March 2025: New In Coagulation
by Donna Castellone • March 05, 2025
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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New accreditation POC requirements for coagulation testing
The POC checklist for coagulation now include requirements for specimen collection and handling. POC testing is being used more frequently and best practices should be utilized. This is a challenging task even for core laboratories. There are three new requirements.
Specimen handling for Whole Blood Testing requires that specimens be handled as per manufacturers requirements or as validated by the laboratory. They may not be heated, refrigerated or frozen and centrifuged samples must be rejected and must not be reconstituted by mixing. This is the same requirement found in the hematology checklist. There is also a requirement for viscoelastic testing to provide recommendation on the utility of testing in clinically meaningful situations. This includes proper test selection, instrument comparability and viscoelastic-testing- based monitoring of antiplatelet or anticoagulant medications. Physicians need to understand that there are several assays on the market and they are not all the same and may have different sensitivities to certain disease states or anticoagulants.
Specimen handling for platelet aggregation and function testing must be handled at room temperature prior to testing. They should never be placed on ice or subjected to vibrations.
Coagulation Testing and Therapeutic Anticoagulant Recommendation requires that recommendations are available to clinicians in the following four areas: tests used for monitoring heparin, LMWH, DOAC; utility and limitations of viscoelastic testing; therapeutic ranges and potential interference of anticoagulant medication on coagulation testing. These recommendations can be in an educational bulletin or in a comment associated with the results. It is important to be aware that different POC analyzers may be sensitive to the presence of one anticoagulant and another may not have the same sensitivity. It is important for clinicians to be aware of this.
For all POC coagulation testing it is important to make sure that the laboratory is using the test as stated in the manufacturer's package insert, as per the FDA requirements. Adding these requirements to the checklist will help to ensure that POC testing provides high quality patient care.
AHA Advisory Endorses Endovascular Thrombectomy for Large Core Ischemic Stroke
In patients with large core ischemic stroke (LCIS) results of six trial support endovascular thrombectomy (EVT) as opposed to medical management. Until recently this cohort of patients were excluded from EVT trials and represent about 25% of ischemic strokes attributable to large vessel occlusion among presenting to centers within 8 hours. The data from six trials include: RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2, TESLA, TENSION and LASTE.
The trials (n=1877, mean age 60, with stroke score 16-22) included patients who had major arterial occlusions at the anterior circulation either internal carotid artery or middle cerebral artery. Most patients had good pre-stroke functional status with an average modified Rankin Score [mRS] of 0-1. A total of 78.2% of patients had baseline ASPECTS 3-5, and 16.9% had ASPECTS 0-2. The LASTE trial included a large proportion of patients with very large cores — 56.6% of participants had ASPECTS 0-2. MRI window as 6 hours (RESCUE) and 6.5 hours (LASTE). CT based studies TENSION had an intermediate window within 11 hours completing thrombectomy by 12 hours while ANGEL-ASPECT, SELECT2, and TESLA enrolled patients up to 24 hours.
EVT technique of stent retriever, aspiration, or both, with or without balloon protection, was done by the discretion of the physician. Acute angioplasty, stenting and intra-arterial thrombolysis were variably permitted.
Higher rates of functional independence were observed after EVT versus MM in all trials (30% vs 11.6%). It is not clear whether those with the very largest core stroke volumes benefit from EVT.
Symptomatic hemorrhage rates were low, slightly higher in the EVT groups versus MM (4.0% vs 1.3%). Mortality was more favorable for EVT in four of the six trials.
An update to the AHA 2019 acute ischemic stroke guideline is in process, and publication is expected in early 2026.
Do We Really Know the Stroke Risk From AF?
There is evidence that the risk for stroke patient with untreated AF is declining and is lower than previously predicted by the CHA2DS2–VASc score. The use of warfarin in these patients came from trials conducted more than 30 years ago. Low rates of strokes in device detected AF trials — LOOP, NOAH-AFNET 6, and ARTESIA- found only a 1% rate in the placebo arm which is 75% less than what the scoring system predicts. The discrepancy may be due to the short duration AF is different from symptomatic AF confirmed on a standard ECG. Subclinical AF confers a lower risk of stroke versus clinical AF. But there may also be a decline in stroke risk in the population. This is supported by the Finnish Danish registry.
