Creutzfeldt-Jakob disease lookback study: 21 years of surveillance for transfusion transmission risk.
Transfusion. 2017 Apr 25;:
Authors: Crowder LA, Schonberger LB, Dodd RY, Steele WR
BACKGROUND: Transfusion transmission of human prion diseases has been observed for variant Creutzfeldt-Jakob disease (vCJD), but not for the classic forms of prion disease (CJD: sporadic, genetic, and iatrogenic). Although the presence of prions or misfolded prion proteins in blood has been documented in some patients with the most common form of CJD, sporadic CJD, no transfusion-transmitted cases of CJD have been recognized. Since 1995, the American Red Cross has conducted a lookback study of the recipients of blood products from donors who develop CJD to assess the risk of blood-borne CJD transmission in the United States.
STUDY DESIGN AND METHODS: Blood donors subsequently diagnosed with confirmed or probable CJD were enrolled and the consignees were asked to identify the recipients of their blood products. These donors' transfusion recipients are traced annually with the National Death Index to see if they subsequently die of CJD.
RESULTS: To date, 65 CJD donors have been enrolled along with 826 of their blood recipients. These recipients have contributed 3934 person-years of follow-up and no transfusion-transmitted cases of CJD have been recognized.
CONCLUSION: From this study, as well as other epidemiologic studies, there is no evidence of CJD transfusion transmission; this risk remains theoretical.
PMID: 28444687 [PubMed - as supplied by publisher]
Detection and identification of platelet antibodies using a sensitive multiplex assay system-platelet antibody bead array.
Transfusion. 2017 Apr 25;:
Authors: Metzner K, Bauer J, Ponzi H, Ujcich A, Curtis BR
BACKGROUND: Tests for platelet-specific antibodies are important in the diagnosis of immune platelet disorders. Monoclonal antibody glycoprotein capture assays have been the gold standards in platelet antibody detection for almost 30 years. However, such assays are complex and cumbersome to perform, which limits their routine use. We report the performance of a newly developed, easy to perform platelet antibody bead array (PABA) for the detection of platelet-specific antibodies.
STUDY DESIGN AND METHODS: PABA is the equivalent of the monoclonal antigen capture enzyme-linked immunosorbent assay (ELISA) (MACE) on a bead and instead with fluorescent detection of immunoglobulin (Ig)G platelet antibodies by Luminex. Antibodies against platelet glycoproteins (GP) GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIV, and class I human leukocyte antigen (HLA) could be detected in a patient's serum simultaneously in a single well of a microplate. Results from 80 patient samples and 20 normal donor samples were compared using PABA, MACE, and a commercial ELISA kit.
RESULTS: PABA detected all antibodies, with specificity for human platelet antigens (HPAs) HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b, HPA-4a, HPA-4b, HPA-5a, HPA-5b, HPA-15b, and HLA. Overall, compared with MACE, the sensitivity and specificity of PABA were 99% and 97%, respectively, and both were significantly better than those of the commercial ELISA. PABA had greater analytic sensitivity than MACE for HPA-1a, HPA-3a, and HPA-5b antibodies. In addition, PABA detected HPA-5b and HPA-3b antibodies that were missed by MACE. The overall false-positive rate of PABA compared with MACE was 2.7%.
CONCLUSIONS: The PABA is a rapid, highly sensitive and specific, multiplex bead-based assay for detecting human platelet antibodies. Such a simple yet high-throughput platform will facilitate practical, routine testing for the identification of platelet-specific antibodies.
PMID: 28439930 [PubMed - as supplied by publisher]
Antithrombotic therapy and platelet transfusions in hematologic malignancy patients presenting chemotherapy-induced thrombocytopenia: a French survey.
Transfusion. 2017 Apr 25;:
Authors: Chalayer E, Cavalieri D, Martignoles JA, Genthon A, Tavernier E, Tardy B
BACKGROUND: Patients with hematologic malignancies are at high risk for both thrombosis and bleeding. During the prolonged periods of thrombocytopenia experienced by patients who are receiving intensive chemotherapy, clinicians often hesitate to prescribe any protection against thrombosis. In case of anticoagulant prescription, it is the prescribers' responsibility to weigh risks and benefits for each patient. Current guidelines exist but do not take into account types of thrombosis, patients' comorbidities, or previous bleeding events.
