Fibrinogen, Coagulation, and Ageing.

The World Health Organization estimates that the world's population over 60 years of age will nearly double in the next 30 years. This change imposes increasing demands on health and social services with increased disease burden in older people, hereafter defined as people aged 60 years or more. An older population will have a greater incidence of cardiovascular disease partly due to higher levels of blood fibrinogen, increased levels of some coagulation factors, and increased platelet activity. These factors lead to a hypercoagulable state which can alter haemostasis, causing an imbalance in appropriate coagulation, which plays a crucial role in the development of cardiovascular diseases. These changes in haemostasis are not only affected by age but also by gender and the effects of hormones, or lack thereof in menopause for older females, ethnicity, other comorbidities, medication interactions, and overall health as we age. Another confounding factor is how we measure fibrinogen and coagulation through laboratory and point-of-care testing and how our decision-making on disease and treatment (including anticoagulation) is managed. It is known throughout life that in normal healthy individuals the levels of fibrinogen and coagulation factors change, however, reference intervals to guide diagnosis and management are based on only two life stages, paediatric, and adult ranges. There are no specific diagnostic guidelines based on reference intervals for an older population. How ageing relates to alterations in haemostasis and the impact of the disease will be discussed in this chapter. Along with the effect of anticoagulation, laboratory testing of fibrinogen and coagulation, future directions, and implications will be presented.

Major Bleeding During Thrombolytic Therapy for Acute Lower Limb Ischaemia: Value of Laboratory Tests for Clinical Decision Making, 17 Years of Experience.

OBJECTIVE: Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. METHODS: All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. RESULTS: Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT. CONCLUSION: High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.

Improving the safety of outpatient parenteral antimicrobial therapy for patients with solid tumors.

BACKGROUND AND OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. METHODS: We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. RESULTS: Completeness of ID provider notes improved from a baseline of 77 to 100% (p < .0001) for antimicrobial recommendations, 75 to 97% (p < .0001) for follow-up recommendations, and 19 to 98% (p < .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% (p = .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. CONCLUSIONS: Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

Utility of CD4 count measurement in the era of universal antiretroviral therapy: an analysis of routine laboratory data in Botswana.

OBJECTIVES: National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post-antiretroviral therapy (ART) initiation. We evaluated the utility of CD4 count measurement in Botswana in the era of universal ART. METHODS: CD4 and VL data were analysed for HIV-infected adults undergoing CD4 count measurement in 2015-2017 at the Botswana Harvard HIV-Reference Laboratory. We determined (1) the proportion of individuals with advanced HIV disease (CD4 count < 200 cells/µL) at initial CD4 assessment, (2) the proportion with an initial CD4 count ≥ 200 cells/µL experiencing a subsequent decline in CD4 count to < 200 cells/µL, and (3) the proportion of these immunologically failing individuals who had virological failure. Logistic regression modelling examined factors associated with advanced HIV disease. CD4 count trajectories were assessed using locally weighted scatterplot smoothing (LOWESS) regression. RESULTS: Twenty-five per cent (3571/14 423) of individuals with an initial CD4 assessment during the study period had advanced HIV disease at baseline. Older age [≥ 35 years; adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.8-2.1] and male sex were associated with advanced HIV disease. Fifty per cent (7163/14 423) of individuals had at least two CD4 counts during the study period. Of those with an initial CD4 count ≥ 200 cells/µL, 4% (180/5061) experienced a decline in CD4 count to < 200 cells/µL; the majority of CD4 count declines were in virologically suppressed individuals and transient. CONCLUSIONS: One-quarter of HIV-positive individuals in Botswana still present with advanced HIV disease, highlighting the importance of baseline CD4 count measurement to identify this at-risk population. Few with a baseline CD4 count ≥ 200 cells/µL experienced a drop below 200 cells/µL, suggesting limited utility for ongoing CD4 monitoring.

Adherence to laboratory testing in pediatric liver transplant recipients.

BACKGROUND: The objectives of this retrospective cohort study are to describe rates of adherence to laboratory testing 6 months to 3 years post-liver transplantation and to examine demographic and clinical factors related to lab non-adherence and the association with medication adherence and clinical outcomes. METHODS: Medical chart review was conducted for 54 youth (mean age = 5.0 years) transplanted between 2003 and 2014. Lab adherence (≥80%) was measured as the proportion of completed labs out of the number expected. Immunosuppressant drug-level variability was used as a proxy for medication adherence. Clinical outcomes included LAR, viral infection, hospitalization, and non-routine clinic visit ≥12 months after transplant. RESULTS: Lab adherence decreased substantially over time. Single-parent household (aOR 5.86; 95% CI: 1.38-24.93) and no history of early rejection (aOR 3.96; 95% CI: 1.04-15.24) were independently associated with non-adherence. Lab non-adherence was significantly associated with medication non-adherence (P < .05), LAR (P = .02), and non-routine clinic visits (P = .03). CONCLUSIONS: Systematic monitoring of lab adherence may help in identifying pediatric LT recipients at increased risk for excessive healthcare use and adverse outcomes possibly due to poor disease management.

