Cancer-associated thrombosis: the when, how and why

TABLE 1

Relative risk of venous thromboembolism diagnosis in hospitalised cancer patients

Cancers	Odds ratio
Haematological cancer	26.2
Lung	24.8
Gastrointestinal (bowel, pancreas, stomach, oesophagus)	18.9
Brain	8.0
Kidney	5.8
Skin (melanoma, squamous cell)	3.6
Breast	3.5
Prostate	3.4
Uterine cervix	3.3
Ovarium	2.3
Ear, nose and throat	1.5
Other	6.6

Data from [19].

TABLE 2

Risk factors for cancer-associated thrombosis

Patient-related factors

Inherited thrombophilic factors

Cancer-related factors

Candidate biomarkers

Reproduced from [22] with permission from the publisher.

TABLE 3

Predictive model for chemotherapy-associated venous thromboembolism

Patient characteristics	Risk score
Site of cancer
Very high risk (stomach, pancreas)	2
High risk (lung, lymphoma, gynaecologic, bladder, testicular)	1
Prechemotherapy platelet count ≥350 000 per mm³	1
Haemoglobin level <10 g·dL⁻¹ or use of red cell growth factors	1
Prechemotherapy leukocyte count >11 000 per mm³	1
Body mass index ≥35 kg·m⁻²	1

A risk score ≥3 is a high-risk score, 1–2 is an intermediate score, and 0 is a low-risk score.

TABLE 4

Major randomised trials in cancer-associated thrombosis primary prophylaxis

Trial	Year	Patients n	Drugs evaluated	Major findings
ENOXACAN II [32]	2002	332 (submitted for abdominal or pelvic surgery)	Enoxaparin (31 days) versus placebo (after 10 days of surgery)	Enoxaparin patients presented less VTE events than placebo after 1 (p=0.02) and 3 months (p=0.01). No difference in major bleeding.
PROTECHT [27]	2009	1150	Nadroparin (4 months) versus placebo	Nadroparin patients presented less thrombotic events (venous and arterial) than placebo (p=0.02). No statistical difference in major bleeding.
SAVE-ONCO [28]	2012	3212	Semuloparin (3.5 months) versus placebo	Semuloparin patients presented less VTE events than placebo (p<0.001). No difference in major bleeding.
AVERT [30]	2018	563	Apixaban (180 days) versus placebo	Apixaban patients presented less VTE events than placebo (p<0.001) and more major bleeding (p=0.046) than placebo.
CASSINI [31]	2018	841	Rivaroxaban (180 days) versus placebo	Statistical trend of less VTE events and VTE-related death in rivaroxaban patients (p=0.10). No difference in major bleeding.

VTE: venous thromboembolism.

TABLE 5

Major randomised trials in cancer-associated thrombosis treatment

Trial	Year	Patients n	Drugs evaluated	Major findings
CANTHANOX [35]	2002	146	Enoxaparin versus warfarin	Statistical tendency of warfarin to be more associated with major bleeding (p=0.09) and death (p=0.07) than enoxaparin.
CLOT [36]	2003	672	Dalteparin versus warfarin	Dalteparin was superior to warfarin in VTE recurrence (p=0.002). No difference in major bleeding or mortality.
CATCH [37]	2015	900	Tinzaparin versus warfarin	Statistical tendency of VTE recurrence reduction with tinzaparin (p=07). No difference in major bleeding or mortality.
HOKUSAI-CANCER [45]	2018	1046	Edoxaban versus dalteparin	Edoxaban was non-inferior to dalteparin. Statistical tendency of superiority of edoxaban in VTE recurrence reduction (p=0.09), statistically significant more major bleeding with edoxaban (p=0.04).
SELECT-D [47]	2018	406	Rivaroxaban versus dalteparin	Statistically significant less VTE recurrence (HR 0.43, 95% CI 0.19–0.99) and statistical tendency of more bleeding (HR 1.83, 95% CI 0.68–4.96) with rivaroxaban (oesophagus and gastro-oesophageal junction cancer patients excluded after inclusion of the first 220 patients)
CARAVAGGIO [48]	2019 (expected)	1168 (expected)	Apixaban versus dalteparin	?