November 2023: New In Coagulation
by Donna Castellone, MS, MT(ASCP)S • November 06, 2023
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Optimal Antiplatelet Regimen in "Bi-Risk" ACS?
A bi-risk patient is one that has a high risk of clinically relevant bleeding as well as a high risk of major adverse cardiac and cerebral events (MACCE). The OPT-BIRISK trial in 101 centers in China, of more than 7700 patients ( mean age 65, 41% were female) fell into this category. The primary endpoint was clinically relevant Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding, at 9 months after randomization. The patient criteria for having bi-risk ACS were: < 65 years old with at least one high-bleeding risk criterion and at least one high-ischemia risk criterion.65 to 78 years old with at least one high-bleeding risk criterion or at least one high-ischemia risk criterion > 75 years old. The patients had a mean high ischemic risk criteria of 3.2 and a mean high bleeding risk criteria of 1.4.
In these patients who had acute coronary syndrome who received a stent and completed 9-12 months of DAPT it was observed that those who de-escalated to clopidogrel alone versus clopidogrel and aspirin for 9 months had 25% less bleeding without an increased risk of ischemia. It is questioned that these results may not be applicable to non-Asian cohorts. It was also questioned if these patients may have been a low risk subset of bi-risk patients since more than 1000 patients did not have at least one high risk factor for bleeding or ischemia, nor clinical events in the past 9-12 months on DAPT. As a result, they were not truly high risk when they were randomized. But based on the demographics (65 years of age, 41% female, 52% diabetes, 18% MI history and 15% ischemic stroke) represent a large amount of patients seen in clinical practice.
Longer Edoxaban May Benefit Cancer Patients With Distal DVT
The ONCO-DVT trial looked 604 patients with active cancer and distal DVT. The mean age was 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%). The results showed the difference in patients with isolated distal DVT who received 12 months of edoxaban and few thrombotic events at 1 year versus those at 3 month without a significant increase in bleeding. The study demonstrated the advantage of a longer duration of anticoagulant therapy will less thrombotic events in cancer patients. However, decisions to use this should be based on the risk-benefit of bleeding in individual patients. The study was performed in Japan and may not be generalized to other populations. These findings confirms that cancer associated distal DVT is a marker of poor prognosis and supports the need for extended anticoagulation in patients with active, ongoing cancer.
Major bleeding was slightly increased but not statistically significant in the 12 month group. It is important to understand that bleeding risk probably differs in different cancer types. Up to 75% of patients were treated with low dose edoxaban due to their low weight.
FDA Greenlights Balfaxar for Warfarin Reversal in Urgent Surgery & Invasive Procedures
The FDA has approved a prothrombin complex concentrate- human Ians (Balfaxar) to reverse acquired coagulation factor deficiency caused by vitamin K antagonist such as warfarin. More than 2.4 million people are on warfarin to prevent blood clots. This can be used in adults who require urgent surgery or invasive procedures. This is a human plasma derived, nonactivated four-factor prothrombin complexs concentrate (4F-PCC) containing factor II, VII, IX, and X as well as protein C and S by replacing these deficient factors caused by warfarin therapy.
Data from the LEX-209 study of 208 patients randomly assigned to receive with Balfaxar, or Kcentra ( also a 4F-PCC). At 30 minutes post infusion, 78.1% of patients on Balfaxar had an INR of 1.5 in contrast with 71.8% of those who received Kcentra. Dosing of Balfaxar should be on the basis of the patient INR value and body weight. It is contraindicated in patients with HIT, IgA deficiency with known antibodies against IgA.
Strategy to Prevent Blood Clots, Deaths in Lung/GI Cancer
The TARGET-TP trial evaluated the safety and efficacy of thrombophylaxis before and during anticancer therapy for lung and GI cancers. Patients were grouped into low and high risk thromboembolism risk groups based on their D-dimer and fibrinogen levels. Two hundred high-risk patients were randomized 1:1 to enoxaparin for 90 days, extended to 180 days based on patients ongoing risk, or no thromboprophylaxis (control) with an additional 128 low risk patients were observed without anticoagulation or randomization. The primary outcome was thromboembolism at 180 days, with secondary outcomes of bleeding, survival and risk model evaluation.
