Effectiveness of a Calculation-Free Weight-Based Unfractionated Heparin Nomogram With Anti-Xa Level Monitoring Compared With Activated Partial Thromboplastin Time.

BACKGROUND: Accurate monitoring of intravenous unfractionated heparin (UFH) is essential to mitigate the risk of adverse drug events associated with dosing errors. Although recent data support anti-factor Xa (anti-Xa) monitoring preferentially over activated partial thromboplastin time (aPTT) to improve time to therapeutic anticoagulation, the utility of incorporating anti-Xa monitoring with a calculation-free weight-based UFH nomogram has not been formally evaluated. OBJECTIVE: The primary objective of this study was to evaluate the time to therapeutic anticoagulation of a calculation-free weight-based UFH nomogram integrated with anti-Xa monitoring versus a historical control of aPTT monitoring utilizing manual dose calculations. METHODS: This was a retrospective analysis of patients with anti-Xa monitoring and a novel calculation-free weight-based UFH nomogram compared with a historical control with aPTT monitoring and manual calculations. RESULTS: A total of 103 patients in the aPTT cohort and 100 patients in the anti-Xa cohort were analyzed. The anti-Xa cohort achieved goal therapeutic target 3.8 hours sooner than the aPTT cohort (P = 0.03). Patients with anti-Xa monitoring required 1 fewer adjustment per 2.5 patient-days of UFH with the venous thromboembolism nomogram (P = 0.02). Patients in the aPTT cohort required more infusion interruptions because of supratherapeutic values (P = 0.007) and boluses because of subtherapeutic values (P = 0.044). There were no differences in rates of thromboembolism, major bleeding, or clinically relevant nonmajor bleeding between the cohorts. CONCLUSION AND RELEVANCE: This study demonstrated that anti-Xa UFH monitoring integrated with a calculation-free nomogram results in faster time to therapeutic anticoagulation and fewer dose adjustments compared with aPTT monitoring with manual calculations.

Clinical utility and impact of the use of the chromogenic vs one-stage factor activity assays in haemophilia A and B.

Treatment of haemophilia A/B patients comprises factor VIII (FVIII) or factor IX (FIX) concentrate replacement therapy, respectively. FVIII and FIX activity levels can be measured in clinical laboratories using one-stage activated partial thromboplastin time (aPTT)-based clotting or two-stage chromogenic factor activity assays. We discuss strengths and limitations of these assays, providing examples of clinical scenarios to highlight some of the challenges associated with their current use for diagnostic and monitoring purposes. Substantial inter-laboratory variability has been reported for one-stage assays when measuring the activity of factor replacement products due to the wide range of currently available aPTT reagents, calibration standards, factor-deficient plasmas, assay conditions and instruments. Chromogenic activity assays may avoid some limitations associated with one-stage assays, but their regulatory status, perceived higher cost, and lack of laboratory expertise may influence their use. Haemophilia management guidelines recommend the differential application of one or both assays for initial diagnosis and disease severity characterisation, post-infusion monitoring and replacement factor potency labelling. Efficient communication between clinical and laboratory staff is crucial to ensure application of the most appropriate assay to each clinical situation, correct interpretation of assay results and, ultimately, accurate diagnosis and optimal and safe treatment of haemophilia A or B patients.

Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini-review.

A common inquiry in coagulation laboratories is how to interpret an unexpected, isolated prolonged activated partial thromboplastin time (APTT). In this context, isolated means together with a normal prothrombin time (PT) and/or normal international normalized ratio (INR). This finding may lead to contact with laboratory doctors for further advice on a diagnostic strategy. Occasionally, the need for a diagnostic algorithm can be subacute, where surgery has to be postponed until an explanation for the isolated, prolonged APTT has been established. Activated partial thromboplastin time as a coagulation test was developed to monitor patients with hemophilia. Different APTT reagents display considerable differences in their sensitivity to deficiencies of coagulation factors. An isolated, prolonged APTT is seen in (a) individuals/patients with lupus anticoagulants, (b) patients in treatment with anticoagulants, mainly heparin, and (c) patients with deficiencies of specific coagulation factors. In this tutorial review, we summarize what may cause an isolated prolonged APTT and we present a simple diagnostic algorithm to differentiate between lupus anticoagulants (common) and factor deficiencies (rare). The identification of an isolated prolonged APTT as well as the underlying cause can be of the utmost importance in ensuring the correct therapeutic follow-up.

