June 2024: New In Coagulation
by Karen Medecke • June 24, 2024
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
Please Note: many linked teasers require account/subscription in order to view full articles. Medscape registration is free of charge.
What Is Going on With Catheter-Based Pulmonary Embolism Devices in the Real World?
Using information from electronic health records, information from 435,296 patients who received a PE diagnosis were identified. Of those patients, 0.48% received advanced therapy with either mechanical thrombectomy FlowTriever or EKOS ultrasound-guided catheter directed thrombolysis system.
Disparities included that Black and patients women were disproportionately less likely to receive advanced care. When looking at safety studies, major bleeding at 7 days using advanced therapies were more likely applied to white versus Black patients and women versus men. No difference was found for in-hospital mortality and stroke. All analysis was hypothesis generating.
Using the information from Big-Data can aid toward establishing equitable and patient centric care. The Truveta Data Platform was the source of data. Currently the field of PE intervention lacks class I indications for procedures, mandated national registries and designated center of excellence. More work is needed to determine who actually benefits from advanced PE therapies.
The latest device, the AlphaVac F18 which was investigated in the APEX-AV study is the latest device to demonstrate substantial equivalence to current devices. Another device in development is the Helo PE system which was designed to combine aspiration technology with an in-catheter agitator that dislodges clot material.
Impact of Recombinant Replacement Therapy Detailed in Genetic Clotting Disorder
Patients with congenital thrombotic thrombocytopenic purpura (TTP) are missing ADAMTS 13 protein. TTP causes clotting in the small blood vessels that can lead to severe bleeding, strokes and organ damage. A recombinant replacement Adzynma restored levels and decreased acute TTP events including thrombocytopenia. Acute TTP events are defined as a drop in platelets by at least 50% from baseline or less than 100,000 due to consumption, as well as a doubling of LDH. Data was based on 30 of 48 randomized TTP patients. The small number of participants is due to the rarity of congenital TTP so the trial did not have statistical hypothesis and only 95% confidence intervals could be used. This treatment can lead to preventing long-term organ damage by minimizing the formation of platelet rich microthrombi. ADAMTS13 levels increased from a mean of 19% with standard care versus 101% with recombinant therapy.
The randomized crossover study required 6 months of standard care then switched to 6 months of recombinant therapy, and the second group also switched from recombinant to standard. Standard replacement of ADAMTS13 is given prophylactic or on demand as infusion of FFP, plasma treated with solvent detergent or ADAMTS13 containing plasma derived factor VIII/von Willebrand factor concentrates. This is dependent on donor plasma and in hospital infusions as well as severe and treatment limiting allergic reactions to plasma. The recombinant treatment is easier, only minutes and less side effects. Severe adverse events occurred in 14% of patients on standard therapy versus 7% on recombinant therapy which included headache, migraine, nasopharyngitis and diarrhea. 32 patients had completed the trial in the prophylactic cohort (all adults and adolescents) and another 14 patients (including eight younger than 12 years of age) were still underway in the trial. Follow up is planned for 6 years for approximately 77 participants.
Reasons for Heightened Thrombotic Risk in Rheumatoid Arthritis Remain Unclear
Despite being a rare event, subjects with rheumatoid arthritis (RA) have an increased risk for VTE when compared to the general population. Based on data from 117,050 from people living in England and Wales the incidence of VTE (n=23,410) was 0.44% vs 0.26% (n=93,640) matched controls, making the risk 46% higher.
Reasons for this occurrence have been focused on the role of disease activity and inflammation. With the use of JAK [Janus kinase] inhibitors, have emerged in which shows a signal of increased VTE risk from a number of studies. This is occurring despite the JAK inhibitors controlling inflammation. Another observational analysis was performed to evaluate risk; one study looked at age, sex and BMI, the other the duration of RA, and the third look at estrogen based oral contraceptives or HRT. RA patients were matched in a 4:1 ratio to people without RA.
