Donors With Immune Thrombocytopenia: Do They Pose a Risk to Transplant Recipients?

Transplant-mediated alloimmune thrombocytopenia (TMAT) from donors with immune thrombocytopenia (ITP) can result in significant bleeding complications in the recipient. The risk to a recipient of TMAT if they receive an organ from a donor with ITP is unknown. The outcomes of recipients of organs from deceased donors with ITP recorded in the UK Transplant Registry between 2000 and 2015 were reviewed. Twenty-one deceased organ donors had a predonation diagnosis of ITP. These donors were significantly more likely to have died from intracranial hemorrhage than were all other deceased organ donors (85% vs. 57%, p < 0.001). Organs from donors with ITP resulted in 49 organ transplants (31 kidney, 14 liver, four heart), with only one case of TMAT, which occurred in a liver transplant recipient and resulted in death from bleeding complications 18 days posttransplantation. The recipient of a kidney from the same organ donor was not affected. Unadjusted 5-year patient and graft survival was significantly worse for liver transplant recipients from donors with ITP compared with liver transplant recipients from donors without ITP (64% vs. 85%, p = 0.012). Organs from donors with ITP may be considered for transplantation, but livers should be used with caution.

A fatal case of transplantation-mediated alloimmune thrombocytopenia following liver transplantation.

OBJECTIVE AND IMPORTANCE: Transplantation-mediated alloimmune thrombocytopenia (TMAT) occurs when leukocytes transferred in a donor organ from a patient with immune thrombocytopenia (ITP), mount a response against recipient platelets. We present the first fatal case of TMAT following liver transplantation and review its aetiology and treatment. CLINICAL PRESENTATION: The liver donor had ITP and died from an intracranial haemorrhage. The recipient platelet count fell to 2 × 109/l on post-operative day 2. Treatment refractory thrombocytopenia resulted in pulmonary haemorrhage and death. TMAT did not occur in a kidney recipient from the same ITP donor. INTERVENTION: Extramedullary haematopoiesis was identified in the donor liver biopsy. Antibodies against platelet GPIb/IX were demonstrated in both donor and recipient. The thrombocytopenia was refractory to platelet transfusions, intravenous immunoglobulin, methylprednisolone, rituximab, romiplostim, plasmapheresis, vincristine and splenic artery embolization. On review of the literature, severe thrombocytopenia (<10 × 109/l) has started within 3 days of transplantation in all reported TMAT cases. Serious non-fatal bleeding was observed in 3/5 previously reported cases. The optimal treatment is unclear. TMAT should resolve as donor lymphocytes are eliminated but re-transplantation may be required in severe refractory cases. TMAT has been reported in recipients of a liver but not kidney or heart transplant from ITP donors, probably because of the greater burden of co-transplanted lymphoid tissue. CONCLUSION: Before using the liver of an ITP donor, the recipient's fully informed consent is required. However, the risk of TMAT from an ITP donor is currently unknown and systematic review of donor registries is needed.

Linear-scaling calculation of Hartree-Fock exchange energy with non-orthogonal generalised Wannier functions.

We present a method for the calculation of four-centre two-electron repulsion integrals in terms of localised non-orthogonal generalised Wannier functions (NGWFs). Our method has been implemented in the ONETEP program and is used to compute the Hartree-Fock exchange energy component of Hartree-Fock and Density Functional Theory (DFT) calculations with hybrid exchange-correlation functionals. As the NGWFs are optimised in situ in terms of a systematically improvable basis set which is equivalent to plane waves, it is possible to achieve large basis set accuracy in routine calculations. The spatial localisation of the NGWFs allows us to exploit the exponential decay of the density matrix in systems with a band gap in order to compute the exchange energy with a computational effort that increases linearly with the number of atoms. We describe the implementation of this approach in the ONETEP program for linear-scaling first principles quantum mechanical calculations. We present extensive numerical validation of all the steps in our method. Furthermore, we find excellent agreement in energies and structures for a wide variety of molecules when comparing with other codes. We use our method to perform calculations with the B3LYP exchange-correlation functional for models of myoglobin systems bound with O2 and CO ligands and confirm that the same qualitative behaviour is obtained as when the same myoglobin models are studied with the DFT+U approach which is also available in ONETEP. Finally, we confirm the linear-scaling capability of our method by performing calculations on polyethylene and polyacetylene chains of increasing length.

Towards better blood transfusion--recruitment and training.

Recent national initiatives in blood transfusion safety in the UK have created the need for an expansion in haematologists subspecializing (wholly or in part) in transfusion medicine. In 2008, there are 62 transfusion consultants in the UK, but only 42 are full time, and only 19 have hospital sessions. Despite the need for expansion, recruitment appears difficult. The English blood transfusion service, National Health Service Blood and Transplant (NHSBT), is undergoing major reconfiguration, and the current practice of transfusion training for haematology specialists primarily at blood centres with little or no hospital training is not sustainable or desirable. Delivering a high-quality transfusion programme to haematology trainees is best achieved through an increased emphasis on hospital-based training. Improved research opportunities, joint NHSBT/hospital posts and a separate subspecialty training curriculum may stimulate interest in transfusion medicine.

An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF.

Increasing demand on the apheresis service makes efficient harvesting of peripheral blood stem cells (PBSCs) essential. A total of 168 adult patients with haematological malignancy were primed using low-moderate dose cyclophosphamide (1.5-3 g/m(2)) with G-CSF 5-10 microg/kg per day. Harvesting was booked and peripheral blood (PB) counts first checked between 6 and 10 days post-priming. One hundred and thirty (77%) patients harvested successfully (total harvest yield > or =2 x 10(6) CD34(+)/kg) and the median PBSC collection per procedure was 2.18 x 10(6)/kg (range 0.1-14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34(+) cell count correlated significantly with harvest yield (r=0.8448, P<0.0001). A PB CD34(+) count > or =10/microl predicted a collection of > or =2 x 10(6)/kg (positive-predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6-8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34(+) count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service.