Thanks for your help with this short case. We examined this blood film of an unwell female:
The most striking abnormality is red cell fragmentation. This can be seen in:
- AIHA/Evans’ syndrome
- Pregnancy-associated (HELLP, pre-eclampsia, malignant hypertension, fatty liver of pregnancy)
- Drugs – quinine, simvastatin, tacrolimus/ciclosporin, interferon, clopidogrel
- Malignant hypertension
- Infections – viral (CMV, adenovirus, HIV) and bacterial (meningococcus, clostridium perfringens, pseudomonas)
- Lupus nephritis
- Malignancy-associated MAHA and post-transplant
- Catastrophic antiphospholipid syndrome
- G6PD deficiency
- Mechanical valves
- B12 deficiency
- Thrombotic thrombocytopenic purpura
- Homograft rejection – microthrombi in transplant
- Thalassaemia major
Therefore fragmentation needs to be interpreted with the clinical context but if there is associated thrombocytopenia there needs to be urgent patient review to rule out thrombotic thrombocytopenic purpura. The main cause of TTP is an auto-antibody which depletes ADAMTS13. Rarely patients can have a congenital deficiency of ADAMTS13. There are other types of TTP – sometimes called thrombotic microangiopathies which are not due to ADAMTS13 deficiency (e.g. post transplant, malignancy, HIV, pancreatitis). ADAMTS13’s role is to cleave high molecular von Willebrand factor but without this HMW vWF circulates and causes platelet aggregation and micro-thrombi, which in turn cause red cell breakdown due to shear stress.
TTP can present non-specifically. Classically there is fever, neurological impairment and renal impairment but not all of these may be present and there needs to be an index of suspicion. Seeing the above blood film should prompt urgent clinical review by a haematologist. Treatment is with urgent plasma exchange. This needs to happen urgently and if not available FFP infusion is a holding measure. Ideally solvent-detergent FPP which is virally inactivated should be used has there will be high volumes infused. Patients need specialist care and discussion/transfer to a centre that treats TTP is required. Bearing in mind that the incidence is 6/million/year this may not be too often!
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