July 2024: New In Coagulation
by Donna Castellone, MS, MT(ASCP)S • July 10, 2024
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Sugar Substitute Linked to Heart, Thrombotic Risk
Metabolomic studies have linked the low calorie sweetener xylitol to increased cardiovascular and thrombotic risk by 57-80% higher after adjustment for variables. Xylitol is a sugar alcohol found naturally in strawberries, spinach, cauliflower, but it is commercially made from corncobs, birch trees or genetically engineered bacteria. It is used in sugarless gun, breath mints and other processed foods.
Animal model studies showed it raised platelet reactivity and in vivo thrombosis formation. This was demonstrated in 10 healthy individuals who consumed a typical dose of xylitol sweetened drink rapidly. Every measure of platelet activation in every volunteer was impacted when compared to those drinking a sugar sweetened beverage. The initial benefit of these sweeteners was the reduction of excessive sugar intake, reducing weight gain and cardiovascular risk and used in the group at risk for obesity and diabetes. It also extends to other sugar alcohols such as erythritol when healthy volunteers were challenged with an erythritol sweetened drink.
Increased platelet adhesion under flow was seen in experiments with isolated human platelet, platelet rich plasma, whole blood and animal models. Additionally, augmented activation of glycoprotein IIb/IIIa and expression of p-selectin was observed using flow post addition of xylitol. This may warrant a closer look at sugar alcohol sweeteners as a possible cardiovascular hazard and the impact of chronic exposures.
Blood Test a 'Game Changer' for Faster Diagnosis, Treatment of LVO Stroke
Treatment of large vessel occlusion (LVO) stroke may be expedited using clinical scoring (FAST-ED) (score, > 2) and blood testing. Using cutoff levels of two blood biomarkers, glial fibrillary acidic protein (GFAP; 213 pg/mL) and the D-dimer (600 ng/mL) investigators were able to detect LVOs with 81% sensitivity and 93% specificity within 6 hours of onset of symptoms. GFAP has been linked to brain bleeds and traumatic brain injury and can be used to detect intracerebral hemorrhage.
Acute LVO is one of the most treatable stroke types due to endovascular thrombectomy (EVT), but this requires specialized equipment and teams found mostly at stroke centers. Early identification of LVO is crucial. The TIME trial was conducted to assess the sensitivity and specificity of the biomarkers. This was an observational prospective cohort trial on consecutive patients referred for suspected stroke and time from symptom onset was under 18 hours. Clinical data, hematology results, imaging studies (LVO vs non-LVO), ischemic stroke, hemorrhagic stroke or TIA. They were evaluated with FAST-ED, RACE, and Emergency Medical Stroke Assessment.
Of 323 patients in the final study sample, 29 (9%) had LVO ischemic stroke, and 48 (15%) had non-LVO ischemic stroke. Another 13 (4%) had hemorrhagic stroke, 12 had TIA (3.7%), and the largest proportion of patients had stroke mimic (n = 220; 68%), which included encephalopathy, hyperglycemia, hypertensive emergency, migraine, posterior reversible encephalopathy syndrome, and undetermined. In patients with LVO ischemic stroke the concentration of D-dimer was significantly higher in these patients, and GFAP was also significantly increased in patients with hemorrhagic stroke. In combination with the scoring system these results showed a specificity of 94% and sensitivity of 71%. When data was analyzed for just patient identified within 6 hours of symptoms results showed a specificity of 93% and a sensitivity of 81%. Having a tool that can identify non hemorrhagic LVO versus hemorrhage stroke is essential.
Thrombectomy Less Beneficial in Large-Core Stroke
A randomized trial, SELECT2 showed that patients with large-core ischemic stroke benefit with thrombectomy when compared with medical management. In a secondary analysis of the data, it shows that patients with a volume of ≥26mL rated as severe hypodensity within their lesions indicating more evolved tissue injury, the benefit from thrombectomy is not certain and increases the risk for hemicraniectomy. Data was used from 322 patients to determine if the occurrence of severe hypodensity modified the effect of thrombectomy.
