Cancer histology and natural history of patients with lung cancer and venous thromboembolism (August 2022)

This study investigated the possible impact of lung cancer histology (adenocarcinoma, squamous or other types) on the incidence rates of VTE recurrences, major bleeding or death occurring throughout the course of anticoagulation among lung cancer patients.

The cohort consisted of patients with cancer and VTE – 293 (61%) with adenocarcinoma, 98 (20%) with squamous, 44 (9.1%) with small-cell and 9.8% with other forms. In half the patients with adenocarcinoma, VTE occurred within the first 90 days of cancer diagnosis. During anticoagulation, 14 patients developed VTE recurrences, 15 had major bleeding and 218 died. Among the group with adenocarcinoma, major bleeding was lower than the rate of VTE recurrences, however the reverse occurred with other cancer types.

Risk factors of arterial thrombotic events after unprovoked venous thromboembolism, and after cancer associated venous thromboembolism (June 2022)

Approximately 20–30% of patients with new cases of VTE are connected with underlying malignancy, whereas up to 25–50% of incidents VTE are considered to be unprovoked. An association has been found with VTE and arterial thrombotic events (ATE) or ischemic stroke, particularly with VTE from an unknown source. This study investigated the risk factors for arterial thrombosis among individuals with unprovoked VTE or CAT.

The cohort follow-up period was 68 months and included 3156 participants (71% with unprovoked VTE and 29% had CAT). Among the patients with unprovoked VTE, 7.8% had at least one ATE; ischaemic stroke occurred in 63.2%; 23% suffered acute myocardial infarction (AMI); and 39% died during follow-up. From the CAT group, 6.2% had at least one ATE; ischaemic stroke occurred in 75.4%; 14% had AMI; and 63% died during follow-up.

The findings from this research found that the risk of ATE in these population groups is high and is determined by age (>65 years compared with <50 years); and cardiovascular risk factors (e.g. past history of symptomatic atherosclerosis). The risk may also be influenced by VTE anticoagulation therapy (LMWH vs VKA). The study also found that the risk of ATE was lower in patients treated with DOAC compared with VKA, however the results were not statistically significant.

Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients – 30 months follow‐up (May 2022)

LMWH is the recommended VTE treatment among cancer patients. Recently, new data suggested oral factor Xa-inhibitors has emerged as the preferred option to treat DVT and PE in adults with cancer. The aim of this study was to assess the efficacy and safety of low-dose apixaban for 30 months, after initial 6 months of full-dose treatment as this therapy had not been previously investigated in CAT.

The research included 298 cancer patients and received full-dose apixaban (5mg twice daily) for 6 months. After this period 196 patients with active cancer continued with low dose apixaban (2.5mg twice daily) for a further 30 months. The highest rate of recurrent VTE was during the first month of full-dose anticoagulation and after 12 months began a constant decrease until study completion. The incidence rate of major bleeding was highest during the first month of full-dose treatment and again started to reduce and remain low during the following 30 months.

Despite the incidence rate of both recurrent VTE and major bleeding showing marked reductions after the nine or 12-month stage, the precise time for dose reduction remains unclear. The findings may be the result of patients with the highest risk of recurrent VTE and bleeding discontinued with the study during the first 6 months.

Although the study findings show that dose reduction of apixaban was the cause for the outcomes, the authors cannot be sure.  A study limitation was the lack of randomisation which prevents a comparison between full-dose and low-dose apixaban. However, due to the broad inclusion criteria the results can be representative of the general population.

The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other haematological malignancies (May 2022)

Cancer associated thrombosis (CAT) is associated with significant morbidity and mortality. Multiple myeloma (MM) is linked with one of the highest rates of thrombosis even in spite of widespread use of thromboprophylactic agents.

The pathophysiology of thrombosis in MM is multifactorial and patients with MM appear to display a hypercoagulable phenotype with potential contributory factors including elevated von Willebrand Factor (VWF), activated protein C (APC) resistance, impaired fibrinolysis and abnormal thrombin generation. This review investigated the pathophysiological mechanisms underpinning thrombosis in MM and mainly the role of VWF/FVIII in haematological malignancies with a focus on thrombotic risk and emerging evidence for contribution to disease progression.

One study reported that the association between coagulation factor levels and VTE risk can be largely explained by VWF/FVIII, which are correlated with an increased risk of thrombosis. Research also found that ADAMTS13 deficiency or dysfunction is a contributing factor as ADAMTS13 activity levels are decreased in cancer patients.  Thrombotic microangiopathy can also occur in association with cancer and may be associated with ADAMTS13 deficiency. Studies in patients with solid tumour malignancies have shown that a combination of elevated plasma VWF:Ag levels together with lower ADAMTS13 activity are associated with increased risk of CAT and decreased overall survival.

Despite the evidence that VWF/FVIII does increase haematological conditions, further systematic evaluation is required to fully evaluate its prognostic predictive potential for either thrombosis or survival rates. Also, even with the current thromboprophylaxis approaches, patients with MM remain at high risk for thrombotic complications. However improved understanding of the crosstalk between MM and coagulation pathways in contributing to thrombosis associated with MM may identify new prognostic biomarkers and therapeutic strategies.

