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Suspected acute promyelocytic leukaemia demands particular urgency
because life-threatening coagulopathy may require treatment before molecular confirmation is available.
It is the M3 subtype of acute myeloid leukaemia,
and its biology explains its urgency.
A translocation between chromosomes 15 and 17 fuses PML with RARA.
The fusion protein blocks retinoic acid signalling,
so maturation halts at the promyelocyte stage.
The marrow fills with hypergranular promyelocytes whose Auer rods lie in bundles,
the faggot cells of the film.
The malignancy itself progresses over weeks, but the granules kill within days.
Those granules are packed with tissue factor,
and the cells overexpress annexin II.
Tissue factor ignites the extrinsic pathway throughout the circulation,
producing disseminated intravascular coagulation.
Annexin II converts plasminogen to plasmin, adding primary hyperfibrinolysis.
Consequently the prothrombin time and activated partial thromboplastin time lengthen together,
fibrinogen falls and D-dimer climbs.
Platelets are consumed as well.
The patient bruises, bleeds from the gums and, in the worst cases,
haemorrhages into the brain or lungs.
Early haemorrhagic death, not refractory leukaemia, is the principal threat.
Suspected acute promyelocytic leukaemia demands particular urgency
because life-threatening coagulopathy may require treatment before molecular confirmation is available.
The rule follows from the biology.
All-trans retinoic acid is started as soon as morphology
and the coagulation profile suggest the disease,
at 45 milligrams per square metre daily, without waiting for PML-RARA confirmation.
Retinoic acid overrides the differentiation block, promyelocytes mature,
granule release subsides and the coagulopathy resolves.
Meanwhile platelets are transfused to keep the count above 30 to 50 × 10⁹/L,
and cryoprecipitate maintains fibrinogen above 1.5 grams per litre.
Fresh frozen plasma corrects a prolonged prothrombin time.
Central venous lines, lumbar puncture and intramuscular injections are avoided,
and the coagulation screen is repeated every six hours.
Retinoic acid alone induces remission but cannot sustain it,
and relapse follows monotherapy.
Standard therapy pairs retinoic acid with arsenic trioxide,
which degrades the fusion protein.
Low and intermediate risk patients are cured without conventional chemotherapy,
whereas high risk disease adds an anthracycline.
Differentiation syndrome is the price of success.
As promyelocytes mature en masse, patients develop fever, weight gain, pulmonary infiltrates,
breathlessness, hypotension and serous effusions.
Dexamethasone 10 milligrams twice daily is given at the first suspicion,
and retinoic acid is withheld temporarily if the syndrome is severe.
Tumour lysis is the second early hazard.
Dying cells release urate, potassium and phosphate, and the phosphate precipitates calcium,
so calcium falls.
Hydration with allopurinol prevents new urate formation.
Rasburicase degrades existing urate and is reserved for high risk
or established lysis.
Because it generates hydrogen peroxide, it is contraindicated in glucose-6-phosphate dehydrogenase deficiency.
Suspected acute promyelocytic leukaemia demands particular urgency
because life-threatening coagulopathy may require treatment before molecular confirmation is available.