Haematological Emergencies

Chapter 35
Haematological Emergencies


Quentin A. Hill1 and Amin Rahemtulla2


1 Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK


2 Department of Haematology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK


Haematological emergencies will often result in an unstable patient who requires intensive support. A number of these conditions have been dealt with in other chapters, but some additional topics are covered, including tumour lysis syndrome (TLS), superior vena cava (SVC) syndrome, chemotherapy- or radiotherapy-induced lung injury, malignant spinal cord compression (MSCC), renal failure following high-dose methotrexate, inadvertent administration of intrathecal vincristine and lymphoma with pericardial involvement.


Tumour lysis syndrome (TLS)


Tumour lysis syndrome is a life-threatening complication that arises when the rapid lysis of tumour cells leads to the release of intracellular cytokines, nucleic acids (catabolized to uric acid) and metabolites (phosphorus, potassium) into the circulation. This overwhelms the body’s normal homeostatic mechanisms resulting in hyperkalaemia, hyperphosphataemia, hyperuricaemia and secondary hypocalcaemia [1]. TLS can occur within a few hours or even before chemotherapy but is most commonly seen 12–72 h after initiation of treatment. It can result in renal failure, seizures, cardiac arrhythmia, multi-organ failure and death.


Diagnosis


Cairo and Bishop classified TLS according to clinical and laboratory features. In laboratory TLS [2], there is an abnormality in two or more of the metabolic complications below occurring within 3 days before or up to 7 days after chemotherapy:















Uric acid ≥476 µmol/L or 25% increase from baseline
Potassium ≥6.0 mmol/L or 25% increase from baseline
Phosphate ≥1.45 mmol/L or 25% increase from baseline
Corrected calcium ≤1.75 mmol/L or 25% decrease from baseline

Clinical TLS was defined as laboratory TLS plus one or more of the following:



  • Creatinine greater than 1.5 × upper level of normal
  • Cardiac arrhythmia/sudden death
  • Seizure
    Pathophysiology and clinical manifestations:
  • Hyperkalaemia can cause lethargy, nausea, vomiting, diarrhoea, muscle weakness, paraesthesiae and ECG changes such as tall tented T waves, widened QRS complex and ventricular arrhythmias, which may be fatal.
  • Hyperphosphataemia and secondary hypocalcaemia can cause anorexia, vomiting, confusion, carpopedal spasm, tetany, seizures and arrhythmias. Calcium pyrophosphate crystals may precipitate in various organs and contribute to acute kidney injury.
  • Hyperuricaemia may cause non-specific symptoms such as nausea, vomiting, anorexia and lethargy. It causes renal injury by crystal-dependent mechanisms. Uric acid nephropathy develops when uric acid crystals get deposited in the renal tubules and collecting ducts.
  • Renal impairment reduces urinary excretion of potassium and phosphate, leading to fluid retention, pulmonary oedema and a metabolic acidosis. This predisposes to further renal urate deposition, and multi-organ failure may ensue.

Risk factors:



  • Tumour type – Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), lymphoblastic lymphoma (LL), acute lymphoblastic leukaemia (ALL) and highly proliferative and treatment-sensitive solid organ tumours
  • Tumour burden – bulky disease, extensive bone marrow infiltration, high white blood count (WBC) (in acute leukaemia) and raised lactate dehydrogenase (LDH) (>2× ULN)
  • Other factors – renal impairment, elevated uric acid, oliguria, hypotension, dehydration and nephrotoxic drugs

Management


The best management of this condition is prevention, and ensuring good hydration and urine output is central to this. The initial assessment of all newly presenting patients should include tumour type, burden and cell lysis potential. Also, review the WBC, LDH, uric acid, phosphate, potassium, calcium, creatinine, urine output and cardiovascular status.


Patients who do not already have clinical TLS can then be categorized into low, intermediate and high risk. Several expert groups recently constructed algorithms defining risk and recommending a risk-stratified management approach to TLS [1, 3] (Table 35.1).


Table 35.1 Tumour lysis syndrome (TLS) recommendations based on TLS risk.