In the first group that looked at age, sex and weight. Based on the adjusted hazard ratios comparing the VTE risk in women and men without RA were 1.62 and 1.52, for age groups 2.13 (18-49 years), 1.57 (50-69 years), and 1.34 (70 years and older). The highest risk was in the youngest group but there was an increased risk in all groups. When looking at BMIs the highest risk occurred in the lowest BMI group. The aHRs were 1.66, 1.60, and 1.41 for the BMI categories of less than 25 kg/m2, 25-30 kg/m2, and more than 30 kg/m2, respectively.
In regard to duration of RA, 63.9% of adults with RA received a diagnosis within 2 years, 7.6% 2-5 years and 9.8% within 5-10 years, and 18.5% at 10 or more years after diagnosis. There was no evidence of VTE excess risk related to time since diagnosis when compared to the control group with a risk o 1.49 at 0-2 years of diagnosis up o 1.63 for greater than 10 years of diagnosis.
When looking at oral contraceptives and HRT, of the 16,664 women with RA 3.3% had used an estrogen-based oral contraceptive and 4.5% had used HRT and 65,448 without RA, 3.9% and 3.8% in the control group, respectively. The risk was 52% higher for VTE in women with RA. However, the sample size was small.
The take home message is that RA is associated with a risk of VTE. However the study is observational and confounding variables may contribute additional risks.
Thrombectomy Led to Fewer Deaths in Patients With Acute Stroke and a Large Infarct
The LASTE trail compared medical care alone versus thrombectomy and medical care in patients with acute stroke and unrestricted infarcts. The trial was stopped early because of the support shown with thrombectomy. A total of 333 patients (France and Spain) were randomized 1:1 thrombectomy plus medical care (median age 73, 82% men) or medical care alone (median age 74, 88% men). Baseline infarct volume was larger than other trials at 135ml or greater. At 90 days the Rankin score was 4 indicating moderately severe disability in thrombectomy group versus 6 in the control group indicating death. Death from any cause occurred in 36.1% of the thrombectomy group versus 55.5% in the control group.
Patients with unrestricted and large infarcts have the most severe strokes along with a high mortality, very high morbidity and a high risk of disability. Concern was raised that while results are preventing these people from dying, they are being improved just to become disabled.
Step-Down Antiplatelet Strategy Pairs Well With DCB Angioplasty
The first randomized trial to look at antiplatelet de-escalation post drug coated balloon (DCB) in ACS patients was named REC-CAGEFREE II. The trial used a stepwise strategy of DAPT de-escalation using aspirin plus ticagrelor for 1 month, 5 months of ticagrelor monotherapy, then 6 months of aspirin monotherapy. DCBs are angioplasty balloons that deliver an antiproliferative drug, leaving no permanent metal behind. This strategy showed noninferiority versus standard 12-month DAPT. The trial included 1948 subjects who were randomized to one of two DAPT strategies after successful DAPT implantation. Average age was 59 and 75% were male. Up to 30% had diabetes, 30% prior PCI and 20% HBR, 60% had unstable angina and the remaining 40% had acute MI.
DAPT de-escalation primary endpoint was 9.0% compared with 8.7% with standard DAPT including all cause death, stroke, MI, revascularization and bleeding on intention to treat analysis. Bleeds were reduced in the de-escalation setting. These results support DCB technology allows less intense antiplatelet therapy post PCI.
It is noted that the study population was selected for DCB suitability and not an ACS population. These patients had 56% small vessel disease, 45% bifurcation, 19% in stent restenosis and 10% diffuse lesions.
