Come back when you're infected: pharmacy access to sterile syringes in an Arizona Secret Shopper Study, 2023.

BACKGROUND: Pharmacies are critical healthcare partners in community efforts to eliminate bloodborne illnesses. Pharmacy sale of sterile syringes is central to this effort. METHODS: A mixed methods "secret shopper" syringe purchase study was conducted in the fall of 2022 with 38 community pharmacies in Maricopa and Pima Counties, Arizona. Pharmacies were geomapped to within 2 miles of areas identified as having a potentially high volume of illicit drug commerce. Daytime venue sampling was used whereby separate investigators with lived/living drug use experience attempted to purchase syringes without a prescription. Investigator response when prompted for purchase rationale was "to protect myself from HIV and hepatitis C." A 24-item instrument measured sales outcome, pharmacy staff interaction (hostile/neutral/friendly), and the buyer's subjective experience. RESULTS: Only 24.6% (n = 28) of 114 purchase attempts across the 38 pharmacies resulted in syringe sale. Less than one quarter (21.1%) of pharmacies always sold, while 44.7% never sold. Independent and food store pharmacies tended not to sell syringes. There emerged distinct pharmacy staff interactions characterized by body language, customer query, normalization or othering response, response to purchase request and closure. Pharmacy discretion and pharmacy policy not to sell syringes without a prescription limited sterile syringe access. Investigators reported frequent and adverse emotional impact due to pharmacy staff negative and stigmatizing interactions. CONCLUSIONS: Pharmacies miss opportunities to advance efforts to eliminate bloodborne infections by stringent no-sale policy and discretion about syringe sale. State regulatory policy facilitating pharmacy syringe sales, limiting pharmacist discretion for syringe sales, and targeting pharmacy-staff level education may help advance the achievement of public health goals to eliminate bloodborne infections in Arizona.

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%.

Lupus anticoagulant increases activated partial thromboplastin time (PTT) prolongation in incubated 1:1 mix.

UNLABELLED: Our study analyzes the effects of incubation time and strength of lupus anticoagulant (LAC) on clotting times and prolongation of activated partial thromboplastin time (PTT) 1:1 mix assays with incubation. The prolongation in seconds of PTT 1:1 mix after incubation in the confirmed presence or absence of LAC was correlated to strength of the LAC as well as length of incubation (1 vs. 2 hours). Our study suggests that when screening for possible Factor VIII (FVIII) inhibitors, a 2 hour incubation of a PTT 1:1 mix increases the frequency of false positives as compared to 1 hour incubation, and that most of these false positives are due to LACs. Prolongation of clotting times for PTT 1:1 mixes in patients with LAC is influenced by both length of incubation time and strength of the LAC. CONCLUSIONS: When using PTT 1:1 mixes to screen for FVIII inhibitors, the effect of a possible LAC on the interpretation of the PTT prolongation should be considered. This effect is influenced by both incubation time and LAC strength.

Plasma-diluted thrombin time to measure dabigatran concentrations during dabigatran etexilate therapy.

New anticoagulants, like the orally available direct thrombin inhibitor (DTI) dabigatran etexilate, have recently been introduced into the market for venous thromboembolic prophylaxis and for stroke prevention in atrial fibrillation. While dabigatran has been approved for use without the need for routine therapeutic monitoring, there are clinical scenarios in which monitoring can help guide clinical management. We report herein the application of a recently described plasma-diluted thrombin time (DTI assay) used to monitor intravenous DTI as a useful and easily implemented method to monitor oral DTIs.

comparison of clot-based vs chromogenic factor Xa procoagulant phospholipid activity assays.

We compared 2 commercial plasma procoagulant phospholipid activity (PPA) assays, chromogenic, using bound annexin V to capture phosphatidylserine-containing microparticles, and clot-based. In both, anionic phospholipids accelerated activation of prothrombin by factor Xa. PPA levels were lower in the chromogenic vs the clot-based assay, with poor correlation between methods: normal samples, mean ± SD, 27 ± 17 vs 590 ± 414 nmol/L (n = 24; r(2) = 0.29) and patient samples, mean ± SD, 45 ± 44 vs 401 ± 330 nmol/L (n = 51; r(2) = 0.26). Recovery of phosphatidylserine added to normal, heparinized, and warfarin plasma samples averaged 109% ± 39% using the chromogenic assay but was higher and more varied (mean ± SD, 176% ± 59%) in the clot-based assay. Lupus anticoagulants caused low recovery in both assays. Removal of microparticles by 0.22-µm filtration reduced PPA by 91% in the clot-based and 65% in the chromogenic assay. The clot-based assay showed higher correlation (r(2) = 0.82 vs 0.23) with flow cytometric platelet microparticle counts. The 2 assays measure different aspects of PPA in plasma, with the chromogenic assay primarily measuring smaller microparticles.

Development of a rapid emergency hemorrhage panel.