In the high risk group, thrombotic events were reduced in patents on enoxaparin ( 8% vs 23%), while the 6 month mortality was 13 in this group compared with 26% in the control group, with 7% in the low risk group. Major bleeding was the same in all groups at 2%.
Pulmonary Embolism During COVID Infection a Deadly Mix
A 2020 database review shows that 19.8% of patients presenting with COVID and PE died in the hospital as compared with 7.1% of those with a PE but without COVID. Patients with both COVID and PE were more likely to require vasopressors and ECMO with longer lengths of stay. COVID has been found to be an independent risk factor for developing a PE. These patients were less likely to receive systemic thrombolysis, cathertercatheter directed thrombolysis and thrombectomy. These findings may be attributed to the issue that data was collected in 2020 the first year of the pandemic where there were issues such as lack of PPE, increased patient burden and COVID patients receiving few interventions.
There was information from 425,640 hospitalization for actuteacute PE in which 11% also had COVID. Median patient age was 65, and the majority were women (41.6% with COVID and 50.6% without COVID) and white (53.4% and 70%, respectively); 23% and 19% were African American and 16.4% and 6.7% were Hispanic. Most patients with PE and COVID were more likely to be male, non-white and less likely to have comorbidities. Long term outcomes were not able to be evaluated since the analysis is limited to in hospital outcomes.
Rare Lung Bleeds Cluster in DOAC Users, Implications Unclear
According to the FDA adverse event reporting database, there was a signal of excess diffuse alveolar hemorrhage (DAH) among users of DOAC's with an odds ratio of 12.84. This represents an associated 13 fold increase in DAH in DOACs users. There were 2998 events in which 462 were associated with DOAC and was more frequent in men ( 61%), age between 65-85 (59.3%). To determine true causality factors including patient co-morbidities, medications, organ function, specific DOAC, DOAC dose, duration of anticoagulant use, test results, demographics, and more could be compared to patients with DAH.
An observational pharmacovigilance study analyzed reported adverse events from DOACs apixaban (Eliquis), betrixaban (Bevyxxa), dabigatran (Pradaxa), edoxaban (Savaysa), and rivaroxaban (Xarelto). The most reported DOAC- DAH cases at 47.8% was rivaroxaban, and was followed by apixaban at 27.1%. These are also the two most commonly used DOACs, therefore results may be skewed since the other drugs are less utilized. To date, there are no definitive proof that reports of DOAC-associated DAH were caused by the DOAC.
Blood Thinners Not a Firm Contraindication for tPA, Study Finds
Intracranial hemorrhage rate did not differ regardless of use of antiplatelet or anticoagulants
A retrospective chart review of ED patients evaluated for stroke who received either tPA or a procedural intervention or both. Data was collected on pre-stroke antiplatelet use, anticoagulant use, NIH stroke score, Rankin score (mRS) and 3 month incidence of ICH. ICH and scored were compared to outcomes among patients based on their antithrombotic use. There were 663 stroke activations of those 251 patients received neurointervention: 140 patients received only tPA, 77 thrombectomy and 34 who received both. Patients with an mRS score of 3 had a hemorrhage rate of 16.7%. The main result showed there was no significant differences in ICH between patients regardless of anti-platelet, anticoagulant or when patients used both.
Cryoprecipitate, REBOA Flop for Improving Major Hemorrhage Outcomes
The CRYOSTAT-2 trial looked at adding early high dose cryoprecipitate to standard major hemorrhage protocols as a fibrinogen replacement did not improve all-cause mortality at 28 days when compared with standard of care. This is given to correct coagulation deficiency, in particular a fibrinogen deficiency which occurs in major hemorrhage. The trial included 799 injured patients at 26 UK and US trauma sites. Patients were actively hemorrhaging and being transfused. They were randomized to standard of care or with the addition of three pools of cryoprecipitate within 90 minutes of randomization and 3 hours of injury. There was no improvement and results are not consistent with the biological rational to supplement with fibrinogen in this cohort. Problems may have been due to the median time of 68 minutes to transfusion, 15% of the cryo group not getting it within 24 hours of hospital admission.
