Thromboembolic and bleeding complications following primary total knee arthroplasty : a Danish nationwide cohort study.

AIMS: The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA). METHODS: Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis. RESULTS: We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results. CONCLUSION: Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article: Bone Joint J 2021;103-B(10):1571-1577.

Upper Limb Ischemia by Subclavian Artery Dissection after Osteopathic Manipulation.

We report the case of a young woman who experienced ischemia of upper limb after osteopathic manipulation. Duplex and computed tomography scan showed wall hematoma of the ostium of subclavian artery. The patient spontaneously recovered so that no surgery was necessary. Dissection of vertebral and carotid arteries has been reported after osteopathic manipulations. We report ischemia of upper limb secondary to dissection of subclavian artery. Arterial dissections associated with manipulation should be recorded in a register in order to assess more carefully the vascular risk that this method carries.

Return to theatre following total hip and knee replacement, before and after the introduction of rivaroxaban: a retrospective cohort study.

Rivaroxaban has been recommended for routine use as a thromboprophylactic agent in patients undergoing lower-limb arthroplasty. However, trials supporting its use have not fully evaluated the risks of wound complications. This study of 1048 total hip/knee replacements records the rates of return to theatre and infection before and after the change from a low molecular weight heparin (tinzaparin) to rivaroxaban as the agent of chemical thromboprophylaxis in patients undergoing lower-limb arthroplasty. During a period of 13 months, 489 consecutive patients undergoing lower-limb arthroplasty received tinzaparin and the next 559 consecutive patients received rivaroxaban as thromboprophylaxis. Nine patients in the control (tinzaparin) group (1.8%, 95% confidence interval 0.9 to 3.5) returned to theatre with wound complications within 30 days, compared with 22 patients in the rivaroxaban group (3.94%, 95% confidence interval 2.6 to 5.9). This increase was statistically significant (p = 0.046). The proportion of patients who returned to theatre and became infected remained similar (p = 0.10). Our study demonstrates the need for further randomised controlled clinical trials to be conducted to assess the safety and efficacy of rivaroxaban in clinical practice, focusing on the surgical complications as well as the potential prevention of venous thromboembolism.

Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitro.

Even though new anticoagulants are being devised with the notion that they do not require regular monitoring, when bleeding occurs, it is important to have an antidote and a reliable test to confirm whether the anticoagulant effects are persisting. We examined the effects of five heparinoids, unfractionated heparin (UFH), tinzaparin, enoxaparin, danaparoid and fondaparinux on the traditional APTT and anti-Xa assays as well as on the calibrated automated thrombogram (CAT). We also studied the ability of protamine sulphate (PS), NovoSeven, FEIBA and FFP to reverse maximum anticoagulation induced by the different heparinoids. The CAT was the only test to detect the coagulopathy of all the anticoagulants. PS produced complete reversal of UFH, and this could be monitored with all three tests. Tinzaparin can also be completely neutralised in vitro with high doses of PS, but the maximum enoxaparin reversal achieved with PS is only approximately 60%. Fondaparinux does not significantly affect the APTT and PS has no significant effect on its reversal. Only NovoSeven was able to correct the fondaparinux induced CAT abnormalities whilst having no effect on the anti-Xa level. None of the reversal agents was very effective in danaparoid spiked plasma but NovoSeven, at high dose, increased the ETP by 40% and reduced the anti-Xa level from 0.93 to 0.78 IU/ml. We conclude that the CAT is superior to the traditional coagulation tests in that it not only detects the coagulopathy of all the heparinoids but can be also be used to monitor their reversal.

Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy.

BACKGROUND: Out-of-hospital treatment of patients with deep-vein thrombosis (DVT) is routine in many countries regardless of frequent concomitant asymptomatic pulmonary embolism (PE) in this group. However, patients with symptoms and verified PE are still regularly treated in hospital. The objectives were to test a model for outpatient tinzaparin therapy and to evaluate its safety and efficacy in patients with symptomatic, small or medium-sized PE using quantitative ventilation/perfusion scintigraphy (qV/P SCINT) for patient selection and follow up. MATERIAL/METHODS: This prospective study included 102 patients treated with tinzaparin and warfarin for 5 days at a patient hotel. PE was quantified scintigraphically as loss of perfusion with preserved ventilation at segmental or subsegmental levels (mismatch). Points were attributed to segments of reduced ventilation (RoVent) and perfusion (RoPer). A holistic principle of interpretation was applied. Patients were excluded if they had >14 RoPer points (7 segments) or >7 RoVent points. Clinical follow-up and scintigraphy were repeated at discharge in 100 patients and after 13 months on average. RESULTS: Embolism diminished by 44% after 5 days and demanding symptoms declined. There was no thromboembolic mortality in the trial. At late follow-up, PE had not recurred in patients with resolution after 5 days. In those with insufficient early response, persistent perfusion defects were usually observed. CONCLUSIONS: The results indicate the safety and efficacy of outpatient treatment of PE according to our model and merit larger, multicenter, controlled studies.

Orally administered heparins prevent arterial thrombosis in a rat model.

Our previous studies demonstrated that orally administered heparins prevent thrombosis in a rat jugular vein thrombosis model, where bovine unfractionated heparin (UFH) and the low molecular weight heparin tinzaparin reduced thrombotic incidence by 50% at 7.5 and 0.1 mg/kg, respectively. Our objectives were to determine if similar antithrombotic effects of oral heparin could be observed in an arterial thrombosis model. In this model, filter paper soaked in 30% ferric chloride was applied to the exposed rat carotid artery. A flowmeter recorded blood flow over a 60 min period determining time when the thrombus began forming (TTB) and time till occlusion (TTO). Immediately following, the thrombus was removed, dried and weighed 24 h later. Bovine UFH (7.5 mg/kg), tinzaparin (0.1 mg/kg) or saline was administered by stomach tube at 2, 5 and 25 h prior to thrombus initiation. TTB was significantly increased when UFH was given at 5 and 25 h but not 2 h prior, and when tinzaparin was given at 5 but not 2 or 25 h prior compared to rats given oral saline. TTO was significantly increased for both UFH and tinzaparin when given 5 and 25 h but not 2 h prior (one-way ANOVA). There was no difference in TTO and TTB between UFH and tinzaparin treated groups. A trend in reduction in thrombus weight was observed for UFH at 5 and 25 h prior and tinzaparin at 5 h prior to thrombus initiation (one-way ANOVA). Although no significant changes were observed in activated partial thromboplastin times, Heptest or anti-Xa activity from plasma of heparin treated rats, endothelial heparin concentrations were significantly greater than controls for UFH at 5 h and for tinzaparin at 2, 5, and 24 h. Thus, heparins administered by the oral route are effective antithrombotic agents in arterial as well as venous models.