Thrombosis Update最新文献

DIC is a leading cause of maternal mortality. It is secondary to obstetrical complications such as placental abruption, amniotic fluid embolism, HELLP syndrome, retained stillbirth and acute fatty liver of pregnancy. Abnormal activation of the hemostatic system can be compensated (non-overt) or decompensated (overt) DIC. Specific scores that were adjusted to the physiological changes during pregnancy can diagnose overt and non-overt DIC. The pregnancy specific DIC score has 88% sensitivity, 96% specificity, a LR+ of 22, and a LR-of 0.125 for the diagnosis of DIC. Management of DIC during pregnancy requires prompt attention to the underlying condition leading to this complication, including the delivery of the patient, and correction of the hemostatic problem that can be guided by point of care testing adjusted for pregnancy. Novel therapeutic modalities like fibrinogen concentrate may facilitate the management of DIC in pregnancy in low resources areas.

A 33-year-old female with a history of pulmonary embolism was admitted for surgical treatment of an atrial myxoma. The patient developed right atrial thrombosis during the postoperative period, despite the introduction of anticoagulant therapy. Coagulation tests revealed low levels of circulating fibrinogen (FIB) and the genetic analysis showed mutations in the fibrinogen genes FGA, FGB and FGG, which led to a diagnosis of congenital hypofibrinogenemia. The patient was treated with low-molecular-weight heparin (LMWH) whose dose was tightly adjusted according to the anti-Xa factor activity. The clinical response was favorable with reduction of the size of the cardiac thrombus and pulmonary emboli.

Background

Anticoagulation (AC) adherence after acute pulmonary embolism (PE) is vital to prevent mortality and future recurrence of venous thromboembolism (VTE). We aimed to analyze factors affecting AC adherence after acute PE.

Methods

Consecutive adult patients with CT angiography or V/Q scan confirmed acute PE were included in a single-center retrospective study from April 2016 to May 2020. Adherence data, including AC refill dates, were collected from pharmacies, and adherence measures including Continuous Measure of Medication Acquisition (CMA), Proportion of Days Covered (PDC), and Optimal Medication Adherence (OMA) were calculated per standardized formulas. Univariable and multivariable linear and logistic regression was used to analyze different variables affecting AC adherence.

Results

A total of 118 out of 144 patients had sufficient follow-up data to measure adherence and were included in the final analysis. Mean age was 60 ± 15 years, with 64 (54.2%) women; 70 (59.3%) White, 26 (22%) African American, 13 (11%) Hispanic; 58 (49.2%) patients had private insurance, 48 (40.7%) Medicare, 11 (9.3%) Medicaid. Type of AC comprised of 57 (48.3%) apixaban, 17 (14.4%) rivaroxaban, 8 (6.8%) warfarin, 6 (5.1%) enoxaparin, and 30 (25.4%) patients with changing AC. In univariable regression, African American and Medicaid-insured patients had significantly lower adherence, while advancing age, apixaban usage, and 30-day follow-up clinic visit showed a higher adherence. However, in multivariable regression, African American race (PDC -0.135, p = 0.006, CI (−0.231, −0.040) | OMA Adjusted OR 0.166, p = 0.030, CI (0.033, 0.837)) and other non-White, non-Hispanic races (PDC -0.314, p = 0.009, CI (−0.548, −0.080)) were associated with lower AC adherence.

Conclusion

In our study, African American and other minority race patients showed lower AC adherence after hospital admission for acute PE. Further studies are needed to address underlying contributors and improve adherence in this population.

Introduction

Warfarin maintenance dosing algorithms improve the time in therapeutic International Normalized Ratio (INR) range (TTR), a surrogate marker for clinical outcomes. Despite demonstrated benefit, many anticoagulation providers utilize experience-based dosing instead. This study assessed rates of concordance between experience-based and algorithm-based warfarin dosing at a single anticoagulation clinic.

