Recent updates in the management of thromboembolism - MediBytes January 2022 newsletter

Thrombosis is a major driver impacting the outcomes or mortality in patients with COVID-19. Interleukin-6 is the main driver for the cytokine storm and may be related to hypercoagulability. Lipoprotein(a) levels may increase following the upregulation of interleukin-6. Lipoprotein(a) has antifibrinolytic properties. In a recently published pilot study in December 2021,1 lipoprotein(a) and CRP levels of 219 hospitalized COVID-19 patients (during the first 21 days of their admission) were analyzed. Lipoprotein(a) levels increased significantly by a mean of 16.9 mg/dL in patients with COVID-19 during the first 21 days after admission. In the top tertile of lipoprotein(a) increase, 56.2% of patients with COVID-19 experienced a venous thromboembolism event, as compared to 18.4% of patients in the lowest tertile (RR 3.06, 95% CI 1.61–5.81; p<0.001)

An interesting case report was published in September 2021 by Aconfora D et al.2 This case report highlighted the various receptors that might become a potential target of consideration for counteracting the clinical expressions of COVID-19. It was suggested that early administration of anticoagulants in COVID-19 improved patient outcomes. Low-molecular-weight heparin was commonly adopted for counteracting disseminated intravascular coagulation and venous thromboembolism due to its pharmacodynamics and anti-inflammatory properties. Low-molecular-weight heparin may be considered the new frontier in the treatment of COVID-19 and Long-COVID-19.

Venous thromboembolism is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma have a 9-fold increase in venous thromboembolism risk, likely because of malignancy, treatments, and other additional patient-related factors. In multiple myeloma, thromboembolic events tend to occur within 6 months of treatment initiation, irrespective of the treatment regimen. However, the use of  mmunomodulatory agents, such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for venous thromboembolism.3

Venous thromboembolism is a common complication after bariatric surgery, with the risk being sex-specific. In a study by Wagner J et al. (January 2022),4 enoxaparin twice daily was administered in patients undergoing bariatric surgery. Patients with a body mass index >60 kg/m2 (n = 11) received enoxaparin 60 mg (group 2), and patients with lower body mass index (n = 86) received 40 mg per dose (group 1). Peak anti-factor Xa levels were measured 3 days after surgery. Women had higher anti-factor Xa levels than men; however, the two groups were similar after matching anthropometric values. Linear regression revealed a moderate relationship between weight and anti-factor Xa levels. It was concluded that individual enoxaparin dosage regimens for men and women do not seem to be required. Moreover, a weight-based dosing regimen seems to be a more reasonable choice.

A nested case-controlled analysis (1:4 matching) within a cohort of patients with incident type 2 diabetes between 1995 and 2019 using data from the CPRD GOLD was published in Jan 2022 by R Charlier SH et al.5 Patients with known risk factors for venous thromboembolism prior to the onset of diabetes mellitus were excluded. The exposure of interest was glycemic control measured as HbA1c levels. This analysis found no association between the HbA1c level and the risk of venous thromboembolism. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels >7.0% had a 36%–55% increased relative risk of venous thromboembolism compared to women with HbA1c >6.5%–7.0%. This study raises the possibility that women with type 2 diabetes having HbA1c levels >7% may have a slightly higher risk for unprovoked venous thromboembolism than women with HbA1c levels >6.5%–7.0%. No effect of glycemic control on the risk of venous thromboembolism was observed in men.

    1. Nurmohamed NS, Collard D, Reeskamp LF, et al; Amsterdam UMC Covid-19 Biobank. Lipoprotein(a), venous thromboembolism and COVID-19: A pilot study. Atherosclerosis. 2021 Dec 21;341:43–49. doi: 10.1016/j.atherosclerosis. 2021.12.008.
    2. Acanfora D, Acanfora C, Ciccone MM, et al. The cross-talk between thrombosis and inflammatory storm in acute and long-COVID-19: Therapeutic targets and clinical cases. Viruses. 2021 Sep 23;13(10):1904. doi: 10.3390/v13101904.
    3. Baljevic M, Sborov DW, Lim MY, et al. Optimizing thromboembolism prophylaxis for the contemporary age of multiple myeloma. J Natl Compr Canc Netw. 2022 Jan;20(1):91–95. doi: 10.6004/jnccn.2021.7112.
    4. Wagner J, Wruck H, Lautenbach A, et al. Comparison of anti-factor Xa levels in female and male patients with obesity after enoxaparin application for thromboprophylaxis. Obes Surg. 2022 Jan 5. doi: 10.1007/s11695-021-05875-z.
    5. R Charlier SH, Meier C, Jick SS, et al. Association between glycemic control and risk of venous thromboembolism in diabetic patients: A nested case-control study. Cardiovasc Diabetol. 2022 Jan 4;21(1):2. doi: 10.1186/s12933-021-01432-1.

MAT-IN-2200095 /0.1/01/2022