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Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders.To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia.We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 10The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was0.001 with standard error0.001, indicating good discrimination and excellent calibration.The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP.

Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug–drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient’s cancer status and management change over time.

Cancer-associated venous thromboembolism is a devastating complication of cancer and is associated with significant morbidity and mortality. The cornerstone of cancer-associated venous thromboembolism treatment is anticoagulation, and in recent years, there have been notable randomized clinical trials that have revealed insights into the efficacy and safety of direct oral anticoagulants and low-molecular-weight heparin in the treatment of cancer-associated thrombosis. Deciding on the ideal anticoagulation treatment plan for a patient with a cancer-associated thrombosis is a complex task that requires an understanding of clinical trial data, society guidelines, and, most importantly, consideration of many cancer-related, treatment-related, and patient-related factors. This article summarizes important factors to consider when deciding on anticoagulation therapy for a patient with cancer-associated thrombosis.

Patients with cancer-associated thrombosis (CAT) are treated with full-dose anticoagulation for at least 3 months, but optimal dosing thereafter is unknown.We explored the feasibility of extended prophylactic-dose low molecular weight heparin (LMWH) treatment following a minimum of 3 months of full-dose LMWH.We conducted a multicenter prospective pilot study of patients with CAT who completed at least 3 months of therapeutic-dose LMWH. Patients received 6 months of prophylactic-dose subcutaneous enoxaparin (40 mg once daily). The primary outcome was recurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE), and secondary outcomes included major, clinically relevant non-major (CRNM), and minor bleeding.From August 2016 to May 2019, 52 patients with a mean age of 64.1 years were included. The study was stopped early because of poor recruitment. Breast (23.1%) and colorectal (19.2%) were the most common cancers, and 61.0% had stage IV malignancy. Index CAT consisted of DVT alone in 57.7% of patients and pulmonary embolism (PE) with or without DVT in 42.3%. Patients received a mean of 7.6 months of weight-adjusted LMWH before enrollment. During a mean follow-up of 5.6 months, one patient was diagnosed with recurrent incidental PE (0.0035 events/subject-month). There were no major bleeding events, one CRNM, and one minor bleeding event. Eight (15.4%) patients died; six from cancer and two from respiratory disease unrelated to PE.These results, in part, provide support for trials of extended reduced-dose anticoagulation for the secondary prevention of CAT. (ClinicalTrials.gov: NCT02752607).

Central venous catheters (CVC) are associated with an increased risk of venous thromboembolism (VTE) in patients with cancer. Primary thromboprophylaxis using a direct oral anticoagulant decreases the risk of VTE in intermediate-to-high risk ambulatory cancer patients. We assessed the efficacy and safety of thromboprophylaxis with apixaban in the subpopulation of patients with cancer and a CVC in the AVERT trial.The AVERT study was a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban for primary thromboprophylaxis in patients with cancer initiating chemotherapy who were at intermediate to high risk of VTE. The primary efficacy outcome was objectively confirmed VTE within 180 days of randomization and the primary safety outcome was major bleeding. The hazard ratios (HRs) were calculated using a Cox regression model controlling for age, gender, and center.A total of 217 patients had a CVC and were included in the subgroup analyses with 126 and 91 patients receiving apixaban or placebo, respectively. VTE occurred in 6 (4.8%) patients in the apixaban group and 17 (18.7%) patients in the placebo group (HR 0.26; 95% CI, 0.14-0.47; p 0.0001). Major bleeding occurred in 2 (1.6%) patients in the apixaban group and 2 (2.2%) patients in the placebo group (HR 0.69; 95% CI, 0.20-2.35; p = 0.556).Primary thromboprophylaxis with apixaban in patients with cancer and a CVC was associated with a reduced risk of VTE in the AVERT study population, without an increased risk of bleeding. (Funded by the CIHR and Bristol-Myers Squibb-Pfizer Alliance; NCT02048865).

Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS.312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female.At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (-3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59).This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed.ClinicalTrials.gov, number NCT02679664.

