Tumour Lysis Syndrome

Also known as: TLS, Tumor lysis syndrome

Tumour lysis syndrome is an oncological emergency caused by rapid release of intracellular contents from dying tumour cells, producing the characteristic tetrad of hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia, with consequent acute kidney injury, arrhythmia, seizures and death.

It occurs most often shortly after starting cytotoxic chemotherapy, but can follow radiotherapy, corticosteroids or targeted agents, and can occur spontaneously in highly proliferative disease before any treatment is given.

The highest-risk settings are Burkitt lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia with high white cell counts, and high-grade lymphomas, particularly with bulky disease, raised baseline LDH, pre-existing renal impairment or volume depletion.

Venetoclax in chronic lymphocytic leukaemia is a specific modern risk requiring structured ramp-up and monitoring.

It is far more effectively prevented than treated, which is why risk stratification before treatment is the central clinical task.

Cairo-Bishop criteria are used, distinguishing laboratory from clinical tumour lysis syndrome.

Laboratory TLS — two or more of the following within 3 days before to 7 days after starting treatment:

Uric acid raised, or a 25% increase from baseline
Potassium raised, or a 25% increase
Phosphate raised, or a 25% increase
Calcium reduced, or a 25% decrease

Clinical TLS — laboratory TLS plus one or more of: acute kidney injury (creatinine rise), cardiac arrhythmia or sudden death, or seizure.

Investigations:

Baseline before treatment: potassium, phosphate, calcium, uric acid, LDH, renal function, and urine output — establishing the baseline is what makes the 25% change criteria usable
Frequent monitoring during the at-risk period: every 4–8 hours in high-risk patients for the first 24–72 hours, and at least daily in intermediate-risk patients
ECG and cardiac monitoring for hyperkalaemia and hypocalcaemia
Strict fluid balance and urine output monitoring
LDH and white cell count as markers of tumour burden and proliferation rate

Prevention, which is where the greatest benefit lies:

Risk-stratify every patient before starting treatment, based on tumour type, bulk, LDH, white cell count and baseline renal function
Aggressive intravenous hydration is the single most important preventive measure, typically 2–3 L/m²/day started before treatment, maintaining a high urine output. This dilutes and clears the released solutes
Allopurinol for low and intermediate risk, started 24–48 hours before treatment; it blocks xanthine oxidase and prevents further uric acid formation, but does not remove uric acid already present, which is why it is preventive rather than a rescue treatment
Rasburicase for high-risk patients and for established tumour lysis syndrome; it converts uric acid to allantoin and lowers uric acid within hours. It is contraindicated in G6PD deficiency, where it causes severe haemolysis and methaemoglobinaemia, so G6PD status must be considered before use in at-risk populations
Urinary alkalinisation is no longer recommended: it increases uric acid solubility but promotes calcium phosphate precipitation, and the balance of harm has moved against it
Avoid nephrotoxins and potassium- or phosphate-containing fluids and supplements

Established tumour lysis syndrome:

Continue aggressive hydration with close attention to fluid balance
Hyperkalaemia is the most immediately life-threatening component and is managed as in the hyperkalaemia entry: calcium for cardiac protection, insulin-glucose and salbutamol to shift, and binders or dialysis to remove
Hyperphosphataemia: phosphate binders, and dialysis where severe
Hypocalcaemia: treat only if symptomatic, since giving calcium in the presence of high phosphate promotes calcium phosphate precipitation and worsens renal injury. This is a deliberate departure from the usual approach to hypocalcaemia
Rasburicase for hyperuricaemia
Renal replacement therapy for refractory hyperkalaemia, severe hyperphosphataemia, fluid overload, or established acute kidney injury; the threshold for dialysis is lower than in other settings given the rate at which derangement can progress

Referral: haematology or oncology, with critical care and nephrology involvement early in high-risk or established cases.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Sickle Cell Disease

Also known as: SCD

Autosomal recessive hemoglobinopathy caused by a point mutation in the β-globin gene (glutamic acid → valine at position 6), producing abnormal hemoglobin S (HbS).

Under hypoxic/acidotic/dehydrated conditions, HbS polymerizes, distorting red cells into a rigid sickle shape, causing hemolysis and vaso-occlusion.

Most common severe genotype: HbSS (sickle cell anemia); other clinically significant genotypes include HbSC disease and HbS-beta thalassemia (generally milder than HbSS but still clinically significant).

Sickle cell trait (HbAS, heterozygous carrier): generally asymptomatic, protective against severe malaria, but can rarely cause complications under extreme hypoxia (high altitude, extreme exertion) : important to distinguish from disease.

Vaso-occlusive crisis (VOC) most common acute presentation: severe pain, typically in bones (long bones, spine, ribs), triggered by cold, dehydration, infection, stress, hypoxia; can affect any organ
Dactylitis (hand-foot syndrome): often the earliest presentation in infants, painful swelling of hands/feet
Acute chest syndrome (ACS): new pulmonary infiltrate on imaging + fever and/or respiratory symptoms; leading cause of mortality in SCD, requires urgent recognition and management, can be triggered by infection, fat embolism (from bone marrow infarction), or atelectasis from VOC
Splenic sequestration crisis (mainly infants/young children before autosplenectomy occurs): sudden splenic enlargement, pooling of blood, rapid Hb drop, hypovolemic shock ; life-threatening emergency
Aplastic crisis: parvovirus B19-triggered, sudden cessation of erythropoiesis, severe anemia with low reticulocyte count
Chronic hemolysis: jaundice, pallor, gallstones (pigment stones from chronic hemolysis), leg ulcers
Priapism: painful, prolonged erection; urological emergency, risk of permanent erectile dysfunction if untreated
Stroke: significant risk especially in children ; ischemic (children) or hemorrhagic (adults) ; requires urgent recognition; silent cerebral infarcts also occur, screened via transcranial Doppler in children
Chronic complications: avascular necrosis (femoral/humeral head), retinopathy (proliferative, especially HbSC), chronic kidney disease (papillary necrosis, glomerulopathy), pulmonary hypertension, functional asplenia (increased risk of encapsulated organism infection ; pneumococcus, H. influenzae, meningococcus), growth delay in children, leg ulcers
Increased infection susceptibility: functional asplenia by early childhood in HbSS ; high risk of overwhelming sepsis from encapsulated organisms, any fever in SCD child/adult requires urgent evaluation

