Introduction When monitoring heparin, anti-Xa assays are susceptible to interference from apixaban taken before admission and can result in inappropriate dose adjustments that can negatively affect patient care. Methods We derived a novel assay, termed corrected heparin (CH), using quantified values from a chromogenic anti-Xa assay with heparin calibrators before and after heparinase treatment to eliminate any interference from apixaban within the patient sample. We retrospectively assessed 469 specimens from 72 patients at our institution who had their unfractionated heparin infusion monitored using the CH assay because of known apixaban use. These patients were included in the study if they had detectable apixaban levels (>0.1 IU/mL by anti-Xa). Results The analytical performance of the assay was evaluated, and precision was found to be 8.8% within 1 day and 13.3% over multiple days, with acceptable linearity (R2 = 0.997). Evaluation of clinical performance was compared with the partial thromboplastin time (PTT), showing a lack of correlation similar to comparisons between the PTT and anti-Xa assay (Blood Coagul Fibrinolysis 1993;4:635–8). The mean time to a therapeutic result in this cohort was 10 hours and 10 minutes. The CH assay was used to determine how long the apixaban was detected by the anti-Xa assay. The majority of patients (80%) still had measurable anti-Xa assay interference from apixaban at 24 hours after the last apixaban dose. Conclusions We have developed and evaluated an assay capable of quantifying heparin in the presence of apixaban. This assay showed acceptable performance in both analytical and clinical performance.
A markedly prolonged activated partial thromboplastin time (APTT) was observed in a 61-year-old woman with bruising and a decreasing hematocrit. Coagulation laboratory evaluation was sought to determine the cause of the prolonged APTT and bleeding. Evaluation demonstrated that, rather than identifying a coagulopathy, the APTT prolongation was most likely artifactual. The APTT was actually very short. With a combination of a relatively strong activating APTT reagent (Dade Actin; Dade, Miami, FL) and a fixed lag phase in the automated The activated partial thromboplastin time (APTT) is a routine and widely used coagulation assay. Although perhaps most commonly used as a routine admission laboratory or preoperative screening test, its greatest utility is in the detection of hemostatic defects in patients with bleeding.1 The APTT is now performed almost exclusively on automated coagulation instruments, rather than by a manually operated technique, such as a fibrometer. Inherent in the program of most automated coagulation instruments is a period of up to 20 seconds after addition of the activator and calcium before optical density measurements are read to avoid interpreting turbulence as evidence of clot formation. Ordinarily the APTTs of patients are longer than this lag phase. However, a strong activating APTT reagent may have a normal range of 20-25 seconds or even shorter. Short APTTs may be observed in acutely ill patients because of marked elevations of Factor VIII:C or fibrinogen 2 and in patients with disseminated intravascular coagulation caused by the presence of activated clotting factors.3 The use of this combination of an instrument with a long lag phase and a strong activator to evaluate a patient with a short APTT may result in an APTT shorter than the lag phase. When this happens, the instrument only begins recording at the end of the lag phase (ie, after the clot has formed) and records no change in light transmission during the entire recording period, suggesting that no clot has formed. This type of error can be particularly misleading in the evaluation of a patient with active bleeding. CASE REPORTA 61 -year-old woman with chronic rheumatoid arthritis and pulmonary fibrosis was seen for evaluation of ecchymoses, which developed spontaneously over her left upper chest during a 2-day period. Laboratory studies showed a normal prothrombin time and a markedly prolonged APTT (Table 1). Her hematocrit, which during the past year had been in the range of 30-35%, was decreased to 25%. She was admitted to the hospital for evaluation. Her medications on admission included methylprednisolone, nizatidine, verapamil, triamterene, hydrochlorothiazide, ciprofloxacin, albuterol by inhaler, and 4 L of oxygen by nasal cannula. Examination showed a well-demarcated dark ecchymosis over her left upper chest extending into the axilla. No hematoma was palpable. Multiple smaller (< 5 cm) ecchymoses were found on the arms and legs. Her stools tested negatively for occult blood. The patient received four units of fresh-fr...
Background Heparin-induced thrombocytopenia (HIT) is an immune-mediated, adverse reaction to heparin in which heparin binds platelet factor 4 (PF4), triggering the development of heparin-PF4 antibodies (HITAb). HITAbs bind and activate platelets, causing thrombosis, platelet consumption, and thrombocytopenia. Heparin is replaced with relatively costly nonheparin anticoagulants until HIT can be ruled out. HIT diagnosis consists of a HITAb immunoassay with reflex to a serotonin release assay (SRA) for confirmation of positive results. Recently, a fully automated latex immunoturbidimetric assay (LIA) for detection of HITAbs received FDA clearance. We sought to verify the performance characteristics of the LIA with the aim of implementing the test in a high-volume university hospital laboratory. Methods The in-house HITAb LIA was performed on the Instrumentation Laboratory TOP700 analyzer using HemosIL HIT-Ab(PF4-H) reagent. The comparator method, a HITAb ELISA, was performed at a reference laboratory with positive results reflexed to SRA. All samples (36 total) sent to the reference laboratory for HIT testing from December 2017 to November 2018 were aliquoted and run in parallel by LIA. Intra-assay precision was assessed by running manufacturer-provided low and high control samples 10 times in succession, while interassay precision was assessed by running low and high samples every day for 10 days. Turnaround time to HITAb result was retrieved from the electronic medical records for HIT testing performed 60 days before and after in-house test implementation. Results The agreement between the LIA and ELISA was 92% (33/36). One discordant sample tested negative by ELISA and was not assessed by SRA. Another tested positive by ELISA and negative by LIA and was confirmed negative by SRA. The final discordant sample tested negative by LIA but positive by ELISA and was confirmed positive by SRA. Thirty-three percent (12/36) of samples tested positive for HITAb by ELISA and were reflexed to SRA. Both the ELISA and LIA showed 83% agreement (10/12) with the SRA. The coefficient of variance (CV) for the intra-assay precision studies was 18% and 5% for the low and high controls, respectively. The CV for the interassay precision studies was 28% and 5% for the low and high controls, respectively. Postimplementation quality control data revealed 61% and 20% imprecision on the low and high level controls, respectively, which declined significantly when reagents were removed from the instrument and refrigerated within 2 hours. The turnaround time for HITAb results was reduced by 74% (10.5 vs 41 hours) after in-house test implementation, significantly reducing the need for administration of nonheparin anticoagulants. Conclusion The LIA and ELISA methods compared favorably, allowing for clinical implementation of the LIA. The shortened turnaround time of the LIA significantly reduced the time to rule out HIT, enhancing patient care and reducing drug costs. The assay imprecision warrants further investigation regarding reagent stability.
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