Retrospective study of clinical settings, indications and consequences of measurement of direct oral anticoagulant plasma levels in Northern Tasmania, Australia.

BACKGROUND: Routine monitoring of direct oral anticoagulant (DOAC) levels is not recommended but may be useful in certain clinical situations. There is a knowledge gap regarding the clinical use of DOAC levels in Australian hospitals. AIMS: To evaluate the clinical settings, indications and changes to anticoagulant management associated with DOAC levels in a tertiary hospital in Northern Tasmania, Australia. METHODS: Patients with one or more DOAC levels (dabigatran, rivaroxaban or apixaban) requested between January 2017 and December 2022 were identified. Retrospective chart review was performed to evaluate the clinical settings, indications, adequacy of request information and changes to clinical management associated with the measurement of DOAC levels. RESULTS: One hundred and twenty-nine DOAC measurements (54 rivaroxaban, 66 apixaban and nine dabigatran) were performed in 98 patients between January 2017 and December 2022. Annual requests for DOAC levels increased significantly between 2017 and 2019 and remained stable between 2020 and 2021 but declined in 2022. Overall, the most common indication for a DOAC level was renal impairment, followed by bleeding and recurrent thrombosis. Approximately 25% of requests were for acute bleeding with a reversal/haemostatic agent given in 45% of patients, while 10% were prior to urgent surgery. Measurement of DOAC levels was associated with a change in management in 50% of cases. 10% of requests did not specify anticoagulant history. CONCLUSION: Trends in requests for DOAC levels have changed over time. Clinician education regarding the importance of providing specific anticoagulant history is essential. Future prospective studies investigating the clinical utility of DOAC levels in different clinical settings are needed.

Bone marrow fibrosis impact on response to azacitidine in myelodysplastic syndromes.

Bone marrow fibrosis in myelodysplastic syndromes (MDS) has been associated with poor outcome. However, these studies were conducted prior to the widespread use of azacitidine in the management of MDS. Our study aimed to assess whether treatment with azacitidine ameliorates the inferior outcome in MDS with fibrosis. A retrospective study of all patients diagnosed with MDS and treated with azacitidine over 3 years in two institutions was performed. A total of 21 patients were included in this study. Approximately half of these had moderate to severe bone marrow fibrosis at the start of treatment with azacitidine. The median overall survival was 34 months in patients with non-fibrotic bone marrow compared to 14 months in patients with fibrotic marrow (p=0.0007). Median event-free survival was 26 months versus 12 months (p=0.0027) in patients with non-fibrotic and fibrotic marrow, respectively. In multivariate analysis, bone marrow fibrosis was an independent factor in overall survival. Transfusion requirement was not different between the two groups. Despite the small sample size, we observed a worse outcome in azacitidine treated patients with MDS and fibrotic marrow. We suggest a prospective larger study to confirm the above finding.

Prospective cohort study on the use of low molecular weight heparin calibrated anti-Xa assay for measurement of direct oral Xa inhibitors in ex vivo patient samples.