Emergency medicine misconceptions: Utility of routine coagulation panels in the emergency department setting.

BACKGROUND: Coagulation panels are ordered for a variety of conditions in the emergency department (ED). OBJECTIVE: This narrative review evaluates specific conditions for which a coagulation panel is commonly ordered but has limited utility in medical decision-making. DISCUSSION: Coagulation panels consist of partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR). These tests evaluate the coagulation pathway which leads to formation of a fibrin clot. The coagulation panel can monitor warfarin and heparin therapy, evaluate for vitamin K deficiency, evaluate for malnutrition or severe systemic disease, and assess hemostatic function in the setting of bleeding. The utility of coagulation testing in chest pain evaluation, routine perioperative assessment, prior to initiation of anticoagulation, and as screening for admitted patients is low, with little to no change in patient management based on results of these panels. Coagulation testing should be considered in systemically ill patients, those with a prior history of bleeding or family history of bleeding, patients on anticoagulation, or patients with active hemorrhage and signs of bleeding. Thromboelastography and rotational thromboelastometry offer more reliable measures of coagulation function. CONCLUSIONS: Little utility for coagulation assessment is present for the evaluation of chest pain, routine perioperative assessment, initiation of anticoagulation, and screening for admitted patients. However, coagulation panel assessment should be considered in patients with hemorrhage, patients on anticoagulation, and personal history or family history of bleeding.

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.

The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

BACKGROUND: To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. METHODS: The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. RESULTS: The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. CONCLUSION: C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid.

Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations.

When administering unfractionated heparin (UFH), therapeutic levels of anticoagulation must be achieved rapidly and maintained consistently in the therapeutic range. The basic assays for monitoring UFH therapy are the activated partial thromboplastin time (APTT) and/or the chromogenic antifactor Xa or antithrombin assays. For many laboratories, the APTT is the preferred standard of practice; however, the APTT is a surrogate marker that only estimates the heparin concentration. Many factors, including patient variation, reagents of the APTT, UFH composition, and concentration can influence the APTT result. This article reviews various methods to determine the heparin therapeutic range and presents recommendations for the laboratory to establish an APTT heparin therapeutic range for all sizes of hospitals.

Diagnostic accuracy of silica clotting time method for lupus anticoagulant in a clinical population with various symptoms of antiphospholipid syndrome.

INTRODUCTION: Correct interpretation of lupus anticoagulant (LA) tests is crucial for diagnosis of antiphospholipid syndrome (APS). This study assessed diagnostic accuracy of the SCT method in a clinical population with various symptoms of APS. MATERIAL AND METHODS: Altogether 60 APS patients were consecutively recruited from a relevant clinical population. All cases had stable positivity of at least one of the reference tests (two other LA methods; anticardiolipin- and anti-ß2-glycoprotein-I antibodies). Controls (n = 62) with negative reference tests were also consecutively recruited from the same clinical population. RESULTS AND CONCLUSIONS: Receiver operator characteristic (ROC) analysis for the SCT test to identify the APS cases showed area under the curve of 0.82 (95% CI 0.75-0.90). The positive cut-off defined by a non-parametric method (99 percentile in a healthy population) had specificity of 92%, but low sensitivity of 53%. The optimal cut-off corresponded to the 97.5 percentile (67% sensitivity and 92% specificity). Combined sensitivity of the positive diluted Russell Viper Venom time (dRVVT) and SCT tests was 73%, while specificity remained 92%. The sensitivity of the SCT method varied in different clinical subgroups and was highest in patients with rheumatic diseases and in patients with triple positivity of three reference methods.

Variability in combinations of APTT reagent and substrate plasma for a one-stage clotting assay to measure factor VIII products.

INTRODUCTION: An investigation of the suitability of reagents for measuring FVIII products in a one-stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII-deficient plasma (F8DP), even though the APTT-based OSA is comprised of APTT reagents and factor-deficient plasma. AIM: A single-centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. METHODS: FVIII:C in nine types of FVIII product-spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. RESULTS: F8DP-dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP-3). This lower TR was not observed with alternative manufacturing lots of F8DP-3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP-3. CONCLUSION: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur.

Are tube fill volumes below 90% a rejection criterion for all coagulation tests?