Results showed that as hypodensity increased (≥ 26 mL) the endovascular therapy decreased and was no longer associated with a favorable outcome compared with medical management. A previous analysis of this trial also showed that patients with large core strokes treated with thrombectomy, clinical outcomes worsened as presenting ischemic injury estimates increased.
The results suggest the possibility of excluding patients who are least likely to benefit, however confirmation is needed along with further research.
Mechanical Thrombolysis Effective in Pulmonary Embolism
The AlphaVac System (APEX-AV) was FDA approved as a catheter-directed mechanical PE extraction system. The Acute Pulmonary Embolism Extraction Trial treated 122 patients. This was a prospective, single arm, multicenter adult trial in patients with acute intermediate-risk of PE, 14 days duration confirmed by CT. The procedure took 37.2 ± 17.7 minutes.
The AlphaVac Ssystem (APEX-AV) was FDA approved as a cathertercatheter-directed mechanical PE extraction system. The Acute Pulmonary Embolism Extraction Trial treated 122 patients. This was a prospective, single arm, multicenter adult trial in patients with acute intermediate-risk of PE, 14 days duration confirmed by CT. The procedure took 37.2 ± 17.7 minutes.
There are several comparative trials in the pipeline evaluating catheter directed thrombolysis including: PEERLESS trial is comparing a flow treatment device with catheter-directed thrombolysis, HI-PEITHO trial is comparing it with anticoagulation alone, and PE-TRACT study is comparing catheter-directed thrombolysis with anticoagulation in patients with large clots and normal blood pressure.
Why Are We Undertreating So Many Pulmonary Embolisms?
Only a small fraction of patients with PE are receiving advanced therapies based on big data analysis. The role of invasive therapy in high-intermediate risk patients is unclear since there are no Class 1 guideline recommendation but there is a trend that these patients are being treated invasively.
Analysis of data was mined from Truveta which is a collective of health systems that provide regulatory grade EH data for research. It included 105 million diagnoses of which 435,296 were for PE and of those 2072 or 0.48% of patients received advanced therapy. Patients were treated with ultrasound-assisted catheter-directed thrombolysis or mechanical thrombectomy. White patients were most likely to receive advanced therapy versus black patients (0.5% vs 0.37%) and women less than men (0.41% vs 0.55%). However, bleeding events occurred more in white patients and women. This study highlights the potential of big data to identify disparities in care and outcomes.
Late-Window Tenecteplase for Stroke Works When Thrombectomy's Out of the Question
The TRACE-III trial determined that late administration of tenecteplase improved clinical outcomes when thrombectomy was not immediately available. Tenecteplase is a thrombolytic agent that is given as a single bolus which makes it more popular than alteplase which is given as an infusion. The benefit was seen in LVO ischemic stroke when given in place of standard therapy alone such as antiplatelets. The trial was conducted at 58 centers in China and included 516 patients (median age 67 and 68% male) who presented within 4.5-24 hours after they were known to be well. Eligible patients were adults with LVO of the middle cerebral artery or internal carotid artery based on CT or MRI angiography with salvageable brain tissue.
Using Tenecteplase in patients who do not have access to thrombectomy could improve functional outcomes in patients on an international scale. When compared to control groups the safety outcomes of TRACE-III were similar (13.3% and 13.1%) however symptomatic ICH within 36 hours occurred in excess for the Tenecteplase group (3% vs 0.8%). Prior to using thrombolytic agents, patients should be evaluated for hypodensity on CT.
rFVIIa and Management of Severe Postpartum Hemorrhage Clinical Practice Guidelines (2024)
The Journal of Maternal-Fetal & Neonatal Medicine published clinical practice guidelines on the use of recombinant factor VIIa for the management of severe postpartum hemorrhage. It can be considered after first-line measures to control bleeding. First-line measures include uterotonic agents; tranexamic acid; intravenous administration of fluid, blood, blood products, and fibrinogen; laceration suturing; curettage; and uterine tamponade. After a cesarean section rFVIIa can be given after first line surgical measures such as uterine compression sutures, vessel ligation, and uterine tamponade, have failed to control bleeding. If bleeding is non-severe it can be used in conjunction with uterine artery embolization. It can also be administered to a patient with severe postpartum hemorrhage prior to a patient being transferred from a birthing unit to a larger medical center.
