Publications by authors named "Briony Cutts"

11 Publications

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HOW Collaborative position paper on the management of thrombocytopenia in pregnancy.

Aust N Z J Obstet Gynaecol 2021 Jan 12. Epub 2021 Jan 12.

Westmead Hospital, Sydney, New South Wales, Australia.

Thrombocytopenia in pregnancy is a common occurrence, affecting up to 10% of women by the time of birth. These recommendations aim to provide pragmatic guidance on the investigation, diagnosis and management of thrombocytopenia in pregnancy; including safety of neuraxial anaesthesia and precautions required for birth. Management of neonatal thrombocytopenia is also addressed. The authors are clinicians representing haematology, obstetric medicine, maternal-fetal medicine, and anaesthesia. Each author conducted a detailed literature review then worked collaboratively to produce a series of unanimous recommendations. The recommendation strength is limited by the lack of high-quality clinical trial data, and represents level C evidence.
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http://dx.doi.org/10.1111/ajo.13303DOI Listing
January 2021

Clinical consequences of the extremely rare anti-PP1Pk isoantibodies in pregnancy: a case series and review of the literature.

Vox Sang 2020 Dec 16. Epub 2020 Dec 16.

Department of Haematology, Westmead Hospital, Sydney, NSW, Australia.

Background: The absence of the red cell antigens P, P1 and P , known as 'p', represents an extremely rare red cell phenotype. Individuals with this phenotype spontaneously form anti-PP1P isoantibodies, associated with severe haemolytic transfusion reactions, recurrent spontaneous abortion and haemolytic disease of the fetus and newborn (HDFN).

Methods: We report a series of four successful pregnancies in three women with anti-PP1P isoantibodies, one complicated by HDFN, another by intrauterine growth restriction, all managed supportively. We also review the literature regarding the management of pregnancy involving anti-PP1P isoimmunization.

Results: The literature surrounding anti-PP1P in pregnancy is limited to a very small number of case reports. The majority report management with therapeutic plasma exchange (TPE) with or without intravenous immunoglobulin. The relationship between titre and risk of pregnancy loss remains unclear, though a history of recurrent pregnancy loss appears important. Although a positive cord blood direct antiglobulin test is frequently noted, clinically significant HDFN appears uncommon, though possible.

Conclusion: Early initiation of TPE in high risk patients should be strongly considered. If possible, pregnancies should be managed in a high-risk obstetric or maternal fetal medicine service. The fetus should be monitored closely with interval fetal ultrasound and middle cerebral artery peak systolic volume Doppler to screen for fetal anaemia. Timely sourcing of compatible blood products is likely to be highly challenging, and both directed and autologous donation should be contemplated where appropriate. The International Red Cell Donor Panel may also provide access to compatible products.
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http://dx.doi.org/10.1111/vox.13042DOI Listing
December 2020

Venous thromboembolism prophylaxis of the obese postpartum patient: A cross-sectional study.

Aust N Z J Obstet Gynaecol 2020 06 12;60(3):376-381. Epub 2019 Sep 12.

The Royal Women's Hospital Pharmacy Department, The Royal Women's Hospital, Melbourne, Victoria, Australia.

Background: Obesity increases risk of venous thromboembolism (VTE) in obstetric patients regardless of delivery mode and for up to six weeks postpartum.

Aim: This study aimed to examine postpartum pharmacological VTE prophylaxis practices for obese women at an Australian tertiary referral hospital.

Materials And Methods: Medical records were retrieved for obese obstetric patients who delivered during May 2016-May 2017. Records were examined for demographic data, VTE risk factors, and LMWH (low-molecular-weight heparin) use. Due to lack of specific Australian or local guidelines, practice was evaluated using recommendations from the Royal College of Obstetricians and Gynaecologists (RCOG-UK). Patients with BMI (body mass index) <30, incomplete/unavailable medical records, and those discharged from other health services were excluded.

Results: One hundred and eight postpartum patients (70 caesareans, 38 vaginal deliveries) with a BMI ≥ 30 kg/m were reviewed. Of these patients, 53 (49.1%) had a BMI ≥ 40 kg/m . Ninety-eight of 108 (90.7%) patients had ≥2 VTE risk factors including a BMI ≥ 30 kg/m . One hundred and three of 108 (95.4%) patients were indicated for postpartum VTE prophylaxis with LMWH, and 77 of 103 (74.8%) patients received it. Three of five patients meeting criteria for ≥6 weeks of LMWH thromboprophylaxis had it prescribed. Of the 72 patients whose weight exceeded 90 kg and who also received LMWH, 32 (44.4%) were prescribed a weight-adjusted dose.