Source: Cairo et al. [3]. Reproduced with permission of John Wiley & Sons, Ltd.















































































Low-risk disease (LRD) Intermediate-risk disease (IRD) High-risk disease (HRD)
STa N/A N/A
MM N/A N/A
CML N/A N/A
Indolent NHL N/A N/A
HL N/A N/A
CLLb N/A N/A
AML and WBC <25 × 109/L and LDH <2 × ULN AML with WBC 25–100 × 109/L
AML and WBC <25 × 109/L and LDH ≥2 × ULN 		AML and WBC ≥ 100 × 109/L
Adult intermediate-grade
NHL and LDH <2 × ULN 		Adult intermediate-grade NHL and LDH ≥2 × ULN N/A
Adult ALCL Childhood ALCL stage III/IV N/A
N/A Childhood intermediate-grade NHL stage III/IV
with LDH <2 × ULN 		N/A
N/A ALL and WBC <100 × 109/L and LDH <2 × ULN ALL and WBC ≥100 × 109/L and/or LDH ≥2 × ULN
N/A BL and LDH <2 × ULN BL stage III/IV and/or LDH ≥2 × ULN
N/A LL stage I/II and LDH <2 × ULN LL stage III/IV and/or LDH ≥2 × ULN
N/A N/A IRD with renal dysfunction and/or renal
 involvement
IRD with uric acid, potassium and/or phosphate > ULN
Prophylaxis recommendations
Monitoring Monitoring Monitoring
Hydration Hydration Hydration
±Allopurinol Allopurinol Rasburicasec

ST, solid tumours; MM, multiple myeloma; CML, chronic myeloid leukaemia; NHL, non-Hodgkin’s lymphoma; HL, Hodgkin’s lymphoma; CLL, chronic lymphoid leukaemia; AML, acute myeloid leukaemia; WBC, white blood cell count; LDH, lactate dehydrogenase; ULN, upper limit of normal; ALCL, anaplastic large cell lymphoma; N/A, not applicable; ALL, acute lymphoblastic leukaemia; BL, Burkitt lymphoma/leukaemia; LL, lymphoblastic lymphoma.


aRare ST, such as neuroblastoma, germ cell tumours and small cell lung cancer or others with bulky or advanced stage disease, may be classified as IRD.


bCLL treated with fludarabine and rituximab, and/or those with high WBC (≥50 × 109/L) should be classified as IRD.


cContraindicated in patients with a history consistent with glucose-6-phosphate dehydrogenase deficiency (G6PD). In these patients, rasburicase should be substituted with allopurinol.


Preventative strategies for high-risk patients:



  • Monitor urine output, fluid balance and electrolytes. Biochemistry every 6 h initially, de-escalating dependent on clinical response.
  • Adequate hydration by IV fluids (usually 3 L/m2/day, avoid potassium) and aim for a urine output of 100 mL/h. Where urine output remains poor, a loop diuretic may be considered [1].
  • Consider deferral of chemotherapy for 24–48 h to ensure adequate hydration and urine output depending on clinical urgency. Alternatively, consider a lower-intensity prephase treatment, e.g. initial steroid monotherapy for patients with ALL.
  • Rasburicase (0.2 mg/kg in 50 mL normal saline infused over 30 min) for up to 7 days. This recombinant urate oxidase catalyzes the oxidation of uric acid to allantoin, which is soluble and readily excreted by the kidneys. Uric acid levels can be reduced within 4 h, improve renal function and thereby reduce phosphate. In contrast, allopurinol takes 24–72 h before effectively preventing uric acid formation and cannot actively remove uric acid already formed. Usually, 1–3 days of rasburicase is adequate. No dose adjustment is required for renal or hepatic impairment. Side effects include rash and urticaria due to allergy. Rasburicase is contraindicated in patients with methaemoglobinaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and conditions, which can cause haemolytic anaemia.
  • Allopurinol can be given orally or IV after completing rasburicase therapy. Allopurinol blocks the conversion of xanthines to uric acid. Since this would reduce the effect of rasburicase, they should not be given together.

Prevention for moderate-risk patients should include adequate hydration with IV fluids. Hospital in-patient, monitoring of urine output is recommended with biochemical monitoring, initially every 12 h. Allopurinol should be started 1–2 days before treatment and continue for 3–7 days afterwards. Allopurinol can be given orally or IV at a dose of 300 mg/m2/day (maximum 600 mg/day) in one to three divided doses [4]. Dose reductions for renal or liver impairment are required. Low-risk patients are usually managed on an outpatient basis, and hydration can be achieved orally.


Urinary alkalinization (e.g. with sodium bicarbonate) has been used to increase excretion of uric acid but decreases calcium phosphate solubility and lacks evidence of benefit. It is no longer recommended and should be avoided in established TLS, if rasburicase has been used or phosphate elevated.


Established TLS:


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Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Haematological Emergencies

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