Idiopathic factor V inhibitor in a patient starting haemodialysis.

A 74-year-old Pacific Island man with end-stage renal failure planning to start haemodialysis presented with persistent bleeding after tunnelled dialysis catheter insertion. The laboratory findings revealed a prolonged activated partial thromboplastin time of 118 s, prothrombin ratio of 4.2, factor V activity of <2% and a factor V inhibitor of 40 Bethesda Units. No clear underlying aetiology was identified. The bleeding settled with conservative measures and the factor V inhibitor was successfully treated with oral cyclophosphamide for 6 weeks.

Retrospective Analysis of the Effectiveness of a Reduced Dose of Idarucizumab in Dabigatran Reversal.

BACKGROUND: The recommended dose of idarucizumab, the specific reversal agent for dabigatran etexilate, is 5 g. However, published data showed biochemical reversal after an initial 2.5 g dose. OBJECTIVES: This study aims to retrospectively compare the clinical effectiveness of 2.5 and 5 g doses of idarucizumab used in dabigatran reversal in three hospitals in Auckland, New Zealand. METHODS: All patients receiving idarucizumab for dabigatran reversal between April 1, 2016 and December 31, 2018 were included. The primary outcome was the likelihood of receiving a second dose of idarucizumab during the same admission. Secondary outcomes included normalization of coagulation profiles, and 30-day thrombotic, bleeding, and mortality rates. RESULTS: Of 329 patients included, 206 received an initial 2.5 g dose and 123 received a 5 g dose. The median age was 78 years and median creatinine clearance was 50 mL/min. Most patients (62.6%) required idarucizumab for an urgent procedure, while 37.4% presented with bleeding. A 2.5 g dose was not associated with an increased rate of receiving a second dose (odds ratio [OR]: 0.686, 95% confidence interval [CI]: 0.225-2.090). A similar proportion of patients in each group achieved a normal activated partial thromboplastin time (73.8 vs. 80.0%, p = 0.464) and dilute thrombin clotting time (95.9 vs. 91.4%, p = 0.379) following idarucizumab infusion. There was no increase in the rate of death (OR: 0.602, 95% CI: 0.292-1.239), thrombosis (OR: 0.386, 95% CI: 0.107-1.396), or bleeding (OR: 0.96, 95% CI: 0.27-3.33) in the 2.5 g dose group compared with the 5 g dose group. CONCLUSION: An initial 2.5 g dose of idarucizumab appears effective for dabigatran reversal in the real-world setting.

A machine learning PROGRAM to identify COVID-19 and other diseases from hematology data.

AIM: We propose a method for screening full blood count metadata for evidence of communicable and noncommunicable diseases using machine learning (ML). MATERIALS & METHODS: High dimensional hematology metadata was extracted over an 11-month period from Sysmex hematology analyzers from 43,761 patients. Predictive models for age, sex and individuality were developed to demonstrate the personalized nature of hematology data. Both numeric and raw flow cytometry data were used for both supervised and unsupervised ML to predict the presence of pneumonia, urinary tract infection and COVID-19. Heart failure was used as an objective to prove method generalizability. RESULTS: Chronological age was predicted by a deep neural network with R2: 0.59; mean absolute error: 12; sex with AUROC: 0.83, phi: 0.47; individuality with 99.7% accuracy, phi: 0.97; pneumonia with AUROC: 0.74, sensitivity 58%, specificity 79%, 95% CI: 0.73-0.75, p < 0.0001; urinary tract infection AUROC: 0.68, sensitivity 52%, specificity 79%, 95% CI: 0.67-0.68, p < 0.0001; COVID-19 AUROC: 0.8, sensitivity 82%, specificity 75%, 95% CI: 0.79-0.8, p = 0.0006; and heart failure area under the receiver operator curve (AUROC): 0.78, sensitivity 72%, specificity 72%, 95% CI: 0.77-0.78; p < 0.0001. CONCLUSION: ML applied to hematology data could predict communicable and noncommunicable diseases, both at local and global levels.

Fixed-dose three-factor prothrombin complex concentrates is safe and effective in warfarin reversal.

BACKGROUND: Reversal of warfarin with prothrombin complex concentrates (PCC) is required in cases of significant bleeding or need for urgent surgery. A weight-based regimen is commonly, but a fixed-dose approach is also feasible with clinically equivalent outcomes. The purpose of this audit is to review the clinical and laboratory outcomes of patients treated in our centre where fixed-dose PCC is used for warfarin reversal. AIMS: The primary objective was to evaluate the post-reversal international normalised ratio (INR). The secondary objectives were the proportion of patients requiring repeat PCC and 30-day complication rates (death, haemorrhage and thrombosis). A subgroup analysis was also performed to compare the outcomes of those who received a dose of ≤15 IU/kg (reduced dose) with those who received >15 IU/kg (standard dose). METHODS: Patients who received three-factor PCC for warfarin reversal between 1 January and 31 December 2016 were identified and analysed. Clinical data and PCC dosages were extracted from electronic patient records. RESULTS: A total of 144 patients were analysed. The median INR pre-reversal was 3.25 (range 1.4-10), which reduced to 1.5 (0.9-3.0) post-reversal. Eighty-seven percent of patients achieved a post-reversal INR of less than 2 and 55% less than 1.5. Sixteen patients required a repeat dose. Complications occurred in 22 (15.3%) patients, which consisted of 15 deaths, 7 thrombosis and 2 haemorrhage. No statistically significant differences in the primary and secondary outcomes were noted between reduced-dose and standard-dose subgroups. CONCLUSION: Our results support the use of fixed-dose PCC for warfarin reversal in a day-to-day clinical practice in a hospital setting.

Distinctive features of polycythaemia vera in New Zealand Polynesians.

AIM: The aim of this study was to examine a potential ethnic disparity in the phenotype of polycythaemia vera (PV) between New Zealand European and Polynesian patients. METHOD: A retrospective review of medical records was conducted at Middlemore Hospital to identify adult patients with PV diagnosed between 1987 and 2007. Data extracted included diagnostic criteria, ethnicity, age, complications and survival. RESULTS: Eighty-eight adult patients with PV were identified during 1987-2007, 49 (55.7%) were Europeans and 36 (40.9%) Polynesians. The most striking finding was that Polynesian patients presented almost 14 years younger than Europeans (mean age of 54 years versus [vs] 68, respectively; P<.001). The white cell and platelet counts were higher in Polynesians compared with Europeans (mean white cell count of 22x109/L vs 13x109/L; mean platelet count of 648x109/L vs 512x109/L, respectively; P<.05 for both). The rate of JAK2 V617F mutation in Polynesians was 96%, equivalent to other large cohorts of European patients. The rates of long-term complications were comparable between Polynesians and Europeans, but the predicted impact on life expectancy was more severe for Polynesians. CONCLUSION: New Zealand Polynesian patients present with a distinctive PV phenotype. Their younger age at presentation suggests a different risk factor profile or a higher genetic susceptibility. We hope our observations initiate larger epidemiological and genetic studies to help elucidate the cause.