Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

Cavernous Sinus Thrombosis Linked to COVID-19 Infection: a Case Report.

The severity of SARS-CoV-2 virus infection is mainly related to its respiratory complications. However, it can also lead to a large variety of thromboembolic events. Symptoms may include headache, fever, and neurological disorders. Since 2020, the clinical presentation of COVID-19 infection has become increasingly varied, leading in some cases to complex symptom associations, including numerous neurological symptoms. SARS-CoV-2 may lead to neurotropism which could reach the central nervous system and all cranial nerves. Cavernous sinus thrombosis is a rare condition and may occur as a complication of ear, nose, and throat (ENT) or facial infections. A 73-year-old man without personal or family history of thrombosis was referred to the emergency room for a sudden appearance of diplopia and ptosis, 3 days after testing positive for COVID-19 infection. An initial head CT-scan found no signs of stroke. He underwent a cerebral MRI 7 days later, which revealed a thrombosis of his right cavernous sinus. A brain CT scan 7 days later showed regression of the thrombosis with complete recanalization of the cavernous sinus. This was accompanied by a complete regression of diplopia and fever. He was discharged from the hospital 10 days after hospital admission. In this case report, we describe a rare event of cavernous thrombophlebitis following a COVID-19 infection.

Pulmonary Embolism in the Cancer Associated Thrombosis Landscape.

In cancer patients, pulmonary embolism (PE) is the second leading cause of death after the cancer itself, most likely because of difficulties in diagnosing the disease due to its nonclassical presentation. The risk of PE recurrence and possibly the case-fatality rate depends on whether the patient presents a symptomatic PE, an unsuspected PE, a subsegmental PE, or a catheter-related PE. Choosing the best therapeutic option is challenging and should consider the risk of both the recurrence of thrombosis and the occurrence of bleeding. The purpose of this review is to provide an overview of the clinical characteristics and the treatment of cancer-associated PE, which could benefit clinicians to better manage the deadliest form of thrombosis associated with cancer. After a brief presentation of the epidemiological data, we will present the current attitude towards the diagnosis and the management of cancer patients with PE. Finally, we will discuss the perspectives of how the medical community can improve the management of this severe medical condition.

Screening cancer after venous thromboembolism: How many abnormal tests before diagnosing cancer? An analysis of practice.

INTRODUCTION: Since Trousseau, we knows that venous thrombemboembolism (VTE) can reveal occult cancer. Different strategies of cancer screening have been evaluated: they are often time-consuming, cause stress and anxiety, and frequently require second-look examinations (due to the risk of false positives), with ultimately a very low yield (about 5%). We evaluated the number of suspect cancer tests before reporting them to the number of cancers finally diagnosed, after a VTE, in the setting of practice's analysis. METHODS: We studied retrospectively patients hospitalized for a VTE and with a cancer screening, between 2011 and 2012. Screening cancer was defined by performing at least one of the following tests: PSA, fecal occult blood test, mammography, abdominopelvic iconography (abdominal ultrasound and/or abdominal CT scan). We recorded the suspected cancer tests, the cancers diagnosed, their stage and the survival. These results were expressed as a percentage with a 95% confidence interval. RESULTS: Out of the 491 patients treated for a VTE, screening cancer was performed on 295 patients (median age 66.2 years). Nineteen PSA (16.7%, 95% CI [10.3-25]) were abnormal, with 2 localized prostate cancers. Nineteen fecal occult blood tests (15.3%, 95% CI [9.5-23]) were positive, with 2 local cancers. Five mammograms suspected cancer (4.7% 95% CI [1.6-10.8]) for one confirmed. Thirty-eight abdomino-pelvic iconographies (14.4% 95% CI [10.4-19.2]) were suspect, with 7 confirmed cancers, 6 being metastatic at times of diagnostic. CONCLUSION: Among the 607 tests performed, 81 were suspected of cancer (13.3%) for only 12 cancers confirmed (2.0%). Screening cancer exposes patients to several false positive tests.

Direct oral anticoagulants: Current indications and unmet needs in the treatment of venous thromboembolism.

The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor IIa. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase-III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery.