October 2023: New In Coagulation
by Donna Castellone, MS, MT(ASCP)S • September 26, 2023
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Post-COVID Cognitive Deficits Linked With Clotting Proteins
During the first wave of the pandemic, 1800 patients hospitalized for COVID mean age 58 and 37% female, two coagulation proteins were predictive with deficits at 6 and 12 months. Data was collected from 57 US healthcare centers. High levels of fibrinogen correlated with both objective and subjective cognitive. While elevated D-dimer relative to CRP were linked with sugjective cognitive deficits and occupational impact mediated by fatigue and shortness of breath. The D-dimer was specific to COVID but the high fibrinogen was a risk for cognitive deficits regardless of cause. These findings suggest that hypercoagulation may be involved.
There are three possible mechanisms that may be responsible. The first may involve blood clots in the brain which may affect cognition; the second relates to the direct effect of fibrinogen on the brain; the third involved blood clots in the lung which may lead to hypoxia or fatigue and can have cognitive manifestations. It is not known how cognitive problems or why they develop and persist post COVID. This defect is 36% more common in COVID than in respiratory tract infections.
Steady VKA Therapy Beats Switch to NOAC in Frail AF Patients: FRAIL-AF
The FRAIL-AF trial was a randomized, open label, multi-center trial that compared therapy with vitamin K antagonists (VKAs) to novel oral anticoagulant (NOAC). Older patients were deemed frail if they were 75 years of age or older and scored 3 or more on the facility indicator. There were 1330 patients, mean age 83, randomly assigned to switch from their INR guided VKA treatment to a NOAC and were followed for 12 months. A total of 662 patients were switched while 661 remained on VK Frailty is a clinical syndrome defined as people having high biological vulnerability, dependency on others and a reduced capacity to resist stressors. It has a prevalence of 12%, with AF a prevalence of 18%.
Results showed that switching from VKA to NOAC in frail older patients with AF can result in up to 69% more bleeding and a hazard ration of 1.69, without any benefit on secondary clinical endpoints. This includes all cause mortality and thromboembolic events. The original hypothesis was that NOAC would cause less bleeding. The trial was stopped after there were 101 primary outcome events (major bleed, non-major bleed) in the NOAC arm as compared to 62 in the VKA arm. This was driven by clinically relevant non-major bleeding.
In previous trials NOACs are preferred over VKA in non-frail AF patients (RE-LY with dabigatran, ROCKET-AF with rivaroxaban, ARISTOTLE with apixaban, and ENGAGE-AF with edoxaban). There was less major bleeding while stroke was comparable with warfarin. These patients were younger in age (70-73).
STEMI Trial Fails to Support Post-PCI Anticoagulation
The randomized trial RIGHT looked at the evaluation of postprocedural anticoagulation (PPA) in patients undergoing a primary percutaneous coronary intervention (PCI) for an ST-segment elevation myocardial infarction (STEMI). The results showed that there was no significant benefit or harm when three different regimens were compared to a placebo. It was concluded that routine PPA with low dose anticoagulation after primary PCI in STEMI patients is safe, but it doesn't improve ischemic outcome at 30 days.
In the trial, 2856 STEMI patients undergoing PCI were randomized equally to either a placebo or PPA. In the PPA group, patients received either bivalirudin, enoxaparin or heparin with an ACT of 150-200 seconds. This was given over 4. 8 hours or until discharge. This was conducted at 53 Chinese centers. Patients were excluded if they presented with unstable disease, prior coronary artery bypass grafting or an indication for anticoagulation other than PPA.
There was no difference at 30 days between the placebo and PPA in the primary endpoint (rate 2.5%) of all cause death, non-fatal MI, non-fatal stroke, stent thrombosis or urgent revascularization. There was a slight increase of bleeding events in the placebo group, but it did not reach statistical significance.
Aspirin Still Needed in First Month After PCI: STOPDAPT-3
The initial thought prior to the STOPDAPT-3 trial was the removing a patient from aspirin in the post-acute phase after PCI is associated with a lower bleeding risk without affecting ischemic risk. This trial looked at the efficacy and safety in Japanese patients with cobalt chromium everolimus-eluting stents with ACS or high bleeding risk to drop aspirin and using low-dose prasugrel alone in this initial month post PCI. There were 6002 patients randomly assigned to prasugrel monotherapy or to DAPT with aspirin and prasugrel. Primary endpoints were major bleeding events and cardiovascular events at 30 days. The results showed that it failed to lower bleeding risk compared with DAPT. There was also possible harm due to increased subacute stent thrombosis which was three times higher in the non-aspirin group (0.58% vs 0.17%). Bleeding events were at 4.4% in the prasugrel monotherapy group vs 4.71% on DAPT. Based on these finding, aspirin remains a staple in this phase of PCI in patients without indication for oral anticoagulation.
Platelets in the pipeline: Advancements in platelet technologies
The evaluation of platelet function is important in managing bleeding patients, however there are no tests available to evaluate platelet function in all situations. There are several instruments available, however there are many issues with testing. These include lack of standardization, time sensitivity, dependence on fresh plasma and the tests require highly technical time-consuming activities. Mild bleeding disorders are difficult to diagnose due to subtleties in platelet dysfunction may not be identifiable with current testing options. Patients who have thrombocytopenia and require testing are challenging since platelet testing requires platelet rich plasma and this can confuse a quantitative disorder with a qualitative disorder. New technologies and the development of new platelet function devices can help to meet the clinical needs of platelet function disorders and antiplatelet therapies.
A new FDA cleared analyzer using microfluidic clot occlusion is a global testing system using a single test result to detect primary hemostatic abnormalities as well as antiplatelet therapies. It addresses thrombocytopenia by a special chip that can activate primary and secondary hemostasis in blood samples as low as 10,000/µL. The chip has a flow chamber coated with collagen and thromboplastin mimicking the blood flow seen in small arteries. The methodology looks at as platelets become activated, they block channel flow which increases flow pressure over time. This technology is not yet approved for clinical use in the US.
Nanoscale technology has enabled the activity of platelet clumps and single platelets to be measured. It can assess platelet contractile force under microfluidic shear gradients using micropost and block technology. Measuring contraction has the potential to diagnose multiple types of platelet driven deficiencies or dysfunctions as well as when platelet transfusions are required and to titrate antiplatelet therapies.
Currently light transmission aggregometry (LTA) has been the gold standard that uses various agonists that can measure platelet aggregation and activation pathways. It is time consuming, manual testing requiring specialized technical training and large sample volumes. This is also problematic due to a lack of standardization. Automating aggregometry could provide reproducible, gold standard platelet function without being dependent on specialized technologists. This is being used in Europe but not available in the US.
Another issue with platelet testing is that fresh donor plasma is need for quality control. Blood product technologies are in development that may alleviate some of the issues. Cryopreserved platelets produce active and functional platelets and these may be able to be used as positive controls in platelet function assays. Further studies are needed. Freeze dried places can be stored at ambient temperature for up to three years and rehydrated in water to produce ready to use activated platelets. A clinical trial is underway to investigate their use.
All of these technologies are promising in meeting the needs of the clinical assessment of platelet function.
Pulmonary embolism deaths, disparities high despite advancements in care
Despite many advancements for treatment of PE over the last 20 years, a study from Michigan Medicine finds the death rate for PE remains high and unchanged. Based on data from the CDC, over 100,000 deaths from PE between 2006 and 2019 were analyzed. Results showed there is a higher rate of mortality in men and black patients. The rate was two times higher when compared to white patients. In rural areas, the rate is 4 patients/100,000 patients which is double a metropolitan area.
Bad Blood: Could Brain Bleeds Be Contagious?
This review is based on a commentary.
When something is caused by an infection there are the usual suspects, microbes seen under a scope. However, there are cases where the microbe is too small to be seen unless done under advanced imaging techniques which include viruses or when pathogens are sparse or hard to culture.
It is possible that based on a study, cerebral amyloid angiopathy (CAA) may be the result of an infectious disease. This is characterized by amyloid protein in the brain, some cases are genetic however most are considered idiopathic. Between 5-7% of cognitively normal older adults have CAA, but is higher in those that have ICH. Severe hypertension is the number one cause of brain bleeds, but CAA is second. CAA had been described as sporadic, but some say it may be transmissible with several cases developing after administration of cadaveric pituitary hormone, via dura mater grafts and neurosurgical instruments. No organism had been identified.
The study proposes CAA is caused by some infectious agent and may be transmitted in the blood, meaning it could be transmitted from donated blood. Researchers in Sweden and Denmark were able to trace blood donors and outcomes between 1970 and 2017 (760,000 in Sweden and 330,000 in Denmark). There were 99% of donors were never had any brain bleed, but some did within 5 years of donating blood, some had a single event others had multiple events. It was then investigated if the people who received those units also had a brain bleed. Results showed the risk of recipients having a brain bleed was lowest if the blood they received were from patients who never had a brain bleed, higher if they had a single event and highest if it was from a person who had multiple bleeds.
Confounding variables include blood type, age, sec and indication for transfusion. All there were adjusted.
Ischemic stroke was used as a negative control and no correlation was found between this event as a transmissible agent. These findings do not point to a microbe, virus, prion or toxin. The patients who presented with brain bleeds it is not known if they were CAA associated. Also, no donors had a brain bleed prior to donation, so there is no mechanism for screening, no test, no treatment. These findings do shift away from CAA being a random disease.
JOURNAL CLUB
Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis
Jerrold H Levy, Roman M Sniecinski, Bianca Rocca, Kamrouz Ghadimi, James Douketis, Corinne Frere, Julie Helms, Toshiaki Iba, Andreas Koster, Tara K Lech, Cheryl L Maier, Mathew D Neal, Ecatarina Scarlestscu, Alex Spyropoulos, Marie E Steiner, Alfonso J Tafur, Kenichi A Tanaka, Jean M Connors
J Thromb Haemost, 2023 Aug 22;S1538-7836(23)00641-4.
Abstract
The term heparin resistance (HR) is used by clinicians without specific criteria. We performed a literature search and surveyed our SSC membership to better define the term when applied to medical and intensive care unit patients. The most common heparin dosing strategy reported in the literature (53%) and by survey respondents (80.4%) was the use of weight-based dosing. Heparin monitoring results were similar based on the proportion of publications and respondents that reported the use of anti-Xa and activated partial thromboplastin time. The most common literature definition of HR was >35 000 U/d, but no consensus was reported among survey respondents regarding weight-based and the total dose of heparin when determining resistance. Respondent consensus on treating HR included antithrombin supplementation, direct thrombin inhibitors, or administering more heparin as the strategies available for treating HR. A range of definitions for HR exist. Given the common use of heparin weight-based dosing, future publications employing the term HR should include weight-based definitions, monitoring assay, and target level used. Further work is needed to develop a consensus for defining HR.
Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries
Toon Wei Lim, Alan John Camm, Saverio Virdone, Daniel E Singer, Jean P Bassand, Gregg C Fonarow, Keith A A Fox, Michael Ezekowitz, Bernard J Gersh, Gloria Kayani, Elaine M Hylek, Ajay K Kakkar, Kenneth W Mahaffey, Karen S Pieper , Eric D Peterson, Jonathan P Piccini; GARFIELD-AF and ORBIT-AF Investigators
Clin Cardiol 2023 Aug 18.
Abstract
Background: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs).
Hypothesis: An externally validated model improves ICH risk stratification.
Methods: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register.
Results: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non- VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets.
Conclusions: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.
Unprovoked Venous Thromboembolism: The Search for the Cause
Hunter Mwansa, Mohamed Zghouzi, Geoffrey D Barnes
Med Clin North Am, 2023 Sep;107(5):861-882.
Abstract
Venous thromboembolism (VTE) is a common vascular disorder encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE). There is no data on global estimates of VTE prevalence and incidence. Most patients with unprovoked VTE require secondary thromboprophylaxis upon the completion of the primary treatment phase if they have no high bleeding risk. Risk prediction models can help identify patients at low VTE recurrence risk who may discontinue anticoagulation upon the completion of the primary treatment phase.
