.005

**Prophylaxis against Fatal Post-operative PE with Low-dose UFH **

- 16

- 2

- 0

- 2

- 4

- 6

- 8

- 10

- 12

- 14

- 16

- 18

- Control

- UFH

*Kakkar vv et al Lancet* 1975;2:45–51

## Prevention of Fatal Pulmonary Embolism

-  Kakkar VV et al. Lancet. 1975;2:45-51; Haas S, et al. Thromb Haem. 2005.

- Low dose
-  heparin tid
- (n=11,536)

- LMWH qd
- (n=11,542)

- Low dose
-  heparin tid
- (n=2045)

- Control
- (n=2076)

*P *< 0.005

*P *=NS

## 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.

**Kakkar AK, et al. Thromb Haemost. 2005;94:867-71.**

## PE and Death: Cancer vs. No Cancer

- Death (%)
- Fatal PE (%)
- Non-fatal PE (%)

- All patients (low-dose UFH or LMWH)

- Cancer
- (n=6124)

- 192 (3.1)
- 20 (0.33)
- 5 (0.08)

- No cancer
- (n=16,954)

- 120 (0.7)
- 15 (0.09)
-  4 (0.02)

- 0.0001
- 0.0001

- Kakkar AK et al.Thromb Haem 2005

*P* value

**PE and Death: Cancer vs. No Cancer**

**Notes:**
Query: Please provide us with the complete reference

## Prophylaxis: ambulant patient

**311 women with advanced breast cancer**
**Low-dose warfarin INR 1.3–**1.9

**Thrombosis (%)**

**4.4 %**

**0.7%**

**p=0.03**

**Placebo**

**Warfarin**

**0**

**0.5**

**1**

**1.5**

**2**

**2.5**

**3**

**3.5**

**4**

**4.5**

**5**

**85% VTE reduction**

- Levine M et al. *Lancet *1994;**886**:886–9

## Cumulative Incidence of Recurrent VTE During Anticoagulant Therapy 

**Cumulative Proportion (%)****Recurrent Thromboembolism**

**30**

**20**

**10**

**0**

**Hazard ratio 3.2**

**Cancer**

- No Cancer

**0**
**181**
**661**

**1**
**160**
**631**

**2**

**3**
**129**
**602**

**4**

**5**

**6**
**92**
**161**

**7**

**8**

**9**
**73**
**120**

**10**

**11**

**12**
**64**
**115**

**Time (months)**
**Cancer**
**No Cancer**

- Prandoni P et al Blood 2003

## Cumulative Incidence of Clinically Important Bleeding During Anticoagulant Therapy

**Cumulative Proportion (%)****Major Bleeding**

**30**

**20**

**10**

**0**

**Hazard ratio 2.2**

**Cancer**

**No Cancer**

**Time (months)**
**Cancer**
**No Cancer**

**0**
**181**
**661**

**1**
**170**
**636**

**2**

**3**
**141**
**615**

**4**

**5**

**6**
**102**
**170**

**7**

**8**

**9**
**81**
**127**

**10**

**11**

**12**
**68**
**124**

- Prandoni P et al Blood 2003

## LMWH and survival  

|  | 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.

**1****Kakkar AK, et al. J Clin Oncol. 2004;22:1944-8;****2****Altinbas M, et al. J Thromb Haemost. 2004;2:1266-71;****3****Klerk CP, et al. J Clin Oncol. 2005;23:2130-5;****4****Lee AY, et al. N Engl J Med. 2003;349:146-53.**