Newborn screening (in many countries, universal): hemoglobin electrophoresis or isoelectric focusing/HPLC identifies HbS
Hemoglobin electrophoresis / HPLC: definitive diagnosis, identifies HbS and quantifies percentage, distinguishes SS, SC, S-beta thalassemia, and trait
FBC: chronic anemia (Hb typically 6-9g/dL in HbSS at baseline), reticulocytosis (compensatory, reflects chronic hemolysis)
Blood film: sickle cells, target cells (especially HbSC), Howell-Jolly bodies (functional asplenia marker)
Genetic testing: confirms specific mutations, useful for prenatal diagnosis/genetic counseling
During acute crisis: FBC (compare to baseline ; significant drop suggests sequestration/aplastic crisis), reticulocyte count, LDH/bilirubin (hemolysis markers), blood cultures if febrile, CXR if respiratory symptoms (ACS evaluation), oxygen saturation

Differentials for VOC: osteomyelitis (can coexist/mimic ; Salmonella classically associated with SCD, distinguishing clinically challenging, consider if focal bone pain with fever not responding to standard analgesia), septic arthritis, other causes of acute abdomen if abdominal crisis.

Chronic/preventive management:

Hydroxyurea: disease-modifying, first-line for most patients with HbSS/HbS-beta0 ; increases fetal hemoglobin (HbF), reduces sickling, reduces VOC frequency, ACS episodes, transfusion need, and mortality; starting dose ~15mg/kg/day, titrated to max tolerated dose (monitor FBC for myelosuppression)
Newer disease-modifying agents: voxelotor (HbS polymerization inhibitor, increases Hb affinity for oxygen), crizanlizumab (P-selectin inhibitor, reduces VOC frequency) ; add-on options
Folic acid supplementation (5mg od) ; supports increased erythropoietic demand
Penicillin prophylaxis (children, until at least age 5, sometimes lifelong): penicillin V 125mg bd (<3y) or 250mg bd (≥3y) ; critical given functional asplenia risk of pneumococcal sepsis
Vaccination: full pneumococcal coverage (conjugate + polysaccharide), meningococcal, Hib, annual influenza ; enhanced coverage given asplenia
Transcranial Doppler screening (children, annually from age 2-16): identifies stroke risk, guides prophylactic transfusion decisions
Regular ophthalmology screening (retinopathy, especially HbSC), renal function monitoring, echocardiography for pulmonary hypertension screening

Acute vaso-occlusive crisis:

Analgesia : aggressive, per WHO pain ladder escalated rapidly: start with NSAIDs/paracetamol for mild pain; opioids (morphine, typically IV/PCA) for moderate-severe pain ; individualized dosing, do not undertreat (historically a major issue in SCD pain management), reassess frequently
IV fluids: hydration (isotonic, avoid over-hydration ; ACS/pulmonary edema risk)
Oxygen if hypoxic (not routinely if normoxic)
Warmth, avoid known triggers
Treat/identify precipitant (infection screen if febrile)
Incentive spirometry: reduces atelectasis/ACS risk during hospitalization for pain crisis

Acute chest syndrome: oxygen, IV fluids (cautious), analgesia (balance adequate pain control against respiratory depression risk), empirical antibiotics (cover atypicals ; macrolide + cephalosporin, given difficulty distinguishing infectious from non-infectious triggers), incentive spirometry, bronchodilators if wheeze, blood transfusion (simple or exchange transfusion for severe/rapidly progressive cases) ; low threshold for escalation to ICU/exchange transfusion given mortality risk.

Splenic sequestration: urgent fluid resuscitation, blood transfusion, splenectomy consideration for recurrent episodes.

Stroke: urgent imaging, exchange transfusion (reduces HbS percentage rapidly), chronic transfusion program for secondary prevention.

Priapism: analgesia, hydration, urology involvement ; aspiration/irrigation if prolonged (>4 hours), consider alpha-agonist (etilefrine) intracavernosal, surgical shunt if refractory.

Blood transfusion: simple transfusion for symptomatic anemia/aplastic crisis; exchange transfusion for ACS, stroke, severe sequestration, pre-operative optimization ; reduces HbS% while avoiding excessive viscosity from simple transfusion alone; iron overload monitoring with chronic transfusion programs (chelation therapy as needed).

Curative option: allogeneic hematopoietic stem cell transplant (matched sibling donor, curative) ; considered in severe disease, particularly children with significant complications; gene therapy (increasingly available in some settings) ; emerging curative option.

Patient education: avoid triggers (dehydration, extreme temperature, high altitude/hypoxia, overexertion), prompt fever management (seek care immediately, sepsis risk), genetic counseling for family planning.

Tumour Lysis Syndrome

Overview

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management