Venous thromboembolism (VTE) is categorised as deep venous thrombosis (DVT) and pulmonary embolism (PE). VTE is associated with high morbidity and causes a huge financial burden on patients, hospitals, and governments. Both acquired and hereditary risks factors contribute to VTE. To diagnose VTE, noninvasive cost-effective diagnostic algorithms including clinical probability assessment and D-dimer measurement may be employed followup by compression ultrasonography for suspected DVT patients and multidetector computed tomography angiography for suspected PE patients. There are pharmacological and mechanical interventions to manage and prevent VTE. The pharmacological approaches mainly target pathways in coagulation cascade nonspecifically: conventional anticoagulants or specifically: new generation of anticoagulants. Excess bleeding is one of the major risk factors for pharmacological interventions. Hence, nonpharmacological or mechanical approaches such as inferior vena cava filters, graduated compression stockings, and intermittent pneumatic compression devices in combination with pharmacological interventions or alone may be a good approach to manage VTE.

Key Points: Ibrutinib but not zanubrutinib induces shedding of GPIb-IX complex in an ADAM17-dependent manner; GPIX has not been shown previously. Ibrutinib, but not zanubrutinib, induces shedding of integrin αIIbβ3 by an unknown sheddase.

Both nilotinib, a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML), and ponatinib, a third-generation TKI used in CML and Philadelphia positive acute lymphocytic leukaemia, have been associated with an increase in arterial occlusive events, in contrast to other TKIs such as imatinib and dasatinib. We have previously demonstrated evidence of a pro-thrombotic state associated with nilotinib, using microvascular and arterial thrombosis C57BL/6 mouse models. In this study, we examined ponatinib and determined if a calcium channel blocker could ameliorate the pro-thrombotic and pro-inflammatory phenotypes. In vitro treatment of whole human or murine blood with ponatinib and nilotinib increased platelet activation, adhesion and three-dimensional thrombi over time compared with vehicle control or other TKIs. Treatment of wild-type C57BL/6 mice with ponatinib and nilotinib but not imatinib, dasatinib or vehicle control for 4 hours significantly increased thrombus growth following ex vivo perfusion on collagen and FeCl₃-induced vascular injury of mesenteric arterioles and carotid artery in vivo and increased plasma levels of soluble P-selectin, tumour necrosis factor-α, interleukin-6, interferon-γ and thromboxane B₂ (TxB₂). Ponatinib-treated CML patients had increased ex vivo thrombus formation and a pro-inflammatory phenotype compared with healthy controls. Pre-treatment of mice with the calcium channel antagonist, diltiazem, prior to ponatinib or nilotinib reversed the pro-thrombotic phenotype and the increase in cytokine levels. These observations suggest that the pro-thrombotic effect of nilotinib and ponatinib is partially related to calcium channel activation and TxA₂ generation and this should be explored clinically as a mechanism to prevent vascular events. A.H. performed experiments. F.K., K.B. and A.G. provided intellectual input and review of the article. D.E.J. directed the research and wrote the manuscript.

Introduction: While SARS-CoV-2’s main transmission route is through respiratory droplets, research has found that viral RNA could be detected in blood samples, causing concerns over the safety of blood donations and blood products. This paper therefore aims to systematically search for studies that have addressed their country’s lack of donations and analyse the risk of blood transfusion-transmission. As such, it will answer the question “should blood services focus more on donation vigilance or worry more about the risks of transmission through blood products?” Methods: 38 articles were identified through a systematic review adopting the PRISMA and STROBE guidelines. Meta-analysis was conducted using OpenMeta software. Results: The average decrease in blood donations was found to be 38%, with some regions showing up to 67% decrease. To assess the risk of actual blood transfusion-transmission, three datasets were analysed. Firstly, the viral load in COVID-19 patients was studied and found to have less than 1% detection rate (ARD = −0.831, 95% −0.963, −0.699). Secondly, the prevalence of finding viral RNA in a pool of donations was nearly −1.503 (ARD = −1.538, −1.468). Lastly, recipients who were given blood products of positive donors were found to be −0.911 (ARD 95% = –1.247, −0.575). Discussion/Conclusion: Blood centres should focus more on launching initiatives and policies that would increase their countries’ blood supply as the virus has no direct threat to blood safety.