Conclusion: VTE prophylaxis practices using LMWH in obese postpartum patients, including weight-adjusting doses and extended-course prescribing, appear variable. Limited literature, recommendation discrepancies, and varied awareness of recommendations may be contributing factors. Further education and research regarding this high-risk cohort are warranted.
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http://dx.doi.org/10.1111/ajo.13054DOI Listing
June 2020

Retrospective cohort study comparing the adverse reactions and efficacy of intravenous iron polymaltose with ferric carboxymaltose for iron deficiency anemia.

Int J Gynaecol Obstet 2018 Jun 24;141(3):315-320. Epub 2018 Mar 24.

Pharmacy Department, The Royal Women's Hospital, Parkville, Vic., Australia.

Objective: To examine the adverse drug reactions (ADRs) and the efficacy of intravenous iron polymaltose and ferric carboxymaltose (FCM) among gynecology/obstetric patients with anemia.

Methods: The present retrospective observational study examined data from anemic obstetrics and gynecology patients who received either iron polymaltose or FCM between January 1, 2011, and April 30, 2015, at The Royal Women's Hospital, Victoria, Australia. Patient demographic data, dosage, ADR documentation, and hemoglobin levels were collected from medical records and compared.

Results: The study included 221 patients; 111 and 110 received iron polymaltose and FCM, respectively. ADRs were documented for 18 (16.2%) patients in the iron polymaltose group and 2 (1.8%) in the FCM group (P<0.001), with no incidences of anaphylaxis. Both formulations achieved increased hemoglobin levels within 12 weeks (P<0.001 for both). Mean hemoglobin level increases were similar in both groups among non-pregnant patients (P=0.186), but were greater in the iron polymaltose cohort among pregnant patients (P=0.005). FCM dose compliance was suboptimal, with 8 of 57 (14%) patients who required second visits for doses greater than 1000 mg returning for the infusion.

Conclusion: FCM was associated with a lower incidence of ADRs than iron polymaltose. Patients receiving FCM infusions were less likely to receive their total required iron dose. Further randomized prospective studies are required to compare clinical efficacy of iron polymaltose versus FCM.
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http://dx.doi.org/10.1002/ijgo.12476DOI Listing
June 2018

The utility of the Wells clinical prediction model and ventilation-perfusion scanning for pulmonary embolism diagnosis in pregnancy.

Blood Coagul Fibrinolysis 2014 Jun;25(4):375-8

aThrombosis & Haemophilia Centre, Guy's & St Thomas' Trust, London, UK bDepartment of Haematology cDepartment of Radiology & Nuclear Medicine, Monash Medical Centre, Claydon, Victoria, Australia dDepartment of Nuclear Medicine, Guy's & St Thomas' Trust, London, UK.

Pulmonary embolism is one of the leading causes of mortality in pregnancy in the Western world. No clinical prediction models have been validated in pregnancy. As a result, any pregnant woman presenting with signs possibly consistent with pulmonary embolism is investigated radiologically. This study investigates whether using clinical prediction models for pulmonary embolism in pregnancy should be pursued in future prospective trials. The aim of this study was to retrospectively evaluate the Wells clinical prediction model and ventilation-perfusion scanning for pulmonary embolism in pregnancy. A retrospective study was performed on consecutive pregnant women who presented with suspected pulmonary emboli and underwent ventilation perfusion scanning at two tertiary institutions from 2007 until 2010. The clinical pretest probability was determined as likely or unlikely by two independent clinicians retrospectively using Wells-modified criteria. Scans were determined as normal, nondiagnostic or high probability for pulmonary emboli independently by two experienced radiologists. Disagreements were resolved by a third assessor independently. In 183 pregnant women, the pretest probability was determined as 'pulmonary emboli likely' in 76 (42%) and 'pulmonary emboli unlikely' in 107 (58%) of women. Scans were of high probability in four (2%), nondiagnostic in six (3%) and normal in 173 (95%) of women. This gives the pretest probability using Wells-modified criteria a sensitivity of 100% [95% confidence interval (CI) 0.4-1.0] and a negative predictive value of 100% (95% CI 0.96-1.0). A structured clinical model such as modified Wells criteria may be useful in pregnancy, but further prospective evaluation is required.
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http://dx.doi.org/10.1097/MBC.0000000000000054DOI Listing
June 2014

New directions in the diagnosis and treatment of pulmonary embolism in pregnancy.

Am J Obstet Gynecol 2013 Feb 20;208(2):102-8. Epub 2012 Jun 20.

Thrombosis and Haemophilia Centre, Guy's and St Thomas' Trust, London, UK.

