Statement of the problem: The type and duration of pharmacological thromboprophylaxis post major abdominal surgery remains controversial. Methods of investigation: A systematic review and pooled analysis of literature was performed to assess the risk benefit ratio of the different pharmacological thromboprophylaxis agents compared to placebo or no thromboprophylaxis post major abdominal surgery. A survey of the clinical practice among both general surgeons and thrombosis expert was conducted. Results: The systematic review demonstrated that all five pharmacological thromboprophylaxis regimens were associated with similar rates of overall VTE. The 95% CI of the different estimates overlapped indicating no statistically significant difference between any of the pharmacological interventions and placebo. While all the surgeons and thrombosis experts recommended thromboprophylaxis post major abdominal surgery, over 70% of them recommended it during hospitalization only. Conclusion: Pharmacological thromboprophylaxis was not associated with a significant benefit in reducing the rate of overall VTE events post major abdominal surgery. There is an agreement between general surgeons and thrombosis experts in using LMWH for thromboprophylaxis post major abdominal surgery. However, there is still equipoise around the use of pharmacological thromboprophylaxis post discharge.

Patients with JAK2-positive myeloproliferative neoplasms (JAK2MPN) form a rare patient population, at increased risk of arterial and venous thrombosis. Limited research is available to guide the thromboprophylaxis of these patients. Nonetheless, guidelines and expert opinions recommend the use of low-dose aspirin to decrease the risk of thrombotic complications. In order to build a research program on the thromboprophylaxis of JAK2MPN patients and assess the feasibility of conducting a randomized controlled trial comparing low-dose apixaban to low-dose aspirin for thromboprophylaxis in this patient population, we completed a systematic review and meta-analysis to provide reliable rates of thrombosis and bleeding on aspirin, we performed a survey of practice and a modified Delphi process to assess for heterogeneity in clinical practice and determine future research needs, and we developed a multi-centre, pilot randomized controlled trial on the feasibility of enrolling and retaining this patient population.

Patients with acute spinal cord injury (SCI) have a high risk of venous thromboembolism (VTE) despite receiving thromboprophylaxis. The current standard of care recommended by guidelines is to use low-molecular-weight heparin (LMWH) for thromboprophylaxis for 90 days. This entails once- or twice-daily subcutaneous injections of LMWH for this duration, which is inconvenient for the patients and only partially effective. There are uncertainties about risk factors and the true incidence of SCI-associated VTE, the optimal time to commence thromboprophylaxis, and the optimal duration of thromboprophylaxis. Furthermore, there are currently no studies on the use of direct oral anticoagulants (DOACs) for thromboprophylaxis in patients with SCI. The use of DOACs for prophylaxis in this group can eliminate the inconvenience associated with daily subcutaneous injections for 3 months. To examine the incidence and risk factors of SCI-associated VTE, we performed a retrospective chart review of consecutive adult patients with acute SCI admitted to Hamilton General hospital from 2009 to 2015. The incidence of symptomatic VTE despite the use of thromboprophylaxis was 11% within 90 days of acute SCI; age and presence of other sites of injuries (such as lower limb fractures or pelvic fractures) along with SCI were independent risk factors for symptomatic VTE. To determine the opinion of Canadian spine surgeons about the optimal timing of starting LMWH after acute SCI, a short 5-question electronic survey was sent to the Canadian Spine Society. Data from our survey showed that the understanding about thromboprophylaxis after acute SCI was variable and that most spine surgeons were comfortable with starting LMWH after consultation with the surgeon. Future studies should focus on educational strategies to improve the knowledge base in this area. We will perform a pilot study at the Hamilton General Hospital comparing apixaban versus LMWH for thromboprophylaxis in patients with acute SCI. The use of apixaban for this indication can contribute to cost savings for the healthcare system and increased convenience for the patient. The protocol for the pilot study as well as steps towards a multi-center randomized controlled trial will be detailed in this thesis. / Thesis / Master of Science (MSc)

Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

Objective Formulation of a clinical practice guideline (CPG) for the use of thromboprophylaxis (TP) in pediatric patients with a central venous catheter (CVC). Participants The development team consisted of five experts and a doctoral candidate acting as the primary author. Evidence The guideline was developed utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework. A systematic review of the evidence was performed and evidence was graded using the American Academy of Pediatrics (2004) evidence classifications for CPG recommendations. An appraisal team evaluated the guideline quality utilizing the AGREE Plus platform rating the guideline as “highest quality.” Consensus Employing a modified Delphi methodology, members of the development team reviewed available evidence and voted on proposed Key Action Statements (KAS). Consensus is defined as 80% rating the KAS “usually appropriate.” Conclusion Five KAS are included in the final CPG. Each KAS indicates level of evidence, benefit-harm relationship, and level of recommendation. KAS 1. Providers of hospitalized children (0-18 years of age) may assess for VTE risk factors using the Skrocki VTE risk stratification tool if the patient has a CVC. (Evidence Quality:C, Rec. Strength: Option). KAS 2. Providers of hospitalized children should initiate targeted pharmacologic thromboprophylaxis (tpTP) at the time of CVC insertion or hospital admission (if CVC present on admission). (Evidence Quality: B, Rec. Strength: Strong Recommendation) KAS 3. Providers of hospitalized children with a CVC should implement mechanical thromboprophylaxis (mTP) if the child is immobile (Braden Q score <2) or moderate/ high risk for VTE using the Skrocki VTE risk stratification tool and have no contraindications to mTP. (Evidence Quality: B, Rec. Strength: Recommendation). KAS 4. Providers of hospitalized children with a CVC may prescribe systemic pharmacologic thromboprophylaxis (spTP) if the patient is found to be at high risk for VTE using Skrocki VTE risk stratification tool and the patient has no contraindications to spTP. (Evidence Quality: C, Rec. Strength: Option). KAS 5. Providers of hospitalized children should avoid femoral CVCs, multilumen CVCs and/or percutaneous insertion technique if their benefit does not clearly outweigh their risks. (Evidence Quality: B, Rec. Strength: Recommendation).

Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

Magister Pharmaceuticae - MPharm / Background: Venous thromboembolism (VTE) is reported to be the leading cause of death in hospitalised patients worldwide. Thromboprophylaxis provides a well-established and evidence-based approach to preventing VTE. This approach employs individualised patient risk stratification followed by the provision of pharmacological and/or non-pharmacological prophylaxis. Although various VTE risk assessment models (RAMs) are available, the Caprini RAM offers an objective, evidence-based and validated approach to risk assessment in hospitalised medical patients. Literature findings are indicative of a trend towards both under- and inappropriate VTE prophylaxis prescribing in this patient population. Together with the reported lack of medical practitioner appreciation for VTE risk assessment, the necessity to explore these aspects of practice is evident. Methods: This study used a retrospective, cross-sectional study design. It was conducted at one regional- and two district-level public hospitals in the Cape Town Metropole in the Western Cape province of South Africa. Medical folders of all adult hospitalised medical patients who were admitted to a general medical ward between January and July 2020 were retrospectively reviewed using a uniquely designed data collection tool. The data collection tool included the 2013 version of the Caprini RAM, which was employed to document VTE risk factors and assess overall VTE risk. Thromboprophylaxis regimens prescribed as well as contraindications to pharmacological thromboprophylaxis were also reviewed

Class of 2017 Abstract / Objectives: The first aim is to assess efficacy of aspirin versus enoxaparin in preventing a venous thromboembolism (VTE) after a total knee arthroplasty (TKA) or total hip arthroplasty (THA) within 30 days after discharge. The second aim is to assess the safety of aspirin versus enoxaparin in preventing major bleeding events after a TKA or THA within 30 days after discharge. Methods: This study was a retrospective cohort study with data obtained from an online Veterans Affairs (VA) hospital database. For analysis, the primary outcome was assessed with a Chi-Square test, and the secondary outcome was reported with descriptive statistics.Results: Results: Demographics for 374 patients (TKA, n = 275; THA, n = 99): 90% male, average age of 65, average body mass index (BMI) of 32, 26% smokers, 72% had a history of hypertension, and 60% had a history of dyslipidemia. VTE events 30 days post-operatively: enoxaparin (n = 2), enoxaparin/aspirin (n = 1), and aspirin (n = 2) (P-value = 0.78). Safety events (major bleeding events): enoxaparin (n = 42), enoxaparin/aspirin (n = 7), and aspirin (n = 4). Conclusions: There was no significant difference between the treatment groups for VTE rate 30 days post- operation. The enoxaparin treatment group had the greatest number of safety events compared to the other groups.

No description available.

Comme dans tout cancer, l'association entre myélome multiple et maladie thrombo-embolique veineuse est bien établie. Son incidence au cours du myélome est en moyenne de 10 à 20%. Elle semble plus élevée en cas de myélome de novo et lors de l’utilisation de traitements immunomodulateurs comme le thalidomide. Pourtant, la part de surcroît du risque de thrombose dû à ce traitement n’est pas encore très bien définie. Tout d’abord, nous avons réalisé un bilan de ces pathologies afin de délimiter le champ d’étude grâce à une revue de la littérature. Nous avons ensuite évalué l’incidence de la maladie thrombo-embolique veineuse, identifié les facteurs de risque thrombotique et évalué le classement en groupe de risque des patients présentant un myélome et traités par immunomodulateur grâce à une étude observationnelle, multicentrique, prospective, de la prise en charge des myélomes par les hématologues en France. Par la suite, nous avons réalisé l’analyse médico-économique du seul essai randomisé réalisé à ce jour sur la thrombophylaxie chez les malades présentant un myélome multiple traités par thalidomide en première ligne. Cette étude montre un gain de qualité de vie associé à des économies majeures lors de la prévention de la thrombose par aspirine plutôt que par héparine. Enfin nous avons réalisé 2 études médicales utilisant la génération de thrombine, test biologique de recherche. La première a été effectuée afin d’essayer de prédire les patients qui vont présenter une thrombose. La deuxième a pour but de rechercher l’existence d’une résistance à l’héparine aux doses habituelles utilisées dans cette pathologie / The association between multiple myeloma and venous thromboembolic disease is well established. This incidence in myeloma is on average from 10 to 20%. It appears to be higher in newly diagnosed myeloma and immunomodulatory drugs such as thalidomide might significantly increase the risk. However, the risk of thrombosis due to these treatments is not yet well defined. First, we performed a review of these diseases in order to delimit the field of this study through a literature review. Then, we evaluated the incidence of venous thromboembolic disease in patients with myeloma and treated with immunomodulatory, identified the thrombotic risk factors and evaluated the thrombotic risk assessment based on the physicians choice, through an observational, multicenter, prospective French study. Moreover, we performed the medico-economic analysis of the only randomized trial conducted to date on the thrombophylaxis in patients with multiple myeloma treated with thalidomide in the first line of chemotherapy. This analysis showed a gain in quality of life associated with significant cost savings in the prevention of thrombosis by aspirin rather than heparin. Finally we performed two medical studies using thrombin generation test, a global assay that measures the overall tendency of a plasma sample to form thrombin. The first study was conducted to predict patients who will have thrombosis. The second is performed to know if a heparin resistance with the usual doses in this pathology, exists