In 130,000 patients with new onset AF beginning in 2007 split into three groups using 40,000 patients in blocks of 3-year intervals (2007-2010, 2011-2014, and 2015-2018). There were three main findings: mean age went from 70-73 and score went from 3-3.5,: overall rate of ischemic stroke decreased by 25% with absolute rates going from 36.7-27.6 with a 32% decline in women versus 7% decline in men, and most decreases occurred in older women with higher stroke risk scores. Issues with this study is that it was observational and retrospective however it is based on real world data as shown in the low rates for the placebo group.
A large placebo controlled randomized trial of oral anticoagulation in AF is needed with longer duration AF episodes as an entry criteria. Another area is LAAC closure performed on patients who struggle with anticoagulation. Maybe a trial of LAAC vs no treatment in older patients with AF and co-morbidity. It is important that evidence that guides practice should be current. It is important to study new therapies as well as old therapies and dogmas.
Endovascular Therapy Hits a Wall for Stroke Clots Lodged in Mid-Size Vessels
The benefit of EVT did not extend to strokes from mid-size vessel occlusions or distal vessel occlusions when compared to best medical therapy as demonstrated in two randomized trials. (DISTAL included 543 people with an isolated occlusion of medium or distal vessels. And ESCAPE-MeVO included 530 people with symptomatic strokes attributed to medium-vessel occlusion.
In the DISTAL trial all-cause mortality was higher with EVT versus standard of care (15.5% vs 14.0%) and death rates were significantly higher in ESCAPE-MeVO (13.3% vs 8.4%, adjusted HR 1.82, 95% CI 1.06-3.12). Both trials showed increase of symptomatic intracranial hemorrhage vs standard of care. DISTAL (2.6% vs 5.9%) and ESCAPE-MeVO (2.2% vs 5.4%). Results support that mechanical thrombectomy should no longer be performed in this setting.
The trials had different designs and times of enrollment, as well as different vessels treated and still showed a consistent lack of efficacy. However, the participants being older (mean age of 77 & 75) and having higher baseline disability may also have contributed to a reduction in EVT benefit.
A Reality Check for Minimally Invasive Evacuation Surgery on Sudden Brain Bleeds
Minimally invasive surgery (MIS) with the Artemis Neuro Evacuation device for ICH failed to meet expectations in the MIND trial. Outcomes at 180 days were the same as those who had medical management (MM). A benefit was detected at the 30-day mark that applied to deep and lobar bleeds but did not persist for 90 or 180 days. The MIND trial was stopped early due to diminishing odds of success. The trial saw a low 30-day mortality overall with 9.8% MM and 7.2% with MIS.
A previous study, ENRICH, showed neurological benefit in patients with acute ICH particularly lobar supratentorial hemorrhages at 180 days using the Myriad device. The MIND used Artemis Neuro Evacuation device which targeted an area markedly narrower than the ENRICH device. Of bleeds in the MIND trial 70.8% were deep and 29.2% were lobar. Deep bleeds affected younger patients, men and people with more comorbidities associated with more severe stroke symptoms and smaller ICH volumes.
MIND enrolled adults up to 80 years presenting with moderate-large (20-80 mL) supratentorial ICH, presenting within 24 hours of symptom onset, with a stroke score of 6, previously without disability. Patients were randomized 2:1 MIS or MM, MIS occurred with 72 hours of the bleed. Final sample analysis was 236 individuals which was too low for a powered analysis. Patients had a median age of 60, under 40% were women,and a NIH score of 18. Time to randomization was 19.5 hours for the control group and 22 hours for the MIS group. Comparisons showed the MIS results did not show any better or worse survival, however, the serious adverse event of symptomatic evolution of perihematomal edema were less in the MIS arm.