Andexanet Shows Efficacy in Acute ICH With Factor Xa Inhibitors
Andexanet has been used to treat patients with acute ICH in patients on factor Xa inhibitors which has led to less expansion of hematoma volume but was associated with thrombotic events. Andexanet alfa is a form of human factor Xa, a reversal agent that binds and sequesters Xa inhibitor molecules, restoring thrombin generation. ANNEXA-1 included 530 people of which 263 were randomized to Andexanet (high-dose or low-dose bolus over 15 to 30 minutes followed by a continuous infusion over 2 hours) and 267 to usual care (prothrombin complex) with an average age of 79, and just under half were female. Hemostatic efficacy was defined in a period of 3 measures within 12 hours. This included expansion of hematoma by 35% or less, an increase of less than 7 points on the NIH stroke scale and no receipt of rescue therapy. This was achieved in 67% of patients compared with 53.1% receiving standard care. The median percent change in anti-factor Xa activity between baseline and 1-2 hour nadir was 94.5% with the Andexanet versus 26.9% with the usual care. However, 10.3% on the reversal agent had a thrombotic event versus 5.6% on standard care. Ischemic stroke occurred in 6.5% and 1.5% of participants. The mechanism of thrombotic events with Andexanet is uncertain.
FDA OKs Second Gene Therapy for Hemophilia B
A second gene therapy, fidanacogene elaparvove, has been approved for use in adult men with moderate to severe hemophilia B. It is to be used in patients currently treated with prophylactic factor IX with a history of life-threatening hemorrhage, or spontaneous bleeding episodes and do not have neutralizing antibodies to the adeno-associated virus serotype Rh74var capsid. This allows patients to produce FIX without infusions after a one time infusion. The initial gene therapy, etranacogene dezaparvovec was approved in November 2022.
The phase III trial BENEGENE-2 included 45 men with moderate to severe hemophilia B (FIX activity
Four Might Be the Magic Number for Anticoagulation of Subclinical Afib
In a subanalysis of the ARTESiA trial looked to distinguish who would benefit from anticoagulation with apixaban in patients with device detected subclinical atrial fibrillation (SCAF) without increasing their bleeding risk. The trial included 4,012 patients randomly assigned to double-blind, double-dummy treatment with apixaban (5 mg twice daily, or 2.5 mg twice daily when indicated) or aspirin (81 mg daily). Patients included SCAF detected by pacemaker, defibrillator or cardiac monitor, with an episode longer than 6 minutes but not greater than 24 hours. CHA2DS2-VASc score of ≥3, or any score if the patient had a history of stroke or was age 75 years or older. Patients were excluded if they had a history of clinical AF, an ongoing indication for OAC, a history of uncorrected major bleeding in the prior 6 months, or low creatinine clearance. The mean age was 76.8.
Results showed that in 39% of subjects who had a CHA2DS2-VASc score under 4 had just 0.04 strokes prevented by use of apixaban versus aspirin with 1.28 bleeds per 100 patients. In those with a risk score of 4 (39%) there were 2.25 strokes prevented at the cost of 0.05 bleeds. Those over the risk score of 4 (27%) a larger benefit occurred with 3.95 strokes prevented and 1.70 bleeds, so at a greater risk. The stroke rate detected in subclinical AF is very low and treated patients with clinical Afib had a stroke rate of 1.6% and untreated patients were even lower. It is important to balance the risk of stroke versus bleeding and must be based on each patient.
Subclinical Afib events are detected in about one-third of patients with implanted cardiac devices. Guidelines don't recommend any anticoagulation, even though studies have suggested a slight increased stroke risk. The ARTESiA shows that the patients CHA2DS2-VASc score may be a way to stratify patients to guide OAC.
Bleeding Risk Clarified in Patients With Ischemic Stroke Receiving tPA
A higher risk for ICH was seen in patients with acute ischemic stroke (AIS) on antiplatelet therapy treated with thrombolysis, however the absolute increased risk is small and should not prevent withholding this treatment. The recommendation for AIS patients is IV-tpa within 4.5 hours of stroke onset to reduce stroke related morbidity.