The diagnosis and management of pulmonary embolism in pregnancy is difficult, because diagnostic procedures and the use of anticoagulants potentially can expose mother and fetus to adverse effects. This article reviews evidence for current best practice and emerging novel techniques for the diagnosis of pulmonary embolism in pregnancy and includes clinical prediction models, biomarkers, and diagnostic imaging that may offer improvement in the diagnosis and investigation of pulmonary embolism in pregnancy in the future. The usefulness of new anticoagulant agents (fondaparinux, rivaroxaban, and dabigatran) in managing pulmonary embolism in future pregnancies is also explored.
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http://dx.doi.org/10.1016/j.ajog.2012.06.035DOI Listing
February 2013

Palifermin-induced acral erythrodysaesthesia variant in the treatment of acute myeloid leukaemia.

Australas J Dermatol 2011 Feb 24;52(1):59-61. Epub 2010 Aug 24.

Department of Dermatology, The Alfred Hospital, Prahran, Victoria, Australia.

The recombinant human keratinocyte growth factor, palifermin, offers a potential means of reducing or preventing mucositis in patient undergoing intensive cancer treatments. This case report details the development of acral erythrodysaesthesia in one patient who underwent palifermin treatment prior to high-intensity re-induction chemotherapy for acute myeloid leukaemia.
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http://dx.doi.org/10.1111/j.1440-0960.2010.00682.xDOI Listing
February 2011

Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice.

Blood 2009 Oct 26;114(17):3629-32. Epub 2009 Aug 26.

Wallenberg Laboratory, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase-activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS-induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RAS(G12D) in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS.
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http://dx.doi.org/10.1182/blood-2009-02-205146DOI Listing
October 2009

Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease.

Blood 2008 Aug 23;112(4):1357-65. Epub 2008 May 23.

Wallenberg Laboratory, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Hyperactive signaling through the RAS proteins is involved in the pathogenesis of many forms of cancer. The RAS proteins and many other intracellular signaling proteins are either farnesylated or geranylgeranylated at a carboxyl-terminal cysteine. That isoprenylcysteine is then carboxyl methylated by isoprenylcysteine carboxyl methyltransferase (ICMT). We previously showed that inactivation of Icmt mislocalizes the RAS proteins away from the plasma membrane and blocks RAS transformation of mouse fibroblasts, suggesting that ICMT could be a therapeutic target. However, nothing is known about the impact of inhibiting ICMT on the development of malignancies in vivo. In the current study, we tested the hypothesis that inactivation of Icmt would inhibit the development or progression of a K-RAS-induced myeloproliferative disease in mice. We found that inactivating Icmt reduced splenomegaly, the number of immature myeloid cells in peripheral blood, and tissue infiltration by myeloid cells. Moreover, in the absence of Icmt, the ability of K-RAS-expressing hematopoietic cells to form colonies in methylcellulose without exogenous growth factors was reduced dramatically. Finally, inactivating Icmt reduced lung tumor development and myeloproliferation phenotypes in a mouse model of K-RAS-induced cancer. We conclude that inactivation of Icmt ameliorates phenotypes of K-RAS-induced malignancies in vivo.
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http://dx.doi.org/10.1182/blood-2007-06-094060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515151PMC
August 2008

GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer.

J Clin Invest 2007 May;117(5):1294-304

Wallenberg Laboratory, Institute of Medicine, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.

Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
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http://dx.doi.org/10.1172/JCI30868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857236PMC
May 2007

Rce1 deficiency accelerates the development of K-RAS-induced myeloproliferative disease.

Blood 2007 Jan 14;109(2):763-8. Epub 2006 Sep 14.

Wallenberg Laboratory, Department of Medicine, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden.

The RAS proteins undergo farnesylation of a carboxyl-terminal cysteine (the "C" of the carboxyl-terminal CaaX motif). After farnesylation, the 3 amino acids downstream from the farnesyl cysteine (the -aaX of the CaaX motif) are released by RAS-converting enzyme 1 (RCE1). We previously showed that inactivation of Rce1 in mouse fibroblasts mislocalizes RAS proteins away from the plasma membrane and inhibits RAS transformation. Therefore, we hypothesized that the inactivation of Rce1 might inhibit RAS transformation in vivo. To test this hypothesis, we used Cre/loxP recombination techniques to simultaneously inactivate Rce1 and activate a latent oncogenic K-RAS allele in hematopoietic cells in mice. Normally, activation of the oncogenic K-RAS allele in hematopoietic cells leads to rapidly progressing and lethal myeloproliferative disease. Contrary to our hypothesis, the inactivation of Rce1 actually increased peripheral leukocytosis, increased the release of immature hematopoietic cells into the circulation and the infiltration of cells into liver and spleen, and caused mice to die more rapidly. Moreover, in the absence of Rce1, splenocytes and bone marrow cells expressing oncogenic K-RAS yielded more and larger colonies when grown in methylcellulose. We conclude that the inactivation of Rce1 worsens the myeloproliferative disease caused by oncogenic K-RAS.
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http://dx.doi.org/10.1182/blood-2006-05-024752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785091PMC
January 2007