Implementation and evaluation of a warfarin patient self-management (PSM) program among experienced patients in a U.S. academic health system
Ryan P Fleming, Sara R Vazquez, Daniel M Witt
J Thromb Thrombolysis 2023 Aug 7.
Abstract
Warfarin patient self-management (PSM) is when a patient independently manages their warfarin therapy using a decision-support tool provided by their anticoagulation provider. Clinical trials of PSM, conducted predominantly in Europe, have consistently demonstrated superior efficacy without compromising safety. However, the evidence-based practice of PSM is rarely utilized in the United States (U.S.). We describe initiatives completed to implement a successful PSM program among experienced warfarin-taking patients in a U.S. academic health system by overcoming perceived barriers. The results showed PSM resulted in similar or improved INR control, and an estimated 68% reduction in pharmacist workload.
Effect of previous INR control during VKA therapy on subsequent DOAC adherence and persistence, in patients switched from VKA to DOAC
Tessa Elling, Eelko Hak, Jens H J Bos, Vladimir Tichelaar, Nic J G M Veeger, Karina Meijer
Thromb Haemost 2023 Sep 6.
Abstract
Introduction Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR<70%). Poor INR control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC non-adherence and non-persistence, in patients who switched from VKA to DOAC. Methods 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen and Statistics Netherlands. DOAC prescriptions were used to determine non-adherence and non-persistence. INR control (i.e. TTR, time under therapeutic range (TUR) and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC non-persistence / non-adherence. Results On VKA, 67.7% of the patients had a TTR below 70%. DOAC non-persistence was 39.8% (95% CI 33.4-45.5%) during a median follow-up of 34.4 months [IQR 19.1-49.2]. Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC non-persistence (HR 1.14, 95% CI 0.69-1.87) and DOAC non-adherence (OR 1.38, 95% CI 0.67-2.84), nor were TUR and INR variability. Conclusion Previous INR control during VKA therapy is not associated with subsequent DOAC non-adherence and non-persistence. This study suggests that INR control on VKA cannot, and therefore should not be used for predicting DOAC adherence or persistence.
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, Michael H 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; ACR/EULAR APS Classification
Criteria Collaborators
Ann Rheum Dis 2023 Aug 28.
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.
Heparin Induced Thrombocytopenia - Pathophysiology, Diagnosis and Treatment: A Narrative Review
Ahmad A Alhanshani
Int J Gen MeD, . 2023 Aug 30;16:3947-3953.
Abstract
Heparin-induced thrombocytopenia (HIT) is a life-threatening, immune-mediated complication following heparin exposure and is considered to be the most severe adverse reaction to heparin treatment that is not associated with bleeding. Development of autoantibodies against platelet factor 4 (PF4) - heparin complex constitutes the basis of the pathophysiological changes in patients suffering from HIT, which then binds to the surface of platelets and monocytes, thus provoking their activation and subsequent aggregation, ultimately leading to the formation of thrombosis. Formation of arterial and venous thrombosis is aggravated by the simultaneous activation of platelets and monocytes with a substantial mortality rate. The incidence of HIT is reported to be significantly lower in pediatric patients compared with adults. Diagnosis of HIT in pediatric population remains a clinical entity supplemented by laboratory evaluation. The positive predictive value of laboratory evaluation is further elevated by the use of scoring systems and predictive models used for hastening the diagnosis of HIT. Use of alternative anticoagulants like direct thrombin inhibitors and factor Xa inhibitors form the mainstay of treatment in cases of HIT, however, more prospective studies would be required in the pediatric population to delineate definitive guidelines for proper management of patients in this age-group. This article delivers diagnostic and treatment approach in case of patients with HIT, wherein the pathophysiology, clinical manifestations, diagnostic approach and the management of patients with HIT has been described.
Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity: Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan
Kazunori Toyoda, Shuji Arakawa, Masayuki Ezura, Rei Kobayashi, Yoshihide Tanaka, Shu Hasegawa, Shigeo Yamashiro, Yoji Komatsu, Yuka Terasawa, Tomohiko Masuno, Hiroshi Kobayashi, Suzuko Oikawa, Masahiro Yasaka
J Atheroscler Thromb 2023 Aug 26.
