Thrombosis Journal最新文献

We congratulate Hägg et al. on their study investigating cancer incidence and mortality following first-ever venous thromboembolism (VTE), which provides valuable insights into VTE as a potential marker for underlying malignancies. However, we highlight concerns regarding healthy user bias, the unclear follow-up duration, and inconsistent adjustment in the statistical analysis. We also suggest the use of the Fine-Gray subdistribution hazard model to address competing risks, and the accurate reporting of sex-gender terminology. Lastly, we advise caution in concluding a high incidence of cancer following first-ever VTE without pre-VTE data for comparison and recommend acknowledging potential surveillance bias when interpreting the higher cancer detection rate within 6 months of VTE diagnosis.

Background and aim: The D-dimer to fibrinogen ratio (DFR) represents an emerging and significant clinical biomarker. However, its correlation with cerebral venous thrombosis (CVT) remains underexplored. This retrospective cohort study aims to elucidate the association between DFR values and the severity and prognosis of CVT.

Methods: Severe CVT was defined as the presence of at least 1 of the following risk factors: mental status disorder, coma state, intracranial cerebral hemorrhage, or thrombosis of the deep cerebral venous system. The modified Rankin Scale was utilized to assess functional outcomes. DFR measurements were obtained within 24 h of hospital admission. Logistic regression analysis was employed to determine the prognostic significance of DFR. After Bonferroni correction, a two-tailed P value < 0.017 (0.05/3) was considered statistically significant.

Result: A total of 196 patients were included in the study, among whom 85 patients were diagnosed with severe CVT, and 35 and 14 patients experienced short-term and long-term adverse outcomes, respectively. Receiver operating characteristic curve analysis demonstrated that DFR has predictive value for severe CVT, poor short-term and long-term outcomes, with area under the curve values of 0.690 [95% CI: 0.617-0.764, P < .001], 0.773 [95% CI: 0.701-0.845, P < .001], and 0.754 [95% CI: 0.619-0.886, P = .002], respectively. DFR ≥ 0.253 was identified as a significant predictor of severe CVT [adjusted odds ratio (aOR) (95% CI): 2.03 (1.10-3.75), P = .024]. Additionally, DFR ≥ 0.322 and DFR ≥ 0.754 were significantly associated with poor short-term outcomes at discharge [aOR (95% CI): 2.63 (1.43-4.76), P = .002] and poor long-term outcomes at 12 months [aOR (95% CI): 2.86 (1.32-6.25), P = .008], respectively.

Conclusion: Elevated DFR is associated with increased severity of CVT. Additionally, higher DFR levels can predict poorer clinical outcomes in CVT.

Background: Atrial fibrillation is a growing epidemic in Africa. Anticoagulation, considered the backbone for non-valvular atrial fibrillation (NVAF) management, is limited to warfarin as the mainstay of available anticoagulation therapy in most low- and middle-income countries (LMIC). The optimal time in the therapeutic range (TTR) while on warfarin is essential to avoid bleeding and thromboembolic complications. This study assessed anticoagulation control in patients with NVAF on warfarin in Johannesburg, South Africa.

Methods: We conducted a cross-sectional retrospective study on patients with NVAF managed in the Division of Cardiology, at a tertiary-level academic centre in Johannesburg, South Africa, between 1 January 2015 and 31 December 2019. Anticoagulation control for patients with NVAF was assessed by calculating the TTR using the Rosendaal method.

Results: The study population comprised 177 patients diagnosed with NVAF. The mean age was 65.0 ± 13.1 years. The median TTR among patients with NVAF was 46% [interquartile range (IQR): 8.7-86.0], and 63 (35.6%) patients with NVAF had a TTR ≥ 70% (optimal anticoagulation control). Patients with poor anticoagulation control (TTR < 70%) were on warfarin for a shorter duration compared with those with optimal anticoagulation control [56 days (IQR: 43-84) vs. 70 days (IQR: 56-140), p = 0.0013]. The mean CHA₂DS₂-VASc score was 4 ± 1.5, and it did not differ between patients with poor or optimal anticoagulation control. Among the 175 patients with available HAS-BLED scores, 21 (12.0%), 112 (64.0%) and 42 (24.0%) were at a low, moderate, and high risk for bleeding, respectively. Of the 21 patients in the HAS BLED low-risk category, only 4 (19.0%) had a TTR < 70% (p < 0.001). Warfarin toxicity was documented in 13 (7.3%) patients.

Conclusion: In our study, a TTR ≥ 70%, suggesting optimal anticoagulation control, was found in only 35.6% of patients with NVAF on warfarin.

Background: Bleeding complications following intramuscular (IM) injections are generally considered rare with reported incidence of 0.06%. However, evidence on safety of IM injections among anticoagulated hospitalized patients is lacking. The objective of the current study was to examine the incidence of injection site bleeding complications following IM injection among anticoagulated hospitalized patients.

