Acute Promyelocytic Leukaemia Presenting as Bleeding in a Minor Burn Patient: A Case Report

1. Introduction and Clinical Significance

Introduction : Thermal injuries are a major global health problem, particularly in low- and middle-income countries like South Africa, and scald burns are a leading cause of burn injuries in the paediatric population [1], resulting in significant morbidity and mortality. Acute burn-induced systemic inflammatory response syndrome is a major physiological response to the burn injury and is characterised by a massive release of pro-inflammatory mediators affecting multiple organ systems. Burn injuries depress the immune function, increasing the risk of infection. Burn-associated coagulopathies result from depletion and impaired synthesis of coagulation factors as well as thrombocytopaenia [2]. Notably, Bahemia et al. demonstrated that the degree of platelet decline can predict poor outcomes in severe burns if not acted upon [3]. Thrombocytopaenia in burn patients typically occurs during the early phase and often improves by day five to seven of the injury [4]. When pancytopaenia develops or persists, it can often be associated with new-onset sepsis warranting a complete septic work-up. However, when haematological derangements appear disproportionate to the burn severity and microbiological investigation yields negative results, alternative diagnoses other than sepsis should be considered as part of the differential diagnosis.

Acute promyelocytic leukaemia (APL), a subtype of acute myeloid leukaemia, is a rare but potentially fatal malignancy primarily affecting adults [5]. Patients typically present with signs and symptoms of bone marrow failure, including anaemia, neutropaenia, and thrombocytopaenia. The latter may manifest clinically as coagulopathy. On examination, there may be evidence of organ infiltration such as hepatosplenomegaly. There are often no clearly identifiable causes, although prior chemotherapy, radiation, and congenital disorders have been described as associated risk factors [6]. APL treatment with single-agent All-Trans Retinoic Acid (ATRA) achieves remission in a substantial proportion of APL patients, both at initial diagnosis and in recurrent cases. Paediatric APL treatment protocols largely derive from therapeutic advances established in adult populations, since the condition rarely occurs in childhood. Paediatric treatment regimens typically utilise ATRA at lower dosages, commonly 25 mg/m²/day given as divided doses throughout the day [7].

Clinical Significance: The overlap between burn-related physiological derangements and APL-associated coagulopathy may contribute to similarities in clinical and laboratory findings during the acute phase of the burn injury. Furthermore, anaemia, thrombocytopaenia, and neutropaenia may be observed in both conditions, which complicated the initial clinical assessment. This case is notable due to the unusual combination of a relatively minor 4% total body surface area burn with severe haemorrhage, profound cytopaenias, disseminated intravascular coagulation, and delayed recognition of underlying acute promyelocytic leukaemia in the acute burn setting where concurrent acute malignancy was not expected.

2. Case Presentation

2.1. Demographic Details and Medical History

We present a case of a 12-year-old African female who sustained a minor 4% total body surface area (TBSA) superficial partial thickness hot water burn on her right leg in 2025. Her minor burn was appropriately managed at a local community clinic and she was discharged home on paracetamol and ibuprofen and did not warrant referral to the Burn Unit for admission. Her past medical history included no known co-morbidities, no allergies, no travel history, and no family history of malignancies or haematological conditions. Her mother reported an uncomplicated pregnancy and birth with normal developmental history. Further collateral history from her mother revealed a history of abdominal pains and a runny nose two months prior treated at a local clinic. This was followed by two episodes of flu-like symptoms treated with amoxicillin by a general practitioner. During these recent illnesses, there was unquantified weight loss as reported by the mother.

2.2. Symptoms and Signs

She presented to Chris Hani Baragwanath Academic Hospital six days post-burn with a history of seven episodes of haematemesis and two episodes of malaena. On initial examination in the emergency department, she was found to be pale, warm to the touch, not jaundiced, with minor cervical lymphadenopathy. Her weight was appropriate for her age with a body mass index of 18.7. The rest of the systemic exam was unremarkable with no evidence of hepato- or splenomegaly and bruising. The 4% (calculated by rule of nines) burn wound on her right distal thigh and proximal leg was clean, dark pink, and dressed with paraffin gauze. Her vitals included a sinus tachycardia of 176 bpm with a blood pressure (BP) of 105/52 mmHg and a temperature of 37°C, with laboratory workup showing lactate of 2.9 mmol/L, a low haemoglobin of 3.3 g/dL, a raised white cell count of 20.8 x10⁹/L, and a low platelet count of 11 x10⁹/L.

2.3. Intervention and Outcomes

Institutional resuscitation protocols for haemorrhagic shock were followed, and she received fluid resuscitation, transfusion with four units of red blood cells, three units of fresh frozen plasma, and one and a half mega units of platelets (one mega unit contains four single unit platelets). Pantoprazole and octreotide infusions were also initiated.

With ibuprofen being the suspected trigger for the gastric bleeding and her haemorrhagic shock, she was booked for an emergent gastroscopy. The findings were evidence of a pangastritis with punctate bleeding. Post-gastroscopy on day two of admission, she was admitted to our Burn Unit intensive care unit, intubated, where she was managed by a multidisciplinary team consisting of paediatric and general surgeons, critical care intensivists, critical care-trained nurses, and allied rehabilitation staff. Her parameters improved with her heart rate down to 150 bpm, BP 121/85 mmHg, lactate of 1.8 mmol/L, haemoglobin 8.4 g/dL.