IntroductionAfter deep vein thrombosis, up to 50% of patients develop post-thrombotic syndrome (PTS). PTS is a chronic condition that reduces quality of life (QOL). Cornerstones of PTS treatment include the use of elastic compression stockings but this treatment is usually incompletely effective and is burdensome. Venoactive drugs have been reported to be effective to treat chronic venous insufficiency (CVI). However, the level of evidence supporting their use in CVI in general and in PTS in particular is low.Methods and analysisThe MUFFIN-PTS trial is an academic, publically funded, multicentre randomised placebo-controlled trial assessing the efficacy of micronised purified flavonoid fraction (MPFF, Venixxa), a venoactive drug, to treat PTS. Eighty-six patients with PTS (Villalta score (VS) ≥5) and experiencing at least two of the following PTS manifestations among daily leg heaviness, cramps, pain or oedema will be randomised to receive 1000 mg of oral MPFF or a similar appearing placebo for 6 months, in addition to their usual PTS treatment. Total study follow-up will be 9 months, with visits at inclusion/baseline, 3, 6 and 9 months. Primary outcome is the proportion of patients with improvement in VS in each group, where improvement is defined as a decrease of at least 30% in VS or a VS Ethics and disseminationPrimary ethics approval was received from Centre intégré universitaire de santé et de services sociaux (CIUSSS) West-Central Montreal Research Ethics Board. Results of the study will be disseminated via peer-reviewed publications and presentations at scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT03833024); Pre-results.

Clinical decisions for NSCLC patients are often based on TNM stage, which does not account for different histological subtype. Whether histological subtype affects survival still remains unclear. The main objective of this study was to determine the extent to which the survival outcomes of patients with early-stage NSCLC differ by histological subtype.Retrospective cohort study of SEER data base. Patients with stage IA and IB NSCLC that underwent surgery with lymph node dissection were included. The primary outcome was the time to death. Cox proportional hazards models were used to identify risk factors associated with overall survival (OS). The secondary outcome was the time to death from lung cancer. A Cox model and a Fine-Gray subdistribution hazards model in which death from causes other than lung cancer was considered a competing risk event were used to identify risk factors for death from lung cancer.Analysis of the SEER database identified 28,584 NSCLC patients, of whom 19,750 (69 %) had adenocarcinoma and 8834 (31 %) had squamous cell carcinoma. In the multivariate for OS, older age (p 0.001), male gender (p 0.001), pneumonectomy (p 0.001), larger tumor size (p 0.001), squamous cell carcinoma (p 0.001) not being Hispanic or Asian were associated with increased risk of death. In the competing risk model, older age (p 0.001), male gender (p 0.001), pneumonectomy (p 0.001), larger tumor size (p 0.001), and squamous cell carcinoma (p 0.001) were was associated with an increased risk of death from lung cancer.This study suggests that among patients with stage I NSCLC, those with squamous histology have a higher risk of mortality than those with adenocarcinoma histology taking into account competing risks.

Background The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups. Methods We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12 months. Results In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference [RD], 4.4%; 95%-CI, −4.1% to 12.8%). The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, −0.3%; 95%-CI, −10.0% to 9.5%), 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95%-CI, −10.1–12.4), 3.1% and 11.7% for breast cancer (RD, −8.6; 95%-CI, −19.3–2.2), 8.9% and 10.9% for hematological malignancies (RD, −2.0; 95%-CI, −13.1–9.1), and 10.4% and 17.4% for gynecological cancer (RD, −7.0; 95%-CI, −19.8–5.7). In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding. Conclusion Edoxaban has a similar risk-benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.

Eck RJ, Elling T, Sutton AJ, et al.

Buparlisib is an orally available pan-Class I PI3K inhibitor, that is more potent than idelalisib in vitro. Its distinct toxicities include hyperglycemia, hypertension, and mood disturbance. IND216...

Importance Unprovoked venous thromboembolism (VTE) can be the first manifestation of cancer. It is unclear if extensive screening for occult cancer including a comprehensive computed tomography (CT) scan of the abdomen/pelvis is cost-effective in this patient population. Objective To assess the health care related costs, number of missed cancer cases and health related utility values of a limited screening strategy with and without the addition of a comprehensive CT scan of the abdomen/pelvis and to identify to what extent testing should be done in these circumstances to allow early detection of occult cancers. Participants and setting Cost effectiveness analysis using data that was collected alongside the SOME randomized controlled trial which compared an extensive occult cancer screening including a CT of the abdomen/pelvis to a more limited screening strategy in patients with a first unprovoked VTE, was used for the current analyses. Main outcomes and measures Analyses were conducted with a one-year time horizon from a Canadian health care perspective. Primary analysis was based on complete cases, with sensitivity analysis using appropriate multiple imputation methods to account for missing data. Results Data from a total of 854 patients with a first unprovoked VTE were included in these analyses. The addition of a comprehensive CT scan was associated with higher costs ($551 CDN) with no improvement in utility values or number of missed cancers. Results were consistent when adopting multiple imputation methods. Conclusions and relevance The addition of a comprehensive CT scan of the abdomen/pelvis for the screening of occult cancer in patients with unprovoked VTE is not cost effective, as it is both more costly and not more effective in detecting occult cancer.