Anemia, Postpartum Hemorrhage, and Maternal Death: An Intervention in Africa Has Global Implications for Improving Outcomes
In developed nations the rate of maternal mortality (MM) is 5-20 per 100,000 live births while in Sub Saharan Africa it is as high as 500-1000 maternal deaths manly due to nutritional deficiencies. Postpartum hemorrhage (PPH) is also a major contributor as was identified in an analysis of the WOMEN-2 trial from data collected from 8879 consecutive deliveries at a hospital in Mozambique from 2019-2021. Based on cryoprecipitate production, early massive transfusion, and standard PPH care, postintervention outcomes for 6087 deliveries were assessed. PPH interventions occurred with cryoprecipitate (39.26%) and tranexamic acid (16.11%). Significant improvements were seen in the intervention group MM rates were 1104/100,000 (1.10%) vs 279/100,000 (0.28%), and PPH rates were 14.01 vs 4.90% in the groups. Infant mortality also improved (3.44% vs 2.59%).
Factors that significantly associated with PPH included eclampsia, preterm delivery, maternal age under 20, maternal age over 35 and pre-eclampsia. Laboratory data from 13% of women revealed that anemia or thrombocytopenia were associated with PPH. The mechanism for this is not well understood. The rate of anemia is milder in the US and may be underrecognized therefore the relationship between anemia and PPH has been missed. It is important to be aware of and recognize iron deficiency anemia during pregnancy.
Some Contraceptives Carry Higher Venous Thromboembolism Risk Than Others
VTE and the risk when using hormonal contraceptive varied by method and dose. Combined pills and injections had the highest risk. Risks for VTE per 10,000 person- years were: combined pills :10, vaginal rings 8.0, patches 8.1, progestin-only pills 3.6, injections 11.9, IUDs 2.1, implants 34., and no contraceptive use 2.0. Combined hormonal contraceptives in particular those with third generation progestins were associated with the highest risk (up to 14.2) while IUDs contained the lowest risk. Research has shown that that depot medroxyprogesterone acetate, a high dose and potent injectable progestin, may have increased VTE risk.
The Danish study of almost 1.4 million women between the ages of 15 and 49 (2011-2021) determined use through prescription records. Any women with a history of thrombosis or other comorbidities that increased the risk of thrombosis were excluded. There were 2691 VTEs that occurred. A limitation was the homogeneity of the population.
Updated Guidance on Anesthesia with Antithrombotic/Thrombolytic Therapy
Updated guidance has been released by the American Society of Regional Anesthesia and Pain Medicine (ASRA) regarding antithrombotic or thrombolytic therapy. The major changes include updates to terminology and when to order drug specific coagulation assays. There are 6 million people in the US taking a DOAC and another 36 million taking antiplatelet medication and up to 20% of those will have a surgical procedure. Neuraxial hematoma's can occur in 1 in 150,000 epidurals and about 1 in 220,000 spinals, so it is difficult to know what the risk is and it is rare so it is hard to study. The group focused on patient safety using low dosing and high dosing terminology as opposed to prophylactic and therapeutic. This allowed the dose to be in the setting of specific patient characteristics and indications.
Drug specific assays are becoming easier to access, so updated guidelines offer recommendations around "what the blood test should show and maybe which patients you should actually draw on". Regarding one anticoagulant being safer than another, each one will have a different recommendations and this should allow safety while undergoing procedures.
Brain Bleed Survivors Walk a Razor-Thin Line Taking DOACs
In the PRESTIGE-AF trial, survivors of ICH were protected against future ischemic events using DOACs. However, bleeding events did occur. Patients on DOACs did see a major reduction on the risk of a primary ischemic stroke when on DOAC versus no anticoagulant (adjusted HR 0.05, 95% CI 0.01-0.38). Ischemic strokes occurred at a low 0.83 per 100 patient-years with DOACs versus 8.60 per 100 patient-years with no OAC.
A major risk of recurrent ICH was also seen with DOAC therapy (adjusted HR 11.2, 95% CI 2.01-62.86). The incidence of all ICH events reached 5.00 per 100 patient-years versus 0.82 per 100 patient-years, between DOAC and controls. Maintaining a balance between bleeding and ischemic events is a challenge. Data from the ENRICH-AF and ASPIRE trial should aid in this risk-benefit analysis.
Initial observational data and meta analysis suggested no increase in ICH in those treated with vitamin K antagonists and preliminary data on DOACs showed encouraging safety trends. An individualized approach should be heeded to determine risk stratification of these patients. This may include alternative therapies such as left atrial appendage closure.
