Safety and efficacy of anticoagulant treatment in patients with ovarian vein thrombosis: a systematic review and meta-analysis of observational studies.

Background: The role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain. Objectives: We aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients. Methods: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883). Results: We included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I2 = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I2 = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I2 = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I2 = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies. Conclusion: There is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE.

Anticoagulation for Splanchnic Vein Thrombosis in Myeloproliferative Neoplasms: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimal anticoagulation management in patients with myeloproliferative neoplasms (MPN) experiencing splanchnic vein thrombosis (SpVT) requires balancing risks of bleeding and recurrent thrombosis. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the incidence of bleeding and thrombosis recurrence in patients with MPN-SpVT. METHODS: We included retrospective or prospective studies in English with ≥ 10 adult patients with MPN-SpVT. Outcomes included recurrent venous thrombosis (SpVT and non-SpVT), arterial thrombosis, and major bleeding. Pooled rates per 100 patient years with 95% confidence intervals (CIs) were calculated by DerSimonian-Laird method using random-effects model. RESULTS: Out of 4624 studies screened, 9 studies with a total of 443 patients were included in the meta-analysis with median follow-up 3.5 years. In the 364 patients with MPN-SpVT treated with anticoagulation, pooled event rate for major bleeding was 2.8 (95% CI 1.5-5.1; I2=95%), for recurrent venous thrombosis was 1.4 (95% CI 0.8-2.2; I2=72%) and for arterial thrombosis was 1.4 (95% CI 0.6-3.3; I2=92%) per 100 patient years. Among 79 patients (n=4 studies) who did not receive anticoagulation, pooled event rate for major bleeding was 3.2 (95% CI 0.7 - 12.7; I2=97%), for recurrent venous thrombosis 3.5 (95% CI 1.8 - 6.4; I2=88%) and for arterial thrombosis rate 1.6 (95% CI 0.4 - 6.6; I2=95%) per 100 patient years. CONCLUSIONS: Patients with MPN-SpVT treated with anticoagulation have significant risks for both major bleeding and thrombosis recurrence. Further studies are necessary to determine the optimal anticoagulation approach in patients with MPN-SpVT.

Trials of interventions for ovarian and testicular germ cell tumors registered in ClinicalTrials.gov: A cross-sectional study.

INTRODUCTION: There is unmet need in the treatment of ovarian and testicular germ cell tumors (GCTs). This study analyzed registered trials of interventions for GCTs. MATERIALS AND METHODS: We included trials of interventions for GCTs registered on ClinicalTrials.gov by July 29, 2022. We analyzed their interventions, outcome measures and study design. RESULTS: We included 142 trials registrations; 42 (30 %) for ovarian GCTs, 50 (35 %) for testicular GCTs, and 50 (35 %) trials for both. The majority of the trials were completed (56 %) and did not have results available (75 %). Most trials were in Phase 2. Information about the study design were not reported for many analyzed trials. Most trials had a single-group assignment (44 %) and were open-label (68 %). The median planned number of enrolled participants was 43. Most registrations used medicine(s) (87 %), either as a single type of intervention or in combination. The most commonly used type of medicine was chemotherapy (54 %). Primary outcome was not reported in 23 % of registrations, and secondary outcomes were not reported in 35 % of registrations. Overall survival was used in 6 % of registrations as a primary outcome and in 31 % of registrations as a secondary outcome. CONCLUSIONS: Few trials on GCTs were registered on ClinicalTrials.gov, and their number was declining in recent times. Most registrations did not report relevant information about the study design, or results if completed. More effort is needed to foster trials on GCTs, as well as to optimize the management of the registrations and foster the publication of research results.

Allogeneic platelet-rich plasma for knee osteoarthritis in patients with primary immune thrombocytopenia: A randomized clinical trial.

The treatment of painful KOA in adult patients with ITP has not been well studied yet. We conducted a prospective, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of intra-articular allogeneic PRP injections on symptoms and joint structure in patients with KOA and ITP. 80 participants were randomly allocated in a 1:1 ratio to allogeneic PRP group or saline group. The primary outcome was the WOMAC total score at 12 months post-injection. The number of patients in each group who achieved MCID of primary outcome showed a statistically significant difference only at 3-month (27/39 vs. 5/39, p = 0.001) and 6-month (15/39 vs. 3/38, p = 0.032). The difference in WOMAC total score exceeded the MCID only at 3 month (mean difference of -15.1 [95% CI -20.7 to -9.5], p < 0.001). Results suggest that allogeneic PRP was superior to placebo only with respect to symptoms at 3-month of follow-up.

Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.

Splanchnic Vein Thrombosis: The State-of-the-Art on Anticoagulant Treatment.

Splanchnic vein thrombosis (SVT) is a rare type of venous thromboembolism occurring within the splanchnic venous system. Portal vein thrombosis is the most common presentation, while Budd-Chiari syndrome is the least common. Liver cirrhosis and abdominal solid cancer are the main local risk factors for SVT, whereas myeloproliferative neoplasms are the predominant systemic risk factors. Signs and symptoms of SVT are nonspecific and include abdominal pain, gastrointestinal bleeding, and ascites. Asymptomatic SVT is not uncommon, and the majority would be detected incidentally on routine abdominal imaging performed for the follow-up of liver diseases and tumors. The management of SVT aims to prevent thrombus progression, promote vessel recanalization, and prevent recurrent venous thromboembolism. Anticoagulation should be started early in order to increase the chances of vessel recanalization and reduce the risk of portal hypertension-related complications. Direct oral anticoagulants have been included in recent guidelines, as alternatives to vitamin K antagonists, after clinical stability has been reached; however, caution is required in patients with liver or kidney dysfunction. Treatment duration is based on the presence (or absence) and type (transient vs. permanent) of risk factors. This narrative review aims to summarize the latest evidence on SVT, with a particular focus on the anticoagulant treatment in special categories of patients (e.g., liver cirrhosis, solid cancer, myeloproliferative neoplasms, pancreatitis, incidentally detected SVT, Budd-Chiari syndrome, and chronic SVT).

A comparative in vitro study of the anticoagulant effect of branded versus generic rivaroxaban.

BACKGROUND: Several generic formulations of rivaroxaban were recently marketed to be used interchangeably with their branded equivalent. However, there have been no previously published studies that directly compared the in vitro anticoagulant effect of branded vs. generic rivaroxaban. The aim of this in vitro study was to compare the effects of three raw rivaroxaban materials, obtained from the branded (Xarelto®) and two generic (Rivarolto® and Rivaroxaban Sandoz®) rivaroxaban formulations on an array of coagulation assays. METHODS: A pool of normal plasma was spiked with several concentrations of the three rivaroxaban (range 50-750 ng/ml). The concentrations were assessed with a rivaroxaban calibrated anti-Xa assay and confirmed by ultra-high-performance liquid chromatography-mass spectrometry coupled with tandem mass spectrometry (UHPLC-MS/MS). The following assays were performed: Prothrombin time (PT), activated Partial Thromboplastin time (aPTT), Diluted Russell's Viper Venom Test (dRVVT), Thrombin time (TT), Clauss Fibrinogen, Factor VII, VIII and IX assays, and thromboelastography. RESULTS: The results obtained by the three rivaroxaban at similar concentrations were comparable. Increasing concentrations of the three rivaroxaban showed a strong positive correlation with the PT, aPTT and dRVVT assays (r > 0.95, p < 0.01 for all), and a strong negative correlation with the Factors assays (r < -0.95, p < 0.01 for all). TT and Clauss Fibrinogen were not affected by rivaroxaban. No significant difference was identified in the mean assays' results obtained by the three rivaroxaban. CONCLUSION: This study showed that the branded and generic rivaroxaban exert an identical in vitro anticoagulant effect across a wide range of concentrations.