Background In 2010, wait-times for new patients referred to see a haematologist at our outpatient tertiary care centre clinic exceeded 6 months. The provision of written recommendations for a subset of referred patients was undertaken to reduce patient wait-times. These recommendation letters outlined possible causes of the abnormality for which the patient was being referred and suggested a course of action for follow-up, and patients were then managed by their referring practitioner. We sought to characterize the cohort of patients for whom written recommendations were written and assess whether written recommendations were a satisfactory alternative for the referring practitioner. Methods All haematology patient referrals managed with written recommendations in 2010 were included in the study and were assessed one year later. Referring practitioners who received written recommendations were sent a short survey to evaluate their satisfaction with this process. Results A total of 444 of 2400 referrals were managed with a letter. At 1-year follow-up, 58 (13%, 95% CI) of the abnormalities which prompted the referral had resolved and 201 (45%, 95%CI) had remained stable. There was a single haematology-related death during the 1-year follow-up and the haematological abnormality worsened in 4 (1%) patients. Of 203 (71%) referring practitioners who responded to the satisfaction survey, 90% (95% CI) indicated that they would be satisfied with written recommendations in the future. Interpretation The provision of written recommendations appears to be a safe and satisfactory alternative to an inperson outpatient assessment in certain well-defined subsets of stable outpatients with haematologic abnormalities.

Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis.We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode.Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P = 0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24).Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb-Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.).

Management of anticoagulant therapy for the treatment of venous thromboembolism (VTE) in cancer patients is complex because of an increased risk of recurrent VTE and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent VTE and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental VTE, to prevent recurrent VTE, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug–drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient’s cancer status and management change over time.

Background Several barriers exist for training and retention of clinician scientists, including difficulty in navigating research-related tasks in the workplace and insufficient mentorship. Objective Our aim was to identify what core research knowledge and skills are important for the success of clinician scientists in thrombosis research, and trainees' perceived confidence in those skills, in order to develop a targeted educational intervention. Methods A pre-tested online survey was administered to trainees and research faculty of the Canadian thrombosis research network, CanVECTOR, between September 2016 and June 2017. The importance (research faculty) and confidence (trainees) of 45 research knowledge/skills were measured using a 5-point Likert scale. Results The survey response rate was 49% (28/57) for research faculty and 100% (10/10) for trainees. All research faculty rated developing a good research question, grant writing and writing strategies for successful publication as ‘very’ or ‘extremely’ important for trainees to learn to better transition in becoming independent researchers. Other important areas included practical aspects of research. A qualitative thematic analysis of open text responses identified ‘time management’ and ‘leadership and teamwork’ as additional important research skills. Confidence reported for each topic varied across trainees. There were three research knowledge and/or skills that ≥ 75% of research faculty deemed highly important and ≥ 50% of trainees reported lacking confidence in: grant writing, the peer-review grant process, and knowledge translation strategies. Conclusions Developing a good research question, communicating research ideas and results and the practical aspects of research are important areas to focus future efforts in thrombosis research training.

Background The risk of recurrent venous thromboembolism (VTE) in cancer patients despite anticoagulant therapy is high. Clinical factors and pro-coagulant markers may identify high-risk patients and guide decisions about intensifying anticoagulation therapy. Aims To evaluate whether serial measurements of pro-coagulant markers can identify patients at high risk of recurrent VTE. Methods In this multicenter, prospective cohort study, patients with active cancer and acute deep vein thrombosis or pulmonary embolism were enrolled. Patients received standard low-molecular-weight heparin therapy and were followed for 6 months. D-dimer and soluble P-selectin levels were measured at baseline and 1, 4, 5, 12, and 24 weeks post treatment initiation. The association between recurrent VTE and a previously developed risk score, baseline values of the biomarkers, and individual relative changes from baseline were assessed. Results We enrolled 117 cancer patients (22% lung, 21% colorectal, 9% breast) with a mean age of 63 years; 62% had metastatic cancer. Eleven patients (9.4%) developed recurrent VTE, including two cases of fatal pulmonary embolism. VTE recurrence rates were 7.8% (95% CI, 3.1–18) in patients with a risk score of ≤0 points compared to 11% (95% CI, 5.2–20) for those with a score of ≥1 point (hazard ratio 1.3; 95% CI, 0.39–4.5). Baseline P-selectin levels but not D-dimer levels were significantly associated with a high risk of recurrence; the risk was four-fold higher in patients with elevated P-selectin levels than in those with normal levels (hazard ratio 4.0; 95% CI, 1.1–14). Changes in biomarker levels during treatment were not associated with recurrent VTE. Conclusion Baseline P-selectin but not D-dimer levels predict recurrent VTE and may be a valuable addition to clinical prediction rules to select patients for more intensive therapy or closer observation.

Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol. Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group. Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.

Essentials Heparin-induced thrombocytopenia (HIT) is a thrombogenic condition that is difficult to treat. We evaluated rivaroxaban as a treatment option in patients with suspected or confirmed HIT. One patient had recurrent thrombosis and 9/10 patients with thrombocytopenia had platelet recovery. Rivaroxaban may be an effective and safe treatment option for HIT. SummaryBackground Rivaroxaban is a direct oral anti-Xa inhibitor that has the potential to greatly simplify treatment of heparin-induced thrombocytopenia (HIT). Objectives To evaluate the efficacy and safety of rivaroxaban in this patient population, we conducted a multicenter, single-arm, prospective cohort study of patients with suspected or confirmed HIT. Patients/Methods Twenty-two consecutive adults with suspected or confirmed HIT received rivaroxaban 15 mg bid until a local HIT assay result was available. Participants with a positive local assay result continued rivaroxaban 15 mg bid until platelet recovery (or until day 21 if they had acute thrombosis at study entry), then stepped down to rivaroxaban 20 mg daily until day 30. Results and Conclusions The primary outcome measure, incidence of new symptomatic, objectively-confirmed venous and arterial thromboembolism at 30 days, occurred in one HIT-positive participant (4.5%; 95% confidence interval [CI], 0–23.5%) and one HIT-positive participant required limb amputation despite platelet recovery. Platelet recovery was achieved in nine out of 10 HIT-positive patients with thrombocytopenia. Rivaroxaban appears to be effective for treating patients with confirmed HIT, although the small number of patients enrolled limits precision.

Risk factors predictive of occult cancer detection in patients with a first unprovoked symptomatic venous thromboembolism (VTE) are unknown. Cox proportional hazard models and multivariate analyses were performed to assess the effect of specific risk factors on occult cancer detection within 1 year of a diagnosis of unprovoked VTE in patients randomized in the Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial. A total of 33 (3.9%; 95% CI, 2.8%-5.4%) out of the 854 included patients received a new diagnosis of cancer at 1-year follow-up. Age ≥ 60 years (hazard ratio [HR], 3.11; 95% CI, 1.41-6.89; ITALIC! P= .005), previous provoked VTE (HR, 3.20; 95% CI, 1.19-8.62; ITALIC! P= .022), and current smoker status (HR, 2.80; 95% CI, 1.24-6.33; ITALIC! P= .014) were associated with occult cancer detection. Age, prior provoked VTE, and smoking status may be important predictors of occult cancer detection in patients with first unprovoked VTE. This trial was registered atwww.clinicaltrials.govas #NCT00773448.

• A subset of women enrolled in the REVERSE II study underwent a second, blinded assessment for signs of post-thrombotic syndrome (hyperpigmentation, edema, redness).

Background:Occipital condyle syndrome is characterized by severe, unilateral, occipital headache and ipsilateral twelfth-nerve palsy. It is associated with skull-base metastasis.Cases:We identified two patients with sub-acute onset of severe, unilateral, occipital headache and ipsilateral tongue paralysis. The first patient was a 58-year-old woman with a history of limited stage small-cell lung cancer in clinical remission. The second patient was an otherwise healthy 36-year-old man. Neither patient had any other findings on general medical or neurological examination. One patient had only equivocal findings on initial magnetic resonance imaging (MRI), and the other patient's MRI was normal. Although initial work-up for metastatic disease was normal, the first patient developed severe bone pain over the next few months, and follow-up investigations demonstrated metastases to her spine, tibia, skull base and brain. The second patient improved initially, but was admitted to hospital three months later with constitutional symptoms and pancytopenia. Bone marrow and lymph node biopsies were consistent with Stage IVB Hodgkin's lymphoma.Conclusion:Occipital condyle syndrome can be the first presentation of disseminated malignancy. Initial imaging of the brain and skull base may be normal, and recognition of this syndrome warrants thorough investigation and close follow-up.