The study included 321,819 patients with a mean age of 69 years (16% Black and 69% White) from the Get With the Guidelines (GWTG) stroke registry. Of those 36.5% used single platelet therapy (SAP: aspirin, clopidogrel, prasugrel, or ticagrelor monotherapy), and DAPT (aspirin-clopidogrel, aspirin-ticagrelor, or aspirin-prasugrel combination therapy) was used in 6.8% prior to IV-tPA. Pre-stroke risk factors were accounted for by a propensity score subclassification algorithm. The primary outcome was ICH documented by imaging within 36 hours of treatment.
Symptomatic ICH occurred in 2.9% among those not taking antiplatelet therapy, 3.8% of those taking SAPT, and 4.1% among patients treated with DAPT. After subclassification and adjustments, ICH risk was 13% higher with pre-stroke SAPT exposure and 28% higher in DAPT exposure. When compared with no pre-stroke antiplatelet therapy the SAPT and DAPT groups had a 0.9% and 1.2% increased risk for ICH.
A secondary outcome using the modified Rankin Scal (mRS) score evaluated functional outcomes at outcomes that was adjusted for covariates. Function independence was less likely with SAPT compared to no antiplatelet however the difference was small. A slight increase was seen in DAPT patients of in hospital mortality. The study was not sufficiently powered to know which DAPT combinations increased this occurrence.
Results suggest DAPT should not preclude treatment with thrombolysis. This was a retrospective, observational study, subject to selection bias and may not generalize to non US population. Indication bias may occur due to the lack of matching patient characteristics. Also missing were antiplatelet dosage and time of last ingestion.
JOURNAL CLUB
Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention
A Systematic Review and Patient-Level Meta-Analysis
Marco Valgimigli, MD, PhD; Felice Gragnano, MD, PhD; Mattia Branca, PhD; et alAnna Franzone, MD, PhD; Bruno R. da Costa, PhD; Usman Baber, MD; Takeshi Kimura, MD; Yangsoo Jang, MD, PhD; Joo-Yong Hahn, MD; Qiang Zhao, MD, PhD; Stephan Windecker, MD; Charles M. Gibson, MD; Hirotoshi Watanabe, MD; Byeong-Keuk Kim, MD; Young Bin Song, MD; Yunpeng Zhu, MD; Pascal Vranckx, MD, PhD; Shamir Mehta, MD; Kenji Ando, MD; Sung Jin Hong, MD; Hyeon-Cheol Gwon, MD; Patrick W. Serruys, MD; George D. Dangas, MD; Eùgene P. McFadden, MD2; Dominick J. Angiolillo, MD, PhD; Dik Heg, PhD; Paolo Calabrò, MD, PhD; Peter Jüni, MD6; Roxana Mehran, MD; for the Single Versus Dual Antiplatelet Therapy (Sidney-3) Collaboration
Abstract
Importance Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor.
Objective To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI.
Data Sources MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction.
Study Selection Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI.
Data Extraction and Synthesis Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.
Main Outcomes and Measures The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding.
Results Analyses included 6 randomized trials including 25,960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06;
Conclusions and Relevance This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.
Temporarily Reversing Warfarin With Low-Dose 4-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Patients Undergoing an Invasive Procedure
Byron Stevenson , A Joshua Roberts , William E Dager
Ann Pharmacotherapy 2024 Apr 27:10600280241248172
Abstract
Abstract
Background: American Association for Thoracic Surgery and The International Society for Heart and Lung Transplantation (AATS/ISHLT) guidelines recommend warfarin in patients with continuous-flow left ventricular assist devices (LVADs) to reduce the risk of device thrombosis and systemic embolization. Left ventricular assist device patients often undergo elective and emergent procedures that require interrupted anticoagulation. Data and experience vary on the optimal strategy to rapidly reverse warfarin in LVAD patients when an emergent procedure is planned.
Objective: The purpose of this study was to describe the use of 4-factor prothrombin complex concentrate (PCC4) for warfarin reversal in patients with LVADs undergoing elective and emergent procedures.