Laboratory monitoring during treatment of onychomycosis in pediatric patients: A survey of provider perspectives and practices.

BACKGROUND/OBJECTIVES: Literature regarding the cost and necessity of laboratory monitoring during oral antifungal treatment in adults has recently been published. However, consensus guidelines for the treatment and monitoring of pediatric patients with systemic antifungals for onychomycosis are lacking. We sought to evaluate both the practice trends and perspectives of pediatric dermatology providers who treat pediatric onychomycosis. METHODS: An electronic survey was administered to providers belonging to the Society for Pediatric Dermatology (SPD) and/or Pediatric Dermatology Research Alliance (PeDRA) regarding their clinical practice and reasoning for laboratory monitoring during the treatment of pediatric onychomycosis. RESULTS: One hundred and twenty-one providers completed the survey (12.5%). 77% identified themselves as pediatric dermatologists. A majority practice in the academic setting (51%), and 54% were primarily only pediatric providers. All respondents prescribe oral terbinafine for onychomycosis. 88% of respondents always or almost always confirm the diagnosis of onychomycosis prior to prescribing oral terbinafine for onychomycosis. 39% always or almost always routinely order baseline laboratory tests while 40% never or almost never do. 41% never or almost never order monitoring laboratory tests during treatment while 32% always or almost always do. 91.5% have never discovered a significant reaction to terbinafine with routine monitoring. CONCLUSION: Pediatric dermatology providers are very likely to confirm the diagnosis of onychomycosis prior to systemic treatment. Significant variability was found in pretreatment and treatment laboratory monitoring, reasons for laboratory monitoring or deferral of testing, and timing of testing among providers. Knowledge of current practice trends as well as provider perspectives may be useful in the future development of consensus guidelines.

Laboratory measurement of factor replacement therapies in the treatment of congenital haemophilia: A United Kingdom Haemophilia Centre Doctors' Organisation guideline.

Assay discrepancies can occur with laboratory monitoring of FVIII and FIX replacement therapy, particularly for the extended half-life products. This guideline collates current published data and provides advice on appropriate choice of assays for laboratory measurement of replacement therapy for patients with Haemophilia A and B without inhibitors. It is recommended that each haemophilia centre should ensure that appropriate laboratory assays are available for FVIII and FIX products in local clinical use. Patient samples should be assayed against calibrators traceable to WHO Plasma International Standards. Assay discrepancies are common especially for the extended half-life FVIII and FIX products, and assays of these products may need to be verified with the specific CFC being used.

Compliance with laboratory monitoring guidelines in outpatient HIV care: a qualitative study in the Netherlands.

Evidence-based guidelines in HIV care aim to improve patients' health outcomes, quality of care, and cost-effectiveness. Laboratory monitoring plays an important role in assessing clinical status of patients and forms an integral part of HIV treatment guidelines. The Dutch HIV monitoring foundation (Stichting HIV Monitoring) previously observed variation between HIV treatment centres in the Netherlands in terms of compliance with guidelines for performing laboratory tests. Drawing on qualitative research methods, this article aims to describe factors that influence guideline compliance for laboratory monitoring in outpatient HIV care in the Netherlands. Twelve semi-structured in-depth interviews were conducted with a convenience sample of physicians from four HIV treatment centres. In general, physicians perceived laboratory guidelines as useful. However, unclear online visual representation of the guidelines, a lack of set reminders for tests, and assessment of patients' risk behaviour, which differs per patient, were identified as barriers to guideline compliance. The compartmentalisation of the Dutch healthcare system was viewed as hampering guideline compliance. A clinical-decision-support tool could possibly facilitate compliance with laboratory monitoring guidelines. Moreover, better alignment of HIV outpatient care, municipal health services and primary care, in terms of laboratory testing, could optimize efficiency, increase cost-effectiveness, and improve quality of HIV care.

Laboratory Monitoring and Transfusion Guidelines to Influence Care in Patients Undergoing Multilevel Spinal Fusion Surgery.

