Immature platelet fraction as a predictor of platelet count recovery following allogeneic bone marrow transplantation.

The immature platelet fraction (IPF) is a marker of increased platelet production. An increase in IPF is associated with increased marrow production; therefore, a subsequent increase in a bone marrow transplant recipient during the pancytopenic phase may correlate with platelet recovery and engraftment. We performed a retrospective cohort study and evaluated 32 patients who underwent allogeneic bone marrow transplantation. Patients had platelet count, neutrophil count, platelet transfusion and IPF recorded over a period extending from stem cell infusion, day 0, to day 30. The outcomes analysed were platelet count versus time and IPF versus time to establish the predictive ability of the IPF to determine platelet count recovery. Further analysis was performed to confirm the strength of the correlation and the sensitivity of the IPF in predicting a platelet count greater than 50 at day 30. The IPF was shown to rise 5 days prior to platelet count increase. An IPF rise was also shown to correlate with higher average platelet counts at day 30 of transplant. The utility of the IPF in predicting a platelet count of over 50 at day 30 was strongest between days 11 and 15 with an area under the curve (AUC) of 0.79. An IPF of 2.0 or above had 69% sensitivity and 85% specificity for predicting a platelet count of greater than 50 by day 30. In allogeneic bone marrow transplantation, the IPF is a reliable predictor of platelet recovery. The mean IPF between day 11 and day 15 is the most sensitive in predicting a robust platelet count of greater than 50 by day 30.

MPN: The Molecular Drivers of Disease Initiation, Progression and Transformation and their Effect on Treatment.

Myeloproliferative neoplasms (MPNs) constitute a group of disorders identified by an overproduction of cells derived from myeloid lineage. The majority of MPNs have an identifiable driver mutation responsible for cytokine-independent proliferative signalling. The acquisition of coexisting mutations in chromatin modifiers, spliceosome complex components, DNA methylation modifiers, tumour suppressors and transcriptional regulators have been identified as major pathways for disease progression and leukemic transformation. They also confer different sensitivities to therapeutic options. This review will explore the molecular basis of MPN pathogenesis and specifically examine the impact of coexisting mutations on disease biology and therapeutic options.

Atypical features in a patient with acute promyelocytic leukaemia: a potential diagnostic pitfall.

Acute promyelocytic leukaemia (APML) is a malignancy with a high cure rate; however, delay in diagnosis or treatment can result in morbidity and mortality. APML has characteristic clinical, morphological, immunophenotypic and molecular features. In patients with acute leukaemia, a high index of suspicion is required to exclude APML. Very rarely APML patients at diagnosis can demonstrate atypical features. We reported a patient whose bone marrow features resembled acute myeloid leukaemia with predominantly agranular blasts, devoid of Auer rods and expressing CD34 and HLA-DR on flow cytometry. APML was not suspected initially but after cytogenetic and molecular genetic studies demonstrated t(15;17), appropriate therapy with ATRA+ chemotherapy was instituted and the patient showed remarkable and sustained response to treatment. This case highlights the fact that morphology and immunophenotyping are useful but not infallible indicators for these malignancies and, ultimate diagnoses will require detection of the characteristic molecular markers.

Bleeding associated with acquired factor V inhibitor in a patient on warfarin treated successfully with prednisolone.

An 85-year-old man on warfarin for atrial fibrillation presented with skin bleeding. International normalised ratio (INR) and activated partial thromboplastin time (APTT) were elevated and did not correct even after warfarin reversal with vitamin K, prothrombin complex concentrate (PCC) and fresh frozen plasma. Mixing coagulation studies with normal plasma suggested the presence of an inhibitor rather than the multiple coagulation factor deficiencies expected with warfarin. Assays of the common-pathway coagulation factors revealed factor V concentration <2% with inhibitor level elevated to 11 Bethesda units. The bleeding resolved following a course of corticosteroids. Coagulation studies and factor V level returned to normal along with resolution of the inhibitor. We report the case of the diagnostic dilemma posed and successful therapy implemented despite the limited evidence-based data being available for the treatment of this rare condition.