However, she continued to bleed post-procedure on the pantoprazole infusion. Thromboelastography was done for her, which displayed a need for cryoprecipitate and further fresh frozen plasma, as well as further red cell blood transfusions. With her low platelet count (18 x 10⁹/L.), low fibrinogen (1.3 g/L), and prolonged Partial Thromboplastin Time (33.2 sec), she was diagnosed with disseminated intravascular coagulation. The precipitant of the disseminated intravascular coagulation was initially suspected to be burn wound sepsis. Blood cultures were done, and she was started on empiric amoxicillin/clavulanic acid and clindamycin. The blood cultures yielded no bacterial growth. Her wound showed no signs of local sepsis on following exposures and was dressed with paraffin gauze during her stay.

She displayed ongoing transfusion requirements due to the upper gastrointestinal bleeding and rapid clinical deterioration. By Day four, she had developed multi-organ dysfunction, including respiratory failure (ventilator oxygen requirement exceeding 70%), cardiovascular failure (shock requiring noradrenaline and adrenaline at 1 μg/kg/min), renal failure (anuria), hepatic dysfunction (deranged liver enzymes), and persistent bicytopaenia.

Her persistent anaemia and thrombocytopaenia were considered disproportionate to the severity of the minor burn injury and prompted peripheral blood smear examination to investigate alternative causes. The lab confirmed a diagnosis of acute myeloid leukaemia, and the Haematology Department was consulted at 13h50 and the local Haematology-Oncology protocol was initiated . Treatment with oral All-Trans Retinoic Acid daily at 10mg manè 20mg noctè (25 mg/m²/day) and intravenous Daunorubicin at 75mg on alternative days (Days 1, 3 and 5) was initiated at 14h50 after laboratory confirmation of acute promyelocytic leukaemia, all on day four of admission. Subsequently, a Fluorescence In Situ Hybridisation (FISH) test was also requested confirming acute promyelocytic leukaemia (t(15;17) PML-RARA positivity.

Renal replacement therapy using continuous veno-venous haemodialysis due to her haemodynamic instability was initiated on Day six. The patient continued to require ongoing multiple blood transfusions and, despite maximal medical therapy, developed progressive peripheral ischaemia involving the digits in the setting of refractory shock and worsening multi-organ failure . Further escalation of therapy was no longer possible, and the patient died on day eight.

The blood cultures drawn during her clinical deterioration on days five and six flagged positive after her demise with a carbapenem-resistant Enterobacterales, Klebsiella pneumoniae, and a Pseudomonas putida requiring meropenem and colistin antimicrobial therapy.

Table 1. Ms X’s blood results.

Test + (Normal range)	Day 1	Day 2	Day 4	Day 5	Day 6	Day 7	Day 8
White cell count (3.90-10.2 X109/L)	20.8	22.28	87.88	113.85	52.51	23.71	4.69
Haemoglobin (10.3-15.5 g/dL)	3.3	6.4	5.4	7.0	8.1	5.3	5.4
Platelet count (180-440 X109/L)	11	18	16	28	13	4	5
C-Reactive Protein (<10 mg/L)		245	361		14	300	198
Procalcitonin (<0.1 ug/L)		128	253.20		254	221.2	111.60
Peripheral blood smear			Features in keeping with AML with concern for APL				Features in keeping with known diagnosis .Severe neutropaenia
Blood culture		No growth after 5 days	No growth after 5 days	Carbapenem-Resistant Enterobacterales Klebsiella Pneumoniae	1.Klebsiella Pneumoniae 2.Multi-drug resistant Pseudomonas Putida
Urea (1.8-5.7 mmol/L)	11.6	15.6		29.9	36.4	39.9	26.5
Creatinine (37-63 mmol/L)	237	331		625	649	568	314
International Normalised Ratio (<1.1)	1.66	1.57	1.64	1.46		1.59
D-Dimer (<0.25 mg/L)				>17.60	>17.60	>17.60
Fluorescence In Situ Hybridization			60% cells positive for translocation t(15;17) q(24;21) . PML/RARA fusion gene

Table 1. Ms X’s blood results.