Drug-specific anti-Xa chromogenic assays are recommended for measurement of direct anti-Xa inhibitor levels but are not routinely available in many institutions. We performed a prospective study to determine: (1) the relationship between low molecular weight heparin (LMWH) calibrated anti-Xa measurements and apixaban or rivaroxaban levels measured using drug-specific anti-Xa assays and, (2) if a LMWH calibrated anti-Xa assay can be used to detect clinically significant apixaban or rivaroxaban levels. Haematology outpatients on rivaroxaban or apixaban for at least 72 h were recruited for this study. Anti-Xa LMWH assay was performed using the Innovance Heparin Anti-Xa kit/calibrator. Drug-specific levels were determined using STA-Liquid anti-Xa kit/STA-Apixaban or STA-Rivaroxaban calibrators. Serial dilutions with pooled normal plasma were performed for specimens with anti-Xa LMWH activity greater than 1.50 ng/mL to obtain anti-Xa levels within the reportable range (0.10-1.50 ng/mL) and multiplied by the dilution factor to determine actual anti-Xa level. Seventy-five (39 rivaroxaban, 36 apixaban) specimens from 67 patients (mean age 60.3 years; 53.3% males) were available for analysis. Rivaroxaban levels ranged from <25 to 500 ng/mL while apixaban levels ranged from <20 to 236.1 ng/mL. For both rivaroxaban and apixaban, there was linear and good correlation (R2 = 0.96) between direct oral anticoagulants and anti-Xa LMWH levels. Using the correlation equation from our data, a rivaroxaban concentration of 50 ng/mL [International Society on Thrombosis and Haemostasis (ISTH) threshold for consideration of antidotes in bleeding patients] and 30 ng/mL (ISTH threshold for consideration of reversal agents prior to interventions), corresponds to anti-Xa LMWH levels of 0.50 and 0.35 IU/mL, respectively. For apixaban the corresponding anti-Xa LMWH levels were 0.35 and 0.20 IU/mL, respectively. In conclusion, LWWH calibrated anti-Xa assay can be used in emergency situations to screen for clinically significant apixaban or rivaroxaban levels when drug-specific calibrators are not available.

Two diagnoses from bone marrow biopsy: multiple myeloma and Paget's disease of bone.

Multiple myeloma and Paget's disease of bone show certain similarities such as increased osteoclastic activity and predilection to the axial skeleton. However, pathological and radiological changes of the bones are distinctive between multiple myeloma and Paget's disease of bone. This case report describes a patient who had a concomitant diagnosis of multiple myeloma and Paget's disease evidenced from bone marrow biopsy. Such a co-existence is rare, with only a few cases reported so far.

Acute myeloid leukaemia with t(8;21)(q22;q22.3) and loss of the X chromosome.

Cytogenetic abnormalities occur in approximately 60% of newly diagnosed patients with acute myeloid leukaemia (AML) and are useful in the risk stratification of AML. Translocation between chromosomes 8 and 21-t(8;21)-(q22;q22.3), which carries a favourable prognosis, is found in approximately 5% to 10% of all patients with AML. Additional chromosomal abnormalities have been described in patients with AML with t(8;21), which may impact on the favourable prognosis. We report a patient who had AML with t(8;21)(q22;q22.3) and loss of the X chromosome.

Leucapheresis for management of retinopathy in chronic myeloid leukaemia.

Chronic myeloid leukaemia is a myeloproliferative neoplasm characterised by granulocytic hyperplasia in the bone marrow and the presence of a specific cytogenetic abnormality known as Philadelphia chromosome with fusion of breakpoint cluster region (BCR) and ableson (ABL) genes. Retinopathy is a rare sight-threatening complication of chronic myeloid leukaemia, which occurs due to leucostasis in retinal blood vessels. We report a case of a patient who presented with visual impairment due to leucostasis, who was successfully managed by leucapheresis along with BCR-ABL tyrosine kinase inhibitor.

Diagnostic and therapeutic quandaries in a patient with primary hepatic lymphoma and concurrent hepatitis C infection.

Primary hepatic lymphoma (PHL) is a very rare sub-type of non-Hodgkin's lymphoma and hepatitis C infection may be a contributory factor. The association of hepatitis C infection and PHL causes difficulties in management since safety of rituximab in such situations is unclear due to lack of evidence. The role of anti-viral therapy in combination with chemotherapy is also uncertain. We describe the diagnostic and therapeutic challenges posed by a patient who was diagnosed with PHL and concurrent hepatitis C infection.

Quinine-induced severe thrombocytopenia: the importance of taking a detailed drug history.

Drugs can lead to severe life-threatening thrombocytopenia. The mechanisms of drug-induced thrombocytopenia are increased destruction by immune-mediated platelet destruction or decreased platelet production by bone marrow suppression. Quinine is a drug used for the treatment of malaria and nocturnal leg cramps and is also an important ingredient in some herbal preparations. Quinine can very rarely cause thrombocytopenia by immune-mediated platelet destruction. In a patient with thrombocytopenia, a detailed history of all the medications including over-the-counter medications and herbal preparations is very important.

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.