While the UK-REBOA trial (resuscitative endovascular balloon occlusion of the aorta) found no improvement on standard hemorrhagic care in the ED with possibly increased 90 day mortality. The trial suggests that the procedure delayed or prevented definitive control of the hemorrhage. Twice as many deaths occurred (32 % vs 17%) within 24 hours. The trial was stopped early due to risk of harm.
Both were the first randomized trial to look at the intervention tested. While neither intervention improved outcomes, these studies provided important income pertinent to trauma care.
ITP Drug Shows Benefit in Hospitalized COVID Patients
The FOCUS trial randomized 280 high risk patients to 150-mg oral fostamatinib or matching placebo twice daily plus standard of care for 14 days. Mean age was 52.8, 72.5% were men, and 89.6% were white. Patients who received fostamatinib (a spleen tyrosine kinase inhibitor) in addition to standard treatment, the number of days on oxygen was reduced by a mean of 2.8 days versus those who received placebo and standard treatment. Patients also saw an improvement in clinical status that was statistically significant when compared to the placebo group. Patients also had fewer days in ICU when compared to the placebo group as well as off oxygen within 29 days. Benefits seemed to be more evident in critically ill patients.
Fostamatinib is an FDA approved treatment for ITP, and is a potent anti-inflammatory which exerts effects on mast cells, neutrophils, B cells, macrophages and dendritic cells. This prevents the cascade that leads to a cytokine storm resulting in hyperinflammation seen in severe COVID-19. It has also shown to have beneficial effects on endothelial function, and acute lung and kidney injury. Additionally, it reduces the risk of thrombosis by inhibiting platelet activation.
'Yellow' Blood Products Come With VTE Risk, Study Finds
When post-operative rates of VTE and mortality were evaluated, it was found to be significantly higher in patients receiving FFP along with RBC when compared to those with only RBCs. The mortality was 4.35% at 30 in patients receiving FFP compared toe 3.13% in patients with RBC only. Statistically significant was also the rates for 30 day all VTE episodes: 3.92% vs 2.52%, PE: 1.93% vs 1.30%, DIC: 0.96% vs 0.35%. It is important to be cautious about transfusing yellow blood products during surgery which includes platelets and other non RBC components.
The study examined data from the TriNetX Diamond Network. Procedures involving transfusions beginning in 2006 were reviewed and adjusted for patient demographics, type of surgery and comorbidities, however not included in the database are the factors that might drive the administration of FFP to patients. There were 16,600 patients who received FFP matched to patients who did not. They were matched for age, sex, race/ethnicity, BMI and comorbidities.
The speculation for the reason for thrombosis is that by altering the mix of clotting factors in a patient's system, FFP further promotes a tendency to thrombosis.
Hemoglobin Targets a Good Idea for Massively Transfused Patients
Better survival rates in critically ill patients receiving 10 or more units of blood have better survival rates when hemoglobin levels are within normal ranges. When a retrospective analysis was performed on 476 massively transfused patients treated over 5 years. Patients who received 10 units of RBC within 24 hours were included. Confounding variables were adjusted which included age, sex, race/ethnicity, transfusion indication and number of blood units transfused. Of these patients, 17% died prior to discharge and half experienced cardiovascular events and renal impairment or adverse events from the transfusions. Mortality also correlated with the reason for the transfusions, most deaths were in patients (n=13) who experienced GI hemorrhages. High hemoglobin levels only offered minor protection. However, trauma patients and cardiac surgery had the most benefit from increased hemoglobin. A 22% reduction in odd of in hospital mortality was found for each 1 g/dL increase in hemoglobin. The death rate halved when levels reached 10 g/dL. In general surgery, 41% patients, a mortality rate of 25% in patients with hemoglobin less that 6g/dL but was 10% at10g/dL or more. At present there are no guidelines on when to stop a transfusion protocol and over transfusion is a risk, as well as costly.
