Thrombosis Update最新文献

Heparin-induced thrombocytopenia (HIT) is a prothrombotic autoimmune disorder confirmed by the existence of Heparin-Platelet Factor 4 (HPF4) antibodies. The aim of this work is to study the possible relationship between anti-HPF4 and antiphospholipid antibodies (aPLs) that may explain the discrepancies observed in patients with a suspected HIT (HIT group) with positive immunoassay (HPF4-Elisa) and negative functional assay (heparin-induced platelet aggregation test). So, we performed H-PF4 antibodies research in 31 APS confirmed patients (APL group). All tests performed have been compared to normal controls (n = 34). We found anti-H-PF4 in 7/31 patients of APL group. In parallel, we search for aPLs in 9/34 patients tested positive for anti-HPF4 in HIT group, all of them were positive. All specificities were observed in the two anti-HPF4 positive groups (aβ2GP1 IgM/IgG/IgA, aCL (IgM/IgG/IgA, aPS-PT IgM/IgG). The most associated antibodies with anti-HPF4 are the anti ß2Glycoprotein1 (Odds ratio = 50.1). We suggest that the presence of aPLs in HIT group with anti-HPF4 could be the cause of the discrepancies. In addition, we performed the Heparin Neutralization Assay (HNA) which is specific for anti-HPF4, neutralization was obtained for patients exposed to heparin. Furthermore, we suggest that we should performed a larger cohort to confirm the causal relationship of aPLs and also to expand the tests allowing the differentiation between these autoantibodies.

Cancer patients exhibit an increased risk of venous thromboembolism (VTE), with VTE being the second leading cause of morbidity and mortality in these patients. The implementation of lockdowns following the COVID-19 pandemic has resulted in decreased mobility and delayed access to care, thus further increasing the susceptibility to VTE. Cancer patients may also be at a higher risk of SARS-CoV-2 infection and have been shown to be more likely to experience severe COVID-19 disease compared to patients without cancer. Given that both cancer and COVID-19 exhibit a hypercoagulable state, stasis of blood flow, and endothelial injury, cancer patients with COVID-19 constitute a vulnerable population with a high risk of thrombosis and bleeding. However, to date there are limited studies evaluating whether cancer patients infected with SARS-CoV-2 have a higher VTE incidence than COVID-19 patients without cancer, how to assess the risk of VTE, prophylaxis and treatment in this special population. Herein, we highlight the urgent need for studies in cancer patients with COVID-19 to ensure appropriate patient care and improve clinical outcomes.

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.