Extracorporeal photopheresis (ECP) has been used for over 30 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft-versus-host disease (cGVHD). The lack of prospective randomized trials has led to different centres having different patient selection criteria, treatment schedules, monitoring protocols and patient assessment criteria. ECP for CTCL and cGVHD is available only at six specialized centres across the U.K. In the recent Improving Outcomes Guidance the National Institute for Health and Clinical Excellence endorsed the use of ECP for CTCL and because of the complexity of treatment supported its use in specialized centres and also suggested the need for expansion of this service. In 2005 consultants and senior nurses from all U.K. sites and from Scandinavia formed a Photopheresis Expert Group. This group's first aim was to produce a consensus statement on the treatment of CTCL and cGVHD with ECP using evidence-based medicine and best medical practice, in order to standardize ECP eligibility, assessment and treatment strategies across the U.K.

Hematopoietic stem-cell transplantation remains an important curative therapy for many conditions and its use is increasing annually. Graft-versus-host disease (GvHD) is the major cause of mortality and suffering following allogeneic hematopoietic stem-cell transplantation. Conventional treatments are associated with multiple side effects and are often ineffective. New therapeutic approaches for the control of GvHD are desperately required. Extracorporeal photochemotherapy (ECP) was developed in the 1970s for the treatment of cutaneous T-cell lymphoma and was approved by the FDA as the first selective immunotherapy for a cancer. ECP has also proved an effective therapy for immune-related conditions, particularly GvHD, even in patients refractory to conventional therapies. The treatment involves the mechanical separation of circulating white cells, which are exposed to psoralen and UVA light and then returned to the patient. ECP is extremely well tolerated with minimal side effects and is not associated with the increased rates of infection or relapse of malignant disease typical of conventional immunosuppressive agents. Thus, ECP appears to offer selective immune modulation without generalized immunosuppression, but its mechanism of action remains poorly understood. This review discusses the development of ECP, its use in the treatment of GvHD, as well as current theories of its mechanism of action.

Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not ‘routine’. The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma. If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment. If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s).

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