Limitations to the study included its reliance on administrative records and its single-center design.
Emicizumab Can Delay Immunosuppressive Tx in Acquired Hemophilia A
Acquired hemophilia A is caused by autoantibodies or inhibitors which interfere with Factor VIII activity resulting in severe bleeding. It is rare and can affect individuals of any age, however most often in the elderly. It is controlled by treatment with replacement factor as well as immunosuppressive therapy to stop antibody formation. This can be associated with toxicity, infection and mortality.
In a phase II study, clinically relevant bleeds were prevented when emicizumab was given prophylaxis in newly diagnosed acquired hemophilia A. This also prevented infectious complications of immunosuppressive therapy. This therapy yielded a low mean breakthrough bleeding rate of 0.04 bleeds per patient-week. The study was conducted at 16 hemophilia centers in Germany and Austria. Patients mean age 76 were eligible if they were diagnosed with acquired hemophilia A with a factor VIII of less than 50 IU/dL and a positive inhibitor, were bleeding and did not receive immunosuppressive therapy. They were given a high-dose of emixizumab in the first week, followed by maintenance until week 12. A total of 47 patients were enrolled, after 12 weeks 33 had no bleeding events, seven patients had one bleed, six had two bleeds and one patient had three bleeds with only a few thromboembolic events, severe infection and fatalities. At week 12 or later 29 of the patients began receiving immunosuppressive therapy without any adverse events, 14 experienced remission.
These results confirm the prophylactic activity of emicizumab.
JOURNAL CLUB
Use of Tranexamic Acid in Aesthetic Surgery: A Retrospective Comparative Study of Outcomes and Complications
Omar Fouda Neel, MBBS, MMgt., FRCSC, FACS; Raghad AlKhashan, MBBS Candidate; Emad Abdulrahman AlFadhel, MBBS; Reem Abdulmonem Al-Terkawi, BSIT; Hatan Mortada
Plast Reconstr Surg Glob Open. 2023;11(9):e5229
Abstract
Background: Bleeding is a potential complication of aesthetic surgery. Surgeons have adhered to the principle of minimizing blood loss. Tranexamic acid (TXA) is an antifibrinolytic medication capable of reducing bleeding. This study aimed to investigate TXA and its effect on complications and overall outcomes in aesthetic surgery patients.
Methods: This retrospective chart review of patients undergoing various aesthetic procedures between 2019 and 2022 was conducted in Riyadh, Saudi Arabia. Preoperative and postoperative hemoglobin levels, blood transfusions, and complications were the primary outcomes. Furthermore, the predictors of giving TXA were studied.
Results: In total, 435 patients were included in the study. TXA was administered to 181 patients (41.6%). Significantly higher proportions of patients who received TXA underwent trunk aesthetic surgery (
Conclusions: Although our data show improvement in patient outcomes in multiple aspects, the heterogeneity of our cohort makes us unable to draw definite conclusions to recommend the use of TXA in aesthetic surgery. Thus, a randomized controlled trial is necessary to support the findings of this study.
Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems
Journal of Clinical Oncology Volume 41, Issue 16
Ang Li, MD, MS; Jennifer La, PhD; Sarah B. May, MS; Danielle Guffey, MS; Wilson L. da Costa Jr PhD; Christopher I. Amos, PhD
Abstract
Purpose: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy.
Methods: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS).
Results: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set.
Conclusion: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.
Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease
Amber Sleem, DO; Mark B. Effron, MD; Amanda Stebbins, MS; et alLisa M. Wruck, PhD; Guillaume Marquis-Grave, MD5,; Daniel Muñoz, MD; Richard N. Re, MD; Kamal Gupta, MD; Carl J. Pepine, MD; Sandeep K. Jain, MD; Saket Girotra, MBBS; Jeffrey Whittle, MD; Catherine P. Benziger, MD; Peter M. Farrehi, MD; Kirk U. Knowlton, MD; Tamar S. Polonsky, MD; Matthew T. Roe, MD; Russell L. Rothman, MD; Robert A. Harrington, MD; W. Schuyler Jones, MD; Adrian F. Hernandez, MD
Abstract
Importance Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations.
Objective To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes.
Design, Setting, and Participants This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15,076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023.
Intervention ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months.
Main Outcomes and Measures The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population.
Results Baseline aspirin formulation used in ADAPTABLE was self-reported for 10678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-
1.09;
Conclusions and Relevance In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric- coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population.
2023 ACR/EULAR antiPhospholipid syndrome classification criteria
Medha Barbhaiya, Stephane Zuily, Ray Naden, Alison Hendry, Florian Manneville, Mary-Carmen Amigo, Zahir Amoura, Danieli Andrade, Laura Andreoli, Bahar Artim-Esen, Tatsuya Atsumi, Tadej Avcin, H Michael Belmont, Maria Laura Bertolaccini, D Ware Branch, Graziela Carvalheiras, Alessandro Casini, Ricard Cervera, Hannah Cohen, Nathalie Costedoat-Chalumeau, Mark Crowther, Guilherme de Jesús, Aurelien Delluc, Sheetal Desai, Maria De Sancho, Katrien M Devreese, Reyhan Diz-Kucukkaya, Ali Duarte-García, Camille Frances, David Garcia, Jean-Christophe Gris, Natasha Jordan, Rebecca K Leaf, Nina Kello, Jason S Knight, Carl Laskin, Alfred I Lee, Kimberly Legault, Steve R Levine, Roger A Levy, Maarten Limper, Michael D Lockshin, Karoline Mayer-Pickel, Jack Musial, Pier Luigi Meroni, Giovanni Orsolini, Thomas L Ortel, Vittorio Pengo, Michelle Petri, Guillermo Pons-Estel, Jose A Gomez-Puerta, Quentin Raimboug, Robert Roubey, Giovanni Sanna, Surya V Seshan, Savino Sciascia, Maria G Tektonidou, Angela Tincani, Denis Wahl, Rohan Willis, Cécile Yelnik, Catherine Zuily, Francis Guillemin, Karen Costenbader, Doruk Erkan
2023 Oct;82(10):1258-1270
Abstract
Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR.
Methods: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard.
Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β2-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%.
Conclusion: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.
Hemostatic considerations for gender affirming care
Kathleen Garland, Eric Mullins, Rachel S Bercovitz, Vilmarie Rodriguez, Jean Connors, Nancy Sokkary
Thromb Res2023 Oct:230:126-132.
Abstract
Gender dysphoria or gender incongruence is defined as "persons that are not satisfied with their designated gender" [1]. The awareness and evidence-based treatment options available to this population have grown immensely over the last two decades. Protocols now include an Endocrine Society Clinical Practice Guideline [1] as well as the World Professional Association of Transgender Health Standards of Care (WPATH SOC) [2]. Hematologic manifestations, most notably thrombosis, are one of the most recognized adverse reactions to the hormones used for gender-affirming care. Therefore, hematologists are frequently consulted prior to initiation of hormonal therapy to help guide safe treatment. This review will focus on the scientific evidence related to hemostatic considerations for various gender-affirming therapies and serve as a resource to assist in medical decision-making among providers and patients.
Resuming Anticoagulants in Patients With Intracranial Hemorrhage: A Meta-Analysis and Literature Review
Kareem El Naamani, Rawad Abbas, Marc Ghanem, Marc Mounzer, Stavropoula I Tjoumakaris, M Reid Gooch, Robert H Rosenwasser, Pascal M Jabbour
Neurosurgery 2023 Jul 17.
