Thrombosis Update最新文献

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.

Introduction

Treatment of congenital thrombotic thrombocytopenic purpura (cTTP), a disease characterized by the congenital deficiency of ADAMTS13, remains a challenge as there are no specific treatments available yet, other than therapy based on the use of fresh frozen plasma (FFP). Since cTTP is caused by low levels of ADAMTS13 protein, commercially available coagulation factor concentrates have been considered as potential ADAMTS13 source in place of FFP. The study aimed to validate the therapeutic potential of a plasma-derived factor VIII (FVIII) product as a source of ADAMTS13.

Methods

The quantitation of ADAMTS13 activity levels in eight lots of a plasma-derived FVIII product, (Koāte®) was carried out with three different methodologies: a Fluorescence Resonance Energy Transfer (FRET) assay, a chemiluminescence assay, and a chromogenic ELISA. ADAMTS13 protein antigen levels were measured by the FRET technique as well. In addition, von Willebrand factor (VWF) activity (VWF ristocetin cofactor, VWF:RCo, and VWF collagen binding, VWF:CB) and antigen (VWF:Ag) were measured using chemiluminescence assays. Qualification protocols were applied to the methods used.

Results

The results showed high levels of ADAMTS13 in all eight Koāte® lots analyzed, with antigen and activity levels respectively of 10.72 IU/ml ± 3.94 and 5.62 IU/ml ± 1.39. Despite the significant content of ADAMTS13, VWF integrity seems not to be affected (0.81 ± 0.15 VWF:RCo/VWF:Ag and 0.75 ± 0.15 VWF:CB/VWF:Ag ratios).

Conclusions

These findings suggest that Koāte® could be a potential candidate for the treatment of cTTP, warranting evaluation in a clinical trial.

Background

The risk of adults with a congenital heart defect (ACHD) developing heart failure, stroke, arrhythmias, and the need for valve replacement is increased compared to healthy peers. Evidence for the use of novel oral anticoagulants (NOAC) in this patient group is still lacking and vitamin K antagonists (VKA) are the primary choice for patients with a mechanical valve. The present aim was to determine the rate of thromboembolic and major bleeding events in ACHD patients on VKA therapy.

Methods

This was a retrospective study on ACHD patients on VKA treatment registered in the National Quality Registry for Congenital Heart Disease, SWEDCON, and Atrial fibrillation and Anticoagulation, AuriculA, from Southern Sweden.

Results

213 patients were included with a mean age of 50 years (±18) years and a mean follow-up of 6.6 years (±3.3 years), 16% had complex defects and 41% had valvular VKA therapy indication. In total, 34 complications were registered, of which 14 were thromboembolic events and 20 were major bleeding events. The rate of thromboembolism and major bleeding events was 1.0 (95% CI: 0.6–1.6) and 1.4 (95% CI: 0.9–2.2) per 100 patient-years, respectively. Forty-three patients died during the study period. The mortality rate was 3.1 per 100 patient-years (95% CI: 2.2–4.1).

Conclusion

We found a low rate of thromboembolic events and major bleeding events for low-moderate risk ACHD patients with good quality of VKA anticoagulation. The target of TTR>65% for ACHD patients is recommended.

Background

SARS-COV-2, in most cases, only generates a mild acute respiratory disease. However, patients with severe disease show an exaggerated response of the immune system, creating a pro-inflammatory state, which could cause abnormalities in the coagulation system that increases mortality. Latin American countries, specially those with limited resources, have few studies about clinical features, coagulation and inflammatory biomarkers that could be useful at admission to assess poor outcomes.

Objective

The objective of this study is to describe the clinical features, coagulation, and inflammatory biomarkers, and identify risk factors at admission that are associated poor outcomes in Honduran population.

Methods

A cohort study was conducted. 210 patients were included, which 105 died during hospitalization due to COVID-19 and 105 were discharged alive, between September 2020 and January 2021. Clinical and laboratorial data was retrospectively collected.

Results

57,6% of the population were male. The median age was 58 years. The median time between symptom onset and hospital admission was 6 days. D-dimer median was higher in the dead group compared with the alive group. Poor prognosis factors in the Cox multivariable model were male gender, age, symptom's duration, obesity and an elevated d dimer at admission.

Conclusion

In low-middle income countries, the assessment of these clinical and laboratory tools, especially in those with risk factors for prothrombotic states, could help clinicians to correctly stratify disease prognosis, establish a baseline to evaluate further evolution, and also predict outcomes, thus improving patient management.