Limb deformity induced in chick embryo by hydroxyurea.

Iwama, Masahiko; Sakamoto, Yoshimitsu; Honda, Akira; Mori, Yo

doi:10.1248/bpb1978.6.836

Cited by 6 publications

(4 citation statements)

References 12 publications

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“…There are no reports of teratogenic effects in animals or adverse effects in the admittedly small numbers of pregnancies exposed to this drug. In relation to hydroxycarbamide (hydroxyurea, hydrea), at least one case of hydroxycarbamide causing fetal abnormalities has been reported (Perez‐Echinas et al ., 1994); teratogenicity in animals has also been reported (Butcher et al ., 1973; Wilson et al ., 1975; Thiesen, 1979; Aliverti et al ., 1980; Iwama et al ., 1983; Asano & Okaniwa, 1987). Thus the use of hydroxycarbamide is probably contra‐indicated at the time of conception and during pregnancy.…”

Section: Cytoreductive Therapymentioning

confidence: 99%

How we manage Philadelphia‐negative myeloproliferative neoplasms in pregnancy

Robinson

Harrison

2020

Br J Haematol

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The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and 15% of polycythaemia vera (PV) patients are less than 40 years of age at the time of diagnosis. Thus these diseases are encountered in women of reproductive potential and may be diagnosed in pregnancy or in women being investigated for recurrent pregnancy loss. The incidence of MPN pregnancies is 3Á2/100 000 maternities per year in the UK. The majority of data regarding Philadelphia-negative MPNs relates to patients with ET, for which the literature suggests significant maternal morbidity and poor fetal outcome; specifically maternal thrombosis and haemorrhage, miscarriage, pre-eclampsia, intrauterine growth restriction (IUGR), stillbirth and premature delivery as summarised in the recent systematic review and meta-analysis in Blood, 2018, 132, 3046. The literature for PV is more sparse but increasing and is concordant with ET pregnancy outcomes. The literature regarding primary myelofibrosis (PMF) is even more scarce. Treatment options include aspirin, venesection, low molecular weight heparin (LMWH) and cytoreductive therapy. Data and management recommendations are often extrapolated from other pro-thrombotic conditions or from ET to PV and PMF. Women of reproductive age with a diagnosis of MPN should receive information and assurance regarding management and outcome of future pregnancies. From pre-conceptual planning to the post-partum period, women should have access to joint care from an obstetrician with experience of high-risk pregnancies and a haematologist in a multidisciplinary setting. This paper provides an update with regards to Philadelphia-negative MPN in pregnancy, details local practise in an internationally recognised centre for patients with MPN and outlines a future research strategy.There are no randomised controlled trials of MPN in pregnancy. A national prospective study of maternal and fetal outcomes of pregnant women with a diagnosis of MPN was undertaken via the United Kingdom Obstetric Surveillance System (UKOSS) between January 2010 and December 2012 (Alimam et al., 2016). The study suggests that the incidence of MPN pregnancies is 3Á2/100 000 maternities per year in the UK, i.e. 24 pregnancies per year in the UK. The UKOSS study reported 58 women with a diagnosis of MPN who were pregnant; 47 (81%) essential thrombocythaemia (ET), five (9%) polycythaemia vera (PV), five (9%) primary myelofibrosis (PMF) and one (2%) MPN-unclassified. There were 58 live births. The incidence of miscarriage was 1Á7/100 [95% confidence interval (CI) 0Á04-9Á24] and the perinatal mortality rate was 17/1000 (95% CI, 0Á44-92Á36) live and stillbirths. Incidence of maternal complications was 9% (5/ 57) pre-eclampsia, 9% (5/57) post-partum haemorrhage and 3Á5% (2/57) post-partum haematoma. There wer...

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Section: Cytoreductive Therapymentioning

confidence: 99%

How we manage Philadelphia‐negative myeloproliferative neoplasms in pregnancy

Robinson

Harrison

2020

Br J Haematol

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“…Iwama et al ( 1983 ) , support not indicated, examined potential mechanisms of hydroxyurea‐induced malformations in chicken embryos. On Day 4 of incubation, White Leghorn chicken eggs were injected with 800 µg hydroxyurea.…”

Section: 0 Developmental Toxicity Datamentioning

confidence: 99%

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

Liebelt

Balk

Faber³

et al. 2007

Birth Defects Research Pt B

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“…It has a number of therapeutic actions but a primary effect is the inhibition of the enzyme ribonucleotide reductase and is a small molecule capable of crossing the placenta. Embryotoxicity of hydroxyurea has been documented in many animal species including rats, rabbits and rhesus monkeys (Butcher et al , 1973; Wilson et al , 1975; Theisen, 1979; Aliverti et al , 1980; Iwama et al , 1983; Asano & Okaniwa, 1987). Fetal abnormalities included partially ossified cranial bones, absent orbital sockets, hydrocephaly, missing lumbar vertebrae in rabbits, and similar abnormalities were found in rhesus monkeys where, in addition, growth retardation and increased spontaneous abortion were documented (Theisen, 1979).…”

Section: Hydroxyurea (Or Hydroxycarbamide)mentioning

confidence: 99%

Pregnancy and its management in the Philadelphia negative myeloproliferative diseases

2005

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SummaryThe myeloproliferative diseases (MPDs) present several therapeutic challenges in patients of childbearing potential. The most extensive literature exists for patients with essential thrombocythaemia, with over 200 pregnancies reported in retrospective case series. Yet there is conflicting data in relation to predicting pregnancy outcome and optimal management strategy. Pregnancy is less frequently reported for polycythaemia vera and myelofibrosis. There is a need for collaboration to further our knowledge in this field. Here, the literature is reviewed in detail and experience of different therapeutic strategies in pregnancy discussed. There is increasing understanding about the pathogenesis of placental dysfunction in inherited thrombophilia and antiphospholipid antibody syndrome pregnancy outcomes in these conditions parallel those reported for MPDs. Furthermore several large studies have influenced pregnancy management in these conditions and, whilst not directly applicable to MPDs, this data have potential to inform treatment protocols. This data are reviewed and a personal management strategy for pregnancy in MPD proposed.

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Limb deformity induced in chick embryo by hydroxyurea.

Cited by 6 publications

References 12 publications

How we manage Philadelphia‐negative myeloproliferative neoplasms in pregnancy

How we manage Philadelphia‐negative myeloproliferative neoplasms in pregnancy

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

Pregnancy and its management in the Philadelphia negative myeloproliferative diseases

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