Abstract
Background and objectives: Intracerebral hemorrhage (ICH) is one of the most disabling cerebrovascular events. Several studies have discussed oral anticoagulant (OAC)-related ICH; however, the optimal timing of resuming OAC in patients with ICH is still a dilemma. In this literature review/meta-analysis, we will summarize, discuss, and provide the results of studies pertaining to OAC resumption in patients with ICH.
Methods: Using PubMed, Ovid Medline, and Web science, a systemic literature review was performed in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement on December 20, 2022. Inclusion criteria for the meta-analysis were all studies reporting mean, median, and standard deviation for the duration of anticoagulants resumption after ICH. Thirteen studies met the above criteria and were included in the meta- analysis.
Results: Of the 271 articles found in the literature, pooled analysis was performed in 13 studies that included timing of OAC resumption after ICH. The pooled mean duration to OAC resumption after the index ICH was 31 days (95% CI: 13.7-48.3). There was significant variation among the mean duration to OAC resumption reported by the studies as observed in the heterogeneity test (P-value ≈0).
Conclusion: Based on our meta-analysis, the average time of resuming OAC in patients with ICH is around 30 days. Several factors including the type of intracranial hemorrhage, the type of OAC, and the indication for OACs should be taken into consideration for future studies to try and identify the best time to resume OAC in patients with ICH.
Risk of recurrent stroke in patients with atrial fibrillation treated with oral anticoagulants alone or in combination with anti-platelet therapy
Eur Stroke J, 2023 Sep;8(3):722-730.
Abstract
Introduction: Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular comorbidities may take both antiplatelet and oral anticoagulation therapy (OAC/AP). Our study aims to evaluate the safety and efficacy of OAC/AP therapy as secondary prevention in people with AF and ischaemic stroke.
Patients and methods: We performed a post-hoc analysis of pooled individual data from multicenter prospective cohort studies and compared outcomes in the OAC/AP cohort and patients on DOAC/VKA anticoagulation alone (OAC cohort). Primary outcome was a composite of ischaemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding, while secondary outcomes were ischaemic and haemorrhagic events considered separately. A multivariable logistic regression analysis was performed to identify independent predictors for outcome events. To compare the risk of outcome events between the two cohorts, the relation between the survival function and the set of explanatory variables were calculated by Cox proportional hazard models and the results were reported as adjusted hazard ratios (HR). Finally another analysis was performed to compare the overall risk of outcome events in both OAC/AP and OAC cohorts after propensity score matching (PSM).
Results: During a mean follow-up time of 7.5 ± 9.1 months (median follow-up time 3.5 months, interquartile range ±3), 2284 stroke patients were on oral anticoagulants and 215 were on combined therapy. The multivariable model demonstrated that the composite outcome is associated with age (OR: 1.03, 95% CI: 1.01-1.04 for each year increase) and concomitant antiplatelet therapy (OR: 2.2, 95% CI: 1.48-3.27), the ischaemic outcome with congestive heart failure (OR: 1.55, 95% CI: 1.02-2.36) and concomitant antiplatelet therapy (OR: 1.93, 95% CI: 1.19-3.13) and the haemorrhagic outcome with age (OR: 1.03, 95% CI: 1.01-1.06 for each year increase), alcoholism (OR: 2.15, 95% CI: 1.06-4.39) and concomitant antiplatelet therapy (OR: 2.22, 95% CI: 1.23-4.02). Cox regression demonstrated a higher rate of the composite outcome (hazard ratio of 1.93 [95% CI, 1.35-2.76]), ischaemic events (HR: 2.05 [95% CI: 1.45-2.87]) and bleeding outcomes (HR: 1.90 [95% CI, 1.06-3.40]) in OAC/AP cohort. After PSM analysis, the composite outcome remained more frequent in people treated with OAC + AP (RR: 1.70 [95% CI, 1.05-2.74]).
Discussion: Secondary prevention with combination of oral anticoagulant and antiplatelet therapy after ischaemic stroke was associated with worse outcomes in our cohort.
Conclusion: Further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischaemic stroke in patients with atrial fibrillation.