Real-World Data on Characteristics and Management of Community Patients Receiving Anticoagulation Therapy Who Presented with Acute Bleeding to the Emergency Department at a Regional Australian Hospital: A Prospective Observational Study.

OBJECTIVE: To study patients receiving anticoagulants with or without antiplatelet therapy presenting at a regional Australian hospital with bleeding. The main aims are to explore: (1) patients' characteristics and management provided; (2) association between the type of anticoagulant and antiplatelet agent used and the requirement of reversal; (3) and the length of hospital stay (LoS) in conjunction with bleeding episode and management. METHODS: A prospective cross-sectional review of medical records of all patients who presented at a tertiary referral centre with bleeding while receiving anticoagulation therapy between January 2016 and June 2018. Data included: patients, demographics, investigations (kidney and liver function tests, coagulation profile, FBC), LoS, bleeding site, type of and reason for anticoagulation therapy, and management provided. Data analysis included descriptive statistics, χ2 association, and regression models. RESULTS: Among the 144 eligible patients, 75 (52.1%) were male, and the mean age was 76 years (SD=11.1). Gastrointestinal tract bleeding was the most common (n=48, 33.3%), followed by epistaxis (n=32, 22.2%). Atrial fibrillation was the commonest reason for anticoagulation therapy (n=65, 45.1%). Warfarin was commonly used (n=74, 51.4%), followed by aspirin (n=29, 20.1%), rivaroxaban (n=26, 18.1%), and apixaban (n=12, 8.3%). The majority had increased blood urea nitrogen (n=67, 46.5%), while 58 (40.3%) had an elevated serum creatinine level, and 59 (41.0%) had a mild reduction in eGFR. Thirty-five of the warfarinised patients (47.3%) had an INR above their condition's target range despite normal liver function. Severe anaemia (Hb<80g/L) was reported in 88 patients (61.1%). DOACs were associated with a reduced likelihood of receiving reversal (B= -1.7, P=<.001), and with a shorter LoS (B= -4.1, P=.046) when compared with warfarin, LMWH, and antiplatelet therapy. CONCLUSION: Warfarin use was common among patients who presented with acute bleeding, and the INR in many warfarinised patients exceeded the target for their condition. DOACs were associated with a reduced likelihood of receiving reversal and a shorter LoS than warfarin, LMWH, which might support a broader application of DOACs into community practice.

Assessment of von Willebrand disease and pregnancy outcomes at regional Australian hospitals.

BACKGROUND: von Willebrand disease (vWD) is a heterogeneous hereditary bleeding disorder and is associated with risk of primary postpartum haemorrhage (PPH). DESIGN AND METHODS: An observational study at a tertiary referral centre in Australia of 16 women with 23 deliveries with a median age of 27.5 years (range, 21-39; IQR = 9). Median gestational age at delivery was 39 weeks (range, 35-41; IQR = 1.1). RESULTS: All cases had type 1 vWD, apart from one case with type 2. Patients were managed in combined obstetrics and haematology clinics. PPH occurred in ten deliveries (44%). Intravenous desmopressin was administered in 6 cases, and IV human vWF was administered in 4 cases. Two cases with mild vWD had received oral tranexamic acid. The median Apgar score at 1 and 5 min was 9 (IQR = 1.0), while the median Apgar score at 10 min was 10.0 (IQR = 0.0). One case required transfusion of blood products postdelivery. There were no other significant complications observed. CONCLUSIONS: vWD was associated with a high incidence of primary PPH. Individualised treatment to restore haemostasis, according to the severity of the disease, could achieve as possible, normal haemostasis with favourable outcomes for both mothers and their infants. Further studies to confirm our findings are warranted.

A Prospective Randomised Controlled Trial of a Single Intravenous Infusion of Ferric Carboxymaltose vs Single Intravenous Iron Polymaltose or Daily Oral Ferrous Sulphate in the Treatment of Iron Deficiency Anaemia in Pregnancy.

Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000mg of IPM (n = 82) over 2 hours against 325mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9µg/L, with a mean of 13µg/L. The mean haemoglobin (Hb) was 114g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26g/L; 95% CI: -2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5µg/L; 95% CI: -23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms. In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.

Successful treatment of concomitant metastatic prostate cancer and B-cell non-Hodgkin's lymphoma with R-EPOCH chemotherapy regimen and antiandrogen therapy.

A 70-year-old man presented with left loin pain without urinary symptoms. Initial investigations with CT showed enlarged para-aortic, mediastinal lymph nodes, right-side renal mass and enlarged prostate. A prostatic-specific antigen (PSA) was alarmingly high at 4750 µg/L (normal <4.0 µg/L). Further investigations included positron emission tomography (PET); both prostate-specific membrane antigen and 18-fluorodeoxyglucose as well as bone scan and bone marrow examination confirmed dual malignancies with B-cell non-Hodgkin's lymphoma (B-NHL) and wide spread metastatic prostatic adenocarcinoma (PA) to the skull, spine, pelvis, liver and lungs. The patient was treated with six cycles of rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin(R-EPOCH) containing regimen for B-NHL and goserelin hormonal therapy for PA. Restaging with PET scans thereafter showed complete remission of NHL with disappearance of his metastatic PA and normalisation of PSA levels. R-EPOCH regimen and antiandrogen therapy resulted in a good outcome and remission of both malignancies.

Inherited haemochromatosis with C282Y mutation in a patient with alpha-thalassaemia: a treatment dilemma.

A Caucasian 24-year-old female patient suffers from two hereditary disorders: alpha-thalassaemia, which is prevalent in Asia and rare in Europe, and haemochromatosis, which is prevalent among northern Europe and rare in Asia. The clinical presentation and management of one of these diseases is controversial for the other. She presented 5 years ago with a clinical picture of refractory iron-deficiency anaemia secondary to menorrhagia. On treating her with the standard iron therapy, her anaemia persists although with adquate iron stores. This prompted further investigations that revealed in addition to hereditary haemochromatosis, alpha-thalassaemia because of abnormal blood indices. The treatment of thalassaemia with either iron or blood transfusion is not advisable in haemochromatosis, while standard treatment of haemochromatosis with venesection will worsen the anaemia. As iron chelating agents were not approved in Australia for haemochromatosis, haematinics support was commenced with a satisfactory improvement of anaemia thus allowing for further venesection.