Pediatric Immune Thrombocytopenia Clinical Practice Guidelines (AIEOP, 2024)
Italian Association of Pediatric Hematology and Oncology
ITP is a diagnosis of exclusion. Findings that support the diagnosis include the following:
- Abrupt onset of symptoms
- Recent viral infection
- Recent vaccination (particularly live vaccine)
- Isolated thrombocytopenia (platelet count < 100 × 109/L), with normal red and white blood cell counts, except for bleeding-related anemia
- Previous normal platelet count
- Normal or slightly elevated mean platelet volume
A bleeding assessment tool should be used to grade the severity of bleeding (Buchanan-Adix score or the SMOG (skin, mucosae, and organs, with gradation of severity) score) and should be used on follow-up visits to evaluate response to therapy. In children with no or mild bleeding, they are managed by observation, pharmacologic treatment and hospitalization may be appropriate in select cases. Those with severe spontaneous mucosal bleeding at onset of ITP should be treated. First line treatment could include IV immunoglobulin or intermediate to high dose corticosteroids. Second line treatments include additional first line therapy in combination with thrombopoietin receptor agonists (eg, romiplostim), Immunosuppressive drugs (eg, mycophenolate mofetil, sirolimus), & Rituximab.
Splenectomy is rarely indicated and should only be considered in children older than 5 who present with thrombocytopenia related bleeding despite all medical therapy and whose life is at risk or quality of life is impaired.
Anticoagulation Shows No Benefit in Preventing Second Stroke
Patients who have one stroke are thought to be at a higher risk of a subsequent stroke. Even when treated with edoxaban, there was no risk reduction for an additional stroke, however the risk for major bleeding quadrupled. These findings were a result of a subanalysis of the NOAH-AFNET 6 trial. This included 253 patients who presented with a stroke or TIA as well as device detected AF from the total enrolled 2536 patients. These enrolled patients were 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes. Patients were randomized to either edoxaban or no anticoagulation with results demonstrating there was no significant impact on stroke rate or other cardiovascular outcomes in the edoxaban group.
Subanalysis showed the primary outcome of stroke, systemic embolism and cardiovascular death were similar 11.5% in the edoxaban versus 12.2% in the no-anticoagulation groups. While the rate of recurrent stroke was 3.3% and 4.6% respectively. There were also eight cardiovascular deaths in each group. However there were significantly higher rates of major bleeding – 8 of 10 patients who presented with a major bleed were on edoxaban.
Stroke Risk Scale Helps ID Candidates for Anticoagulation
A stroke risk calculator can help electrophysiologists and cardiologists distinguish which patients with subclinical AF are most likely to benefit from anticoagulation from those who probably wouldn't. CHA2DS2-VASc is a stroke risk assessment tool for people with AF using a scale of 0-9, 0 the lowest risk. It is based on age, sex and medical history. It can be used to put patients into three unique categories where the recommendations are to treat, don't treat, or to consider treatment.
Results were presented based on the subanalysis of ARTESiA trial which compared apixaban and aspirin. This subanalysis broke out stroke/systemic embolism and major bleed risk by subgroups with a score of less than or greater than 4. Results pointed to a score of 4 being the point at which doctors should consider anticoagulation. Those with a score of 4 had 2.3 fewer strokes per 100 patients with no excessive bleeding, and those with a score of <1 presented with a risk of less than 1% and should not receive OAC.
Novel Anti-CD38 Drug Shows Promise for Immune Thrombocytopenia
Immune Thrombocytopenia (ITP) is an autoimmune disease that is caused by autoantibody-mediated platelet destruction. Clinical manifestations include cutaneous and mucosal bleeding. Most fatal bleeding occurs when platelets fall below 30 x 109/L.