PRESTIGE-AF was conducted at 63 EU sites as a phase III open label trial. There were 319 people with a median age of 78-79, 35% female and mostly white. Adults were chosen between 14 days and a year out from their index spontaneous ICH, were diagnosed with Afib, and had an indication for anticoagulation and no contraindication to therapy. They were randomized to DOAC or control group without any OAC. Anticoagulants were determined by site apixaban (53.8%), followed by dabigatran (20.9%) and edoxaban (18.4%). Bleeding outcomes favored the control arm, but secondary outcomes including mortality and major cardiac events did not suggest either strategy was better.
Encouraging DOAC Data for Afib With Various Valvular Heart Diseases
A retrospective cohort showed that in some AF patients with valvular heart disease, DOAC appear to offer better prevention of stroke and thromboembolic events when compared to warfarin. Using insurance records, DOAC treatment was associated with lower risks of ischemic stroke or systemic embolism (HR 0.70) and bleeding (HR 0.72) when compared with VKA. This was seen in patients on rivaroxaban, apixaban but not dabigatran and events were too few on edoxaban. The study had a median follow up of 160 days in patients with AF and VHD and were excluded in those with mechanical heart valves.
The goal of this study was to evaluate whether DOACs can show a risk-benefit profile in those with VHD. Previous results showed poor outcomes with DOACs compared to VKAs in AF patients with mechanical heart valves, as a result US guidelines promote warfarin as first line therapy in this cohort. However, there were concerns about extrapolation of data to patients with other types and degrees of VHD. Currently, as per guidelines patients with mechanical heart valves and moderate to severe rheumatic valve disease cannot be treated with DOACs. But this does reinforce treatment with DOACs is safe and effective in patients with AF in mitral regurgitation, bioprosthetic valves (including mitral), aortic stenosis, tricuspid regurgitation, valve repair, and transcatheter aortic valve implantation.
Anticoagulants No More Dangerous Than Aspirin for Bleeds: Annals
An analysis of randomized clinical trials show that apixaban and dabigatran don't cause more bleeding than aspirin when treating stroke or AF. The anticoagulant rivaroxaban does have a higher risk of bleeding than aspirin. The absolute risk of bleeding is low regardless of anticoagulant or aspirin. Patients usually switch from aspirin to anticoagulant due to developing AF or a PE.
In a pooled analysis of nine randomized trials, the bleeding risk of anticoagulant and aspirin were compared in 26,224 participants with a minimum duration of treatment of 3 months. The average age was 67 with 58% male with a mean follow up time of 20 months. Studies occurred between 2011 and 2024 and including treatment of chronic AF, subclinical AF, VTE or stroke.
No difference for major bleeding or ICH was found between apixaban and aspirin as well as dabigatran. Five studies compared apixaban with aspirin while two looked at dabigatran, the remaining two looked at rivaroxaban and aspirin which had a greater risk of major bleeding and ICH. Overall, there were a total of 566 major bleeding episodes (2.16%) and 172 cases of ICH (0.66%). Clinical factors should inform the prescribing decision and rivaroxaban should not be abandoned and patient bleeding risk should be evaluated. Many clinicians prefer aspirin to balance bleeding risk, however this study shows that anticoagulants are just as safe for many patients.
JOURNAL CLUB
Essential Thrombocythemia: A Review
Ayalew Tefferi, MD; Naseema Gangat, MD; Giuseppe Gaetano Loscocco, MD; et alPaola Guglielmelli, MD, PhD; Natasha Szuber, MD; Animesh Pardanani, MD, PhD; Attilio Orazi, MD; Tiziano Barbui, MD; Alessandro Maria Vannucchi, MD
Abstract
Importance Essential thrombocythemia, a clonal myeloproliferative neoplasm with excessive platelet production, is associated with an increased risk of thrombosis and bleeding. The annual incidence rate of essential thrombocythemia in the US is 1.5/100 000 persons.
