Thrombosis Update最新文献

Introduction

The natural history of venous thromboembolism (VTE) in sickle cell disease (SCD) is incompletely understood. We hypothesized that VTE recurrence is common in SCD and associated with increased disease severity. We sought to understand the short- and long-term clinical outcomes of VTE in SCD.

Methods

We conducted a single-center retrospective chart review study of patients with SCD 18 years and older at our institution between 2003 and 2018. Demographics, hemoglobin (Hb) genotype, medical history, and laboratory values were collected. We recorded VTE occurrence and potential provoking factors, duration of anti-coagulation and subsequent recurrence of VTE. We compared rates of emergency department (ED) visits, and hospitalizations for five years post-VTE to rates of ED visits and hospitalizations among those without VTE.

Results

Fifty-five (23.6%) of 233 individuals with SCD in our cohort (69% HbSS/HbS-β⁰) had a VTE. Increased BMI, prior splenectomy, and white blood cell count were significantly associated with increased risk of VTE while Hb genotype, and severity of anemia were not. Recurrent VTE occurred in 27/55 (49%); 13 VTE recurrences occurred during active treatment with anticoagulants. Patients with a VTE had significantly higher rates of ED visits and hospital admissions than those without a VTE.

Conclusion

Nearly a quarter of our single institution cohort had a VTE with a high recurrence rate even in those receiving anti-coagulation therapy. SCD patients had a higher rate of healthcare utilization after a VTE suggesting a link to disease severity.

Pulmonary embolism (PE) is a major cause of morbidity and mortality worldwide. In the United States alone, it is estimated that up to 100,000 PE-related deaths occur each year. While anticoagulant therapy is highly effective in reducing the risk of mortality in the majority of patients, advanced therapeutics are required in certain high-risk scenarios, such as in the setting of massive PE with haemodynamic compromise where urgent reperfusion therapy is strongly recommended. Conversely, patients with low-risk PE can often be safely managed with anticoagulant therapy alone and without the requirement of advanced therapies or for hospital admission. The optimal approach to management is less clear among patients with intermediate risk PE. In this setting, there is limited data to guide decision-making regarding the role of more aggressive treatment strategies and the competing risks are significant. The Pulmonary Embolism Response Team (PERT) model of care was developed in 2012 in order to support rapid clinical decision-making in the setting of complex acute PE. The PERT draws on expertise across multiple disciplines and provides a framework for timely access to advanced therapeutics when indicated based on consensus decision. The PERT model of PE care has expanded internationally and has led to operational streamlining in PE management through enhanced communication. Registry data suggest that the introduction of the PERT system is associated with an increased use of advanced techniques, such as catheter-directed thrombolysis without a concomitant increase in bleeding complications, although data from randomized trials are lacking. International guidelines have supported the concept of formalizing pathways of engagement between multidisciplinary colleagues. In the absence of randomised trial data, the model of care provided by PERT appears to represent the most effective means of optimizing communication strategies between specialist colleagues to collaborate in the care of individual patients, particularly in scenarios where patients present with complex care needs and where the balance of risks may be difficult to determine.

Introduction

The incidence of thromboembolism during COVID-19 and the use of thromboprophylaxis vary greatly between studies. Only a few studies have investigated the rate of thromboembolism post-discharge. This study determined the 90-day incidence of venous and arterial thromboembolic complications, risk factors for venous thromboembolic events and characterized the use of thromboprophylaxis during and after hospitalization.

Materials and methods

We retrospectively reviewed medical records for adult patients hospitalized for >24 h for COVID-19 before May 15, 2020, in ten Norwegian hospitals. We extracted data on demographics, thromboembolic complications, thromboembolic risk factors, and the use of thromboprophylaxis. Cox proportional hazards regression was used to determine risk factors for VTE.

Results

550 patients were included. The 90-day incidence of arterial and venous thromboembolism in hospitalized patients was 6.9% (95% CI: 5.1–9.3) overall and 13.8% in the ICU. Male sex (hazard ratio (HR) 7.44, 95% CI 1.73–32.02, p = 0.007) and previous VTE (HR 6.11, 95% CI: 1.74–21.39, p = 0.005) were associated with risk of VTE in multivariable analysis. Thromboprophylaxis was started in 334 patients (61%) with a median duration of 7 days (25th–75th percentile 3–13); in the VTE population 10/23 (43%) started thromboprophylaxis prior to diagnosis. After discharge 20/223 patients received extended thromboprophylaxis and 2/223 (0.7%, 95% CI: 0.3–1.9) had a thromboembolism.

Conclusions

The 90-day incidence of thromboembolism in COVID-19 patients was 7%, but <1% after discharge. Risk factors were male sex and previous VTE. Most patients received thromboprophylaxis during hospitalization, but only <10% after discharge.

Acute obstetric coagulopathy secondary to postpartum hemorrhage (PPH) is associated with poor outcome. There is evidence that Tranexamic Acid (TA), an antifibrinolytic drug, is an efficient tool of patient blood management in association with uterotonics to reduce mortality due to postpartum hemorrhage (PPH). Recent trials investigated its preventive administration before PPH. This review summarizes their major results and introduces the ongoing debate on a systematic prophylaxis of coagulopathy before PPH occurs.