BACKGROUND: Rejected samples lead to prolonged turnaround time and delayed diagnosis and treatment of patients. This study was conducted to determine minimum acceptable sample volume in Sarstedt brand coagulation tubes to reduce high sample rejection rate. METHODS: Blood samples were drawn from 20 participants (10 healthy volunteers and 10 patients receiving oral anticoagulant) into coagulation tubes. Six samples were taken from each participant, with tube fill volumes of 100%, 90%, 80%, 70%, 60%, and 50%. Prothrombin time (PT), active partial thromboplastin time (aPTT), and fibrinogen tests were analyzed. RESULTS: According to quality performance specifications, the tube fill volume must be at least 70% for PT and aPTT and 50% for fibrinogen. There was no statistical difference in samples from healthy volunteers for PT, aPTT, and fibrinogen tests when the minimum tube fill volume was at least 80%, 90%, and 50%, respectively. These percentages were 50%, 70%, and 60%, respectively, in patients receiving oral anticoagulant. CONCLUSIONS: Sarstedt tubes meet quality standard specifications at a 70% fill rate for PT and aPTT and a 50% fill rate for fibrinogen. Comprehensive studies with larger populations are needed to accept these values as sample acceptance criteria for the laboratory.

The influence of dead space in blood sampling needle on FVIII level and pharmacokinetic profiles in children with hemophilia.

OBJECTIVE: To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia. METHODS: Children (<18 years) with severe hemophilia A were enrolled. After three days' washout-period, blood samples were collected at pre-dose, 1 h, 3 h, 9 h, 24 h and 48 h post-infusion. At each timepoint, two 2 mL vacuum tubes with 3.2% trisodium citrate were used. The first tube was signed as 'non-standard' (NS) and the second tube was signed as 'standard' (S). FVIII activities were evaluated by one-stage assay. WAPPS-Hemo was used to generate PK profiles like half-life time (t1/2), clearance (CL), trough level and time to 1, 2 and 5IU/dL after a dose of 50 ± 10IU/dL. The FVIII activities at 9 h and 24 h post-infusion were put into WAPPS and thus brought four combinations by true or biased FVIII level that used. RESULT: Compared with standard-collected blood samples, prolonged APTT results (P-values < 0.01) and decreased FVIII activity (P-values < 0.05) were revealed in those non-standard blood samples. The corresponding bias was in positive relation to both APTT-S (r = 0.44, P < 0.0001) and FVIII-S level(r = 0.68, P < 0.001). The FVIII bias percentage got larger as FVIII-S level reduced (r = -0.24, P < 0.01). During the four combinations of FVIII activity at 9 h and 24 h, statistically longer t1/2, lower CL and longer time to 1, 2 or 5IU/dL were observed in 9H-S&24H-S group and 9H-NS&24H-S group. CONCLUSION: While using vacuum tubes for clotting indicators and PK profiles, the dead space of blood sampling needle should be eliminated in advance.

[Method comparison between two hemostasis analyzers: STA R Max3 and Cobas t 511]. / Comparaison de méthode entre deux analyseurs d'hémostase : STA R Max3 et Cobas t 511.

The STA R Max3 (Stago, France) and Cobas t511 (Roche Diagnostics, Germany) are two automated hemostasis analysers that can be used to perform a wide range of tests. The STA R Max3 uses a mechanical clot detection system to measure coagulation times, while the Cobas t511 uses optical detection. The aim of this study was to compare the analytical performance of these two analysers using fresh plasma samples with or without a risk of interference due to hemolysis or lipemia. For plasma samples without interference, acceptable agreement was observed for prothrombin time (PT) (n = 55), activated partial thromboplastin time (APTT) (n = 56), fibrinogen (n = 56) and factor II (n = 43) with R² of 0.907, 0.963, 0.979 and 0.968 respectively. For factor V (n = 43) and D-dimers (n = 45), agreement was less acceptable, with respective R² of 0.756 and 0.887, but with no clinical impact. For hemolysed samples, acceptable results were observed for PT, fibrinogen and D-dimers, but three results were clinically discordant for APTT, and STA R Max3 offered greater robustness for processing highly lipemic samples.

Comparison of six dilute russell viper venom time lupus anticoagulant screen/confirm assay kits.