Methods: This retrospective, single-center, cohort review describes the use of PCC4 in patients with LVADs who require warfarin reversal for elective or emergent procedures. The primary outcome was a composite incidence of pump thrombosis, venous thromboembolism, and ischemic stroke within 30 days of PCC4 administration.
Results: In total, 14 patients received 17 administrations of PCC4. One patient received 3 administrations, and 1 other patient received 2 administrations during separate encounters. The median dose was 500 units or 6.6 units/kg (range = 4.2-14.1 units/kg). Of the PCC4 administrations, 82% (14/17) were for low bleed risk procedures and 76% (13/17) were for elective procedures. There were no cases of pump thrombosis, venous thromboembolism, or stroke within 30 days of the procedure.
Conclusions and relevance: Low-dose PCC4 appears to be a safe and effective temporary reversal strategy for patients with LVADs undergoing low-bleed risk elective procedures.
Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer
Marie-Laure Kürzinger , Chantal El-Haddad , Tatiana Gouin-Soboleva , Zita Fazekas , Denis Granados , Elizabeth Benito-Garcia , Yasmina Djoudi
Pharmacoepidemiol Drug Saf 2024 May;33(5):e5795.
Abstract
Purpose: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer.
Methods: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results.
Results: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups.
Conclusions: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.
Safety and efficacy of direct oral anticoagulants in comparison to warfarin in obese patients with atrial fibrillation: A systematic review and meta-analysis
Alla Adelkhanova Prakash Raj Oli, Dhan Bahadur Shrestha , Jurgen Shtembari Vivek Jha , Ghanshyam Shantha , George Michael Bodziock , Monodeep Biswas, Muhammad Omer Zaman, Nimesh K Patel
Health Sci Rep 2024 Apr 21;7(4):e2044.
Abstract
Background and aim: Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF.
Methods: The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure.
Results: Two thousand two hundred fifty-nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66-0.75) and (OR 0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54-0.83), major bleeding (OR 0.62, CI 0.54-0.72), and composite outcome (OR 0.72, CI 0.63-0.81).
Conclusion: Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.
Relationship between electronically monitored adherence to direct oral anticoagulants and ischemic or hemorrhagic events after an initial ischemic stroke-A case control study
Katharina Rekk, Isabelle Arnet, Fine Dietrich, Alexandros A Polymeris, Philippe A Lyrer, Stefan T Engelter, Sabine Schaedelin, Samuel S Allemann
PLoS One 2024 Apr 25;19(4):e0301421.
Abstract
Background: Patients with atrial fibrillation (AF) have a high risk for recurrent clinical events after an ischemic stroke. Direct oral anticoagulants (DOAC) are prescribed for secondary prevention. Adherence to DOAC is crucial mainly because of their short elimination half-life. Non-adherence to DOAC can negatively impact patients' outcomes. The relationship between (non-)adherence and recurrent clinical events is unknown in AF patients after initial stroke. We investigated adherence to DOAC in stroke survivors with AF who were included in the MAAESTRO study at the University Hospital Basel, Switzerland, between 2008 and 2022.
Methods: This study is a secondary analysis of data from MAAESTRO with a matched nested case-control design and 1:2 ratio. DOAC intake was measured with a small electronic device (Time4MedTM). We defined two arbitrary intervals of 17 days and 95 days as the longest time spans with electronic monitoring data per patient to maximize the number of participants with adequate amount of observation time available for analysis. Taking and timing adherence were calculated retrospectively i.e., prior to the recurrent event for cases. Trendline analysis of adherence over 95 days was calculated. Linear regression analysis was performed after adjusting for the co-variables age and daily pill burden. Sensitivity analysis was performed with controls for intervals in the reverse direction (prospectively).