International audience; Venous thromboembolism may be the earliest sign of cancer. Currently, there is a great diversity in practices regarding screening for occult cancer in a person who has an unprovoked venous thromboembolism. We sought to assess the efficacy of a screening strategy for occult cancer that included comprehensive computed tomography (CT) of the abdomen and pelvis in patients who had a first unprovoked venous thromboembolism. We conducted a multicenter, open-label, randomized, controlled trial in Canada. Patients were randomly assigned to undergo limited occult-cancer screening (basic blood testing, chest radiography, and screening for breast, cervical, and prostate cancer) or limited occult-cancer screening in combination with CT. The primary outcome measure was confirmed cancer that was missed by the screening strategy and detected by the end of the 1-year follow-up period. Of the 854 patients who underwent randomization, 33 (3.9%) had a new diagnosis of occult cancer between randomization and the 1-year follow-up: 14 of the 431 patients (3.2%) in the limited-screening group and 19 of the 423 patients (4.5%) in the limited-screening-plus-CT group (P=0.28). In the primary outcome analysis, 4 occult cancers (29%) were missed by the limited screening strategy, whereas 5 (26%) were missed by the strategy of limited screening plus CT (P=1.0). There was no significant difference between the two study groups in the mean time to a cancer diagnosis (4.2 months in the limited-screening group and 4.0 months in the limited-screening-plus-CT group, P=0.88) or in cancer-related mortality (1.4% and 0.9%, P=0.75). The prevalence of occult cancer was low among patients with a first unprovoked venous thromboembolism. Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit. (Funded by the Heart and Stroke Foundation of Canada; SOME ClinicalTrials.gov number, NCT00773448.).

Background— The perioperative management of dabigatran in clinical practice is heterogeneous. We performed this study to evaluate the safety of perioperative management of dabigatran using a specified protocol. Methods and Results— Patients treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The timing of the last dose of dabigatran before the procedure was based on the creatinine clearance and procedure-related bleeding risk. Resumption of dabigatran was prespecified according to the complexity of the surgery and consequences of a bleeding complication. Patients were followed up for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism, and death. We included 541 cases: 324 procedures (60%) with standard risk of bleeding and 217 procedures (40%) with increased risk of bleeding. The last dose of dabigatran was at 24, 48, or 96 hours before surgery according to the protocol in 46%, 37%, and 6%, respectively, of the patients. Resumption was timed according to protocol in 77% with 75 mg as the first dose on the day of procedure in 40% of the patients. Ten patients (1.8%; 95% confidence interval, 0.7–3.0) had major bleeding, and 28 patients (5.2%; 95% confidence interval, 3.3–7.0) had minor bleeding events. The only thromboembolic complication was transient ischemic attack in 1 patient (0.2%; 95% confidence interval, 0–0.5), and there were 4 deaths unrelated to bleeding or thrombosis. Bridging was not used preoperatively but was administered in 9 patients (1.7%) postoperatively. Conclusion— Our protocol for perioperative management of dabigatran appears to be effective and feasible.

Rivaroxaban is an ideal potential candidate for treatment of heparin-induced thrombocytopenia (HIT) because it is administered orally by fixed dosing, requires no laboratory monitoring and is effective in the treatment of venous and arterial thromboembolism in other settings. The Rivaroxaban for HIT study is a prospective, multicentre, single-arm, cohort study evaluating the incidence of new symptomatic venous and arterial thromboembolism in patients with suspected or confirmed HIT who are treated with rivaroxaban. Methodological challenges faced in the design of this study include heterogeneity of the patient population, differences in the baseline risk of thrombosis and bleeding dependent on whether HIT is confirmed or just suspected, and heterogeneity in laboratory confirmation of HIT. The rationale for how these challenges were addressed and the final design of the Rivaroxaban for HIT study is reviewed.

Direct thrombin inhibitors, specifically orally administered dabigatran etexilate, are emerging as alternatives to warfarin for anticoagulation in the management of atrial fibrillation and venous thromboembolism. The risk associated with bleeding events while taking dabigatran has been documented in multiple randomized controlled trials, but to date, no studies have focused on the risk of bleeding after dental extraction. Extraction of teeth is one of the most common surgical procedures and may cause significant bleeding, so a thorough understanding of the pharmacology of anticoagulant medications is required to prevent complications. With the increasing use of direct thrombin inhibitors, the safe management of patients taking these anticoagulants must be delineated. This review compares dabigatran and warfarin, especially in terms of their effects on dental and oral surgery practice, and examines best management of these patients in light of the existing literature.