PURPOSE: The purpose of this project was to determine whether the use of the modified Northwestern high risk spine protocol in patients undergoing multilevel spinal fusion surgery would result in improved transfusion practices. DESIGN: Preimplementation and postimplementation design. METHODS: A laboratory monitoring and transfusion guideline protocol was implemented in patients undergoing multilevel spinal fusions. Data were collected via a manual retrospective chart review of the electronic medical record before and after implementation of the protocol. FINDINGS: Laboratory values were monitored at guided intervals. There was a statistically significant (P = .004) decrease in the mean hemoglobin value at which a packed red blood cell transfusion was initiated. CONCLUSIONS: Through the use of the protocol, laboratory value monitoring provided quantitative data to aid and improve clinical decision making for practitioners in the perioperative period.

Laboratory Testing of a Cohort of Commercially Insured Users of HIV Preexposure Prophylaxis in the United States, 2011-2015.

To ensure the health and safety of persons taking antiretroviral medication as preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection, Centers for Disease Control and Prevention guidelines recommend initial and follow-up laboratory testing. We assessed the rates of recommended testing, using a commercial insurance claims database. Before taking PrEP, 45% of users were tested for HIV, 55% for syphilis, 43% for chlamydia/gonorrhea, and 38% for hepatitis B, and 31% had their creatinine level measured. By 6 months after PrEP initiation, 38% were tested for HIV, 49% for syphilis, and 39% for chlamydia/gonorrhea, and 37% had their creatinine level measured. Although laboratory testing was less frequent than recommended, testing rates increased over the study period.

[Herpesviral infection as an etiological factor of acute idiopathic optic neuritis]. / Gerpes-virusnaia infektsiia kak étiologicheskii faktor ostrogo idiopaticheskogo opticheskogo nevrita.

PURPOSE: To assess the etiological significance of herpesviral infection (HVI) in patients with acute idiopathic optic neuritis (ON) using clinical and laboratory monitoring. MATERIAL AND METHODS: Clinical and laboratory examinations were conducted for 10 years and were based on the results of etiological monitoring of 79 patients (85 eyes) with acute idiopathic ON in the period of 2005-2015. RESULTS: During a complex examination of 79 patients with acute idiopathic ON, various infectious pathogens were diagnosed in 75 people (94.9±2.1%). HVI was clearly dominant (69 patients - 87.3±2.4%). These patients were divided into 3 etiological groups. The first group - 34 people with herpesviral monoinfection; the second group - 15 people with mixed viral-viral infections; the third group - 20 people with mixed viral-bacterial infections. In the general population of patients with acute idiopathic ON associated with HVI, herpes simplex virus-1 is the most frequent (by more than 2.5 times), the infections of Epstein-Barr virus and cytomegalovirus were detected less often (p<0.05). Active current HVI in the general group of patients was diagnosed in 58 patients (84%). At the same time, reactivation of chronic infection (79.7%) was noted to be prevalent, while primary acute HVI was diagnosed rarely (4.3%). The remaining 11 patients (16%) had chronic persistent HVI. CONCLUSION: Clinical and laboratory monitoring of HVI in patients with acute idiopathic ON has shown the etiological role of herpesviruses in its development. Based on a complex of serological markers in enzyme-linked immunoassay reactions of blood serum, it was found that in patients with acute idiopathic ON the frequency of herpesviral infection is 87.3±2.4%. The proportion of active (etiologically significant) herpesviral infection is 84% of the total group. The results of the clinical and laboratory studies are of great practical importance for verification of the etiologic diagnosis and selection of adequate etiopathogenetic therapy in patients with acute idiopathic ON associated with HVI.

American Gastroenterological Association Institute Clinical Practice Update-Expert Review: Care of Patients Who Have Achieved a Sustained Virologic Response After Antiviral Therapy for Chronic Hepatitis C Infection.

Chronic hepatitis C virus infection is well-recognized as a common blood-borne infection with global public health impact affecting 3 to 5 million persons in the United States and more than 170 million persons worldwide. Chronic hepatitis C virus infection is associated with significant morbidity and mortality due to complications of liver cirrhosis and hepatocellular carcinoma. Current therapies with all-oral direct-acting antiviral agents are associated with high rates of sustained virologic response (SVR), generally exceeding 90%. SVR is associated with a reduced risk of liver cirrhosis, hepatic decompensation, need for liver transplantation, and both liver-related and all-cause mortality. However, a subset of patients who achieve SVR will remain at long-term risk for progression to cirrhosis, liver failure, hepatocellular carcinoma, and liver-related mortality. Limited evidence is available to guide clinicians on which post-SVR patients should be monitored vs discharged, how to monitor and with which tests, how frequently should monitoring occur, and for how long. In this clinical practice update, available evidence and expert opinion are used to generate best practice recommendations on the care of patients with chronic hepatitis C virus who have achieved SVR.