BACKGROUND: The normalized dilute Russell viper venom time (DRVVT) ratio provides a robust assay methodology for lupus anticoagulant (LA) detection. OBJECTIVES: We evaluated six normalized DRVVT LA screen and confirm systems for inter-method consistency. Reagents were purchased from Diagnostica Stago, Inc. (Parsippany, NJ); Precision BioLogic Inc. (Halifax, Nova Scotia, Canada); Siemens Healthcare Inc. (Deerfield, IL); TCoag (Parsippany, NJ); Instrumentation Laboratories (Bedford, MA); and Sekisui Diagnostics (Pfungstadt, Germany). METHODS: For all assays, we employed the STA-R Evolution automated coagulometer, adhering to manufacturers' instructions. LA-positive and LA-negative plasma controls were purchased from Diagnostica Stago and pooled normal plasma (PNP) was purchased from Precision BioLogic. We computed the mean of the reference interval (MRI) and action limits for all kits using LA-negative aliquots from locally sourced normal subjects (n = 42). We then assayed locally sourced LA-positive plasmas (n = 43) and using analysis of variance compared uncorrected screen/confirm ratios and screen/confirm ratios that were normalized using MRI and mean PNP results. RESULTS: The grand mean action limit, MRI + 3 SD, derived from the local normal plasmas, was 1.2, confirming the manufacturers' recommended limits; however, limits must be locally computed. The all-sample p value was less than 0.001, indicating heterogeneity among ratios. When Sekisui ratios were excluded, the p value was 0.14, thus indicating that this method introduced the major difference among methods. Mean screen/confirm ratios computed from LA-positive specimens were 1.91 to 2.04 for reagent systems other than Sekisui, which instead yielded a mean ratio of 1.198, indicating that this method was relatively insensitive to LA. A negative bias was recorded by two lots from the Sekisui system for LA-positive specimens. Screen/confirm ratios from combined LA-positive and LA-negative samples generated a combined range of 1.59 to 1.67 for all reagents except Sekisui, which instead yielded 1.09. The within-run percent coefficient of variation (CV%) was less than 5.0% using all samples. Between-run CV% using Diagnostica Stago LA-positive and LA-negative controls was less than 5.5%. CONCLUSIONS: DRVVT screen/confirm ratios discriminate between LA-positive and LA-negative samples and generally provide acceptable reproducibility. Ratio results may vary among reagent-instrument combinations. In this study, normalization added little to the clinical result interpretation.

Thromboelastography (TEG®) compared to conventional coagulation tests in surgical patients--a laboratory evaluation.

BACKGROUND: Several methods exist for evaluation of hypocoagulation in patients with perioperative bleeding, e.g. thromboelastography (TEG(®)) and conventional methods (platelet count, aPTT, INR and fibrinogen). Considering the vast experience of conventional methods it is important to investigate how well the methods correspond. METHODS: Sixty surgical patients were included prospectively and blood samples were taken perioperatively. TEG(®) and conventional parameters were analyzed simultaneously. An assessment of coagulopathy, based on a synthesis of the conventional methods, was done by two experienced coagulation specialists, blinded from the results of TEG(®) and from the results of each other. Hypocoagulation, defined by TEG(®) parameters; reaction time (R-time), angle, maximal amplitude (MA) and fibrinolysis, was evaluated according to a commonly used algorithm. RESULTS: To detect a platelet count below 150 × 10(9) L(-1), the sensitivity of TEG was 17% (95% CI, 7-36%) with angle and 25% (95% CI, 11-45%) with MA. The sensitivity to detect fibrinogen below 2 g/L was 11% (95% CI, 3-29%) with angle and 21% with MA (95% CI, 8-43%). To detect aPTT more than 40 s and INR more than 1.2 with R-time, the sensitivity was 19% (95% CI, 8-37%) and 0% (95% CI, 0-69%) respectively. The agreement of the evaluator's assessments of hypocoagulation was 100%, but the agreement with the overall TEG(®) analysis was poor with a sensitivity of 33% and a specificity of 95%. CONCLUSION: The agreement between conventional laboratory tests and TEG is poor, but it remains uncertain which type of coagulation tests that best reflects the actual bleeding risk.

Do elevated hematocrits prolong the PT/aPTT?