The relationship between nutritional parameters and thrombosis risk in cancer patients (2022)

Nutrition is an important factor in the treatment and prognosis of cancer; and obesity and cachexia are both conditions in cancer patients. This study aimed to evaluate the relationship between nutritional status and thrombosis risk in various cancer types. This cross-sectional and single-centre study included 582 cancer patients and included a variety of nutritional parameters. The results found a statistically significant association between thrombosis risk and weight, BMI and waist circumference.

Direct oral anticoagulants for cancer‐associated venous thromboembolisms: a systematic review and network meta‐analysis (Feb 2022)

Malignancy is a hypercoagulable state, with over 15% of patients developing DVT and PE, where cancer treatments (e.g. chemotherapy and hormone therapy) can also increase the risk of VTE. Anticoagulation treatment can be challenging due to the increased risk of bleeding, VTE recurrence and medication interactions.

This study aimed to determine the risks of recurrent VTE and bleeding with DOACs compared to LMWH. The meta-analysis included 2907 patients from four RCTs and found ‘high certainty evidence’ that DOAC had a 37% risk reduction of recurrent VTE compared with LMWH. There was no significant difference at 6-month follow-up between DOAC and LMWH with respect to major bleeding risk. There was an increased risk of combined major or clinically relevant non-major bleeding with DOAC, with apixaban showing the highest probability of being the most effective anticoagulant with least bleeding risk.

Venous thromboembolism and cancer: A comprehensive review from pathophysiology to novel treatment (Feb 2022)

Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. Cancer cells override the coagulation pathway by releasing procoagulant factors which eventually activate platelets and inflammatory cells, which in turn stimulate angiogenesis and clot formation.

The review found that the use of thromboprophylaxis for primary prevention is a clinical and research issue. Extended treatment with LMWH or DOACs after discharge of cancer patients decreased VTE events, at the cost of increased bleeding. Assessing the risk of cancer-related VTE is essential, and a systematic review and meta-analysis found that the Khorana score may help clinicians in selecting patients at high risk of VTE.

The Khorana score consists of five clinical parameters - primary tumour site, platelet count, haemoglobin concentration, leukocyte count and BMI (The Khorana score for prediction of venous thromboembolism in cancer patients). Cancer patients with a risk score higher than three before starting the treatment had a 6.7 to 7.1% risk of developing VTE. Furthermore, improvements in the prediction of thrombotic events have been achieved by adding bio-humoral markers (P-selectin and D-dimer levels) to the Khorana’s risk model. This expanded model showed a sensitivity of 96% when patients receive a point score of one, thus reasonably excluding thromboprophylaxis, and a specificity of 98% for those at a higher cut off point (score ≥5) who may benefit from thromboprophylaxis.

How well do European patients understand cancer-associated thrombosis? A patient survey (2022)

As cancer patients are living longer and with an increased risk for cancer-associated thrombosis (CAT), researchers aimed to investigate the awareness and knowledge about CAT among this group. The survey topics included understanding of risk factors, signs and symptoms and interventions to treat CAT.

The survey consisted of 1365 cancer patients/survivors or caregivers from Germany, Greece, Italy, Spain, France and the UK (n = 324). The results found 72% of participants were unaware of their higher-than-normal risk of developing thrombosis. The two main risk factors acknowledged by the participants were 'inactivity for long periods' at 65% and previous thromboses (46%).

In regard to being advised about the risk of thrombosis, the majority (26%) of participants said they first became of aware of CAT when they had their first blood clot. Awareness of actions they could take to reduce the risk of thrombosis was reasonably high for most actions - stretching legs (55%), moving their feet (65%), stop smoking (75%) and going for a walk at 87%. Almost all participants (96%) acknowledged that anticoagulants could effectively treat thrombosis, however only 41% understood that the risk of bleeding was a possible side effect.

There were specific limitations with this survey, including, but not limited to - self-reported voluntary assessment may be that those who participated had a particular interest in VTE; the survey was only available to those in the UK and certain European countries, differences in the healthcare systems between countries may also impact the responses. However, as mentioned above, improving patient understanding of CAT is important and oncology and health care professionals need to provide education across the continuum of care to improve patient outcomes.

Cancer patients’ experiences and understanding of venous thromboembolism (Dec 2021)

This review included nine qualitative studies and one systematic review which investigated cancer patients’ experiences of living with cancer-associated thrombosis (CAT). The study results found four themes which emerged from the data: (i) lack of meaningful information on CAT; (ii) cancer patients were unaware of VTE signs and symptoms; (iii) limited awareness of CAT amongst health care professionals; (iv) acceptability of anticoagulant.

The studies included in this review included participants with both cancer and VTE. There were no qualitative studies which explored cancer patients without VTE and their understanding of VTE, VTE risk, signs and symptoms. It is recommended that VTE in cancer patients should become part of training, education and discussions with health care professionals involved with cancer patients.

In August 2021 we presented a webinar on the topic of Cancer and thrombosis and were fortunate to have two experts in the field Professor the Lord Kakkar, Professor of Surgery from the University College London, and Associate Professor Dr Vivien Chen, University of Sydney as the speakers. Please click here to view the session.