Test + (Normal range)	Day 1	Day 2	Day 4	Day 5	Day 6	Day 7	Day 8
White cell count (3.90-10.2 X109/L)	20.8	22.28	87.88	113.85	52.51	23.71	4.69
Haemoglobin (10.3-15.5 g/dL)	3.3	6.4	5.4	7.0	8.1	5.3	5.4
Platelet count (180-440 X109/L)	11	18	16	28	13	4	5
C-Reactive Protein (<10 mg/L)		245	361		14	300	198
Procalcitonin (<0.1 ug/L)		128	253.20		254	221.2	111.60
Peripheral blood smear			Features in keeping with AML with concern for APL				Features in keeping with known diagnosis .Severe neutropaenia
Blood culture		No growth after 5 days	No growth after 5 days	Carbapenem-Resistant Enterobacterales Klebsiella Pneumoniae	1.Klebsiella Pneumoniae 2.Multi-drug resistant Pseudomonas Putida
Urea (1.8-5.7 mmol/L)	11.6	15.6		29.9	36.4	39.9	26.5
Creatinine (37-63 mmol/L)	237	331		625	649	568	314
International Normalised Ratio (<1.1)	1.66	1.57	1.64	1.46		1.59
D-Dimer (<0.25 mg/L)				>17.60	>17.60	>17.60
Fluorescence In Situ Hybridization			60% cells positive for translocation t(15;17) q(24;21) . PML/RARA fusion gene

Further blood investigation results: Flow test - forward scatter: side scatter and CD45 gating. Immunophenotypic analysis performed on a sample revealed a population of 95-96% large complex cells which fall within the granulocyte gate. They showed features in keeping with acute myeloid leukaemia with features compatible with acute promyelocytic leukaemia. Positive (60% of screened cells) for the translocation of t(15;17)(q24;21), PML/RARA fusion gene. This finding is consistent with the diagnosis of Acute Promyelocytic Leukaemia.

3. Discussion

While literature specifically describing new-onset haematological malignancies presenting in burn patients is limited, Keys et al demonstrated that burn patients with a prior cancer diagnosis had increased odds of developing sepsis, and those with haematological neoplasms exhibited higher odds of poor outcomes [8]. Acute promyelocytic leukaemia is associated with a severe coagulopathy characterised by disseminated intravascular coagulation and hyperfibrinolysis, which contributes substantially to early mortality. Prompt initiation of ATRA is considered a medical emergency. The treatment of APL has progressively improved over time with the introduction of ATRA plus arsenic trioxide, and long-term survival rates are achievable to at least 95% [9]. Peripheral blood smears are not routinely performed for all patients presenting to the Burn Unit with anaemia, thrombocytopenia, or leucopenia. In this case, it was performed due to a complicated presentation and rapid deterioration from a minor burn injury. Cytopaenias, when present following burn injury, are generally attributable to inflammation, sepsis, haemodilution, blood loss, or treatment-related factors and are usually proportional to burn severity and clinical course. However, the marked bicytopaenia and persistent bleeding in this patient with a minor 4% TBSA burn represented a clear discordance, disproportionate to the expected haematologic changes from such a minor injury. The associated marked leucocytosis and elevated procalcitonin initially raised suspicion of sepsis as the underlying cause [10]. However, the negative blood cultures were instrumental in redirecting clinical thinking away from infectious causes toward alternative haematologic pathology.

This rare case represents a unique and challenging diagnosis in a burn patient, with many confounding signs and symptoms that, in the context of burns, would typically not be attributed to malignancy, but to wound sepsis (raised white cell count, raised procalcitonin, anaemia, and thrombocytopaenia).

Peripheral blood smear examination is inexpensive, widely available, and can contribute to identifying alternative haematological pathologies in resource-limited burn units when haematological abnormalities appear discordant with burn severity. In this case, the unexpectedly severe anaemia, thrombocytopenia, transfusion refractoriness, and rapid clinical deterioration from a minor burn injury prompted further investigation and ultimately led to the diagnosis of APL.

Although malignancy is rarely encountered during acute burn management, clinicians are generally more familiar with Marjolin's ulcer, a malignant transformation of chronic burn scars [11], than with acute haematological malignancies presenting coincidentally in burn patients. The underlying pathology in this case was acute promyelocytic leukaemia, with the burn injury serving as a coincidental event that complicated the clinical picture. This case highlights the importance of maintaining a broad differential diagnosis when haematological abnormalities are discordant with the expected clinical course of a burn injury.

4. Conclusions

Persistent cytopaenias and coagulopathy that are disproportionate to burn severity should prompt investigation beyond burn-related complications and sepsis alone. This case highlights the diagnostic challenge posed by overlapping features of burn injury, sepsis, disseminated intravascular coagulation, and acute promyelocytic leukaemia. It underscores the importance of exploring alternative diagnoses in burn patients who present with haematological abnormalities not fully explained by the burn severity and microbiological findings.

The key learning point is that unexpectedly severe haematological abnormalities occurring in the setting of a minor burn injury warrant further evaluation. Patient outcomes may be improved through the development and implementation of structured protocols for the management of cytopaenias in burn patients who demonstrate an inadequate response to conventional therapy. This includes systematic approaches to anaemia and thrombocytopaenia refractory to transfusions, leucopaenia not responding to antimicrobial therapy, and the incorporation of peripheral blood smear analysis, where available, to guide diagnostic evaluation and management.

Limitations: A limitation of this report is that microbiologically confirmed sepsis was identified late in the clinical course, making it difficult to determine the relative contribution of sepsis and acute promyelocytic leukaemia to the patient's clinical deterioration and eventual death. Additionally, acute promyelocytic leukaemia is exceptionally rare in the context of acute burn injury and may represent coincidental presentation rather than a burn-specific phenomenon. These findings may not be generalisable beyond this single case.