Thrombosis Update最新文献

Background

Routine monitoring direct oral anticoagulants (DOAC) is not recommended, yet DOAC levels are frequently measured in clinical practice. Interpretation of levels, especially those outside expected ranges, is challenging. Until now it's unclear which patients are at risk for these levels.

Aim

Identify clinical characteristics of patients with DOAC levels outside expected ranges.

Methods

Patients of 2 Dutch academic medical centers with a DOAC concentration measured between 2012 and 2019 were included. DOAC levels above upper limit peak and below lower limit trough ranges, based on DOAC registration trials, were assigned outside expected range. Differences between patients were evaluated using Chi-square, independent sample-T tests and multivariable logistic regression analysis.

Results

Of 597 patients with DOAC measurement, 108 (18.1%) had levels outside expected ranges. Compared to patients with levels within range, patients with levels above range (n = 64) were older (71.1 vs. 60.6 years), more often had creatinine clearance <50 ml/min (32.8% vs. 13.9%). and used more often interacting (17.2% vs. 6.7%) and/or antiplatelet co-medication (25.0% vs. 13.1%). Patients with levels above (62.5%) and below range (61.4%) more often had atrial fibrillation as DOAC indication versus patients with levels within range (39.1%). Age (OR 1.046 [1.025–1.068]) was associated with levels above range, while dabigatran versus apixaban was associated with levels below range (OR 6.060 [1.836–19.996]).

Conclusion

Particularly older aged patients with additional comorbidity and co-medication had DOAC levels outside expected ranges. Prospective studies are essential to investigate whether identification of patients with levels outside expected ranges is necessary to reduce the risk of clinically relevant adverse events.

Background

Plasma D-Dimer (DD) is a degradation product of cross-linked fibrin and represents the activation of the fibrinolytic and coagulation system. Clinically, DD tests have a high negative prediction value for thrombotic events and can be used to rule-out venous thromboembolism (VTE). The DD cut-off value for VTE in humans is 500 ng/mL; however, the baseline and cut-off values for rats are unknown.

Aims

To systematically evaluate the reported results and methodology of DD tests on rat models.

Methods

A systematic literature search was conducted using MEDLINE, EMBASE and Web of Science to include relevant full-length publications, published abstracts and conference proceedings from Jan-01-2000 to Dec-20-2019 that reported rat DD values. The search strategy used categorical search terms: “rat” AND “D-dimer” OR “fibrin degradation product”. Eligible articles were independently reviewed for strain, age, sex, baseline DD and measurement methodology.

Results

Of the 520 identified records 60 studies were included for qualitative analysis. The three primary rat strains used had a body mass ranging from 160 to 410 g and of both sexes were included in the analysis. There was a significant difference in reported baseline DD that was seen both, within and between rat strains and detection methodologies.

Conclusion

Large discrepancies in reported rat plasma DD values suggest that factors such as species and detection methods can lead to the variation of results and should be considered when designing a rat model that measures DD. We recommend using related negative control models as a baseline DD reference range for each study aiming to measure DD level in rats. Further research is required to establish a standardized reference range for baseline DD levels to help scientists better interpret rat DD test results.

Introduction

The risk of venous thromboembolism (VTE) for individuals with cerebral palsy (CP) is understudied. The objectives were to characterize the incidence of VTE by age and sex for individuals with CP compared with those without CP at the population- and clinical-levels.

Materials and methods

This retrospective cohort study used commercial claims from 1 January, 2011 to 31 December, 2017 from individuals of any age with and without CP. Sex-stratified incidence rate (IR) per 1000 person-years and IR ratio (IRR) of VTE were assessed across the lifespan up to 2-years of follow-up. The IR, IRR, and hazard ratio (HR using Cox regression) of VTE were assessed within 30-days following placement of a central venous catheter (CVC) (in one analysis) and orthopedic surgery (in another analysis).

Results

The 2-year IR of VTE for the full cohorts with (n = 20,486) and without (n = 22,161,726) CP was 19.1 and 9.7 for females (IRR = 1.97; 95%CI = 1.77–2.19) and 19.0 and 8.6 for males (IRR = 2.22; 95% CI = 2.01–2.45). The 30-day HR of VTE post-CVC (CP n = 1963; non-CP n = 558,150) was higher for adult males compared with those without CP (HR = 1.25 by 40 years to 1.80 by 80 years), but was not higher in pediatric males or females of any age compared with those without CP. The 30-day HR of VTE post-surgery (CP: n = 2634; non-CP: n = 1,066,136) was higher for pediatric patients and young adults compared with those without CP (HR = 2.58 to 2.79) There was no signficant difference between the groups among the older age groups.

Conclusions

The risk of VTE was elevated for individuals with CP across the lifespan, and some subgroups of CP had a greater 30-day risk of VTE following CVC placement and orthopedic surgery.