BACKGROUND: Evaluation of hemostasis in bleeding patients requires both accuracy and speed. STUDY DESIGN AND METHODS: As an alternative to point-of-care testing, we developed an emergency hemorrhage panel (EHP: prothrombin time [PT], fibrinogen, platelet count, hematocrit) for use in making transfusion decisions on bleeding patients with a goal of less than 20-minute turnaround time (TAT) when performed in the clinical laboratory on automated instruments. Because point-of-care samples are not checked for clotting or hemolysis, we evaluated their effect on automated testing. RESULTS: TAT was reduced by moving the sample immediately to testing and shortening centrifugation times. Clotting in samples was rare (1.1%) and shortened the PT by only 0.7 seconds. It lowered fibrinogen on average 18%, but resulted in only one of 2300 samples changing from normal to low fibrinogen. Hemolysis had no clinically significant effect on the PT or fibrinogen. Therefore, hemolysis checks were eliminated and clot checks minimized. Initially TAT averaged 15±4 minutes (range, 8-30min), but 9% of samples exceeded the 20-minute goal due to low fibrinogens that slowed testing. A revised fibrinogen assay with expanded calibration range resulted in a TAT of 14±3 minutes (range, 6-28min) with only 2% of samples exceeding the 20-minute goal. By limiting EHPs to patients that were actively bleeding, EHPs accounted for only 8 of 243 coagulation samples per day. CONCLUSION: Limiting EHPs to bleeding patients and modifications to the process and assays used for hemostasis testing lead to TATs of less than 20 minutes for critical testing in the clinical laboratory.

Comparison of plasma with whole blood prothrombin time and fibrinogen on the same instrument.

We compared plasma with whole blood (WB) international normalized ratio (INR) and fibrinogen using the same instrument and reagents. WBINRs were 50% higher than plasma INRs. After increasing the WB sample volume 40% and adjusting the International Sensitivity Index, WBINRs were similar to plasma INRs [adjusted WBINR = 0.99(plasma INR) - 0.02; r(2) = 0.98; n = 155], but the average difference in WB vs plasma INR was 4-fold higher than duplicate plasma INRs. Variation in hematocrit was a major determinant of the accuracy of the WBINR, with increased error at high INRs. The WB fibrinogen assay was highly dependent on the sample hematocrit (r(2) = 0.83), even after the sample volume was adjusted. Accurate WB fibrinogen measurements required a mathematical hematocrit correction. We conclude that WBINR and fibrinogen assays can be performed on point-of-care or automated analyzers, but sample volume must be adjusted to account for hematocrit. Accuracy is limited by variations in hematocrit with worsening accuracy for samples with high INRs or low fibrinogen levels.

Monitoring direct thrombin inhibitors with a plasma diluted thrombin time.

Activated partial thromboplastin time (aPTT) monitoring of direct thrombin inhibitors (DTIs) is vulnerable to interference from many sources. If the baseline aPTT is prolonged, as occurs with lupus inhibitors, alternative methods are required to monitor DTI levels. We compared the plasma diluted thrombin time (1:4 dilution of patient plasma with normal plasma) and the aPTT in patient samples spiked with argatroban, bivalirudin, or lepirudin at three concentration levels. Each drug was spiked into five samples with lupus inhibitors, five samples with deficient vitamin K-dependent factors, three samples with elevated D-dimers, and eight samples with normal baseline aPTT values. The aPTT overestimated the spiked DTI concentration in all samples with lupus inhibitors, low levels of vitamin K-dependent factors, and elevated D-dimers. In samples with normal baseline aPTTs, the aPTT failed to correctly estimate the spiked drug concentration in four of 24 samples spiked with argatroban, seven of 24 spiked with lepirudin, and three of 24 spiked with bivalirudin. The plasma diluted thrombin time was not affected by lupus inhibitors, low vitamin K-dependent factor levels or elevated D-dimer levels and correctly estimated the spiked drug level in 63 of 63 samples spiked with argatroban, 63 of 63 samples spiked with bivalirudin, and 62 of 63 samples spiked with lepirudin. In conclusion, the plasma diluted thrombin time appears to be a viable alternative to the aPTT for monitoring DTI levels, especially in patients with lupus inhibitors or low levels of vitamin K-dependent factors.

Comparing the prothrombin time INR versus the APTT to evaluate the coagulopathy of acute trauma.

INTRODUCTION: In trauma patients, PT/INR or aPTT cutoffs of > or =1.5x normal are often used as triggers for the transfusion of plasma. MATERIAL AND METHODS: To evaluate the ability of the PT/INR or aPTT to predict low coagulation factor levels, these tests were compared to coagulation factor levels in samples with artificially prepared single and multiple factor deficiencies, 9 heparin-contaminated samples, 10 lupus inhibitor-containing samples, 21 samples with elevated factor VIII levels, and 35 samples from acute trauma patients. RESULTS AND CONCLUSIONS: The PT/INR and aPTT showed comparable sensitivity for single or multiple factor deficiencies in artificially deficient plasmas, but the PT/INR was more sensitive than the aPTT to low coagulation factor levels in actual trauma patients (sensitivity 84% versus 50%). The aPTT can show false positives with lupus anticoagulants and heparin contamination and false negatives in samples with elevated factor VIII. Thus, in the acute trauma setting, the PT/INR cutoff is a more reliable indicator of reduced coagulation factor levels.

Comparison of three methods for measuring factor VIII levels in plasma.

We compared 1-stage clot-based, chromogenic, and immunoassay methods for measuring factor VIII in plasma with a focus on the measurement of elevated levels of factor VIII. The chromogenic assay showed the best interassay imprecision for factor VIII levels near 150 IU/dL. The best correlation was between the 1-stage clot-based and chromogenic factor VIII assays (r2 = 0.934), and the lowest correlation was between the 1-stage clot-based and antigenic factor VIII assays (r2 = 0.821). The presence of heparin, low-molecular-weight heparin, lepirudin, or lupus inhibitors in the sample resulted in major interference in the 1-stage clot-based assay but not the chromogenic or antigenic factor VIII assays. Overall, the chromogenic factor VIII activity assay was the optimal method, showing good precision, the best overall correlation with other assays, and no interference from heparin, low-molecular-weight heparin, lepirudin, or lupus inhibitors.