False-positive pregnancy test after transfusion of solvent/detergent-treated plasma.

BACKGROUND: The transmission of pathogens, antibodies, and proteins is a possible consequence of blood product transfusion. A female patient had an unexpected positive serum ß-human chorionic gonadotropin result, indicative of pregnancy, after she had received a transfusion with 1 unit of platelet concentrate, 4 units of red blood cells, and 4 units of pooled solvent/detergent-treated plasma (Octaplas). STUDY DESIGN AND METHODS: To investigate the possibility of passive transfusion of ß-human chorionic gonadotropin from the plasma transfusion, one additional unit from the same batch was thawed and analyzed. To validate the ß-human chorionic gonadotropin assay for use in solvent/detergent-treated plasma and to investigate any interference in the assay, dilution experiments were performed using the implicated plasma batch diluted with male and non-pregnant female sera. Also, plasma from a known pregnant woman was diluted with Octaplas (tested negative for ß-human chorionic gonadotropin) and with a male serum to validate the assay for use in solvent/detergent-treated plasma. RESULTS: The implicated solvent/detergent-treated plasma had a mean ß-human chorionic gonadotropin level of 91.5 mIU/mL. Results from the dilution experiments revealed an excellent correlation (r > 0.99) between ß-human chorionic gonadotropin measurement in solvent/detergent-treated plasma and male serum and no over or under recovery of the expected results. Further measurements of ß-human chorionic gonadotropin levels in the female recipient revealed an estimated half-life of 6 hours. CONCLUSION: This case demonstrates the importance of considering the possibility of passive transmission of analytes to a patient from the transfusion of blood products. Furthermore, the measurement of ß-human chorionic gonadotropin is valid in solvent/detergent-treated plasma using a Roche Cobas analyzer.

A model comparing how rapidly transfusion of solvent detergent plasma restores clotting factors versus infusion of albumin-saline.

BACKGROUND: A recent randomized controlled trial demonstrated the bioequivalence between universally applicable and AB0 compatible transfusion plasma in healthy volunteers. There was a limited change in coagulation factor levels and inhibitors before and after plasmapheresis and subsequent plasma transfusion. The aim of this extension trial was to investigate the true capacity of these plasma products to restore baseline levels of coagulation factors and inhibitors after plasma depletion in comparison to haemodilution induced by infusion of albumin solution. MATERIALS AND METHODS: Fourteen healthy subjects, who completed both plasma transfusion periods, underwent an additional plasmapheresis (600 mL) followed by an infusion of 1200 mL albumin (3.125%) in a third period. RESULTS: The fibrinogen levels, as well as other clotting factors (FII, FV, FVII and FXI), decreased by 10% after plasmapheresis, and subsequent infusion of albumin solution further aggravated this drop in clotting factors to approximately 20-25%. The clotting factors with a long half-life were not even restored 24 hours after infusion of albumin solution, whereas those with a short half-life were replenished by endogenous synthesis within 24 hours. In contrast, transfusion of either plasma product rapidly restored all clotting parameters and inhibitors (protein S and plasmin inhibitor) immediately after transfusion. CONCLUSION: This study demonstrates that albumin solution induces an enhanced dilution of clotting factors and inhibitors, whereas both plasma products quickly compensated for the experimental loss of these plasma proteins.

Recovery, safety, and tolerability of a solvent/detergent-treated and prion-safeguarded transfusion plasma in a randomized, crossover, clinical trial in healthy volunteers.

BACKGROUND: Octaplas LG is a prion-depleted version of a previous generation product called Octaplas S/D. We compared the recovery, safety, and tolerability of these two pharmaceutical-grade plasmas. STUDY DESIGN AND METHODS: In this comparative, block-randomized, open-label, active-controlled, crossover Phase I trial, 60 healthy adult volunteers received single transfusions of 1200 mL of parent product (in Period 1) and of the LG plasma product (in Period 2) or vice versa. In both periods, plasmapheresis (600 mL) preceded the transfusion. Blood samples were drawn before and after apheresis and 15 minutes, 2 hours, 24 hours, and 7 days after end of plasma transfusion, to assess recovery, safety, and tolerability. The primary efficacy endpoints were the changes in coagulation factors and hemostatic variables compared to baseline; their relative recovery was computed in the per-protocol analysis (n = 43). Safety and tolerability were assessed (n = 60). RESULTS: Variations in coagulation factors and hemostatic variables over time were similar between the two treatments and within normal range; 90% confidence intervals for the derived recovery data were within predefined limits of equivalence. Both products were well tolerated. The advanced manufacturing process also significantly increased plasmin inhibitor concentrations after transfusion in vivo. CONCLUSION: The LG plasma product was bioequivalent to its predecessor with respect to recovery of clotting factors and demonstrated comparable safety and tolerability in healthy volunteers. Both products compensated well for the loss of clotting factors after apheresis (NCT01063595).

Safety of a universal, virus-inactivated and prion-depleted, pharmaceutical-quality plasma: a randomized, double-blind, clinical trial in healthy volunteers.

BACKGROUND: Universal plasma is intended to be transfused irrespective of the blood group. We compared the safety and tolerability of a novel, universal blood group-independent plasma with an ABO-matched plasma. STUDY DESIGN AND METHODS: In this randomized, double-blind, active-controlled, crossover, Phase I trial, 30 healthy adult volunteers (blood group A, B, or AB) were randomly assigned to transfusion of 1200 mL of Uniplas LG and 1200 mL of Octaplas LG (both Octapharma AG) or vice versa. In both periods, plasmapheresis (PPh, 600 mL) preceded the infusion. Blood samples were drawn before and after PPh and 15 minutes, 2 hours, 24 hours, and 7 days after end of plasma transfusion, to assess safety and efficacy. The primary safety outcome was change in hemoglobin (Hb) concentration; secondary safety outcomes were direct antiglobulin test (DAT), complement activation, free Hb, haptoglobin, and indirect bilirubin. Efficacy was assessed by evaluation of coagulation variables. RESULTS: Variations of Hb concentration were similar between treatments and within normal range; 90% confidence interval was within predefined limits of equivalence. No subject exhibited a positive DAT. All other secondary variables which could reflect hemolytic transfusion reactions (HTRs) fell within normal range; this suggests that no HTRs occurred. Most adverse events were of mild intensity; two subjects experienced dyspnea, leading to the withdrawal from the study of one subject. CONCLUSION: Universal plasma was equivalent to ABO-matched plasma with respect to safety and tolerability. Eliminating the risk of ABO incompatibility, this universal plasma represents an advance over blood group-specific plasma.

Prothrombin complex concentrate (Octaplex) in patients requiring immediate reversal of oral anticoagulation.

INTRODUCTION: Rapid reversal of anticoagulant effect from the use of vitamin K antagonists (VKA) is essential when acute bleeding or emergency surgery occurs. Prothrombin complex concentrates (PCCs) produce a more rapid effect with a better clinical outcome, and do not cause volume overload as compared with fresh-frozen plasma (FFP). Octaplex is a modern, double virus safeguarded PCC with balanced content of vitamin K-dependent coagulation factors, which ensures fast onset of action and efficacious treatment, i.e. rapid correction of international normalized ratio (INR). MATERIALS AND METHODS: The main purpose of this study was to demonstrate that Octaplex, when individually dosed, efficiently corrects INR to pre-determined levels in patients under oral anticoagulation who have bleeding complications or are undergoing invasive procedures. To measure the efficacy response, the INR achieved after PCC application per patient was calculated as geometric mean of three measurements within 1 h post-infusion. RESULTS: Sixty patients received a median total Octaplex dose of 41.1 (15.3-83.3) IU/kg body weight (bw). Of 56 patients evaluable in terms of efficacy, 51 (91%) showed a response as pre-defined in the protocol and in 52 (93%) the INR decreased to a value below 1.4 within one hour after dosing. The median INR declined from 2.8 (1.5-9.5) to 1.1 (1.0-1.9) within 10 min. All prothrombin complex coagulation factors recovered in parallel. Three patients had minor adverse drug reactions. One patient showed a non-symptomatic parvovirus B19 seroconversion. No thrombotic side effects were observed. CONCLUSIONS: Octaplex is efficacious and safe in immediate correction of dosage-dependent INR in patients with VKA-related deficiency of prothrombin complex coagulation factors.