Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: A prospective cohort study.

The reversal of dabigatran-associated major bleeding can now be achieved with the antidote idarucizumab. We evaluated activated prothrombin complex concentrate (aPCC) as an alternative for this purpose. Patients treated with dabigatran and suffering a major bleed were treated as per existing hospital protocol with aPCC. They were subsequently recruited for a 30-day follow-up. Effectiveness was evaluated by the treating physician, using an Assessment Guide. Safety outcomes were arterial or venous thromboembolism or death. A comparison was also made with historic cases with dabigatran-associated major bleeds treated with supportive care, by matching 1:2 for type of bleed, age and sex. We aimed at 32 evaluable cases but the study was prematurely discontinued after 14 cases due to the availability of the approved antidote. The effectiveness of aPCC was assessed as Good in 9 (64%), moderate in 5 (36%) and poor in none. There were no thromboembolic events and one death. In the secondary adjudication of effectiveness, using the same criteria and by the same adjudicators as previously done for the historic cases, the outcome was graded for the current cases versus the historic cases as Good, Moderate, or Poor in 10 (71%) versus 16 (57%), 3 (21%) versus 4 (14%), and 1 (7%) versus 8 (29%), respectively. Although supportive care is sufficient to manage many patients with dabigatran-associated bleeding, aPCC might provide an additional benefit to control life-threatening bleeding in selected cases and does not appear to cause an excess of thromboembolic events.

Four-factor prothrombin complex concentrates in paediatric patients - a retrospective case series.

BACKGROUND: Four-factor prothrombin complex concentrates (PCCs) are human plasma-derived products containing coagulation factors II, VII, IX and X as well as proteins C and S. They are licensed in many countries for treatment of bleeding or urgent periprocedural prophylaxis in patients with acquired deficiency of prothrombin complex coagulation factors, typically in the setting of vitamin K antagonist (VKA) usage. Efficacy and safety have been established in the adult population, but there is little information in the literature regarding their use for these indications in the paediatric population. We report on our institution's experience with these products in paediatric patients over a five-year period. METHOD: A retrospective case series study was performed, whereby any patient aged 0-16 years who had received PCCs between 2009 and 2013 was identified. Details regarding patient demographics, indications, dose, relevant bloodwork, additional blood products used, adverse effects and general outcomes were obtained through chart and blood bank reviews. RESULTS: A total of sixteen patients were included in our study, fourteen of whom received PCCs in a perioperative setting. Eleven received product for VKA reversal. Significant improvements in PT INRs were observed in those patients who had timely bloodwork drawn. Five others received product for reasons not related to VKA use. One thrombotic event was detected a day following PCC infusion, but causation is uncertain. CONCLUSION: Within study limitations, when used for rapid reversal of VKAs, efficacy and safety of these products in a paediatric population appear to be similar to those reported in adults.

Interpretation of pretransfusion testing in obstetrical patients who have received antepartum Rh immunoglobulin prophylaxis.

BACKGROUND AND OBJECTIVES: Determining whether anti-D represents active or passive alloimmunization after RhIg administration is challenging. The objectives were to use antibody reaction strength to differentiate patients who may have become RhD alloimmunized during pregnancy from those manifesting passive anti-D and to investigate which methods work best for this determination. MATERIALS AND METHODS: Data were collected from patients residing in the Edmonton region of Canada, ≥18 years old, undergoing antibody screening in late pregnancy, who received 300 µg (1500 IU) of RhIg in the preceding 120 days. A total of 1106 tests were performed on 1050 blood samples from 963 patients: 640 by PEG, 156 by gel-card and 310 by solid-phase methodology. RESULTS: PEG was the least sensitive to passive anti-D, with significantly fewer positive results at ≥8 weeks after RhIg compared to the other methods. Strength of reactivity and time since RhIg injection could be used to identify patients at high risk using PEG as a 4+ reaction at any time, ≥3+ at >2 weeks, ≥2+ at >6 weeks and ≥1+ at >14 weeks. Similarly, the gel-card method thresholds were 4+ at >5 weeks, ≥3+ at >10 weeks and ≥2+ at >15 weeks. Reaction strength by solid-phase was too variable to establish useful thresholds by this method. Infant RhD status did not significantly affect results. CONCLUSION: Patients can be risk stratified for alloimmunization by anti-D reaction strength and time after RhIg administration. The PEG method was the best of those investigated, but the gel-card method can also be used.

Anti-HPA-1b Mediated Posttransfusion Purpura: A Case Report.

Posttransfusion purpura (PTP) is an uncommon, but potentially fatal, transfusion reaction characterized by profound thrombocytopenia and bleeding. PTP is caused by alloimmunization to human platelet specific antigens following blood component transfusion. Although there is evidence of a wide serological spectrum of culprit antibodies implicated, Anti-human-platelet-antigen- (HPA-) 1a is the most common antibody in cases reported. We report a case of posttransfusion purpura in an African American. The patient was negative for HPA-1a antibodies, but anti-HPA-1b was identified with a platelet phenotype of HPA-1a/HPA-1a. Although less common, HPA-1b antibody may be an important consideration in posttransfusion purpura diagnosed in patients of African descent.

Flow cytometric detection of CD79a expression in T-cell acute lymphoblastic leukemias.

We evaluated the lineage specificity of CD79a in acute leukemias using 3-color flow cytometry in 58 consecutive cases. A panel of cell-surface antigens, including myeloid-associated markers, B-cell-associated markers, and T-cell-associated markers, was used. All cases of acute myeloid leukemia were CD79a-, whereas all cases of B-lineage acute lymphoblastic leukemia (ALL) were CD79a+. Three of 8 cases of T-cell ALL showed variable CD79a expression, indicating the presence of a blast subset expressing a relatively high level of CD79a. We investigated the clinical and pathologic characteristics of these 3 cases. All 3 cases had L1 or L2 morphology and expressed surface CD3. None of the other B-cell-associated markers were positive, although 1 case expressed CD13 and CD33. Uncommon random karyotypic abnormalities were identified in all 3 cases. Molecular studies demonstrated monoclonal gene rearrangement of T-cell receptor gamma in 2 of 3 cases. All 3 patients were 18 years old or younger; 1 patient did not enter remission, and 1 had disease relapse in 8 months. Our findings provide further support for the existence of a subset of T-cell ALL coexpressing CD3 and CD79a. Further study of the clinical and biologic significance of this subset may be warranted.

Endogenous Erythropoietin, Tumor Necrosis Factor-α and Interleukin-6 Levels after Peripheral Blood Stem Cell Transplantation.

We investigated the kinetics of plasma concentrations of endogenous erythropoietin (EPO), tumor necrosis factor-α (TNF) and interleukin-6 (IL-6) in patients with metastatic breast cancer who received high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) followed by an administration of recombinant human granulocyte-colony-stimulating factor (rhG-CSF). The plasma levels of these cytokines increased significantly after PBSCT and peak levels were observed on day 6 (median) for EPO, day 14.5 for TNF and day 6 for IL-6. EPO levels inversely correlated with hemoglobin levels (p = 0.0207) but no correlation was found between neutrophil recovery and levels of the cytokines tested. The concentrations of TNF and IL-6 directly correlated with body temperature (p = 0.0470 and <0.0001). The maximum level of IL-6 which occurred within 10 days after PBSCT directly correlated with number of days to achieve a platelet count of >20 X 10(9)/1 (p = 0.0003) and number of platelet transfusions (p = 0.0107), suggesting that the high concentrations of IL-6 could be associated with delayed platelet recovery.