Genetic factors affecting thrombosis in patients with essential thrombocythemia by heparin treatment

The fading role of triple therapy in patients with atrial fibrillation and acute coronary syndrome: a Bayesian network meta-analysis

Cost-effectiveness of edoxaban versus dalteparin for the treatment of cancer-associated thrombosis Abstract Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.

Dual versus triple therapy for patients with atrial fibrillation and acute coronary syndrome: a meta-analysis and trial sequential analysis of randomized controlled trials

Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients Abstract The aim of the study was to investigate the possible role of coagulation factor XIII (FXIII) plasma activity and its gene (F13A1) Val34Leu variant as well as thrombospondin-2 gene (THBS2) T/G 3′UTR and thrombospondin-4 gene (THBS4) Ala387Pro variants in the development of myocardial infarction (MI) in young patients. The studied group consisted of 158 patients aged < 50 years with MI, and the control groups consisted of 150 healthy people aged < 50 years and 202 patients suffering from MI aged ≥ 50 years. Factor XIII activity was measured by photometric assay; genetic variants were determined using the restriction fragment length polymorphism (RFLP) method. FXIII activity was significantly higher in the young MI group compared with young healthy controls and the MI ≥ 50 group (126.2 U/dl vs. 109.6 U/dl, p < 0.0001; 126.2 U/dl vs. 119.8 U/dl, p = 0.01, respectively). FXIII activity did not correlate with F13A1 gene variants. F13A1, THBS2 and THBS4 genotypes were equally distributed in all studied groups. There was also no statistically significant differences in the prevalence of the extended CC/TT/GG haplotype of F13A1/THBS2/THBS4 variants between the young MI group and the young healthy control group and between the young MI group and the MI aged ≥ 50 group. In conclusion, our study revealed that increased FXIII activity is associated with an increased risk of MI in young patients. None of studied single genetic variants—F13A1 Val34Leu, THBS2 T/G 3′UTR and THBS4 Ala387Pro—and the extended CC/TT/GG haplotype of F13A1/THBS2/THBS4 genes was associated with MI in young age.

Concurrent presentation of a hemorrhagic pericardial effusion and venous thromboembolism in malignancy: a systematic review of case studies Abstract The concurrent presentation of symptomatic malignant pericardial hemorrhage and venous thromboembolism is a rare event that poses a clinical dilemma. Existing VTE guidelines do not indicate when, or if, anticoagulation therapy should be started after the treatment of the pericardial bleed. We performed a systematic review to compile the published clinical evidence on the occurrence of coexisting pericardial hemorrhage and VTE in cancer patients and to describe the clinical presentations and bleeding and thrombosis outcomes before and after anticoagulation therapy. We studied published case reports on patients with cancer who presented to the hospital with pericardial hemorrhage and VTE through April 11, 2019. We found seven published case reports. All patients had suffered from a pulmonary embolism and had pericardiocentesis during hospitalization. Five patients (71%) had lung cancer. Four patients (57%) were started on anticoagulation after pericardial drainage and survived the index event. Two patients (29%) were not started on anticoagulation after pericardiocentesis; only one of these patients survived the hospitalization. Pericardial bleeding risk in cancer may be inherent to malignancy, and it is unclear if anticoagulation use increases the risk of recurrent pericardial bleeding. The management of pericardial bleeding typically requires pericardiocentesis, and clinical registries, prospective collaboration projects, and case adjudication are needed to establish the safety of initiation of antithrombotic therapy in such patients.