Observations Patients with essential thrombocythemia have a persistent platelet count of 450 × 109/L or greater. The differential diagnosis includes myeloproliferative neoplasms (polycythemia vera, primary myelofibrosis, chronic myeloid leukemia); inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus; infections; splenectomy; iron deficiency anemia; and solid tumors such as lung cancer. Approximately 90% of individuals with essential thrombocythemia have genetic variants that upregulate the JAK-STAT (signal transducer and activator of transcription 5) signaling pathway, including Janus kinase 2 (
Conclusions Essential thrombocythemia is a rare clonal myeloproliferative neoplasm associated with an increased risk of venous and arterial thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. Based on individual risk factors for thrombosis, persons with essential thrombocythemia may be treated with low-dose aspirin, either alone or in combination with a cytoreductive drug such as hydroxyurea.
Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy - A Secondary Analysis of the ARCADIA Randomized Clinical Trial
Maarten G. Lansberg, MD; Max Wintermark, MD; Hui Chen, MD; et alGeorge Howard, PhD; Christy Cassarly, PhD; Qi Pauls, MS; Stephanie Kemp, BS; Tashia L. Harris, BS; Balaji Krishnaiah, MD; Robert J. Stanton, MD; Michael J. Lyerly, MD, MSPH; Benjamin R. Miller, MD; Eric E. Smith, MD; David L. Tirschwell, MD; Kevin N. Sheth, MD; Hooman Kamel, MD; William T. Longstreth Jr, MD, MPH; Mitchell S. V. Elkind, MD, MS; Joseph P. Broderick, MD5; Ronald M. Lazar, PhD
Abstract
Importance In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.
Objective To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.
Design, Setting, and Participants ARCADIA-MRI, an ancillary study to the ARCADIA trial with a median follow-up period of 27 months, enrolled participants from 75 sites in the US from November 14, 2019, until December 2, 2022. Participants in ARCADIA were invited to coenroll in ARCADIA-MRI if they had not permanently discontinued the study drug and had no contraindications on magnetic resonance imaging (MRI). A total of 310 (31%) of the 1015 ARCADIA participants enrolled in ARCADIA-MRI and of those 174 (56%) with adequate quality baseline and follow-up MRI were included in the present analyses.
Interventions MRI performed at the time of the index stroke served as the baseline image unless it was unavailable or of insufficient quality, in which case a new research MRI was obtained. A follow-up research MRI was performed upon each participant's completion of participation in the ARCADIA parent study.
Main Outcomes and Measures The primary outcome was incident nonlacunar covert infarct on the follow-up MRI assessed by 2 independent raters who were masked to treatment assignment.
Results Baseline characteristics were balanced between the apixaban (n = 79) and aspirin (n = 95) arms. The mean (SD) age was 66 (10.6) years, and the median (IQR) modified Rankin Scale (mRS) score 1 (0-2). Ninety-one participants (52.3%) were male. During the median (IQR) follow-up of 811 (487-1288) days, the risk of incident nonlacunar covert infarcts was lower in the apixaban group (5.1%) than the aspirin group (17.9%) (weighted relative risk, 0.29; 95% CI, 0.10-0.83).
Conclusions and Relevance Apixaban compared to aspirin was associated with fewer incident nonlacunar covert infarcts among a subset of patients with a recent cryptogenic ischemic stroke and atrial cardiopathy who were enrolled in ARCADIA.
Contemporary Hormonal Contraception and Risk of Venous Thromboembolism
Harman Gailan Hassan Yonis, MD1; Lina Steinrud Mørch, PhD; Ellen Løkkegaard, PhD; et alKristian Kragholm, PhD; Amalie Lykkemark Møller, PhD; Christian Torp-Pedersen, DrMedSci; Amani Meaidi, PhD
Hormonal contraception is a recognized risk factor for venous thromboembolism (VTE), with the risk influenced by estrogen dose and progestin type. However, VTE risk with newer formulations containing low-dose estrogen, novel progestins, and bioidentical estrogen requires further investigation. This study examined VTE risk across contemporary hormonal contraceptives.
Methods
Using Danish national registers, we conducted a nationwide cohort study including all females aged 15 to 49 years without a history of thrombosis, cancer, thrombophilia, liver or kidney disease, infertility treatment, hormone therapy, oophorectomy, hysterectomy, polycystic ovary syndrome, and endometriosis (eTable 1 in Supplement 1). Females were followed up from January 1, 2011, or their 15th birthday until July 1, 2021, emigration, death, or an exclusionary event.
