Laboratory tests at hospital admission showed normal electrolytes, liver enzymes, impaired kidney function (urea 27.6 mmol/l, creatinin 246 µmol/l), decreased haemoglobin (7.8 mmol Fe/l), normal mean corpuscular volume, decreased platelet count (24×109/l), elevated bilirubin (36 µmol/l) and LDH (1981 U/l), decreased haptoglobin (<0.05 g/l), red cell fragments and a negative Coombs test consistent with a microangiopathic haemolytic anaemia. No underlying cause for the haemolysis was found: coagulation tests were normal, including a normal a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (>100%) as an indicator of von Willebrand Factor (vWF) protease activity.
Our patient was extensively screened for an underlying cause of TTP, which was not found:
a CT scan of the thoracic and abdominal regions showed no evidence for a primary tumour or metastases. His prostate-specific antigen level was normal. A bone marrow specimen showed a normal trilinear haematopoiesis and no morphological abnormalities except for an increase in megakaryocytes, and no evidence for a monoclonal B cell population. Virological tests for infections with HIV, cytomegalovirus and Epstein–Barr virus were negative. In addition, no infection with Escherichia coli 0157:H7, which can be associated with the TTP-associated haemolytic uremic syndrome, could be detected. The antinuclear antibody test (ANA) was negative.
Other causes of coma, in particular hypertensive leucoencephalopathy, cerebral venous sinus thrombosis and ischaemia in the posterior circulation, were ruled out as CT and MRI scans of the brain both with and without contrast appeared normal. In addition, EEGs repeatedly showed no evidence for (non-convulsive) status epilepticus. A lumbar puncture showed no cerebrospinal fluid abnormalities (normal glucose corrected for serum glucose levels, normal protein, immunoglobulin G (IgG) and IgG-index, absence of pleiocytosis, negative for neurotropic viruses including herpes simplex virus 1 and 2, varicella zoster, entero and parechoviruses). Serum lupus anticoagulant and anticardiolipin antibodies were absent, as were paraneoplastic antibodies, and the ANA profile was negative, which rendered (viral) encephalitis, autoimmune or systemic diseases and vasculitis all unlikely. Since our patient did not receive any analgesics or sedatives, and urea and creatinin levels were stable (although elevated) in a 4-day period prior to the first deterioration of his GCS score, a toxic-metabolic encephalopathy is also unlikely to have caused the first coma in our patient. However, it is possible that the half-life of the midazolam our patient received during his stay at the ICU may have been prolonged given the concomitant uraemia, which may have lengthened the duration of his coma and may have (partly) caused his second relapse.