Transplant Associated Microangiopathy (TAM)
For a comprehensive review see Obut, F., et al. (2016). "Post-bone marrow transplant thrombotic microangiopathy." Bone Marrow Transplant 51(7): 891-897.
Diagnosis
- There are several sets of criteria which variously combine some or all of the following features:
- LDH increased
- Schistocytes increased (>4% or >2/high power field)
- Platelet count <50
- Creatinine increased (1.5-2.0 x ULN)
- DAT negative
- Haptoglobin decreased
- In addition to the above, clinical features are hypertension, CNS complications including seizures, stroke and visual impairment.
- Normal ADAMTS13 activity.
- Onset can be from day +3 to more than 1-2 years post SCT but on average is around days 100-150. It is possibly more frequent after allogeneic MUD SCT and it may be seen with lower frequency after RIC SCT and autografts.
- TMA may be limited to a single organ, e.g. kidney.
- If a renal biopsy is unsafe a skin biopsy may show microvascular deposition of C5b-9 which is supportive of the diagnosis.
Pathophysiology
Post-transplant TMA is a systemic disease mediated by activation of the alternate complement pathway. It is possibly driven by endothelial damage mediated by:
- Calcineurin inhibitors (cyclosporin, tacrolimus)
- Infection, particularly adenovirus
- Total body irradiation
- Acute graft-versus-host disease
Prognosis
- LDH levels and the % of fragmented red cells may provide a guide to prognosis. Increased LDH and >10% red cell fragments indicate a severely affected patient.
- In one series, around one third of patients died or developed end-stage renal failure in the first year.
Management
- Withdrawal of any triggers, e.g. cyclosporin/tacrolimus, control of GvHD by increased steroids, and Mycophenolate Mofetil (MMF) are recommended.
- Plasmapheresis is ineffective and can potentially exacerabte TMA by activating complement.
- Avoid any nephrotoxic drugs, e.g. aciclovir and co-trimoxazole.
- Complement pathway inhibitors – these are not routinely available but are currently being investigated within clinical trials, e.g. OMEROS study, in NZ.
Topic Code: 9094
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