STUDY DESIGN AND METHODS: We proposed to gain insight into hematologists' beliefs about antithrombotic prescription in hematologic malignancy patients, to design future clinical trials. Therefore, we conducted a survey in France to evaluate the practices among a panel of hematologists.
RESULTS: We found that more than 92% of the respondents prescribed therapeutic anticoagulation in case of pulmonary embolism or deep venous thrombosis. In the case of therapeutic anticoagulation, only 64% of the physicians reconsidered treatment under a platelet threshold of 50 × 10(9) /L. None of the respondents decided to renounce treatment, nor to discontinue it because of thrombocytopenia, except in distal venous thrombosis or superficial vein thrombosis. One-fifth of clinicians proposed the insertion of a vena cava filter.
CONCLUSION: As observed in the United States and Canada, we noticed discrepancies between recommendations and current practices in France. This highlights the urgent need to conduct studies to evaluate both efficacy and safety of antithrombotics in patients with hematologic cancer and thrombocytopenia.
PMID: 28439927 [PubMed - as supplied by publisher]
Concentrated lyophilized plasma used for reconstitution of whole blood leads to higher coagulation factor activity but unchanged thrombin potential compared with fresh-frozen plasma.
Transfusion. 2017 Apr 25;:
Authors: Iapichino GE, Ponschab M, Cadamuro J, Süssner S, Gabriel C, Dieplinger B, Egger M, Schlimp CJ, Bahrami S, Schöchl H
BACKGROUND: During massive hemorrhage, it is recommended to transfuse red blood cells, platelet concentrate, and fresh-frozen plasma in a ratio close to 1:1:1. To avoid the thawing process of fresh frozen plasma, lyophilized plasma (LP) is increasingly used. Evidence is limited on the activity of coagulation factors in reconstituted blood using LP and concentrated LP versions.
STUDY DESIGN AND METHODS: Whole blood from ten healthy volunteers was separated into red blood cell, fresh frozen plasma, and platelet concentrate units. Aliquots of red blood cells and plasma concentrate were mixed with either fresh frozen plasma (200 mL) or LP at reconstitution ratios of 2:1:1, 1:1:1, and 1:1:2. LP was used either at the recommended standard volume of 200 mL (LP200) or was more concentrated at volumes of 100 and 50 mL (LP100 and LP50, respectively). The hemostatic capacity of each reconstituted whole blood sample was tested with blood cell counts, standard coagulation tests, factor activity, thrombin generation, and viscoelastic assays.
RESULTS: Hematocrit, platelet counts, and fibrinogen levels of the three ratios were similar between FFP200 and LP200 units but were lower compared with the corresponding ratios in LP100 and LP50 units. The activity of procoagulant and anticoagulant factors increased linearly with the increasing plasmatic fraction and, at 1:1:2 ratio, was significantly higher in LP50 units compared with FFP200 and LP200 units. Thrombin generation was similar throughout the four plasma groups at any ratio.
CONCLUSIONS: Decreasing the dilution volume of LP facilitates reaching higher hematocrit and coagulation protein levels without a relevant increase in thrombin generation. This is due to preserved balance between procoagulant and anticoagulant factors in the concentrated LP preparations.
PMID: 28439902 [PubMed - as supplied by publisher]
Optimizing autologous nonmobilized mononuclear cell collections for cellular therapy in pediatric patients with high-risk leukemia.
Transfusion. 2017 Apr 25;:
Authors: Even-Or E, Di Mola M, Ali M, Courtney S, McDougall E, Alexander S, Schechter T, Whitlock JA, Licht C, Krueger J
BACKGROUND: The manufacturing of cellular products for immunotherapy, such as chimeric antigen receptor T cells, requires successful collection of mononuclear cells. Collections from children with high-risk leukemia present a challenge, especially because the established COBE Spectra apheresis device is being replaced by the novel Spectra Optia device (Optia) in many institutions. Published experience for mononuclear cell collections in children with Optia is lacking. Our aim was to compare the two collection devices and describe modified settings on the Optia to optimize mononuclear cell collections.
STUDY DESIGN AND METHODS: As a quality initiative, we retrospectively collected and compared data from mononuclear cell collections on both devices. Collected data included patient's clinical characteristics; collection parameters, including precollection lymphocyte/CD3 counts, total blood volumes processed, runtimes, and side effects (including complete blood count and electrolyte changes); and product characteristics, including volumes and cell counts. Collection efficiencies and collection ratios were calculated.
RESULTS: Twenty-six mononuclear cell collections were performed on 20 pediatric patients: 11 with COBE and 15 with Optia. Adequate mononuclear cell products were successfully collected with a single procedure from all patients except one, with mean calculated mononuclear cell collection efficiency that was significantly higher from Optia collections compared with COBE collections (57.9 ± 4.6% vs 40.3 ± 6.2%, respectively; p = 0.04). CD3-positive yields were comparable on both machines (p = 0.34) with significantly smaller blood volumes processed on Optia. Collected products had larger volumes on Optia. No significant side effects attributed to the procedure were noted.
CONCLUSION: Mononuclear cell apheresis using the Optia device in children is more efficient and is as safe as that with the COBE device.
PMID: 28439898 [PubMed - as supplied by publisher]
Platelet lysate obtained via plateletpheresis performed in standing and awake equine donors.
Transfusion. 2017 Apr 25;:
Authors: Sumner SM, Naskou MC, Thoresen M, Copland I, Peroni JF
BACKGROUND: Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses.
STUDY DESIGN AND METHODS: Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and coagulation panels and then again at 8, 16, 24, and 48 hours after the procedure. To produce platelet lysate, the platelet concentrate underwent two freeze-thaw cycles followed by centrifugation and filtration processing. The platelet lysate was then analyzed for cellular debris, fibrinogen, and growth factors.
RESULTS: The collected platelet concentration contained a mean platelet yield of 390 × 10(3) /μL. Donor platelet count decreased from a mean of 193 × 10(3) /μL to 138 × 10(3) /μL after plateletpheresis, but no individual was at risk for hemorrhage. Pooled platelet lysate had minimal cellular residue and contained growth factor concentrations at 6.1 ng/mL for transforming growth factor-β1, at 3.5 ng/mL for platelet-derived growth factor-BB, and at 13.8 ng/mL for vascular endothelial growth factor-A.
CONCLUSION: Plateletpheresis using commercially available apheresis equipment is a feasible option for collecting platelet concentrate from equine donors. The lysate generated from the apheresis product contains growth factors and has potential to be used as a fetal bovine serum substitute for cell culture.
PMID: 28439897 [PubMed - as supplied by publisher]
Therapeutic plasma exchange as part of multimodal treatment of acquired hemophilia in a patient with concurrent acute intracerebral bleed and pulmonary embolism.
Transfusion. 2017 Apr 24;:
Authors: Wool GD, Chapel D, Treml A, Miller JL
BACKGROUND: Autoantibodies against Factor VIII (FVIII) define the rare but life-threatening bleeding disorder acquired hemophilia A (AHA). Correction of FVIII deficiency and eradication of the factor inhibitor are the ultimate therapeutic goals in this disorder. Bypassing agents such as recombinant factor VIIa (rFVIIa) or FVIII inhibitor bypassing agent are often used to control coagulopathy before the inhibitor is eradicated. Bypassing agents carry a risk of thrombosis, however.
CASE REPORT: We report a patient with newly diagnosed AHA and thalamic bleed who additionally had active atrial fibrillation and developed a segmental pulmonary embolism, limiting tolerable rFVIIa dosage. This patient with very-high-risk brain bleed and concurrent thrombosis on bypass agent represented a significant management dilemma for which we successfully utilized therapeutic plasma exchange (TPE) to reduce the inhibitor titer.
RESULTS: FVIII inhibitor was undetectable and FVIII level was above the lower limit of normal within 12.5 days from starting TPE. While the patient ultimately died 24 days from admission for reasons unrelated to bleeding, his intracerebral hemorrhage was unchanged in size and no other bleeding morbidity was observed.
CONCLUSION: This patient achieved eradication of FVIII inhibitor and did not have bleed expansion while receiving multimodal therapy including corticosteroids, rituximab, and TPE. We discuss the periprocedural risks of TPE in an acquired hemophilia patient and our multiteam management of that risk.
PMID: 28436106 [PubMed - as supplied by publisher]