Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation.

BACKGROUND: Methylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway. MATERIALS AND METHODS: Fifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7. RESULTS: The velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations. DISCUSSION: The global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations.

The impact of noninvasive, capillary, and venous hemoglobin screening on donor deferrals and the hemoglobin content of red blood cells concentrates: a prospective study.

BACKGROUND: Hemoglobin (Hb) is screened before whole blood donation to protect donors from anemia. Recently, noninvasive methods have become available for Hb screening in blood donors. We compared a noninvasive, a capillary, and a venous method for Hb screening of blood donors. STUDY DESIGN AND METHODS: Consecutive donors were prospectively screened using a noninvasive (Masimo Pronto-7), a capillary (HemoCue Hb 301), and a venipuncture-based method as gold standard (Siemens Advia 2120i) for Hb determination. All measurements were performed in parallel and in duplicate. A cutoff Hb value of 125 g/L (females) and 135 g/L (males) was used for donor acceptance. RESULTS: A total of 553 donors were analyzed; in 38 donors (7%) the noninvasive Hb method was not applicable due to technical reasons. The noninvasive test underestimated (mean bias, -5.9 g/L; 95% limits of agreement, -25.74, 13.88) and the capillary test overestimated Hb values (mean bias, 4.3 g/L; 95% limits of agreement, -8.13, 16.71). Coefficients of variation of duplicate measurements were 1.05 (venous), 2.73 (noninvasive), and 3.23 (capillary). The noninvasive test revealed false low Hb values in 21.2% and the capillary test revealed false high Hb values in 9% of donors compared to the venous method. The negative predictive value of the noninvasive test was 94.3%. CONCLUSION: The noninvasive Hb measurement is a reasonable first-line approach for predonation Hb screening of blood donors but a second method should be available to retest those not testable with the noninvasive device or with Hb values below the cutoffs.

Acquired hemophilia with inhibitors presenting as an emergency: misinterpretation of clotting results during direct oral anticoagulation.

BACKGROUND: Direct oral anticoagulants (DOACs) were recently introduced and are being increasingly prescribed. Most DOACs alter the values of traditional coagulation tests, such as the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT). Although vitamin K antagonists raise the INR value to an extent that mirrors their anticoagulant effect, DOACs do not, in general, alter standard clotting values in any consistent way. Thus, there is a risk that abnormal INR and aPTT values can be misinterpreted. CASE ILLUSTRATION: A woman taking rivaroxaban, a DOAC, presented with ileus and was scheduled for urgent surgery. A prolonged aPTT was, at first, wrongly attributed to rivaroxaban, delaying the correct diagnosis of autoantibody-associated acquired hemophilia (a rare condition with incidence, 1.34-1.48 cases per million people per year). The patient had a history of unusually intense bleeding in the skin and mucous membranes during anticoagulant treatment. Her aPTT had been prolonged even before any anticoagulants were taken. COURSE: The operation was delayed to await the elimination of rivaroxaban. The aPTT was still prolonged 24 hours later. The diagnosis of autoantibody-associated acquired hemophilia was suspected and then confirmed by the measurement of a factor VIII residual activity of 1% and the demonstration of factor VIII inhibition at an intensity of 9.2 Bethesda units per mL. CONCLUSION: The causes of abnormal clotting test results must be clarified before beginning anticoagulant therapy. Unusually intense bleeding during oral anticoagulation should arouse suspicion of a previously undiagnosed acquired coagulopathy, e.g., antibody-associated acquired hemophilia.