A small phase I/II single-arm Chinese study of 22 ITP patients (median age 36, 73% female) showed that an investigational anti-CD38 monoclonal antibody (CM313) increased platelets in ITP to prevent bleeding. All but one patient had two or more consecutive platelet counts of at least 50 × 109/L during the 8-week treatment period. Concurrent therapy with either thrombopoietin-receptor agonists or glucocorticoids was allowed. The cumulative response period was 23 weeks. AE were low grade and infusion related. CM313 was safe, rapid and sustained efficacy in 95% of patients. The targeted therapy induces potent killing of tumor cells through Fc receptor-dependent mechanisms.
The percentage of patients with bleeding decreased from 68% at baseline to 5-10% at weeks 8 and 24 respectively. CM313 infusions effectively suppressed the proliferative function of lymphocytes and reduced serum IgG levels, indicating it's ability to down regulated autoantibody production by clearing plasma cells and maintain a long-term response.
JOURNAL CLUB
Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk: The OPT-BIRISK Randomized Clinical Trial
Yi Li, MD; Jing Li, MD; Bin Wang, MD; et alQuanmin Jing, MD; Yujie Zeng, MD; Aijie Hou, MD; Zhifang Wang, MD; Aijun Liu, MD; Jinliang Zhang, MD; Yaojun Zhang, MD; Ping Zhang, MD; Daming Jiang, MD; Bin Liu, MD; Jiamao Fan, MD; Jun Zhang, MD; Li Li, MD; Guohai Su, MD; Ming Yang, MD; Weihong Jiang, MD; Peng Qu, MD; Hesong Zeng, MD, PhD; Lu Li, MD; Miaohan Qiu, MD; Leisheng Ru, MD; Shaoliang Chen, MD; Yujie Zhou, MD; Shubin Qiao, MD; Gregg W. Stone, MD; Dominick J. Angiolillo, MD, PhD; Yaling Han, MD; for the OPT-BIRISK Investigators
Abstract
Importance Purinergic receptor P2Y12 (P2Y12) inhibitor monotherapy after a certain period of dual antiplatelet therapy (DAPT) may be an attractive option of maintenance antiplatelet treatment for patients undergoing percutaneous coronary intervention (PCI) who are at both high bleeding and ischemic risk (birisk).
Objective To determine if extended P2Y12 inhibitor monotherapy with clopidogrel is superior to ongoing DAPT with aspirin and clopidogrel after 9 to 12 months of DAPT after PCI in birisk patients with acute coronary syndromes (ACS).
Design, Setting, and Participants This was a multicenter, double-blind, placebo-controlled, randomized clinical trial including birisk patients with ACS who had completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months at 101 China centers between February 2018 and December 2020. Study data were analyzed from April 2023 to May 2023.
Interventions Patients were randomized either to clopidogrel plus placebo or clopidogrel plus aspirin for an additional 9 months.
Main Outcomes and Measures The primary end point was Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularization). The primary end point was tested for superiority, and the MACCE end point was tested for sequential noninferiority and superiority.
Results A total of 7758 patients (mean [SD] age, 64.8 [9.0] years; 4575 male [59.0%]) were included in this study. The primary end point of BARC types 2, 3, or 5 bleeding occurred in 95 of 3873 patients (2.5%) assigned to clopidogrel plus placebo and 127 of 3885 patients (3.3%) assigned to clopidogrel plus aspirin (hazard ratio [HR], 0.75; 95% CI, 0.57-0.97; difference, −0.8%; 95% CI, −1.6% to −0.1%;
Conclusions and Relevance Among birisk patients with ACS who completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months before randomization, an extended 9-month clopidogrel monotherapy regimen was superior to continuing DAPT with clopidogrel in reducing clinically relevant bleeding without increasing ischemic events.
Differences in quality of anticoagulation care delivery according to ethnoracial group in the United States: A scoping review
Abstract
Anticoagulation therapy is standard for conditions like atrial fibrillation, venous thromboembolism, and valvular heart disease, yet it is unclear if there are ethnoracial disparities in its quality and delivery in the United States. For this scoping review, electronic databases were searched for publications between January 1, 2011 – March 30, 2022. Eligible studies included all study designs, any setting within the United States, patients prescribed anticoagulation for any indication, outcomes reported for ≥ 2 distinct ethnoracial groups. The following four research questions were explored: Do ethnoracial differences exist in 1) access to guideline-based anticoagulation therapy, 2) quality of anticoagulation therapy management, 3) clinical outcomes related to anticoagulation care, 4) humanistic/educational outcomes related to anticoagulation therapy. A total of 5374 studies were screened, 570 studies received full-text review, and 96 studies were analyzed. The largest mapped focus was patients’ access to guideline-based anticoagulation therapy (88/96 articles, 91.7%). Seventy-eight articles made statistical outcomes comparisons among ethnoracial groups. Across all four research questions, 79 articles demonstrated favorable outcomes for White patients compared to non-White patients, 38 articles showed no difference between White and non-White groups, and 8 favored non-White groups (the total exceeds the 78 articles with statistical outcomes as many articles reported multiple outcomes). Disparities disadvantaging non-White patients were most pronounced in access to guideline-based anticoagulation therapy (43/66 articles analyzed) and quality of anticoagulation management (19/21 articles analyzed). Although treatment guidelines do not differentiate anticoagulant therapy by ethnoracial group, this scoping review found consistently favorable outcomes for White patients over non-White patients in the domains of access to anticoagulation therapy for guideline-based indications and quality of anticoagulation therapy management. No differences among groups were noted in clinical outcomes, and very few studies assessed humanistic or educational outcomes.
Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors
Mark Goldin, Kolton Smith, Ioannis Koulas, Tungming Leung, Mayuri Ravi, Sanjit Parhar, Sejal Shah, Kayla Floyd, Lori Ohanesian, Rachel Bain, Daniella Defonte, Kanta Ochani, Amanda Lin, Bhumi Patel, Nikolaos Tsaftaridis, Jack Jnani, Alex C Spyropoulos
2024 May 13;8(2):e209-e215.2024 Apr.
Abstract
Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes.
Methods We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality.
Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR]: 108.0-337.0 minutes). Components were as follows: 72.5 minutes (IQR: 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR: 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR: 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval [CI]: 1.2-2.0,
Conclusions In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.
Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial
Martina B Goeldlin, Arsany Hakim, Mattia Branca, Stefanie Abend, Markus Kneihsl, Waldo Valenzuela Pinilla, Sabine Fenzl, Beata Rezny-Kasprzak, Roman Rohner, Daniel Strbian, Maurizio Paciaroni, Goetz Thomalla, Patrik Michel, Krassen Nedeltchev, Thomas Gattringer, Else Charlotte Sandset, Leo Bonati, Diana Aguiar de Sousa, P N Sylaja, George Ntaios, Masatoshi Koga, Zuzana Gdovinova, Robin Lemmens, Natan M Bornstein, Peter Kelly Mira Katan, Thomas Horvath, Jesse Dawson, Urs Fischer; ELAN Investigators
JAMA Neurol 2024 May 28:e241450.
Abstract
Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown.
Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation.
Design, setting, and participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis.
Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke.
Main outcomes and measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined.
Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters.
Conclusions and relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke.
Evaluation of Apixaban standard dosing in underweight patients with non-valvular atrial fibrillation: a retrospective cohort study
Khalid Al Sulaiman, Ohoud Aljuhani, Hadeel Alkofide, Manal A Aljohani, Hisham A Badreldin, Mahasen Al Harbi, Ghalia Aquil, Raghad Alhajaji, Rahaf A Alqahtani, Alaa Babonji, Maha Altuwayr, Asma A Alshehri, Mashael Alfaifi, Abdullah F Alharthi, Mohammed Alzahrani, Tareq Al Sulaiman, Nasser Alqahtani, Walaa A Alshahrani, Abdulmalik Al Katheri, Abdulkareem M Albekairy
Thromb J 2024 May 22;22(1):43.
