Acute promyelocytic leukaemia (APL) is a rare but life‑threatening haematologic malignancy that requires immediate clinical attention, as early mortality is largely driven by severe coagulopathy despite non‑specific initial symptoms [1,2]. APL represents a distinct subtype of acute myeloid leukaemia (AML), characterised in the vast majority of cases by the PML::RARA fusion gene, resulting from the chromosomal translocation t(15;17). This leads to a block in myeloid differentiation and the accumulation of abnormal promyelocytes [2,3].

Morphologically, APL presents in two main variants. The classic (hypergranular) form, accounting for approximately 70–80% of cases, is typically associated with cytopenias and heavily granulated promyelocytes. In contrast, the microgranular variant frequently presents with leucocytosis and morphological overlap with other AML subtypes, making diagnosis more challenging [2,3].

A defining feature of APL is its profound disturbance of haemostasis. Abnormal promyelocytes promote both activation of the coagulation cascade and hyper-fibrinolysis through the expression of procoagulant factors, such as tissue factor and cancer procoagulant, as well as fibrinolytic mediators. This frequently results in disseminated intravascular coagulation (DIC) [1,2,4]. Consequently, patients are at high risk of severe bleeding as well as thrombotic complications, particularly during the early phase of the disease [1,4]. This risk needs to be monitored during treatment using guideline-recommended parameters and scoring tools for DIC [5].

Given these complications, rapid laboratory detection is critical. Reliable identification of cytopenias or leucocytosis, combined with the detection of abnormal cell populations through automated flagging and smear review, plays a key role in enabling timely diagnosis and intervention in APL and reducing early mortality [2].

Improved linkage of diagnostic information from, for example, haematology, morphology and clinical flow cytometry allows for earlier diagnosis, followed by genetic confirmation, which is essential for the timely design of a targeted treatment plan [2, 6].

Case results

The patient’s initial complete blood count (CBC) revealed critical pancytopenia: WBC 0.48 × 10³/μL, RBC 2.64 × 10⁶/μL, and PLT 51 × 10³/μL. As malignancy was suspected, blood and bone marrow samples were analysed concurrently three days later, confirming pancytopenia in the peripheral blood (see Fig.1). During the peripheral blood smear review, only 51 white blood cells could be counted by the DI-60 owing to the severe leucocytopenia: three segmented neutrophils with toxic granulation, one basophil, 46 lymphocytes and one monocyte. Some morphological changes in the red blood cells were also observed: Slight microcytosis and macrocytosis, as well as a few ovalocytes and teardrop cells, were seen.

Fig. 1 Repeated patient blood analysis results

The bone marrow smear was analysed using the CellaVision^®DC-1 Bone Marrow Aspirate (BMA) Application and showed promyelocytes and blasts with Auer rods.

Fig. 2 CellaVision® DC-1 BMA Application showing promyelocytes and blast cells with Auer rods

The sample analysis performed by the clinical flow cytometry laboratory showed a CD34-negative and CD45-negative blast population with low side scatter and forward scatter in the blood and bone marrow aspirate. This population was also positive for cytoplasmic MPO, CD13, CD33, CD117 and CD64. Together with the absence of typical lymphatic markers, these findings point to a myeloid leukaemia.

The absent expression of HLA-DR on the blasts, together with the expression of CD123, clearly indicated the presence of APL. The diagnosis of APL was confirmed by the genetic finding of a PML::RARA fusion gene (see Fig. 3).

Fig. 3 Bone marrow aspirate showing CD45-negative/dim cells (left plot) and CD34-negative/CD117-positive cells (right plot), representing the typical APL marker pattern

Table 1: Relevant antigens for differential diagnosis

Haemostasis for patient management

DIC is a common and potentially life-threatening complication of APL because abnormal promyelocytes may trigger systemic coagulation and bleeding. Therefore, monitoring of the coagulation system for the development of DIC is warranted. The International Society on Thrombosis and Haemostasis (ISTH) provides guidance on how to detect and manage DIC [5]. Key laboratory parameters are prothrombin time (PT), plasma fibrinogen levels, plasma D-dimer and platelet count. The current consensus on scoring and score evaluation is shown in Table 2.

Table 2: ISTH scoring for overt and non-overt DIC (adapted from [5])