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is associated with significant morbidity and mortality. Congenital absence of the inferior vena cava (IVC) is reported in current literature as a rare risk factor for DVT. The presence of kidney and IVC abnormalities on computed tomography together with lower limb thrombosis is collectively referred to as KILT syndrome (Kidney and IVC Abnormalities with Leg Thrombosis), an extremely rare cause of extensive bilateral lower limb DVT.

We present a case of KILT syndrome, diagnosed for the first time after the age of 60 years and the first case reported in the Irish population. The patient presented to the emergency department with unilateral limb pain with a prior history of provoked DVT. Clinical gestalt, a high Wells Score, and raised D-Dimer strongly supported a diagnosis of DVT. Lower limb duplex ultrasound confirmed bilateral external iliac and femoral vein thrombus, with computed tomography venography revealing an absent infrarenal IVC and atrophy of the left kidney. The medical team subsequently admitted the patient for therapeutic anticoagulation and investigation. After review by haematology, the patient was discharged on an indefinite duration of anticoagulation with follow-up with our coagulation services. In any patient with bilateral lower limb DVT, comprehensive assessment and investigation, with particular emphasis on imaging, is imperative to exclude rare associated conditions.

Background

Despite the well-established effectiveness of anticoagulants, the risk of their hemorrhagic complications withheld many patients from being maintained on anticoagulant therapy. However, there is no sufficient data on the magnitude and factors associated with anticoagulant-related hemorrhagic complications in resource-constrained settings. Thus this study aimed to assess the magnitude of hemorrhagic complications and associated factors related to anticoagulant therapy among patients at the University Of Gondar Comprehensive and Specialized Hospital.

Methods

A retrospective follow-up study was done on 154 individuals starting from June 2018 to June 2019 on adult patients who had completed their anticoagulant therapy at the University of Gondar specialized and comprehensive hospital. They were selected using a systematic random sampling technique among all patients who had completed their anticoagulant therapy which is heparin, warfarin, or both. A retrospective data after the initiation of anticoagulant therapy was collected. The data collection was conducted from July 1 to August 30, 2019. Bivariable and multivariable logistic regression was used to identify factors. Variables with p < 0.05 were considered statistically significant.

Results

Out of 154 patients who received anticoagulant therapy during the study period, more than half 83 (53.9%) of the participants were female, and the mean age of participants was 54.8 ± 21.1 years. A quarter of patients, 38 (24.7%), 95% CI (17.8, 31.6) who had been on anticoagulant therapy experienced bleeding complications. Being female (AOR = 6.12, 95% CI: 1.81, 20.71, P = 0.004) Aspirin use (AOR = 7.71, 95% CI: 2.24, 26.53, P = 0.001), type of anticoagulant (AOR = 4.94, 95% CI: 1.58, 15.49, P = 0.006), and number of co-morbidities(AOR = 4.99, 95% CI: 1.47, 16.95, P = 0.010) were found to be significantly associated with hemorrhagic complications.

Conclusions

Hemorrhagic complications related to anticoagulant therapy are not rare. Therefore close monitoring of coagulation profiles as well as minimization of risk factors is crucial and needs collaborated work of all health care professionals and decision-makers.

Background

Hypercoagulability is a common complication seen in COVID-19 infection. However, arterial thrombosis such as acute limb ischemia (ALI) is far less common. Data on the incidence and nature of arterial thromboembolic complications in patients with COVID-19 is limited, originating from a few case reports and case series. Data in the African continent are very scarce.

Method

This is a case series of 10 patients with COVID-19 who developed ALI while on treatment at Eka Kotebe General Hospital, Addis Ababa, Ethiopia. All patients with ALI and COVID-19 admitted between February 1, 2021, and December 31, 2021, were retrospectively identified and reviewed. COVID-19 was confirmed by RT-PCR and ALI was confirmed by Doppler ultrasound and/or computed tomography angiography in the presence of clinical suspicion.

Results

A total of 3098 patients were hospitalized with confirmed COVID-19 during the study period. In a series of 10 patients, 8 (80%) males with a median age of 53.5 years were included. All except one (10%) had one or more risk factors for ALI and one had a ‘possible’ case of vaccine-induced thrombotic thrombocytopenia (VITT) associated with ALI. All were admitted with severe COVID-19 and most (80%) developed ALI during hospitalization (median of seven days from admission). The median duration between COVID-19 and ALI symptom onset was 14.5 days (IQR, 11–15). The majority (60%) were taking therapeutic anticoagulation at the time of ALI onset which is the standard of care for patients with severe disease. Five (50%) were successfully revascularized (median time of 3.5 days) and the rest underwent amputation. All survived and were discharged improved.

Conclusion

ALI can occur in the context of COVID-19 even while a patient is on therapeutic dose anticoagulation and in the absence of traditional risk factors. It is wise to be vigilant of this complication for timely intervention and better treatment outcomes.

Venous thromboembolism (VTE) is a frequent disease affecting more than 1 in 12 individuals during their lifetime. VTE is associated with a substantial disease burden due to long-term complications such as recurrence, the post-thrombotic syndrome, and the post-pulmonary embolism syndrome. Despite the knowledge of several risk factors and triggers, more than one third of the VTE events occur in the absence of an obvious provoking factor. In this narrative review, we summarize studies presenting time trends in incidence rates of VTE after year 2000 and discuss potential reasons for the incidence trends as well as challenges for VTE prevention at the population level. Studies from US, Europe and Asia indicate that the incidence rates of VTE have increased slightly during the last twenty years. Of note, this increase has persisted beyond the implementation of computed tomography pulmonary angiography (CTPA) into routine clinical practice. The persisting rates are likely attributed to the concomitant increase in major risk factors for VTE, such as obesity, major surgery, and cancer. Apparently, more widespread use of thromboprophylaxis to high-risk groups have not counteracted the rates noticeably, indicating that an approach to change the risk factor profile in the general population may be warranted. Obesity is recognized as the strongest causal lifestyle factor for VTE with a population attributable fraction of 10–30%. However, the mechanisms by which obesity increases the VTE risk are poorly understood. By integrating multi-omics and system biology approaches, future epidemiological studies should focus on identifying biological pathways that drive thrombogenesis to reveal disease mechanisms and potential targets for prevention.

Thrombosis is a known complication of SARS-CoV-2 infection, particularly within a severely symptomatic subset of patients with COVID-19 disease, in whom an aggressive host immune response leads to cytokine storm syndrome (CSS). The incidence of thrombotic events coinciding with CSS may contribute to the severe morbidity and mortality observed in association with COVID-19. This review provides an overview of pharmacologic approaches based upon an emerging understanding of the mechanisms responsible for thrombosis across a spectrum of COVID-19 disease involving an interplay between immunologic and pro-thrombotic events, including endothelial injury, platelet activation, altered coagulation pathways, and impaired fibrinolysis.

Introduction

Patients with cancer have an increased risk of developing venous thromboembolism (VTE), and subsequently a higher risk of bleeding secondary to anticoagulants. Low-molecular weight heparin (LMWH) has been the standard of care for these patients, with emerging data on the use of direct oral anticoagulants (DOACs). The primary objective of the study was to determine the prevalence of major bleeding events in cancer patients taking DOACs or LMWH for VTE. Secondary objectives included the rate of first VTE recurrence and the effect of concomitant antiplatelet agents and/or significant drug interactions on major bleeding or recurrent VTE.

Materials and methods

Using the electronic medical record at the University of Rochester Medical Center, we retrospectively identified adult patients with active malignancy who had a diagnosis of VTE requiring therapeutic anticoagulation within the study period of July 1st, 2015 to June 1st, 2019. Patients were excluded if they were receiving prophylactic doses of LMWH per the institution VTE guidelines. Data on anticoagulant medications were collected as well as information on major bleeding and recurrent VTE events.

Results and conclusions

There is insufficient evidence of difference in risk of major bleeding among patients who received a DOAC vs LMWH (cause-specific hazard ratio (HR) = 0.77, 95% CI 0.29–2.04, P = 0.60). There was also no evidence of a difference in risk of recurrent VTE between patients who received DOAC vs. LMWH (cause-specific HR = 0.98, 95% CI 0.15–6.26, P = 0.98). These results suggest that DOACs are not significantly less safe than LMWH for patients with cancer.

Purpose

Anticoagulation Stewardship is urgently needed to improve anticoagulation management and bend the current, negative trajectory on anticoagulation-related harm. This manuscript catalogs the origins and the progression of the Anticoagulation Stewardship model and serves as a call to action for healthcare providers and organizations committed to improving the quality and safety of anticoagulation management.

Key elements

Tens of millions of patients around the world currently require anticoagulant therapy to prevent or treat thrombotic events. Concerningly, there is a growing body of evidence confirming that increasing volume and complexity of anticoagulant use is significantly impacting the therapeutic landscape, posing major challenges to safe prescribing and management of these high-risk, yet essential therapies, and leading to increased patient harm including life-threatening bleeding and thrombotic complications across the continuum of care. In response, anticoagulation stewardship programs, modeled after highly successful antimicrobial stewardship efforts, are gaining increased traction to counteract this growing health concern.

Conclusions

The current health care system is inadequate to protect patients from avoidable harms and to maximize the benefits of therapy. Apart from anticoagulation stewardship, there does not currently exist another cross-setting, multidisciplinary model for achieving maximum quality and safety for patients. If we are to collectively meet the challenge that stands before us, we must commit ourselves (as individuals and organizations) to leveraging the available resources to advance the anticoagulation stewardship model while also contributing to the burden of evidence and the effective articulation of the stewardship message.