Thrombotic microangiopathy in hematotoxic snakebites and its impact on the prognosis: an entity often overlooked Abstract Snakebite associated thrombotic microangiopathy (TMA) is a spectrum of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI). We carried out this study to find out the prevalence of TMA in hematotoxic snake envenomation and to analyze its impact on the clinical outcome of patients. Retrospective data were collected from the medical records, hospital and lab information system after institutional ethics committee approval. Hematotoxic snake bite patients were categorized into Group 1 (with TMA) and Group 2 (without TMA). Chi square test, Mann–Whitney ‘U’ test and Odd’s ratio (OR) were used for statistical analysis. Out of 331 snakebite cases admitted, 202 (64.33%) were hematotoxic envenomation with a mean age of 42.26 ± 15.61. Majority were males with a male to female ratio of 2.01:1. Lower limb was the most common site of bite (59.9%). The prevalence of coagulopathy, TMA and AKI observed was 56.4, 18.8 and 37.6% respectively. AKI had a significant risk of undergoing hemodialysis when it was associated with TMA (r = 0.635, OR = 19.3182, P < 0.0001). Higher number of patients in Group 1 received more blood products (r = 0.406, OR = 8.525, P < 0.0001). Prolonged hospital stay (17.25 ± 12.23 vs. 8.86 ± 7.18 days, P < 0.0001) and higher complication rates were (33.33% vs. 11.4%, P < 0.0048) observed in patients with TMA. Snakebite associated TMA has a significant impact on the prognosis and understanding the pathophysiology of this entity will help to formulate guidelines.

Evaluation of weight based enoxaparin dosing on anti-Xa concentrations in patients with obesity Abstract Current treatment dose of enoxaparin is based on total body weight (TBW), however dosage in obesity remains unclear. “Dose capping” commonly occurs if TBW > 100 kg minimising bleeding risk. However, this may result in under-dosing and increasing embolisation risk. The primary objective evaluated efficacy of current dosing strategies in obese patients and determined if resultant anti-Xa concentrations (aXaC) were therapeutic. The secondary objective was to investigate if an uncapped 0.75–0.85 mg/kg (TBW) twice daily dose, advocated by previous authors, results in therapeutic aXaC (0.5–1.0 IU/ml). This retrospective study included 133 patients with a median TBW of 128 kg, producing 59% therapeutic, 15% sub-therapeutic and 26% supra-therapeutic aXaC. Approximately 60% of patients in each dose group (< 0.75, 0.75–0.85 and > 0.85 mg/kg) had a therapeutic aXaC, however the percentage of sub-therapeutic versus supra-therapeutic was higher in the < 0.75 (27% vs 9%) and > 0.85 mg/kg (10% vs 34%) groups respectively. Most patients who weighed 100–119 kg (TBW) received doses > 0.85 mg/kg, however 32% had toxic aXaC. Those between 120 and 139 kg (TBW) had a high percentage of therapeutic aXaC (87%) when dosed < 0.75 mg/kg and a high percentage of supra-therapeutic aXaC (71%) when dosed > 0.85 mg/kg; although numbers were low. Dose reduction occurred in patients > 140 kg (TBW), however < 0.75 mg/kg resulted in higher percentage of sub-therapeutic aXaC (42%). Dosing at 0.75–0.85 mg/kg results in 62% of therapeutic, 14% sub-therapeutic and 24% supra-therapeutic aXaC. This appears to be a “safe” starting dose-range, however all obese patients should have aXaC monitoring due to high inter-patient variability.

Carbamazepine interaction with direct oral anticoagulants: help from the laboratory for the personalized management of oral anticoagulant therapy Abstract Current guidelines recommend caution in prescribing concomitant use of direct-acting oral anticoagulants (DOACs) and antiepileptic drugs due to drug–drug interactions leading to potential risk of DOACs subtherapeutic concentration and treatment failure. Herein we report a significant interaction between carbamazepine (CZP) and apixaban, causing subtherapeutic concentration of the drug in a patient with atrial fibrillation who had a transient ischemic attack (TIA) episode. Another anti-Xa DOAC, edoxaban, administered to the patient after TIA occurrence did not show significant interaction with CZP. In addition to confirm that cautions should be used when antiepileptic and DOACs are concomitantly prescribed, the present case also demonstrates that, in the management of certain subsets of patients who need anticoagulant treatment, measurement of DOAC plasma concentration can help guide a personalized management and avoid adverse clinical outcomes.

Gender differences in thrombogenicity among patients with angina and non-obstructive coronary artery disease Abstract Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL β2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B2 (dTxB2) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9 year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet–fibrin strength (TIP–FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2 mm, p = 0.001), clotting index (0.35 ± 2.22 vs. − 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20 mm of clot strength from an amplitude of 2 mm) (2.2 ± 1.6 vs. 1.7 ± 0.5 min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP–FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.