We have established that our patient is profoundly septic and requires quick, effective resuscitation, which should include consultation with our ITU colleagues – a young patient who is decompensating is a particular worry as it is suggestive of how shocked they have become. In addition it is becoming clear that there is something wrong with his immune system as he has circulating blasts in his peripheral blood.
For med students:
Blasts are immature cells, usually found in very low numbers in the bone marrow and are the precursor/stem cells for mature blood cells. When leukaemia develops these cells lose both the ability to mature (differentiate) and to die (respond to apoptotic signals). The bone marrow is rapidly overwhelmed, meaning that normal blood cells can’t be made (resulting in pancytopenia). Blasts also spill out into the circulating blood. Their appearance is very distinctive and both laboratory analysers and laboratory staff are able to identify these abnormal cells, which will in turn lead to the haematologist being asked to review the blood film and perform further tests to establish the type of leukaemia.
Blasts can circulate in the peripheral blood for other reasons at low levels, but in this case – a young otherwise healthy man with a high blast count (rather than the very occasional cell) – is acute leukaemia until proven otherwise.
Chronic leukaemia is very different and is extremely rare in young people (under 40s). Chronic leukaemias don’t cause an excess of blast cells, but rather an excess of more mature cells. We can discuss chronic leukaemias on another occasion…
Tumour Lysis Syndrome
Tumour lysis syndrome is an oncological emergency. This is a syndrome in which rapid cell death causes release of intracellular ions, proteins, nucleic acids and their metabolites into the plasma. Uric acid is formed by the metabolism of nucleic acids and subsequently crystallises in the renal tubules, resulting in renal damage. Calcium phosphate is also deposited in the tubules, exacerbating damage.
The key laboratory features of TLS are hyperuricaemia, hyperkalaemia, rising urea and creatinine, hyperphosphataemia and hypocalcaemia. Oliguria, pulmonary oedema, cardiac arrhythmias and seizures may be seen. Hyperkalaemia with potentially lifethreatening cardiac arrhythmias may develop within 6 hours of starting chemotherapy where TLS is induced.
Allopurinol is used to in low to moderate risk patients and works by inhibiting the conversion of nucleic acids to uric acid via the xanthine oxidase pathway. Xanthine is produced but is much more soluble than uric acid and thus does not precipitate out in the renal tubules in quantities sufficient to cause catastrophic damage.
Allopurinol has two major drawbacks; firstly it takes 24-48 hours to reach therapeutic effect and secondly it does not influence uric acid levels already present. For this reason it is ineffective in very high risk patients who may have a degree of uricaemia or even TLS at presentation. Rasburicase is a recombinant uric oxidase, which promotes the conversion of urate to allantoin, which is much less nephrotoxic. This significantly reduces uric acid levels within 4 hours of administration and is therefore very effective in managing high risk TLS patients. Remember rasburicase continues to act in the tube, so unless you send a blood sample on ice the uric acid level for your patient will always be undetectable on testing!
TLS requires stringent monitoring of fluid balance, aggressive hydration and early involvement of ITU where renal impairment begins to develop. It also requires doctors to be aware of that TLS may develop even in ‘low risk’ patients and monitoring of renal function within the first few days of commencing chemotherapy is important.
Will, A. and Tholouli, E. (2011), The clinical management of tumour lysis syndrome in haematological malignancies. British Journal of Haematology, 154: 3–13. doi: 10.1111/j.1365-2141.2011.08697.x