Making sense of a haemolysis monitoring and reporting system: a nationwide longitudinal multimethod study of 68 Australian laboratory participant organisations.

BACKGROUND: The key incident monitoring and management systems (KIMMS) quality assurance program monitors incidents in the pre- and postanalytical phases of testing in medical laboratories. Haemolysed specimens have been found to be the most frequent preanalytical error and have major implications for patient care. The aims of this study were to assess the suitability of KIMMS for quality reporting of haemolysis and to devise a meaningful method for reporting and monitoring haemolysis. METHODS: A structured survey of 68 Australian KIMMS laboratory participant organisations was undertaken. Quarterly haemolysis reports (2011-2014) were analysed. RESULTS: Among 110 million accessions reported, haemolysis rates varied according to the reporting methods that participants used for assigning accessions (16% of participants reported haemolysis by specimen and 83% reported by episode) and counting haemolysis rejections (61% by specimen, 35% by episode and 3% by test). More than half of the participants (56%) assigned accessions by episode and counted rejections by specimen. For this group, the average haemolysis rate per 100,000 episodes was 177 rejected specimens with the average rate varying from 100 to 233 over time. The majority of participants (91%) determined rejections using the haemolysis index. Two thirds of participants (66%) recorded the haemolysis manually in laboratory information systems. CONCLUSIONS: KIMMS maintains the largest longitudinal haemolysis database in the world. However, as a means of advancing improvements in the quality of the preanalytical laboratory process, there is a need to standardise reporting methods to enable robust comparison of haemolysis rejection rates across participant laboratories.

Monitoring of anticoagulant therapy in cancer patients with thrombosis and the usefulness of blood activation markers.

Thrombotic diseases caused by cancer progression have been reported as one of the major causes of cancer associated morbidity and mortality along with cancer invasiveness and infectious complications. Moreover, anticoagulant therapy with heparin and heparin-like drugs, or vitamin K antagonists, or the Direct Oral Anticoagulants, is seeing an extended application in cancer patients and offers prolonged life expectancy to oncology patients for whom blood activation and thrombotic events have a variable incidence, depending on cancer type. Laboratory tools are highly useful for identifying patients at thrombotic risk through the measurement of blood activation markers and selecting those appropriate for anticoagulant therapy. Among the pathological markers, DDimer or Extracellular Vesicles have the highest diagnostic value in these pathological conditions. Global assays are useful for dosage adjustment, such as assessing either an induced anticoagulant effect or the measurement of drug activity. Various assays are also developed such as platelet aggregometry techniques for evaluating drug induced- aggregates or methods allowing measurement of the drug activity to its targeted coagulation factors such as: heparin to thrombin or Factor Xa; DOACs to Thrombin or Factor Xa (Dabigatran to thrombin and DiXaIs, Rivaroxaban, Apixaban, and Edoxaban, to Factor Xa). Such explorative techniques help to find the right dosage adjustment to protect patients from developing thrombosis without exposing them bleeding. It also permits exploration of unexpected drug behavior in treated patients, to check the right adherence to therapy in long-term anticoagulant protocols, and prevention of bleeding in patients with impaired renal or hepatic function. Complementary use of blood activation markers brings additional information on the curative effects of the anticoagulant therapy, and allows identification of pro-thrombotic activity in the clinically silent state. These issues are concisely addressed below.

[Laboratory aspects of novel oral anticoagulant treatment]. / Az új orális antikoagulánsokkal történo kezelés laboratóriumi vonatkozásai.

The introduction of novel oral anticoagulants (NOAC) have long been expected drugs and they quickly became used widespread as their clinical effectiveness was as good as, or even better than the previously used only oral anticoagulant drug, the coumarins. Thus, the direct thrombin inhibitor dabigatran and the activated factor X inhibitors (rivaroxaban, apixaban, edoxaban) have become the part of daily therapeutic practice. Their permeation was facilitated by the guideline which suggested that no laboratory monitoring was required during NOAC treatment and this was very convenient for both patients and doctors. The clinical experience obtained in the past years, however have proved that the 'one size fits all' view is oversimplified and there are numerous situations when the determination NOAC levels is unavoidable or highly recommended. This review discusses the laboratory aspects of NOAC treatment, primarily summarizing their effect on the screening tests and special assays of hemostasis and we also describe the correct methods to determine their plasma concentrations. Orv Hetil. 2017; 158(49): 1930-1945.