Outcome was a first diagnosis of lower limb deep venous thrombosis or pulmonary embolism (eTable 1 in Supplement 1). In a sensitivity analysis, we exclusively included VTE diagnoses confirmed by relevant imaging or subsequent anticoagulant prescription redemption.
Hormonal contraception use was determined through redeemed prescriptions,4 including pills with estrogen and progestin (combined pills), vaginal rings, patches, progestin-only pills, intrauterine devices (IUDs), implants, and injections. eTable 2 in Supplement 1 lists all hormonal contraceptives available during the study. Exposure time was calculated from purchased daily doses for short-acting contraceptives and estimated for long-acting methods as 1 year less than the maximum approved duration.
Females were temporarily censored during pregnancy and surgery.
Information on age, calendar year, education, cardiovascular comorbidities, and chronic inflammatory disorders was available for all females. Body mass index (BMI) and smoking were known for some parous females, while family history was available for females with parents in Denmark (eTable 1 in Supplement 1).
Poisson regression provided VTE rate ratios adjusted for age, calendar time, education, hypertension, diabetes, hypercholesterolemia, atrial fibrillation/flutter, systemic connective disorders, inflammatory polyarthropathies, inflammatory bowel diseases, and multiple sclerosis. Absolute rates and rate differences were standardized according to the distribution of these factors in the entire cohort.
We used R software version 4.2.1 (The R Foundation). Statistical significance was defined as a 2-sided 95% CI that did not cross the null. This study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
The Danish Health Data Board and Data Protection Agency granted approval. Informed consent was not required because the data were anonymized.
Results
Among 1 397 235 females followed up for 8 455 601 person-years, 2691 VTEs occurred. eTable 3 in Supplement 1 shows the cohort characteristics. Standardized VTE rates per 10 000 person-years were 2.0 (95% CI, 1.9-2.1) for nonuse, 10.0 (95% CI, 9.2-10.9) for combined pills, 8.0 (95% CI, 4.6-12.8) for vaginal rings, 8.1 (95% CI, 1.5-25.1) for patches, 3.6 (95% CI, 2.8-4.7) for progestin-only pills, 2.1 (95% CI, 1.7-2.6) for IUDs, 3.4 (95% CI, 1.7-6.3) for implants, and 11.9 (95% CI, 4.4-25.6) for injections (Table).
Compared with nonuse, VTE rate ratios were 4.6 (95% CI, 4.2-5.0) for combined pills, 4.5 (95% CI, 3.1-6.5) for vaginal rings, 5.0 (95% CI, 2.1-12.0) for patches, 1.8 (95% CI, 1.4-2.3) for progestin-only pills, 1.0 (95% CI, 0.8-1.1) for IUDs, 2.4 (95% CI, 1.4-4.0) for implants, and 5.7 (95% CI, 3.5-9.3) for injections (Table).
Compared with nonuse, VTE rate ratios were 4.6 (95% CI, 4.2-5.0) for combined pills, 4.5 (95% CI, 3.1-6.5) for vaginal rings, 5.0 (95% CI, 2.1-12.0) for patches, 1.8 (95% CI, 1.4-2.3) for progestin-only pills, 1.0 (95% CI, 0.8-1.1) for IUDs, 2.4 (95% CI, 1.4-4.0) for implants, and 5.7 (95% CI, 3.5-9.3) for injections (Table).
Corresponding additional VTEs per 10 000 person-years were 8.0 (95% CI, 7.2 to 8.7) for combined pills vs nonuse, 6.0 (95% CI, 2.1 to 9.8) for vaginal rings, 6.1 (95% CI, −3.6 to 15.8) for patches, 1.6 (95% CI, 0.7 to 2.6) for progestin-only pills, 0.1 (95% CI, −0.3 to 0.6) for IUDs, 1.4 (95% CI, −0.7 to 3.5) for implants, and 9.9 (95% CI, 0.5 to 19.3) for injections (Table).
VTE excess per 10 000 person-years varied by combined pill formulation (Table), from 3.0 (95% CI, −1.8 to 7.7) for 20-µg estrogen pills with levonorgestrel to 14.2 (95% CI, 9.2 to 19.3) for combined pills containing third-generation progestins. Pills with bioidentical estradiol also showed increased VTE rates.
Associations persisted when exclusively considering confirmed VTE diagnoses.
BMI and smoking data were available for 347 654 females (2 159 859 person-years, 771 VTEs). Family history was available for 1 067 866 females (6 759 035 person-years, 2483 VTEs). Associations remained consistent after adjusting for BMI, smoking, and family history (Table).
Discussion
The study showed VTE risk variation across hormonal contraceptives with highest rates for combined pills, especially those containing third-generation progestins, and no significant difference in risk for IUDs relative to no use. For patches and implants, the increased VTE risk was uncertain due to limited data.
Study limitations included that residual confounding may have remained despite extensive control, and that external generalizability may have been limited by the study population's homogeneity and health profile.
Variation in VTE risk across products underscores the importance of personalized contraceptive counseling.
An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies
J Thromb Haemost 2025 Feb;23(2):731-744.
Katrien M J Devreese, Maria Laura Bertolaccini, D Ware Branch, Bas de Laat, Doruk Erkan, Emmanuel J Favaloro, Vittorio Pengo, Thomas L Ortel, Denis Wahl, Hannah Cohen
Abstract
Antiphospholipid syndrome (APS) diagnosis is dependent on the accurate detection and interpretation of antiphospholipid antibodies (aPL). Lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis. In the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, the type of laboratory parameters remain essentially unchanged compared with the updated Sapporo classification criteria, and aCL and aβ2GPI measurement are still restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively, and a cutoff calculated by the 99th percentile has been abandoned. We must differentiate between classification criteria and assessment of aPL in clinical care. Classification criteria are strict and meant for participant inclusion in studies and trials to study homogeneous populations of patients. In contrast, laboratory detection for APS diagnosis in daily practice is broader, meant to diagnose each APS patient to optimize their management. Nowadays, there is increasing use of measurement of aPL by methods other than ELISAs , the semiquantitative reporting of titers is a matter of debate, as well as the role of the isotypes immunoglobulin (Ig)M and IgA, and the role of other aPL, such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies. Patients diagnosed with the disease may or may not fulfill the classification criteria, and inappropriate use of classification criteria may lead to mis(under)diagnosis. The aim of this guidance, based on literature and expert opinion, is to provide guidance recommendations for laboratory workers and clinicians on routine diagnostic assessment of patients with suspected APS.
Efficacy and safety of anti-Xa direct oral anticoagulants vs. warfarin in patients homozygous for Factor V Leiden and prothrombin G20210A mutations
Ofir Dan, Oleg Pikovsky, Tomer Kerman , Shirly Amar, Anat Rabinovich
J Thromb Thrombolysis, 2025 Feb 1.
Abstract
Factor V Leiden (FVL) and prothrombin G20210A mutation (PGM) are the most common types of inherited thrombophilia, predisposing to increased venous thromboembolism (VTE) risk. The homozygous and compound heterozygous forms of these mutations are extremely rare. While direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) as the primary treatment for VTE, data on their use in patients with high-risk hereditary thrombophilia are limited. To compare the efficacy and safety of DOACs vs. VKA in patients with high-risk hereditary thrombophilia, including FVL and PGM. This retrospective cohort study included adults with homozygous/compound heterozygous FVL and/or PGM who experienced a thrombotic event between 2000 and 2022. The primary outcome was the incidence of recurrent thrombosis in patients with high-risk inherited thrombophilia treated with DOACs versus VKAs. The secondary outcome included a comparison of rates of bleeding complications between these groups. The types of bleeding were defined according to the ISTH criteria. Of 56 patients included 28 received DOACs and 28 received VKAs. There was no significant difference in recurrent VTE rates (1/28, 3.6% DOAC group vs. 0/28, 0% VKA group) or major bleeding (1/28, 3.6% DOAC group vs. 1/28, 3.6% VKA group). This is the largest cohort of patients with high-risk hereditary thrombophilia, providing valuable insights into DOAC use in this group. The findings suggest that DOACs may represent an effective and safe alternative to VKAs. Further research is warranted to confirm these results and optimize anticoagulant management in this challenging patient group.