Methods

Within University of Utah Health Thrombosis Service, patients on a maintenance dose of warfarin with an INR goal of 2.0–3.0 or 2.5–3.5 and who had INR results during November 2019 were included. Experienced-based approaches for out-of-range INRs were compared to a validated dosing algorithm to determine algorithm concordance rates as well as likelihood that algorithm concordance would return the INR into therapeutic range.

Results

During the one-month study period, there were 1120 out-of-range INRs in 770 patients included in this analysis. Providers’ decisions were 50.5% algorithm-concordant for dosing adjustments and 59.2% concordant for follow-up intervals. Algorithm-concordant dosing practices resulted in a significantly higher likelihood of returning the subsequent INR to the target range (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.05–1.68), whereas algorithm-concordant follow-up intervals did not significantly impact return of INR to therapeutic range (OR 0.79, 95% CI 0.62–1.00). Baseline deviation from INR goal was determined to be significantly different between concordant and discordant study groups. Controlling for the deviation magnitude attenuated the significance of dosing concordance rates on return to INR target range (adjusted OR 1.16, 95% CI 0.91–1.48), while impact of follow-up concordance remained not statistically significant (adjusted OR 0.84, 95% CI 0.66–1.07). No provider characteristics were associated with the likelihood of return to INR goal.

Conclusion

Experience-based dosing was concordant with a validated dosing algorithm only half the time. Algorithm-concordant dosing increased the likelihood of returning the next INR to therapeutic range, though controlling for deviation magnitude attenuated the statistical significance of dosing concordance with return to INR goal rates. These findings support further research regarding implementing strategies that promote the use of a validated dosing algorithm among experienced anticoagulation providers.

Introduction

Bevacizumab is an anti-VEGF monoclonal antibody used widely in oncology. It causes an increased risk of both thrombotic events and proteinuria. Thrombotic events are also a known association of nephrotic syndrome, however, drug-induced proteinuria contributing to thrombosis in this patient population has not been reported in the literature.

Methods

Patients treated with bevacizumab from April 2016 to April 2020 at our institution were identified. The primary objective was to investigate the risk of thrombosis in patients who had proteinuria compared to those without proteinuria. Secondary objectives included evaluating other predictors of thrombosis including hypertension, hyperlipidemia, Khorana score, diabetes, atrial fibrillation, tobacco use, and BMI.

Results

Of the 203 patients treated with bevacizumab, 160 had some degree of proteinuria. A thrombotic event occurred in 8/58 (13.8%) of the trace proteinuria cohort, 19/102 (18.6%) of the proteinuria greater than 30 mg/dL cohort and 5/43 (11.6%) of the no proteinuria cohort (p = 0.508). Additionally, thrombotic events occurred in 24/116 (20.7%) of the hypertension cohort compared to 8/87 (9.2%) of the normotensive patients (p = 0.026) and in 15/52 (28.8%) of hyperlipidemic patients vs 17/151 (11.3%) of those with normal lipids (p = 0.003). The Khorana score was not a significant predictor in this population. In further analyzing our data, we found increasing thrombotic events with each addition of the most telling predictors of thromboses in our population: hypertension, hyperlipidemia, and greater than trace proteinuria, such that patients with all three risk factors present vs none had an odds ratio of 6.786 (p = 0.004).

Conclusion

In patients on bevacizumab, hypertension and hyperlipidemia may better predict thrombotic risk than the Khorana score. While overall proteinuria did not reach statistical significance, there was a numerical trend toward higher rates of thrombosis as the degree of proteinuria increased. Finally, incorporating these three risk factors into a clinical risk score may help stratify patients into lower and higher risk categories which may assist clinicians in making decisions about the use of prophylactic anticoagulation in this population.