Laboratory Monitoring of Antiretroviral Therapy for HIV Infection: Cost-Effectiveness and Budget Impact of Current and Novel Strategies.

BACKGROUND: Optimal laboratory monitoring of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) remains controversial. We evaluated current and novel monitoring strategies in Côte d'Ivoire, West Africa. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications -International model to compare clinical outcomes, cost-effectiveness, and budget impact of 11 ART monitoring strategies varying by type (CD4 and/or viral load [VL]) and frequency. We included "adaptive" strategies (biannual then annual monitoring for patients on ART/suppressed). Mean CD4 count at ART initiation was 154/µL. Laboratory test costs were CD4=$11 and VL=$33. The standard of care (SOC; biannual CD4) was the comparator. We assessed cost-effectiveness relative to Côte d'Ivoire's 2013 per capita GDP ($1500). RESULTS: Discounted life expectancy was 16.69 years for SOC, 16.97 years with VL confirmation of immunologic failure, and 17.25 years for adaptive VL. Mean time on failed first-line ART was 3.7 years for SOC and <0.9 years for all routine/adaptive VL strategies. VL failure confirmation was cost-saving compared with SOC. Adaptive VL had an incremental cost-effectiveness ratio (ICER) of $4100/year of life saved compared with VL confirmation and increased the 5-year budget by $310/patient compared with SOC. Adaptive VL achieved an ICER <1× GDP if second-line ART and VL costs simultaneously decreased to $156 and $13, respectively. CONCLUSIONS: VL confirmation of immunologic failure is more effective and less costly than CD4 monitoring in Côte d'Ivoire. Adaptive VL monitoring reduces time on failing ART, is cost-effective, and should become standard in Côte d'Ivoire and similar settings.

Standardized laboratory monitoring with use of isotretinoin in acne.

BACKGROUND: Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care. OBJECTIVE: We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne. METHODS: We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined. RESULTS: Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3 days for hypertriglyceridemia, 61.9 days for alanine transaminitis, and 50.1 days for hypercholesterolemia. LIMITATIONS: This was a single-center experience examining variable isotretinoin laboratory monitoring practices. CONCLUSIONS: In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2 months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended.

Antifactor Xa levels vs. activated partial thromboplastin time for monitoring unfractionated heparin. A pilot study.

WHAT IS KNOWN AND OBJECTIVES: The two most common methods for monitoring unfractionated heparin (UFH) infusion are the activated partial thromboplastin time (aPTT) and the antifactor Xa heparin assay (anti-Xa). The purpose of this study is to compare the performance of an aPTT protocol vs. an anti-Xa protocol in adult patients as defined by the time to reach therapeutic range, the percentage of time the values were within the goal range and the number of times laboratory monitoring was conducted. We then analysed the discordance between paired values of anti-Xa and aPTT. METHODS: This was a single-centre prospective cohort pilot study conducted from 1 September 2013 to 31 May 2014. RESULTS: Eighty-five patients were treated with UFH infusion, aPTT monitoring (n = 48), anti-Xa monitoring (n = 37). The number of times aPTT and anti-Xa values were ordered was (median, IQR) 14 (2-34) vs 7 (2-76); P = 0·23. The time to reach therapeutic range in hours was (mean, SD) 22 (20) aPTT vs 15 (13) anti-Xa; P = 0·08. Therapeutic range (>50-100% of the time) was achieved in only 5 (10%) patients in the aPTT group vs. 21 (57%) in the anti-Xa group; P < 0·01. Supratherapeutic values (>50-100%) were observed in 38 (78%) patients in the aPTT group vs. 14 (38%) in the anti-Xa group; P < 0·01. The discordance between aPTT and anti-Xa was evaluated using 234 paired values from 37 patients. There was discordance between anti-Xa and aPTT values 57% of the time. Two patients had bleeding complications requiring blood transfusion or discontinuation of post-pilot protocol. WHAT IS NEW AND CONCLUSION: Utilizing an anti-Xa protocol to monitor heparin infusion showed favourable results compared with utilizing an aPTT protocol by maintaining values within the therapeutic goal range. The most common discordant pattern in our study was a disproportionate prolongation of aPTT to anti-Xa values. Patients with discordant values presenting with high aPTT to normal anti-Xa values may have an increased risk of bleeding complications.

Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants?

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.