Results: We analyzed 11 cases and 22 matched controls (mean age: 75.9 ± 9.2 years vs. 73.1 ± 8.4 years; n.s.) with similar stroke characteristics (NIHSS, mRS, MoCA) and 36.4% women in each group. Mean adherence values were high and similar between cases and controls (95 days taking: 87.0 ± 18.9% (cases) vs. 90.8 ± 9.8% (controls), n.s.; similar values for timing adherence). Six hemorrhagic and five ischemic events had occurred. Compared to controls, a significantly higher 95 days taking adherence was observed for hemorrhagic events (96.0 ± 5.0% (cases) vs. 88.1 ± 11.5% (controls); p<0.01) and a significantly lower 95 days taking adherence was observed for ischemic events (75.7 ± 24.8% (cases) vs. 94.2 ± 6.2% (controls), p = 0.024). Values for timing adherence were similar. A non-significant downward linear trend of adherence was observed over 95 days independently of the clinical events. The sensitivity analysis showed that the direction of the interval had negligible impact on the 95 days adherence.
Conclusion: Because recurrent ischemic events after an AF-related stroke were associated with low adherence to DOAC <76%, adherence enhancing interventions seem crucial in anticoagulated AF-patients. However, AF-patients with high adherence might benefit from a regular re-assessment of the bleeding risk as hemorrhagic complications were associated with adherence to DOAC >96%.
Pregnancy-Associated Venous Thromboembolism
Omar Seyam , William H Frishman , Wilbert S Aronow
Cardiol Rev 2024 Apr 26.
Abstract
One of the leading causes of maternal death in the United States is venous thromboembolism (VTE), which is influenced by acquired, genetic, and environmental factors. Pregnancy-associated physiological changes that exhibit the characteristics of Virchow's triad: reduced fibrinolysis, increased coagulation factors, trauma, and venous stasis all raise the risk of VTE. Furthermore, multiple gestations, advanced maternal age, cesarean delivery, and obesity are all pregnancy-associated risk factors that also increase the risk of VTE. Management of VTE during pregnancy can be challenging due to the risks and benefits of anticoagulant therapy and potential hazard for both the fetus and the mother. In this review, we discuss the prevalence, pathogenesis, predisposing factors, and therapeutic options such as systemic thrombolysis, mechanical thrombectomy, and catheter-directed thrombolysis.
Performance of direct oral anticoagulant (DOAC) testing by hemostasis laboratories: The Australasian/Asia-Pacific experience
Emmanuel J Favaloro , Sandya Arunachalam, Elysse Dean
Int J Lab Hematol 2024 Apr 21.
Abstract
Introduction: Direct oral anticoagulants (DOACs) reflect anticoagulation agents given to treat or prevent thrombosis, having largely replaced vitamin K antagonists (VKAs) such as warfarin. DOACs are given in fixed daily doses and generally do not need monitoring. However, there may be a variety of reasons that justify measurement of plasma DOAC levels in individual patients.
Methods: We report updated findings for DOAC testing in our geographic region, using recent data from the RCPAQAP, an international external quality assessment (EQA) program, currently with some 40-60 participants in each of the different DOAC (rivaroxaban, apixaban, dabigatran) modules, to assess laboratory performance in this area. Data has been assessed for the past 5 years (2019-2023 inclusive), with 20 samples each per DOAC.
Results: Data shows a limited repertoire of assays in use, and mostly consistency in reported numerical values when assessing proficiency samples. Available assays mostly comprised reagents from four manufacturing suppliers. There was good consistency across what participants identified as 'DOAC detected', but some variability when participants attempted to grade DOAC levels as low vs moderate vs high. Inter-laboratory/method coefficient of variation (CVs) were generally <15% for each DOAC, when present at >100 ng/mL.
Conclusion: We hope our findings, reflecting on mostly consistent reporting of DOAC levels and interpretation provides reassurance for clinicians requesting these measurements, and helps support their implementation in regions where there is a paucity of test availability.
Low recurrent thrombosis rates in single positive antiphospholipid syndrome regardless of type of anticoagulation
Brianna R Bakow, Lisa Yanek, Mark A Crowther, Shruti Chaturvedi
Thromb Res 2024 May:237:88-93.
Abstract
Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aβ2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS.