Mechanism of Bone and Cartilage Maldevelopment in the Warfarin Embryopathy

Pauli, Richard M.

doi:10.1159/000157104

Cited by 35 publications

(13 citation statements)

References 12 publications

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“…Maternal treatment with coumarin derivatives between the 6th and 9th week after conception may cause warfarin embryopathy [Hall et al, 1980]. The same clinical phenotype with an additional congenital, persistent coagulopathy may be caused by an inborn deficiency of the vitamin K epoxide reductase [Pauli, 1988;Pauli et al, 1987;Pauli and Haun, 1993]. Recent data indicate that high concentrations of warfarin in vitro inhibit a specific sulfatase (arylsulfatase E) whose deficiency is responsible for some cases of relatively mild chondrodysplasia punctata.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin K deficiency embryopathy: A phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism

Menger¹,

Lin

Toriello

et al. 1997

Am. J. Med. Genet.

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Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

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Section: Discussionmentioning

confidence: 99%

“…In these children, a defect of vitamin K epoxide reductase has been demonstrated. The condition is called pseudo-warfarin embryopathy referring to its presentation as a biochemical deficiency phenocopy of a teratogen [Pauli, 1988;Pauli et al, 1987;Pauli and Haun, 1993].…”

Section: Introductionmentioning

confidence: 99%

Vitamin K deficiency embryopathy: A phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism

Menger¹,

Lin

Toriello

et al. 1997

Am. J. Med. Genet.

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“…Warfarin, being a low-molecular weight oral anticoagulant (about 1000 Daltons) easily crosses the placenta and reaches the fetal circulation causing warfarin embryopathy by blocking the recirculation of vitamin K leading to deficiency of vitamin K, which results in decreased level of vitamin K dependent clotting factor (II, VII, IX, X) synthesis resulting in haemorrhages in fetal organs. Secondarily, it interferes in vitamin K reductase activity which leads to decrease in vitamin K dependent mineralisation inhibitors (osteocalcin and Gla matrix protein) in cartilage resulting in ectopic calcium deposits in epiphysis and epiphysial stippling 2 4 5. Apart from this, it is also causing premature closure of growth plate resulting in shortening of extremities.…”

Section: Discussionmentioning

confidence: 99%

Di Sala syndrome

Kumar

Bhasker²,

Singh³

et al. 2012

Case Reports

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“…Vitamin K antagonists (FDA category D) have severe teratogenic effects and changing to heparin, usually LMWH (FDA category B), should be considered as soon as pregnancy is confirmed, particularly when high doses are needed 50 51. There are minimal data for new oral anticoagulation (NOAC) therapy during pregnancy.…”

Section: Arrhythmiasmentioning

confidence: 99%