The COVID-19 pandemic has devastated the global community and continues to cause significant morbidity and mortality worldwide. The development of effective vaccines has represented a major step towards reducing transmission and illness severity but significant challenges remain, particularly in regions where vaccine access has been limited. COVID-19 is associated with hypercoagulability and increased risk of thrombosis, with greatest risk among the critically ill. Interestingly, early observational data suggested that anticoagulant therapy might improve clinical outcomes, aside from thrombotic events, in patients with COVID-19. In this review we summarise data generated from three published randomised clinical trials which have sought to determine the effect of therapeutic heparin anticoagulation on efficacy and safety outcomes in hospitalised patients with COVID-19: the multiplatform REMAP-CAP, ACTIV-4a and ATTACC randomised controlled trials and the RAPID trial. In the multiplatform REMAP-CAP, ACTIV-4a and ATTACC randomised controlled trials, therapeutic heparin was not associated with benefit in critically ill patients with COVID-19 compared with usual care (adjusted proportional odds ratio (OR) for increased organ-support free days up to day 21: 0.83; 95% credible interval, 0.67–1.03, posterior probability of futility 99.9%). Conversely, among hospitalised patients without critical illness, therapeutic heparin was associated with an increased probability of organ support-free days alive (adjusted OR, 1.27; 95% credible interval, 1.03–1.58). The RAPID trial also evaluated the effect of therapeutic heparin compared with prophylactic heparin in non-critically ill patients. In this study, therapeutic heparin did not significantly reduce the odds of the primary composite outcome (death, mechanical ventilation or intensive care unit admission) (OR 0.69; 95% confidence interval [CI], 0.43 to 1.10; p = 0.12) but was associated with a significant reduction in all-cause mortality [OR, 0.22 (95%-CI, 0.07 to 0.65)]. Collectively these studies suggest that therapeutic anticoagulation with heparin may reduce the severity of illness and potentially even confer a survival benefit in hospitalised, non-critically ill patients with COVID-19. No benefit for therapeutic anticoagulation with heparin was evident in critically ill patients with COVID-19. Therefore, while the results of additional studies in this evolving field are pending, it is important to approach decisions regarding therapeutic heparin in moderately ill hospitalised patients with COVID-19 in a measured and individualised manner.

Inherited AntiThrombin Deficiency (ATD) is a rare and high-risk thrombophilia. It is associated with a high risk of venous thromboembolism, thrombosis, and the risk is escalated further in the prothrombotic state of pregnancy. Due to the thrombotic tendency it is also associated with placental dysfunction due to placental thrombosis. Untreated mothers with ATD have increased rates of second and third trimester loss, pre-eclampsia & eclampsia, placental abruption, and intra-uterine growth restriction resulting in small for gestational age babies.

We have conducted a comprehensive review of the literature and guidelines & summarise the role of antithrombin, how to test for it, the evidence for its role in thrombosis and obstetric complications and how best to manage this. We also aim to present what we believe is best practise for managing ATD during pregnancy and therefore provide a much needed practical guide.

Managing these women during pregnancy is designed to reduce their risk of thrombosis and late obstetric complications. Due to the rarity of the condition and the ethical difficulties surrounding clinical trials in pregnant women no randomised controlled trials or large observational studies have been conducted in this area; evidence is limited to small cohort studies, which are usually retrospective. Definitions such as ‘miscarriage’ and ‘fetal loss’ are also discordant between studies and associations which makes data comparison difficult. Thus there is limited guidance on the management of ATD in pregnancy. We recommend the use of low molecular weight heparin (LMWH) during pregnancy with regular anti- Xa monitoring to ensure that women receive adequate antithrombotic therapy. Due to the efficacy of LMWH working through potentiation of antithrombin, in those with ATD, high levels of LMWH are usually required. We discuss the use of antithrombin concentrates at times where the use of LMWH is contraindicated, such as during delivery.

Emerging evidence suggests that the type of antithrombin deficiency is important in risk stratification along with the individual's own thrombotic risk factors, thrombosis history and family history.

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.