Venous thromboembolism (VTE) is a common and preventable cause of morbidity and mortality in hospitalized patients. Low molecular weight heparin, low dose unfractionated heparin, fondaparinux and warfarin have been the mainstay options for the prevention and treatment of VTE before the emergence of non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban and edoxaban. Despite the advantages of NOACs in improving patient adherence, none of them are approved for the prevention of VTE in acutely ill medical patients at high risk of thromboembolism. Betrixaban is a new NOAC and a factor Xa inhibitor that was approved for extended duration thromboprophylaxis in these high risk patients. The approval was based on the results of the APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) study. In this Phase III randomized controlled trial, once daily oral betrixaban (35 to 42 days extended duration) was associated with a reduction of composite VTE with no difference in major bleeding when compared to once daily subcutaneous enoxaparin (6 to 14 days standard duration). Betrixaban differs from other NOACs by having a longer half-life, minimal CYP450 interactions and minimal renal clearance. This article provides an overview of betrixaban's pharmacological profile, clinical trial results, and its potential roles in therapy.

Heparin-induced thrombocytopenia (HIT) is a serious complication of the administration of heparin and its derivatives. Non-heparin anticoagulants such as argatroban and fondaparinux are widely used in the management of HIT to compare the effectiveness of argatroban and fondaparinux in the resolution of thrombocytopenia and to compare clinical outcomes in patients with isolated HIT. A retrospective cohort analysis was performed at King Abdulaziz Medical City (KAMC) on patients diagnosed with isolated HIT between 31 Jan, 2014 and 30 June, 2017. Demographics data, non-heparin anticoagulants, related laboratory results, and clinical outcomes were retrieved and analysed. The cohort comprised a total of 95 adult patients who received either argatroban (56 patients) or fondaparinux (39 patients) for isolated HIT. The median age and sex distribution were similar in both argatroban and fondaparinux groups. The mean (+ SD) time (in days) for the resolution of thrombocytopenia was 3.5 (± 1.8) for patients who received argatroban and 3.7 (± 1.7) for patients administered fondaparinux (p = 0.843). Thromboembolic events occurred in five patients (8.9%) administered argatroban and in three patients (7.7%) administered fondaparinux (p = 0.382). There was no significant difference in the rates of bleeding or death (p = 0.829); however, the small number of cases limits our ability to draw conclusions about these outcomes. In this retrospective study, fondaparinux and argatroban were similarly effective in resolving thrombocytopenia, preventing further thromboembolic events, and maintaining safety in patients with confirmed HIT. To confirm this observation, larger prospective studies are needed.

Because no information is available on the use of fondaparinux during breastfeeding, an alternate drug is preferred.[1]

: Ibrutinib is the first drug of a new family of Bruton's tyrosine kinases (Btk)-inhibiting agents, which have proved to be useful for the treatment of several B-cell lymphoid malignancies. This drug is associated to an increased bleeding risk from initial clinical trials especially in association with warfarin. Although Btk plays an important role in platelet signalling, increased bleeding tendency in patients on ibrutinib is more complex than Btk inhibition alone and is because of several antiplatelet mechanisms, namely inhibition of Btk and Tec kinases, which play a key role in platelet activation downstream of the collagen GPVI and Glycoprotein Ib. This risk is increased by concomitant antiplatelet and anticoagulant therapy; both dual antiplatelet therapy and vitamin K antagonists are contraindicated in these patients. Potential ibrutinib users often have age-associated cardiovascular risk factors or conditions and the drug itself may trigger atrial fibrillation requiring antithrombotic therapy. Aspirin and direct oral anticoagulants can be regarded as the antithrombotic therapies of choice if required. Heparin and fondaparinux have also been used in clinical trials. Therefore, the need and duration of antithrombotic therapy must be carefully evaluated and treatment individualized according to clinical circumstances. Ibrutinib withdrawal and platelet transfusion are key for the management of major bleeding not involving the central nervous system.

The choice of the appropriate perioperative thromboprophylaxis for people with cancer depends on the relative benefits and harms of different anticoagulants.

Hospitalized acute medically ill patients are vulnerable to venous thromboembolism (VTE), known as hospital-acquired thrombosis (HAT). The elevated risk of HAT is usually due to a combination of factors, with immobility and a prothrombotic state due to acute illness being the most frequent. The HAT risk persists well after hospital discharge, with more than half of events occurring after patient release. These HAT events may be fatal, and patients who survive the initial event may be subject to VTE recurrence, chronic discomfort from post-thrombotic syndrome and, although rare, may develop chronic thrombo-embolic pulmonary hypertension, which is often debilitating. The risk of HAT can be reduced with effective thromboprophylaxis. Current guidelines recommend thromboprophylaxis with subcutaneous heparin, low molecular weight heparin (LMWH) or fondaparinux for at-risk acute medically ill patients, but reports of real-world practice indicated that some patients do not receive protection in the short-term as outlined by the guidelines. Previous studies that have assessed extended thromboprophylaxis for 4-5 weeks with LMWH or direct oral anticoagulants in medically ill patients found they did not offer a net clinical benefit; any demonstrated efficacy was outweighed by the significantly increased risk of major haemorrhage. Therefore, there is an ongoing need for improved VTE prevention without increasing the risk of bleeding. In the APEX trial, conducted in an acute medically ill population, betrixaban provided a significant reduction in VTE events after 35 to 42 days of treatment compared with short-term enoxaparin without an increase in major bleeding.