At pro-COAG, an annual scientific and educational event on coagulation sponsored by Roche Diagnostics that was last held in Mar 2022, Prof Ng Heng Joo, Head and Senior Consultant at the Department of Haematology at Singapore General Hospital in Singapore, reviewed the causation, development and treatment of venous thrombotic events in cancer and inflammation.

Cancer

The frequency of thrombotic events in cancer is well-attested, especially venous thromboembolisms (VTEs) originating from lower limb deep-vein thrombosis (DVT), which makes up 0.6 to 7.8% of cases. Proximal DVT and arterial thrombosis represent a particular risk due to their propensity to induce pulmonary embolism (PE) and strokes respectively. It is, therefore, important to understand thrombotic mechanisms associated with malignancy, alongside other risk factors, in order to attain optimal treatment outcomes.

Tumour-associated hypercoagulable states result from three interacting mechanisms: endothelial disruption, pro-thrombotic activity by malignant cells, and host pro-coagulant expression. Both tumour- and host-based mechanisms hinge on activation of the intrinsic coagulation cascade by tissue and clotting factors, either directly expressed or stimulated by tumours and platelets. Endothelial disruption can result from either therapeutic intervention or inflammation-induced vascular permeability.

Predictably, advanced malignancies and malignancies of highly vascularised organs present the greatest risk of thrombosis. This is augmented by patient risk factors (e.g. age), immobilisation, burden of comorbidities, and by the inherent prothrombotic properties of chemotherapeutic agents. Thromboprophylaxis (based on direct oral anticoagulant and low molecular weight heparin) is advisable in all hospitalised and high- or intermediate-risk ambulatory cancer patients, as assessed by tools such as the Khorana score and its derivatives [1].

Inflammation

Although similar in outcome, pathological thrombosis resulting from immune system responses to infection or inflammatory triggers is based on exaggerated physiological immunothrombosis. This process involves the upregulation of interleukin receptors and attachment molecules on the vessel wall, the adhesion of neutrophils to vascular endothelium, the activation of monocytes and expression of tissue factors, and the initiation of the coagulation cascade that results in the activation of neutrophils to generate the neutrophil extracellular trap (NETosis) that forms the basis of a thrombus.

Whereas thromboprophylaxis is advisable in cases of infections known to induce a hypercoagulable state (e.g. COVID-19), inflammatory thrombosis does not necessarily respond to anti-coagulant therapy, and may be better treated with anti-inflammatories. Debate is ongoing.

Prof Ng Heng Joo, MD serves as Senior Consultant and Head of the Department of Haematology at Singapore General Hospital; Clinical Professor with Duke-National University of Singapore (NUS) School of Medicine; and Senior Lecturer with the Yong Loo Lin School of Medicine at NUS.

References:

[1] Lee, LH, et al. Front  Cardiovasc Med, 2021;8:669288