Methods: A retrospective comparative study comprised of all hospitalized patients ≥ 18 years old that were treated with ≥ 1 IM injection between 2009 and 2019 in a large tertiary medical center. Bleeding complications were defined as focal hematoma, local bleeding, intramuscular bleeding or compartment syndrome. Each case with IM injection was searched for ICD9 codes (e.g., hematoma, hemorrhage or compartment syndrome) and for indirect evidence suggestive of potential bleeding: hemoglobin drop ≥ 2 g/dl, AST or CPK increase, packed red blood cell transfusion, or abrupt cessation of the anticoagulation. These case were then verified for true injection-site bleeding by natural language processing model and manual review of the electronic medical record.

Results: A total of 71,710 patients were treated with 236,406 IM injections. Mean age 53 (± 22) and 63% were females. Concomitant anticoagulation (Heparins: 90.3%, warfarin: 6.8% and DOACs: 4.7%) occurred in 40,819 IM injections (8189 patients). Suspected bleeding complications at the IM injection site were identified among 7,111 patients following 23,089 IM injections, the majority were unrelated to the IM injection-site (e.g., gastrointestinal bleeding, retroperitoneal, etc.). Two cases were verified as true injection site bleeding complication, both in the anticoagulated group (2/8189, 0.02%).

Conclusion: Bleeding complications at site of IM injections among anticoagulated hospitalized patients are rare, and their risk is probably not higher compared to patients without anticoagulation.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with poor outcomes when untreated, in which ravulizumab or eculizumab are the standard of care where available. It has been proposed to regularly monitor platelet counts as an early response to ravulizumab or eculizumab. This study aimed to investigate the association between the early response to ravulizumab treatment and renal outcomes through 26 weeks in complement inhibitor-naïve adults with aHUS.

Methods: Adult patients with aHUS enrolled in the ALXN1210-aHUS-311 phase III study of ravulizumab were divided into two groups according to the achievement of complete thrombotic microangiopathy (TMA) response, i.e., platelet count and lactate dehydrogenase (LDH) normalization and ≥ 25% improvement in serum creatinine (sCr) from baseline, by 26 weeks and baseline characteristics were compared. Changes in hematologic parameters, platelet count and LDH, were compared between the two groups. Finally, we examined whether early hematologic improvement was associated with renal recovery (dialysis discontinuation or ≥ 25% improvement in sCr from baseline) through 26 weeks.

Results: Of 56 ravulizumab-treated patients, 30 achieved complete TMA response for 26 weeks, and 26 did not. Patients with complete TMA response showed rapid improvements in platelet counts. In patients without complete TMA response, delayed normalization of platelet counts was observed. By day 15, 93.3% (28/30) of patients with complete TMA response at 26 weeks and 26.9% (7/26) of patients without complete TMA response achieved platelet normalization. At 26 weeks, 62.5% (35/56) achieved renal recovery; however, 37.5% (21/56) did not. In patients with renal recovery, 85.7% (30/35) of patients had platelet count normalization by day 15; in patients without renal recovery, 23.8% (5/21) of patients had platelet count normalization (P < 0.0001). Receiver operator characteristic curve analysis showed a moderate association between platelet counts on day 8/15 and renal recovery within 26 weeks (day 8: area under the curve [AUC] = 0.7985; day 15: AUC = 0.8406).

Conclusions: Platelet count normalization occurred in 62.5% (35/56) by day 15 after ravulizumab initiation and was associated with renal recovery through 26 weeks in complement inhibitor-naïve adults with aHUS.

Trial registration: This study was performed as a post-hoc analysis of the ALXN1210-aHUS-311 phase III clinical trial (NCT02949128, registered October 25, 2016).

Background: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM^®.

Methods: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.

Results: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.

Conclusions: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.

Trial registration: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.

Recent years have seen ticagrelor, a potent P2Y12 inhibitor, emerge as a significant advancement in the peri-thrombolytic management of patients with ST-segment elevation myocardial infarction (STEMI), offering a promising alternative to traditional antiplatelet drugs like clopidogrel. This review critically examines the efficacy and safety of ticagrelor during the peri-thrombolytic phase in STEMI patients, drawing on evidence from key clinical trials such as TREAT and MIRTOS, as well as other relevant studies. These investigations underscore ticagrelor's superior platelet inhibition capabilities, which are crucial for minimizing thrombotic complications post-thrombolysis without increasing bleeding risks. Despite its potential, clopidogrel remains the guideline-recommended choice for such patients, leaving the appropriateness of ticagrelor in this context open to debate. By summarizing the current evidence and identifying gaps in our understanding, this study advocates for targeted research to clarify the long-term benefits and optimal deployment of ticagrelor, highlighting its evolving significance in cardiovascular care.

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually "blinded" with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa.