November 2021: New In Coagulation

by Donna Castellone, MS, MT (ASCP) SH • November 17, 2021

Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica.

Combo Thrombectomy Approach No Better for Large Vessel Strokes

Combo Thrombectomy Approach No Better for Large Vessel Strokes | MedPage Today

The ASTER2 trial looked at adding contact aspiration to the initial approach with a stent retriever for large vessel acute ischemic stroke. The study included 408 adults with suspected acute ischemic stroke due to large vessel occlusion in the anterior circulation seen within 8 hours of symptom onset. Centers in France were highly experienced with both contact aspiration and stent techniques. Patients were randomized to either procedure as the initial mechanical thrombectomy approach. Any approved device could be used, but balloon guided catheter was mandatory.

A high level of reperfusion was achieved at the end of the endovascular procedure in 64.5% of patients treated with contact aspiration and stent retriever combined compared with 57.9% with stent retriever use alone. Stroke severity at 24 hours, early and 1 year disability and health related quality of life were similar between groups as well. Safety outcomes were comparable including 90 day mortality and ICH or new embolization. There were fewer cases of type 2 parenchymal hematoma in the combination group.



The Cost of Blood Platelets Is About to Surge

The Cost of Blood Platelets Is About to Surge | MedPage Today

Platelet prices are increasing. Platelets were initially stored in refrigerators to inhibit or slow bacterial growth, but in 1969 hospitals began storing them at room temperature. This resulted in longer platelet survival in a patient post transfusion. However, there have been numerous cases of fatalities due to bacterial contamination of blood platelets and regulatory action to reduce or prevent this has been very slow. In 2019 the FDA issues final guidance outlining recommendations to prevent the transmission of bacteria by platelet transfusion however there are issues with the guidance. The FDA approved large volume delayed sampling without statistically significant date that demonstrated efficacy compared to the current practice of 24-hour culture testing. Compliance must occur by October 1. Compliance using pathogen reduction technology involved introducing a chemical into the bag of platelets and exposing it to UV light. This is the most expensive option and now relies on only one strategy and is risky to have only one choice allowing market dominant suppliers.



Blood marker could help ID those at risk of debilitating peripheral artery disease

Blood marker could help ID those at risk of debilitating peripheral artery disease | MLO

Increased levels of the enzyme circulating fatty acid synthase (cFAS) that manufactures saturated fatty acids. The study conducted by researches at Washington University School of Medicine in St. Louis found that this may also circulate in the bloodstream and not only in blood cells. This may play an important role in the plaque formation found in cardiovascular disease.

Peripheral artery disease (PAD) can lead to chronic limb threatening ischemia. Patients require vascular surgery to improve blood flow. Severe cases may result in amputation. High levels of cFAS could be an accurate predictor of risk for PAD.

Blood was collected from 87 patients prior to undergoing surgery for limb threatening ischemia and found that levels of cFAS were independently associated with this disease. When this was combined with Type 2 diabetes and smoking the presence of the disease could predict the presence of disease with 83% accuracy. It was also noted that cFAS circulates while bound to LD however the issue may be the enzymes that are attached to the LDL.

Investigation of cFAS as a target of a new drug therapies to hinder plaque buildup is ongoing.



Saccular Aneurysm No Bar to Thrombolysis in Ischemic Stroke

Saccular Aneurysm No Bar to Thrombolysis in Ischemic Stroke | Medscape

A study looked at the frequency of ICH following intravenous thrombolysis (IVT) in 3953 ischemic stroke patients over 15 years. It included 132 patients who had a total of 155 aneurysms (144 saccular and 14 fusiform). There was no rupture in 141 saccular UIAs suggesting IVT is safe supporting it is not contraindicated in these patients. Large fusiform aneurysms can rupture post thrombolysis if patients are treated with anticoagulants. IV tissue plasminogen activator (tPA) is the only FDA approved medication. However the study demonstrated that rupture of a saccular aneurysm from IV tPA was uncommon whereas fusiform posterior aneurysms are different in pathophysiology and in outcomes.



CVST After COVID-19 Vaccine: New Data Confirm High Mortality Rate

CVST After COVID-19 Vaccine: New Data Confirm High Mortality Rate | Medscape

A series of cases of cerebral venous sinus thrombosis (CVST) has been linked to the adenoviral vector vaccines that shows the severity of the reactions and the high mortality rate. This condition is much more severe when associated with COVID-19 vaccination with a higher rate of ICH, coma and mortality. Data has been compiled from 19 countries.

CVST has been linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia. In 116 patients, 78 had thrombosis with TTS and were classified as having a vaccine related adverse event. Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine Up to 24% were comatose at presentation with up to 68% having an ICH and 36% having concomitant thromboembolism, up to 47% died during hospitalization. When these patients were compared with 38 patients who had CVST but no concomitant thrombosis and thrombocytopenia and also 207 patients with CVST prior to the pandemic, the rate of mortality in this group was 5% in those who did not have TTS and 3.9% in the prepandemic group. Female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn't allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White.

CVST can also occur in the SARs-CoV-2 infection, but the vaccine associated CVST id different in that this occurrence does not present itself with thrombocytopenia. However it is still associated with a poor prognosis, but appears to have more with the underlying disease.

Currently, fewer cases of vaccine related CVST are being reported. These vaccines are being used in South America and Asia. It is possible that because these countries are vaccinating their elderly who are not so susceptible to this side effect, or may be due to some environmental or genetic factor yet to be discovered.



EU Finds J&J COVID Shot Possibly Linked to Another Rare Clotting Condition

EU Finds J&J COVID Shot Possibly Linked to Another Rare Clotting Condition | Medscape

Drug regulators from the European Union identified a possible link between rare cases of VTE with the J&J shot and recommended this be listed as a side effect. Also recommended was that immune thrombocytopenia (ITP) also be added as an adverse reaction to both J&J and AstraZeneca's vaccine. Both vaccines have been associated with a combination of blood clotting and thrombosis with thrombocytopenia syndrome (TTS). Both vaccines are adenovirus vectors. The VTE condition added to the J&J label was separate from TTS.



Heparin of No Benefit to IVF Patients With Recurrent Implantation Failure

Heparin of No Benefit to IVF Patients With Recurrent Implantation Failure | MedPage Today

A randomized control prospective trial included 165 women ages 18-40 who had at least three consecutive failed IVF cycles. Patients were randomized to a heparin group (n=76) and the rest in the control group (n=73). They were randomized to receive luteal progesterone supplement either alone or with bemiparin (LMWH) on the evening of embryo transfer up until the day of their pregnancy test. If the pregnancy test was positive, LMWH was continued until 12 weeks of pregnancy. Results showed that in (patients who received LMWH implantation failures did not have improved live birth rates after a single embryo transfer compared with those who received no treatment ( 15.6% vs 15.2%.

There was also no significant differences in pregnancy rate at 8 weeks' gestation (34.7% vs 39.4%) or 12 weeks' gestation (28% vs 32.4%). The difference in overall pregnancy rate was 9.3% in favor of the control group (40% vs 49.3%), which was not statistically significant.

There were no major demographic, clinical, type of infertility differences between the two groups nor were their significant differences in the number or oocytes, embryos transferred or differences in maternal adverse events as well as obstetric complications. No significant bleeding events occurred in those who received heparin.



Antithrombotic Therapy Not Warranted in COVID-19 Outpatients

Antithrombotic Therapy Not Warranted in COVID-19 Outpatients | Medscape

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

A randomized, double blind placebo controlled trial conducted across 52 US sites, ACTIV-4B Outpatient Thrombosis trial compared anticoagulant and antiplatelet therapy among 7000 symptomatic but stable outpatients with COVID-19. Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Endpoint was either all cause mortality, symptomatic venous or arterial thromboembolism, MI, stroke of hospitalization due to cardiovascular or pulmonary causes.

Median age was 54 with 59% of participants being female. The median time from diagnosis to randomization was 7 days with initiation of study medication after randomization at 3 days. Primary endpoints occurred in 1 patient in the aspirin group, 1 in the 2.5mg apixaban group, 2 in the 5 mg apixaban group and 1 in the placebo group. There were no major bleeding events and safety and efficacy results were similar in all patient groups.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

Considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended. ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized.



D-dimer Unreliable for Ruling Out Pulmonary Embolism in COVID-19

D-dimer Unreliable for Ruling Out Pulmonary Embolism in COVID-19 | Medscape

The D-dimer assay has been used with clinical prediction scores to rule out PE. In COVID-19 patients, plasma D-dimer levels of 0.05 ug/ml or greater are seen in up to 92.3% of COVID 19 patients, 0.05 is the cutoff point for diagnosis. The high pre-test probability of PE and low specificity observed in this study suggests that the use of D-dimer levels to exclude PE in this population appears to be inappropriate and have limited clinical utility.

In a review of 1541 hospitalized COVID patients and 287 underwent computed tomography pulmonary angiography (CTPA), 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization. When comparing D-dimer levels to CTPA, thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 µg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).

The median D-dimer values were 1.0 µg/mL for 250 patients without PE, and 6.1 µg/mL for 37 patients with PE.D-dimer values ranged from 0.2 µg/mL to 128 µg/mL among patients without PE, and from 0.5 µg/mL to more than 10,000 µg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 µg/mL vs 1.2 µg/mL; P < .001).





Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit

Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit | Medscape

Shimena R. Li, MD; Francis Guyette, MD, MPH; Joshua Brown, MD, MSc; Mazen Zenati, MD, MPH, PhD; Katherine M. Reitz, MD, MSc; Brian Eastridge, MD; Raminder Nirula, MD, MPH; Gary A. Vercruysse, MD; Terence O'Keeffe, MD; Bellal Joseph, MD; Matthew D. Neal, MD; Brian S. Zuckerbraun, MD; Jason L. Sperry, MD, MPH

Annals of Surgery. 2021;274(3):419-426.


Objective: We sought to characterize the timing of administration of prehospital tranexamic acid (TXA) and associated outcome benefits.

Background: TXA has been shown to be safe in the prehospital setting post-injury.

Methods: We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1 hour (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1 hour (DELAYED). We included patients with a shock index of >0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships.

Results: EARLY and DELAYED patients had similar demographics, injury characteristics, and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N = 238, log-rank chi-square test, 4.99; P = 0.03) with no separation for DELAYED patients (N = 238, log-rank chi-square test, 0.04; P = 0.83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.19–0.65, P = 0.001] with no independent survival benefit found in DELAYED patients (HR 1.00, 95% CI 0.63–1.60, P = 0.999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo.

Conclusions: Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirement.



COVID-19 Pandemic and Quality of Care and Outcomes of Acute Stroke Hospitalizations

COVID-19 Pandemic and Quality of Care and Outcomes of Acute Stroke Hospitalizations | Medscape

Xin Tong, MPH; Sallyann M. Coleman King, MD; Ganesh Asaithambi, MD; Erika Odom, PhD; Quanhe Yang, PhD; Xiaoping Yin, MS; Robert K. Merritt, MS

Prev Chronic Dis. 2021;18(8):e82


Introduction: Studies documented significant reductions in emergency department visits and hospitalizations for acute stroke during the COVID-19 pandemic. A limited number of studies assessed the adherence to stroke performance measures during the pandemic. We examined rates of stroke hospitalization and adherence to stroke quality-of-care measures before and during the early phase of pandemic.

Methods We identified hospitalizations with a clinical diagnosis of acute stroke or transient ischemic attack among 406 hospitals who contributed data to the Paul Coverdell National Acute Stroke Program. We used 10 performance measures to examine the effect of the pandemic on stroke quality of care. We compared data from 2 periods: pre–COVID-19 (week 11–24 in 2019) and COVID-19 (week 11–24 in 2020). We used χ 2 tests for differences in categorical variables and the Wilcoxon–Mann–Whitney rank test or Kruskal–Wallis test for continuous variables.

Results: We identified 64,461 hospitalizations. We observed a 20.2% reduction in stroke hospitalizations (from 35,851 to 28,610) from the pre–COVID-19 period to the COVID-19 period. Hospitalizations among patients aged 85 or older, women, and non-Hispanic White patients declined the most. A greater percentage of patients aged 18 to 64 were hospitalized with ischemic stroke during COVID-19 than during pre–COVID-19 (34.4% vs 32.5%, P < .001). Stroke severity was higher during COVID-19 than during pre–COVID-19 for both hemorrhagic stroke and ischemic stroke, and in-hospital death among patients with ischemic stroke increased from 4.3% to 5.0% (P = .003) during the study period. We found no differences in rates of receiving care across stroke type during the study period.

Conclusion Despite a significant reduction in stroke hospitalizations, more severe stroke among hospitalized patients, and an increase in in-hospital death during the pandemic period, we found no differences in adherence to quality of stroke care measures.