Abstract
Background: Recent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg.
Methods: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study's primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate.
Results: A total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively).
Conclusion: This exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.
Evaluating Diagnostic Algorithms for Heparin-Induced Thrombocytopenia using Two Combined Automated Rapid Immunoassays
Anna-Lise Bissola, Yi Zhang, Madison Cranstone, Jane C Moore, Theodore E Warkentin, Donald M Arnold, Ishac Nazy
Semin Thromb Hemost 2024 May 11.
Abstract
Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder caused by antibodies against platelet factor 4 (PF4) and heparin complexes. Rapid immunoassays (IAs) for detection of these antibodies mark a milestone in HIT diagnosis, despite a higher false-positive rate compared with functional platelet-activation assays. However, combining different rapid IAs may help to improve their diagnostic specificity. Here, we compared the individual performance of the latex immunoturbidimetric assay (LIA; HemosIL HIT-Ab [PF4-H]; sensitivity 91.7%, specificity 68.4%) and chemiluminescence immunoassay (CLIA; HemosIL AcuStarHIT-Ab [PF4-H]; sensitivity 92.4%, specificity 85.8%) with their combined performance using two unique diagnostic algorithms in a single prospective cohort of suspected HIT patients. Using the simultaneous algorithm adapted from Warkentin et al, the combined LIA-CLIA had a sensitivity of 99.0% and specificity of 64.3%. The sequential algorithm adapted from Rittener-Ruff et al was applied in two theoretical scenarios to reflect real-world circumstances in diagnostic laboratories where access to clinical information is limited: (1) assuming all patients had an intermediate 4Ts score and (2) assuming all patients had a high 4Ts score. This algorithm correctly predicted HIT in 94.5% (high 4Ts) and 96.0% (intermediate 4Ts) and excluded HIT in 82.6% (high 4Ts) and 80.1% (intermediate 4Ts) of patients in either scenario, respectively. Although both combined algorithms improved diagnostic performance of individual IAs, the simultaneous algorithm showed fewer false predictions (7.9%) than the sequential algorithm (intermediate 4Ts: 37.6% and high 4Ts: 41.5%) and proved more practical as it does not rely on physician evaluations. Our findings highlight the importance of accounting for clinician and interlaboratory variability when evaluating diagnostic tests for HIT.
Changes in Time in Therapeutic Range Within a Warfarin Anticoagulation Clinic Following Introduction of Direct Oral Anticoagulants
Preethi Samuel , Kaitlyn Cassidy, Pauletta Lazarevskiy, Rebecca Cope
J Pharm Pract 2024 May 26:8971900241256779.
Abstract
Background: As direct oral anticoagulants (DOACs) have become widely recommended as first-line anticoagulation therapy, patients who remain on warfarin are likely those unable to afford, adhere to, or utilize DOAC therapy due to the presence of a contraindication. It is currently unknown how availability of DOACs have affected populations being managed at warfarin (VKA) anticoagulation clinics.
Methods: This was a retrospective chart review assessing warfarin-treated patients at an outpatient anticoagulation clinic. The primary endpoint was the 6-month time in therapeutic range (TTR) before and after DOACs were recommended as first-line therapy by clinical guidelines. Study periods were January to June 2015, before DOACs were recommended over VKA, and January to June 2022, when DOACs were often recommended over VKA. TTR, demographic changes, and the presence of contraindications to DOAC therapy in the clinic population between the two time periods were assessed.
Results: No difference in 6-month TTR was observed between study periods (59% in 2015 vs 63% in 2022;
Conclusion: Availability of DOACs did not seem to significantly affect the population or management of warfarin-treated patients at an outpatient anticoagulation clinic, however, contraindications and potential challenges to use of DOAC therapy are present in many patients.