Venous thromboembolism (VTE) is a serious complication during and after hospitalization, yet is a preventable cause of in-hospital death.Without VTE prophylaxis, the overall VTE incidence in medical and general surgery hospitalized patients is in the range of 10% to 40%, while it ranges up to 40% to 60% in major orthopaedic surgery. With routine VTE prophylaxis, fatal pulmonary embolism is uncommon in orthopaedic patients and the rates of symptomatic VTE within three months are in the range of 1.3% to 10%.VTE prophylaxis methods are divided into mechanical and pharmacological. The former include mobilization, graduated compression stockings, intermittent pneumatic compression device and venous foot pumps; the latter include aspirin, unfractionated heparin, low molecular weight heparin (LMWH), adjusted dose vitamin K antagonists, synthetic pentasaccharid factor Xa inhibitor (fondaparinux) and newer oral anticoagulants. LMWH seems to be more efficient overall compared with the other available agents. We remain sceptical about the use of aspirin as a sole method of prophylaxis in total hip and knee replacement and hip fracture surgery, while controversy still exists regarding the use of VTE prophylaxis in knee arthroscopy, lower leg injuries and upper extremity surgery. Cite this article: EFORT Open Rev 2018;3:136-148. DOI: 10.1302/2058-5241.3.170018.

This case report describes the development of a rash in a patient admitted with large bowel obstruction secondary to carcinoma of the sigmoid colon. The patient underwent a Hartmann's procedure and right hemicolectomy for a metastatic deposit at the terminal ileum. On postoperative day 3, the patient developed a bullous haemorrhagic rash on the thighs, flanks and abdomen, associated with a sharp drop in platelet count. Suspicion of heparin-induced skin necrosis was raised, and prophylactic enoxaparin was switched to fondaparinux. Skin biopsy results later confirmed the diagnosis. Clinical suspicion of heparin-induced skin necrosis is essential and should prompt a switch between prophylactic agents, in order to prevent potentiation of this life-threatening side effect.

Cleavage of heparan sulfate proteoglycans (HSPGs) by the enzyme heparanase modulates tumour-related events including angiogenesis, cell invasion, and metastasis. Metalloshielding of heparan sulfate (HS) by positively charged polynuclear platinum complexes (PPCs) effectively inhibits physiologically critical HS functions. Studies using bacterial P. heparinus heparinase II showed that a library of Pt complexes varying in charge and nuclearity and the presence or absence of a dangling amine inhibits the cleavage activity of the enzyme on the synthetic pentasaccharide, Fondaparinux (FPX). Charge-dependent affinity of PPC for FPX was seen in competition assays with methylene blue and ethidium bromide. The dissociation constant (Kd ) of TriplatinNC for FPX was directly measured by isothermal titration calorimetry (ITC). The trend in DFT calculated interaction energies with heparin fragments is consistent with the spectroscopic studies. Competitive inhibition of TAMRA-R9 internalization in human carcinoma (HCT116) cells along with studies in HCT116, wildtype CHO and mutant CHO-pgsA745 (lacking HS/CS) cells confirm that HSPG-mediated interactions play an important role in the cellular accumulation of PPCs.

Major orthopedic surgery, mainly entailing hip fracture surgery, hip and knee arthroplasty, is associated with significant morbidity and mortality, which are especially attributable to the high risk of postoperative VTE. Such a considerable risk is mainly due to a procoagulant state sustained by several important mechanisms, including massive release of procoagulants from tissue and bone damage, blood vessel injury, reduced venous emptying, perioperative immobilization and cement polymerization, among others. The risk of VTE during and after major orthopedic surgery approximates 50-80% in patients with no thromboprophylaxis, and persists for up 3 to 6 months after surgery. The anticoagulant or antithrombotic armamentarium entails several anticoagulants such as heparin, coumarins, fondaparinux, and the recently developed DOACs inhibiting either activated factor Xa (i.e., rivaroxaban, apixaban, edoxaban) or thrombin (i.e., dabigatran), as well as aspirin, i.e., the oldest antiplatelet drug to be ever discovered and used in clinical practice. The current guidelines are not in complete agreement regarding the choice of the ideal thromboprophylaxis, since some consider aspirin, and some discourage it. Recent evidence seems to support the use of aspirin in selected situations and in selected protocols. Therefore, we believe that consideration should be made about increasing the use of this old but still effective drug for perioperative prophylaxis of VTE, especially in patients for whom the administration of DOACs may be challenging.