Nonvascular neurological manifestations of antiphospholipid antibodies (aPLAbs) are emerging and, among these, several neuropsychiatric shymptoms. Psychiatric diseases are gradually being considered as organic illnesses of the brain. The role of blood-brain barrier regulation is under scrutiny, and increased permeability is thought to play a precipitating role. Neuropsychiatric manifestations in women with antiphospholipid syndrome (APS) are suspected of being secondary to direct binding and the effect of aPLAbs on neurons and glial cells once the permeability of the blood-brain barrier has been altered. Placental diseases, sometimes mediated by aPLAbs, are risk factors for schizophrenia in the offspring, and babies born from women with aPLAbs can develop learning disabilities and autism spectrum disorders. Women with APS more often develop mood disorders as time goes by, and diffusion tensor imaging has evidenced subtle changes in their white matter. More data are urgently needed and the therapeutic management remains to be properly planned.

Background

Both andexanet alfa and 4F-PCC reversal strategies have been associated with thrombotic events. It remains unclear whether the risk is associated with the reversal agent or the lack of re-initiation of anticoagulation.

Objective

The aim of this study was to describe anticoagulant (AC) re-initiation patterns in patients presenting with major bleeding while on a FXai requiring reversal, and to describe associated post-reversal thrombotic events.

Methods

This was a single-center retrospective cohort study. Patients were included if they received FXai reversal with andexanet alfa or 4F-PCC for major bleeding.

Results

Fifty-seven patients met inclusion criteria; of these patients, 34 received andexanet alfa and 23 patients received 4F-PCC. Most patients were prescribed AC for atrial fibrillation. The most common indications for reversal were intracranial hemorrhage 68%, followed by gastrointestinal bleeding 19%. AC was re-initiated at either prophylactic or therapeutic doses in 59% in the andexanet alfa recipients and 65% in the 4F-PCC recipients within 30 days. In those who restarted AC within 30 days, the median time to re-initiate AC was three days [IQR: 1–3]. Thrombotic events occurred in 3% of patients in the andexanet alfa group and 13% in the 4F-PCC group (7% overall rate). None were receiving anticoagulation at the time of the event.

Conclusion

Anticoagulation was restarted in approximately half of the patients who received a reversal agent for a life-threatening bleed. The thrombotic risk was 7% at the 30 day follow up period. Continuous assessment of bleeding and thrombosis is important for post-reversal management of patients with major bleeding events.

Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus pandemic, several highly effective and safe vaccines have been produced at remarkable speed. Following global implementation of vaccination programmes, cases of thrombosis with thrombocytopenia following administration of adenoviral vector-based vaccines started being reported.

In this review we discuss the known pathogenesis and epidemiology of so-called vaccine induced thrombocytopenia and thrombosis (VITT). We consider the available guidelines, diagnostic laboratory tests and management options for these patients. Finally, we discuss important unanswered questions and areas for future research in this novel pathoclinical entity.

Patients with cancer are at increased risk of venous thromboembolism (VTE). Risk assessment models can help identifying high-risk populations that might benefit from primary thromboprophylaxis. Currently, the Khorana score is suggested to select patients for primary thromboprophylaxis. However, risk stratification with the Khorana-score remains imperfect, which led to the development of subsequent clinical risk assessment models (PROTECHT-, CONKO-, ONKOTEV-, TiCat-, COMPASS-CAT-score). Further, recently, a simplified, personalized risk prediction tool for cancer-associated VTE, incorporating cancer type and D-Dimer levels has been proposed by Pabinger et al. (CATSCORE). Also, novel models have been designed specifically for specific tumour types, such as lung cancer (ROADMAP-CAT), gynaecological cancer (THROMBOGYN), lymphoma (THROLY), or multiple myeloma (SAVED-; IMPEDE VTE-score). In the present narrative review, we comprehensively summarize available data on currently available risk assessment models for VTE in patients with cancer, provide a critical discussion on their clinical utility, and give an outlook towards future developments.

Background

COVID-19-associated coagulopathy is incompletely understood.

Objectives

To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED).

Patients/methods

Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant.

Results

COVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922).

Conclusions

Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

Introduction

The acute disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS COV-2) is accompanied by a hypercoagulable state. Multiple publications have described the venous thromboembolic events associated with coronavirus disease 2019 (COVID-19) but arterial thromboembolic events have yet to be described.

Cases description

We describe five COVID-19 patients that developed severe morbidity as a result of occlusive arterial thromboembolic events occurring despite treatment with low molecular weight heparin. All cases presented with an acute confusional state and were accompanied by rapid elevations of lactate and D-dimers and leukocytes. The end organs involved were the kidneys, spleen, liver, lungs, central nervous system, intestines and limbs. Only one of the five patients survived.

Conclusion

COVID-19 is associated with not only venous but also arterial thromboembolic events. Further research is required to clarify the incidence, causes and possible modes of prevention of this potentially lethal disease complication.