Abstract
Aims: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. W e aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan.
Methods: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open- label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment.
Results: A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events.
Conclusion: Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.
Phenotypes of disseminated intravascular coagulation
Takeshi Wada, Satoshi Gando
Thromb Haemost 2023 Sep 1.
Abstract
Two phenotypes of disseminated intravascular coagulation (DIC) are systematically reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic phenotype is the activation of coagulation, insufficient anticoagulation with endothelial injury, and plasminogen activator inhibitor-1 (PAI-1)-mediated inhibition of fibrinolysis, leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic phenotype is defined as massive thrombin generation commonly observed in any type of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying disorder that results in severe bleeding due to excessive plasmin formation. Three major pathomechanisms of systemic hyperfibrinogenolysis have been considered: i) acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial cells and t-PA rich storage pools, ii) enhancement of the conversion of plasminogen to plasmin due to specific proteins and receptors that are expressed on cancer cells and endothelial cells, and iii) alternative pathways of fibrinolysis. DIC with fibrinolytic phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin degradation products (FDP) and the FDP/D-dimer ratio are important for the diagnosis of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears to be one of the few methods to be effective in the treatment of systemic pathologic hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms, establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic phenotype are urgent issues in the field of thrombosis and hemostasis.
Intensive Statin Therapy Versus Upfront Combination Therapy of Statin and Ezetimibe in Patients With Acute Coronary Syndrome: A Propensity Score Matching Analysis Based on the PL-ACS Data
Joanna Lewek, Jacek Niedziela, Piotr Desperak, Krzysztof Dyrbuś, Tadeusz Osadnik, Piotr Jankowski, Adam Witkowski, Agata Bielecka-Dąbrowa, Dariusz Dudek
Journal of the American Heart Association. 6 Sep 2023
Abstract
Background: We aimed to compare statin monotherapy and upfront combination therapy of statin and ezetimibe in patients with acute coronary syndromes (ACSs).
Methods and Results: The study included consecutive patients with ACS included in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a national, multicenter, ongoing, prospective observational registry that is mandatory for patients with ACS hospitalized in Poland. Data were matched using the Mahalanobis distance within propensity score matching calipers. Multivariable stepwise logistic regression analysis, including all variables, was next used in propensity score matching analysis. Finally, 38023 consecutive patients with ACS who were discharged alive were included in the analysis. After propensity score matching, 2 groups were analyzed: statin monotherapy (atorvastatin or rosuvastatin; n=768) and upfront combination therapy of statin and ezetimibe (n=768 patients). The difference in mortality between groups was significant during the follow-up and was present at 1 (5.9% versus 3.5%;
Conclusions: The upfront combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that in high-risk patients, such an approach, rather than a stepwise therapy approach, should be recommended.
Perioperative Management of Oral Anticoagulants and Antiplatelet Therapy in Hand and Wrist Surgery
Gregory G. Gallant, MD, MBA; Jonas L. Matzon, MD; Pedro K. Beredjiklian, MD; Michael Rivlin, MD
J Am Acad Orthop Surg. 2023;31(15):820-833.
Abstract
There is wide variability in the management of patients on antithrombotic therapy requiring surgery of the hand and wrist. There are no specific guidelines regarding whether to temporarily cease or continue oral anticoagulants and antiplatelet agents. Discontinuation of these medications before surgery can lead to perioperative thromboembolic or ischemic events. On the other hand, continuation can lead to intraoperative or postoperative bleeding complications. This review discusses various anticoagulants and antiplatelet agents with special considerations for their management, analyzes the current literature, summarizes current recommendations, and provides direction for additional research.
Abelacimab for Prevention of Venous Thromboembolism
Peter Verhamme, M.D., B. Alexander Yi, M.D., Ph.D., Annelise Segers, M.D., Janeen Salter, B.S.N., Daniel Bloomfield, M.D., Harry R. Büller, M.D., Gary E. Raskob, Ph.D., and Jeffrey I. Weitz, M.D.
Abstract
Background: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.
Methods: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery.
Results: Venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group.
Conclusions: This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA Eudra)