phenprocoumon and Abnormalities--Drug-Induced

The aim of this observational cohort study was to specify the risk of the vitamin K antagonist (VKA) phenprocoumon during first trimester of pregnancy, in particular to estimate the risk of birth defects and spontaneous fetal loss. Four hundred eight pregnancies with phenprocoumon exposure were compared to 1,642 pregnancies neither exposed to VKA nor to other major teratogens or fetotoxicants. There was no typical warfarin embryopathy in our exposed cohort. However, the overall rate of major birth defects was significantly increased (7.4 % vs 2.3 %; adjusted odds ratio [OR

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abortion, Therapeutic; Adult; Anticoagulants; Birth Weight; Blood Coagulation; Drug Administration Schedule; Drug Substitution; Female; Humans; Infant, Newborn; Logistic Models; Odds Ratio; Phenprocoumon; Pregnancy; Pregnancy Trimester, First; Premature Birth; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Young Adult

Topics: Abnormalities, Drug-Induced; Anticoagulants; Antiphospholipid Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Infant, Newborn; Infant, Premature, Diseases; Maxillofacial Abnormalities; Phenprocoumon; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Ultrasonography, Prenatal; Vitamin K

A 23-year-old woman had received a mechanical bileaflet mitral valve prosthesis because of severe mitral valve insufficiency caused by an acute bacterial endocarditis with vegetations. One year after the operation the patient suffered on two miscarriages under oral anticoagulation by phenprocoumon. Present, she was referred to our center with the question of conversion to low molecular weight heparine because of continued yearning for a baby.. At admission the woman was in good general and nutritional condition. Echocardiography showed a regular prosthetic function. Blood analysis, electrolyte parameters and enzyme values were normal, further laboratory investigations revealed a factor-V-Leiden-mutation. A chromosomal analysis detected no aberrations.. The oral anticoagulation by phenprocoumon was switched to subcutaneous low molecular weight heparine in therapeutical dosage. Anti-factor-Xa-activity was controlled at regular intervals. Further pregnancy was uneventful for both, mother and child. A healthy infant was born by caesarean section at 40 (th) week of gestation.. Treatment with anticoagulation by phenprocoumon is indispensable for mechanical heart valve protheses. Conversion to low molecular weight heparine is possible in patients who insistent request to conceive. The anticoagulation by low molecular weight heparine avoids teratogenic effects during pregnancy because the placenta is impermeable to that heparin. Furthermore, prophylaxis of thromoses by low molecular weight heparine is probably in almost the same manner as by phenprocoumon.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Anticoagulants; Endocarditis, Bacterial; Factor V; Female; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Heterozygote; Humans; Mitral Valve; Mitral Valve Insufficiency; Phenprocoumon; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombosis; Young Adult

Coumarin embryopathy (CE) is a well-documented sequelae of prenatal exposure to vitamin K antagonists. We report on a female premature infant (25 weeks' gestation) born to a mother who had received phenprocoumon during pregnancy following mechanical heart valve replacement. The infant presented with impaired coagulation, intraventricular and minor parenchymal cerebral haemorrhages and midface hypoplasia typical of CE. In addition, there was hepatopathy with conjugated hyperbilirubinemia, elevated liver enzymes and repeated episodes of hypoglycemia upon attempts to discontinue glucose supplementation, all lasting for 4 months. There was corneal opacity with anterior segment dygenesis in the left eye, and persistent pupillary membrane, cataract and persistent hyperplastic primary vitreous in the right eye. While liver disease is an uncommon but serious side effect of vitamin K antagonists, this is the first report describing neonatal hepatopathy as part of CE. In anticoagulation of pregnant women with mechanical heart valves, vitamin K antagonists should be used with utmost restraint.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Chemical and Drug Induced Liver Injury; Corneal Opacity; Endocarditis, Bacterial; Eye Abnormalities; Face; Female; Fetus; Heart Valve Prosthesis; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Phenprocoumon; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Acenocoumarol; Adverse Drug Reaction Reporting Systems; Anticoagulants; Birth Weight; Female; Fetal Diseases; Gestational Age; Humans; Phenindione; Phenprocoumon; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Prospective Studies; Vitamin K; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Female; Humans; Phenprocoumon; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thrombophlebitis

A case of Warfarin embryopathia is shown. The newborn, whose mother had been treated with Marcoumar (Phenprocoumon 3 mg/day) during the whole pregnancy because of a hereditary protein-S-deficiency showed the typical symptom of nasal hypoplasia. Coumarol derivates pass the placental membrane and are known as teratogenic. Recent retrospective and prospective studies show that the risk of fetal or embryonal teratogenic injury is about 25-30% if Coumarol derivates are given through the 6th to the 9th week of pregnancy. It is possible to nearly avoid those injuries when Heparin is used for anticoagulant therapy in this period and Coumarol itself is used in the lowest possible therapeutic dose.

Topics: Abnormalities, Drug-Induced; Female; Glycoproteins; Humans; Infant, Newborn; Nose; Phenprocoumon; Pregnancy; Pregnancy Complications, Hematologic; Protein S; Risk Factors; Thrombophlebitis

Topics: 4-Hydroxycoumarins; Abnormalities, Drug-Induced; Acenocoumarol; Adult; Chondrodysplasia Punctata; Female; Humans; Phenprocoumon; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third