What's New in Coagulation - April 2017

Want to be in the know? Check out our monthly compilation of the latest studies, guidelines, and discussions in coagulation.

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Hospital Transfer Linked to Worse Stroke Thrombectomy Outcome

The results of the STRATIS study registry suggests that patients who are sent to a comprehensive center may have better outcomes in patients that have ischemic stroke. These findings were presented at the International Stroke Conference. Patients who were sent to a comprehensive center, even if 20 miles further would have delayed TPA treatment by 2 minutes but receive endovascular therapy 90 minutes sooner. One of the issues with this is getting the correct patients to the correct center which may involve a reorganization of internal systems.

The registry includes 984 patients from 55 sites from both academic and nonacademic centers in the US who received thrombectomy within 8 hours from symptom onset. The median time between emergency services and the start of the endovascular procedure was 152 minutes. Each hour of delay was associated with an 8.3% relative decline in good outcomes.

Rivaroxaban Promising Alternative to Fondaparinux for Superficial Vein Thrombosis

The SURPRISE study prospectively evaluated patients with superficial- vein thrombosis and compared rivaroxaban to the more costly injections of fondaparinux. This randomized trial was conducted at 27 centers in Germany. Patients (n=427) were randomly assigned to 10 mg oral rivaroxaban or 2.5 mg fondaparinux for 45 days. The primary efficacy outcome was a combination of symptomatic deep-vein thrombosis (DVT) or pulmonary embolism, SVT progression or recurrence, and all-cause mortality, within 45 days of treatment initiation. Seven (3%) of patients on rivaroxaban and four (2%) in the fondaparinux group experienced the primary outcome. There were no major bleeds were found in either group.

Fibrinogen Concentrate Won't Cut Blood Loss at Cardiac Surgery

A small randomized study has shown that fibrinogen concentrate infusion in cardiac-surgery patients did not have a significant difference in blood loss when compared to a placebo. There may be a benefit in the postoperative period. The study randomized 120 patients undergoing CABG to receive either fibrinogen concentrate or a placebo, with a bypass time of 200 minutes. Blood loss was determined during the period of intervention and closure of the chest as loss between 60mL and 250mL or greater. There was no significant difference of blood loss between groups. The mean dose of fibrinogen concentration entering ICU was 3.1 g vs. 1.7 g/L in the placebo group. Post surgery (24 hours) fibrinogen concentrates were 3.3 g/L versus 3.1 g/L in the placebo group. More adverse events were seen in the fibrinogen group when compared to the placebo group; 4 strokes vs. 2, 3 MI vs 1 and 2 deaths vs none respectively. However, fewer blood products were used in the fibrinogen group versus placebo.

Vast Majority of Patients With AF Receive Suboptimal Anticoagulation

Patients with AF appear to not be receiving optimal oral anticoagulant treatment while others do not take prescribed OACs contributing to higher stroke rates. Those patients who did take NOAC or therapeutic warfarin who did have strokes, were less severe with lower mortality rates. If guidelines for anticoagulants were better followed, up to 88,000 strokes could be prevented. Of the patients studied- 40% were taking antiplatelet medication, 30% had no antithrombotic medications and 14% were on subtherapeutic warfarin, with 8%. Additionally, patients who did not take their prescriptions were also investigated. This showed that 36% of patients on dabigatran and 32% of patients on rivaroxaban were no longer taking them 6 months after being prescribed. These patients had an 80% increased risk for stroke or death. Since NOACs do not need to be monitored, this may contribute to noncompliance, since no one is reminding them to take their medication.

Analyses Signal NOAC Benefit in Uncharted AF Populations

In the analysis of the ENGAGE AF-TIMI 48 trial, edoxaban was found to be a good alternative to warfarin in individuals with AF and bioprosthetic valves. Previously, NOACS were not recommended in this cohort of patients due to the lack of data. This study included approximately 189 patients. In 2.8 years of follow up, those treated with a high dose had similar rates of stroke or systemic embolism and major bleeding in comparison with warfarin. Coronary events was halved in these patients form 11.07% to 4.32% with high doses of edoxaban.

NOACs Are Favored Over Warfarin: I'm (Almost) Okay With That

According to a registry study GLORIA-AF, the choice for anticoagulants has shifted from warfarin to the NOAC drugs, with prescriptions for NOACs outnumbering warfarin 48% to 32%. The reasons seem to be ease of use, no monitoring and no interaction with drugs. Trials have shown that NOACs were as good or better than warfarin, which was then supported by real world data. However there are still some concerns with this finding in particular with the information, limitations and bias in trials. This included research misconduct in which dabigatran bleeding risks information was concealed. Other studies had questionable practices and even falsification of data.

Subdural Hematoma Rates Rise With Higher Antithrombotic Use

It has been observed that with the increased utilization of antithrombotic drugs the incidence of subdural hematoma has also increased in particular in patients >/=75 years of age and on a VKA. This conclusion came from regional and national data looking at over 10000 patients. Noted in that cohort, the patients with subdural hematoma, 47.3% were using antithrombotic medications. The study demonstrated that low-dose aspirin was associated with a small risk for subdural hematoma; use of clopidogrel and a direct oral anticoagulant (DOAC), with a moderate risk; and use of a VKA, with a higher risk, with the highest risk being in patients on VKA and an antiplatelet drug. Caution should be used when prescribing these drugs and treatments should not be used for longer than needed.

Simple, Five-Item Risk Score May Predict Early Post-PCI Bleeding Risk

A scoring system for dual antiplatelet therapy has been developed called the PRECISE-DAPT for patients on aspirin and P2Y12. There were 5 predictors identified as out of hospital TINI risk predictors which includes: previous bleeding, age, white blood cell count, baseline hemoglobin and creatinine clearance. This scoring system as opposed to others, provides validation and the ability to affect treatment decisions on DAPT length of use and balancing the risk between bleeding and ischemic events. Most patients (88%) received DAPT which included aspirin and clopidogrel, however for acute coronary syndrome prasugrel and ticagrelor are recommended. The study also noted a significant increase in bleeding on patients with long term 12-24 months versus a short duration of 3-6 months of DAPT. However, longer duration reduced ischemic end point of MI, stent thrombosis and stroke. While the scoring system can improve the accuracy of clinical decision, case by case judgement still needs to be considered.

No Benefit of Hemostatic Therapy in Patients With 'Spot Sign' ICH

There is no effective treatment in patients with intracerebral hemorrhage. Two trials SPOTLIGHT and STOP-IT used computed tomographic angiography (CTA) to recruit patients by looking for a bright area of contrast or a spot sign. This bright area indicates active bleeding along with predicting hematoma expansion and clinical deterioration. This method of detection was investigated too implement treatment quickly at an early stage when the bleed is still small. The trials were stopped due to poor recruitment. There was no significant benefit of FVII on the primary or secondary outcome. The data does support using the spot sign as a clinical tool in the ED.

EINSTEIN CHOICE: Rivaroxaban Beats Aspirin for VTE Recurrence

The Einstein choice trial showed that rivaroxaban was more effective than aspirin in preventing VTE post 6-12 months of therapy, without an increased risk of bleeding. This was the first study to compare the safety and effectiveness of rivaroxaban and aspirin. The role of the DOAC is safe without any increased risk of bleeding. There was no significant difference in major bleeding between the three groups, occurring in 0.5% of rivaroxaban 20-mg patients, 0.4% of rivaroxaban 10-mg patients, and 0.3% of those receiving aspirin. Patients in this study were younger than typical VTE patients therefore results may not be applicable to older patients.

Additionally, patients were only treated for up to 12 months, and may require longer treatments. Also, a follow up study will be performed to see if low dose rivaroxaban is equally effective.


Use of Oral Anticoagulant Therapy in Older Adults With Atrial Fibrillation After Acute Ischemic Stroke

Emer R. McGrath, MB, PhD; Alan S. Go, MD; Yuchiao Chang, PhD; Leila H. Borowsky, MPH; Margaret C. Fang, MD, MPH; Kristi Reynolds, PhD, MPH; Daniel E. Singer, J Am Geriatr Soc. 2017;65(2):241-248.


Objective: To explore barriers to anticoagulation in older adults with atrial fibrillation (AF) at high risk of stroke and to identify opportunities for interventions that might increase use of oral anticoagulants (OACs).

Design: Retrospective cohort study.

Setting: Two large community-based AF cohorts.

Participants: Individuals with ischemic stroke surviving hospitalization (N = 1,405, mean age 79).

Measurements: Using structured chart review, reasons for nonuse of OAC were identified, and 1-year poststroke survival was assessed. Logistic regression was used to identify correlates of OAC nonuse.

Results: Median CHA2DS2-VASc score was 5, yet 44% of participants were not prescribed an OAC at discharge. The most-frequent (nonmutually exclusive) physician reasons for not prescribing OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), participant or family refusal (14.9%), older age (11.0%), and dementia (9.4%). Older age (odds ratio (OR) = 8.96, 95% confidence interval (CI) = 5.01-16.04 for aged ≥85 vs <65) and disability (OR = 12.58, 95% CI = 5.82-27.21 for severe vs no deficit) were the most-important independent predictors of nonuse of OACs. By 1 year, 42.5% of those not receiving an OAC at discharge had died, versus 19.1% of those receiving an OAC (P < .001), far higher than recurrent stroke rates.

Conclusion: Despite very high stroke risk, more than 40% of participants were not discharged with an OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These individuals' high 1-year mortality rate confirmed their high level of comorbidity. To improve anticoagulation decisions and outcomes in this population, future research should focus on strategies to mitigate fall risk, improve assessment of risks and benefits of anticoagulation in individuals with AF, and determine whether newer anticoagulants are safer in complex elderly and frail individuals.