The Clinical and Laboratory Standards Institute guidelines require special processing of whole blood specimens with hematocrits greater than 55% due to the possibility of spurious prolongation of routine coagulation studies (PT, aPTT). As samples with hematocrits above 60% are rare at our institution, our study seeks to determine the effect of relative citrate excess on routine coagulation studies in samples with hematocrits of 60% to determine whether special processing is necessary. A calculated volume of 3.2% citrate was added to 1 mL aliquots of 40 whole blood samples in citrated tubes from adult patients to simulate a hematocrit of 60%. A dilutional control was created by adding an equivalent volume of saline to a separate 1 mL aliquot. Routine coagulation studies (PT, aPTT) were run on both samples on the STA Compact Analyzer in accordance with manufacturer instructions. While a paired Student's t-test demonstrated a clinically significant change in both PT and aPTT with the addition of citrate (p = 0.0002 for PT and p = 0.0234 for aPTT), clinical management would not have been altered by any observed change. More interestingly, we observed a shortening of 27/40 PTs and 23/40 aPTTs rather than the expected prolongation. Based on our data, no adjustment of citrate volume appears to be necessary in samples with hematocrits less than or equal to 60%.

Approaches to investigating common bleeding disorders: an evaluation of North American coagulation laboratory practices.

Bleeding disorders commonly result from deficiencies or defects in von Willebrand factor (VWF), platelets, coagulation factors, or fibrinolytic proteins. The primary goal of our study was to assess current North American coagulation laboratory practices for diagnosing bleeding disorders, using an on-line patterns-of-practice survey of diagnostic laboratory members of the North American Specialized Coagulation Laboratory Association. The survey examined laboratory approaches to evaluating bleeding disorders, with specific questions about the tests and test panels offered and compliance to recent guideline recommendations on diagnosing von Willebrand disease (VWD) and platelet function disorders. All laboratories responding to the survey performed a prothrombin time/international normalized ratio, an activated partial thromboplastin time, and coagulation factor assays, and many tested for VWD and platelet disorders. However, few laboratories had test panels that evaluated the more common bleeding disorders and few performed some assays, including VWF multimer assessments and assays for fibrinolytic disorders. Additionally, the cutoffs used by laboratories to diagnose type 1 VWD varied considerably, with only a minority following the National Heart Lung Blood Institute recommendations. In contrast, laboratories that tested for platelet function disorders mostly complied with aggregation testing recommendations, as published in the recent North American guidelines. Our results indicate that there are some gaps in the strategies used by laboratories to diagnose bleeding disorders that might be addressed by development of further guidelines and test algorithms that emphasize evaluations for common bleeding disorders. Laboratories may also benefit from guidelines on test interpretation, and external evaluation of their bleeding disorder testing strategies.

Usefulness of cumulative summation of differences method for determining APTT reagent suitability.

OBJECTIVE: The Cumulative Summation of Differences (CUSUM) is a recommended method for determining the consistency of one lot of Activated Partial Thromboplastin Time (APTT) reagent to another. This study investigates the usefulness of the CUSUM as a primary method for determining reagent suitability for APTT testing. METHOD: Results for lot comparison, reference range and Ex-Vivo heparin sensitivity studies were obtained using the Beckman Coulter ACL TOP coagulation analyzer. APTT testing was performed using HemosIL SynthASiL w/CaCl and Heparin Xa testing was performed using the HemosIL Liquid Heparin Assay. Samples from normal patients and from patients taking heparin were tested. RESULTS: The CUSUM calculation showed a difference in APTT reagent lot means that is within the acceptable range for this method, suggesting that the reagents were comparable. Reference range and heparin sensitivity studies demonstrated a clinically significant difference between the two reagent lot numbers tested. CONCLUSION: The CUSUM method of evaluating reagent lot variation of APTT reagents should be used with caution as it may not completely reflect the performance of the reagent. Clinically significant differences between reagent sensitivity may not be detected. The results of reference range and heparin sensitivity studies should also be considered when determining the suitability of APTT reagents. In addition, due to research evidence that using the APTT test for monitoring patient anticoagulation therapy is problematic, an evaluation of the benefits of using other study methods and multiple study methods is suggested as well as continued examination of the use of the APTT as the test of choice for UF heparin monitoring.

Reflex factor coagulation testing in patients with an unexplained prolonged aPTT: An institutional retrospective review.

BACKGROUND: We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution. METHODS: We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes. RESULTS: Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder. CONCLUSION: Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor.