scholarly journals Fetal Effects of Coumadin Administered During Pregnancy

Blood ◽  
1970 ◽  
Vol 36 (5) ◽  
pp. 623-627 ◽  
Author(s):  
J. HIRSH ◽  
J. F. CADE ◽  
A. S. GALLUS
Keyword(s):  
Cesarean Section ◽  
Vitamin K ◽  
Early Pregnancy ◽  
Vitamin K Antagonists ◽  
Practical Method ◽  
Coagulation Factors ◽  
Coagulation Defect ◽  
In Pregnancy

Abstract The safest and most practical method of administering long-term anticoagulants in pregnancy is uncertain because treatment of the mother with vitamin K antagonists may be complicated by hemorrhage in the fetus. The effects on the fetus of giving coumadin in pregnancy was evaluated in rabbits. When coumadin was given from early pregnancy until term, all of the fetuses were stillborn with widespread hemorrhages. However, the fetuses were born alive and without hemorrhage when (1) coumadin was stopped 4-5 days before delivery, at which time the level of coagulation factors had almost returned to normal and (2) when delivery was performed by cesarean section at a time when the fetal coagulation defect was severe. It is suggested that the risk of fetal hemorrhage is high only when fetuses with a severe coagulation defect are exposed to the trauma of delivery.

scholarly journals Case Report: Successful Long-Term Management of a Low-Birth Weight Preterm Infant With Compound Heterozygous Protein C Deficiency With Subcutaneous Protein C Concentrate Up to Adolescence

2021 ◽  
Vol 9 ◽  
Author(s):  
Johannes Pöschl ◽  
Wolfgang Behnisch ◽  
Bernd Beedgen ◽  
Navina Kuss
Keyword(s):  
Cesarean Section ◽  
Vitamin K ◽  
Protein C ◽  
Vitamin K Antagonists ◽  
Compound Heterozygous ◽  
Protein C Deficiency ◽  
Protein C Concentrate ◽  
Protein C Activity ◽  
Heterozygous Protein C Deficiency

Homozygous/compound heterozygous forms of congenital protein C deficiency are often associated with severe antenatal and postnatal thrombotic or hemorrhagic complications. Protein C deficiency frequently leads to severe adverse outcomes like blindness and neurodevelopmental delay in children and may even lead to death. The most widely used long-term postnatal treatment consists of oral anticoagulation with vitamin K antagonists (e.g., warfarin), which is supplemented with protein C concentrate in acute phases. Subcutaneous infusions have been described in infants mostly from 2 months of age after severe postnatal thrombosis, but not in newborns or premature infants without thromboembolism. We report the first case of a compound heterozygous protein C-deficient preterm infant, born at 31+5 weeks of gestation to parents with heterozygous protein C deficiency (protein C activity 0.9% at birth). We focus on both prenatal and perinatal management including antithrombotic treatment during pregnancy, the cesarean section, and continuous postnatal intravenous and consecutive subcutaneous therapy with protein C concentrate followed by a change of therapy to direct oral anticoagulants (DOACs) (apixaban). We report successful home treatment with subcutaneous protein C concentrate substitution overnight (target protein C activity >25%) without complication up to 12.5 years of age. We propose that early planned cesarean section at 32 or preferably 34 weeks of gestation limits potential maternal side effects of anticoagulation with vitamin K antagonists and reduces fetal thromboembolic complications during late pregnancy. Intravenously administered protein C and early switch to subcutaneous infusions (reaching about 3 kg body weight) resulted in sufficient protein C activity and has guaranteed an excellent quality of life without any history of thrombosis for 13 years now. In older children with protein C deficiency, as in our case, DOACs could be a new therapeutic option.

Idiopathic venous thrombosis

2006 ◽  
Vol 26 (01) ◽  
pp. 52-54 ◽  
Author(s):  
P. A. Kyrle
Keyword(s):  
Chronic Disease ◽  
Venous Thrombosis ◽  
Vitamin K ◽  
Clinical Benefit ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Antithrombin Deficiency ◽  
Optimal Duration ◽  
Risk Of Treatment

SummaryVenous thrombosis is a chronic disease with a recurrence rate of approximately 30% within 5-8 years. The optimal duration of secondary thromboprophylaxis in these patients entails balancing the risk of recurrence against the risk of treatment-associated bleeding. There is agreement that patients with a first idiopathic venous thrombosis should receive vitamin K antagonists for at least 3-6 months. Convincing trials showing a clinical benefit in terms of morbidity or mortality with respect to expansion of anticoagulation beyond 6 months are lacking. Nevertheless, some subgroups of patients with venous thrombosis may benefit from indefinite anticoagulation. Thus, patients with antithrombin deficiency, combined or homozygous defects, more than one unprovoked episode of thrombosis, the lupus anticoagulant or high factor VIII plasma levels are good candidates for long-term prevention.

Long-term use of vitamin K antagonists and incidence of cancer: a population-based study

Blood ◽  
2011 ◽  
Vol 117 (5) ◽  
pp. 1707-1709 ◽  
Author(s):  
Vittorio Pengo ◽  
Franco Noventa ◽  
Gentian Denas ◽  
Martino F. Pengo ◽  
Umberto Gallo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Study Groups ◽  
Population Based ◽  
Hazard Ratio ◽  
Population Based Study ◽  
Incidence Of Cancer ◽  
Overall Mortality

Abstract Whether long-term use of vitamin K antagonists (VKAs) might affect the incidence of cancer is a longstanding hypothesis. We conducted a population-based study including all cancer- and thromboembolism-free patients of our health area; study groups were defined according to chronic anticoagulant use to VKA-exposed and control groups. Cancer incidence and cancer-related and overall mortality was assessed in both groups. 76 008 patients (3231 VKA-exposed and 72 777 control subjects) were followed-up for 8.2 (± 3.2) years. After adjusting for age, sex, and time-to-event, the hazard ratio of newly diagnosed cancer in the exposed group was 0.88 (95% confidence interval [95% CI] 0.80-0.98; P < .015). VKA-exposed patients were less likely to develop prostate cancer, 0.69 (95% CI 0.50-0.97; P = .008). The adjusted hazard ratio for cancer-related and overall mortality was 1.07 (95% CI 0.92-1.24) and 1.12 (95% CI 1.05-1.19), respectively. These results support the hypothesis that anticoagulation might have a protective effect on cancer development, especially prostate cancer.

scholarly journals The international normalized ratio (INR) as seen in a population of patients with atrial fibrillation and cerebral infarction undergoing long-term treatment with vitamin K antagonists

2015 ◽  
Vol 28 (4) ◽  
pp. 269-272
Author(s):  
Anna Szczepańska-Szerej ◽  
Magdalena Wojtan ◽  
Beata Szajnoga
Keyword(s):  
Atrial Fibrillation ◽  
Cerebral Infarction ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Blood Parameters ◽  
Term Treatment ◽  
Adequate Treatment ◽  
Long Term Treatment

Abstract It is estimated that nearly 20% of all cerebral infarctions in the total population are the result of a complication of atrial fibrillation (AF). While oral anticoagulation with vitamin K antagonists (AVKs) substantially reduces this risk, this requires regular monitoring of the international normalized ratio (INR) in order to achieve therapeutic levels (2,0-3,0). The aim of this study was to evaluate a group at high risk of cerebral infarction, among patients with AF undergoing long-term treatment with VKAs, taking into account the significance of therapeutic INR values. The analysed group consisted of 90 acute ischaemic stroke patients with paroxysmal or chronic “non-valvular” AF, receiving treatment with VKAs. As a result of the study, therapeutic INR values (≥ 2) were seen in thirty-five of these individuals (38,8%), while 55 (61,2%) showed non-therapeutic INR values. Moreover, there were no differences in demographics, vascular risk factors, biochemical and morphological blood parameters, mean CHA2DS2-VASc score and TOAST classification between either of the two groups. Furthermore, no additional factor that would increase their risk of cerebral infarction during the adequate treatment with VKAs was found. However, patients with non-therapeutic INR values had a statistically significantly higher frequency of concomitant moderate pathology of the bicuspid valve, p<0.05. Hence, a lack of proper control of INR can proved to be particularly dangerous for this subgroup of patients. Hence, this is a group with an elevated risk of cerebral infarction and therefore requires special oversight of VKA treatment or NOA treatment.

Oral anticoagulant treatment: friend or foe in cardiovascular disease?

Blood ◽  
2004 ◽  
Vol 104 (10) ◽  
pp. 3231-3232 ◽  
Author(s):  
Leon J. Schurgers ◽  
Hermann Aebert ◽  
Cees Vermeer ◽  
Burkhard Bültmann ◽  
Jan Janzen
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin K ◽  
Heart Valves ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Arterial Calcification ◽  
Adverse Side Effect ◽  
Oral Anticoagulant Treatment ◽  
Carboxyglutamic Acid

Abstract Calcification is a common complication in cardiovascular disease and may affect both arteries and heart valves. Matrix γ-carboxyglutamic acid (Gla) protein (MGP) is a potent inhibitor of vascular calcification, the activity of which is regulated by vitamin K. In animal models, vitamin K antagonists (oral anticoagulants [OACs]) were shown to induce arterial calcification. To investigate whether long-term OAC treatment may induce calcification in humans also, we have measured the grade of aortic valve calcification in patients with and without preoperative OAC treatment. OAC-treated subjects were matched with nontreated ones for age, sex, and disease. Calcifications in patients receiving preoperative OAC treatment were significantly (2-fold) larger than in nontreated patients. These observations suggest that OACs, which are widely used for antithrombotic therapy, may induce cardiovascular calcifications as an adverse side effect.

Long-term quality of VKA treatment and clinical outcome after extreme overanticoagulation in 14,777 AF and VTE patients

2015 ◽  
Vol 113 (04) ◽  
pp. 881-890 ◽  
Author(s):  
Nic J. G. M. Veeger ◽  
Nakisa Khorsand ◽  
Hanneke C. Kluin-Nelemans ◽  
Hilde A. M. Kooistra ◽  
Karina Meijer ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Clinical Outcome ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
P Value ◽  
Risk Of Bleeding ◽  
Increased Risk

SummaryVitamin K antagonists (VKA) are widely used in atrial fibrillation and venous thromboembolism (VTE). Their efficacy and safety depend on individual time in the therapeutic range (iTTR). Due to the variable dose-response relationship within patients, also patients with initially stable VKA treatment may develop extreme overanticoagulation (EO). EO is associated with an immediate bleeding risk, but it is unknown whether VKA treatment will subsequently restabilise. We evaluated long-term quality of VKA treatment and clinical outcome after EO. EO was defined as international normalized ratio (INR) ≥ 8.0 and/or unscheduled vitamin K supplementation. We included a consecutive cohort of initially stable atrial fibrillation and venous thromboembolism patients. In EO patients, the 90 days pre- and post-period were compared. In addition, patients with EO were compared with patients without EO using a matched 1:2 cohort. Of 14,777 initially stable patients, 800 patients developed EO. The pre-period was characterised by frequent overanticoagulation, and half of EO patients had an inadequate iTTR (< 65 %). After EO, underanticoagulation became more prevalent. Although the mean time between INR-measurements decreased from 18.6 to 13.2 days, after EO inadequate iTTR became more frequent (62 %), p-value < 0.001. A 2.3 times (95 % confidence interval [CI] 2.0–2.5) higher risk for iTTR< 65 % after EO, was accompanied by increased risk of bleeding (hazard ratio [HR] 2.1;CI 1.4–3.2), VKA-related death 17.0 (HR 17.0;CI 2.1–138) and thrombosis (HR 5.7;CI 1.5–22.2), compared to the 1600 controls. In conclusion, patients continuing VKA after EO have long-lasting inferior quality of VKA treatment despite intensified INR-monitoring, and an increased risk of bleeding, thrombosis and VKA-related death.Note: There have been no previous presentations, reports or publications of the complete data that appear in the article. Parts of the data in this article have been presented as a poster at the American Society of Hematology (ASH) congress 2013, New Orleans, United States.

Role of vitamin K-dependent proteins in the arterial vessel wall

2011 ◽  
Vol 31 (04) ◽  
pp. 251-257 ◽  
Author(s):  
M. L. L. Chatrou ◽  
C. P. Reutelingsperger ◽  
L. J. Schurgers
Keyword(s):  
Vascular Calcification ◽  
Vitamin K ◽  
Independent Predictor ◽  
Vitamin K Antagonists ◽  
Venous Blood ◽  
Coagulation Factors ◽  
Coagulation Cascade ◽  
High Intake ◽  
Smooth Muscle Cell Migration

SummaryVitamin K was discovered early last century at the same time as the vitamin K-antagonists. For many years the role of vitamin K was solely ascribed to coagulation and coagulation was thought to be involved only at the venous blood side. This view has dramatically changed with the discovery of vitamin K-dependent proteins outside the coagulation cascade and the role of coagulation factors at the arterial side. Vitamin K-dependent proteins are involved in the regulation of vascular smooth muscle cell migration, apoptosis, and calcification. Vascular calcification has become an important independent predictor of cardiovascular disease. Vitamin K-antagonists induce inactivity of inhibitors of vascular calcification, leading to accelerated calcification. The involvement of vitamin K-dependent proteins such as MGP in vascular calcification make that calcification is amendable for intervention with high intake of vitamin K. This review focuses on the effect of vitamin K-dependent proteins in vascular disease.

Long-Term Vitamin K Antagonists and Cancer Risk

2019 ◽  
Vol 42 (9) ◽  
pp. 717-724 ◽  
Author(s):  
Mohammed Shurrab ◽  
Kieran L. Quinn ◽  
Abhijat Kitchlu ◽  
Cynthia A. Jackevicius ◽  
Dennis T. Ko
Keyword(s):  
Cancer Risk ◽  
Vitamin K ◽  
Vitamin K Antagonists

Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification

2009 ◽  
Vol 101 (04) ◽  
pp. 706-713 ◽  
Author(s):  
Thilo Krueger ◽  
Ralf Westenfeld ◽  
Harald Peter Kühl ◽  
Vincent Brandenburg ◽  
Andreas Horst Mahnken ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Reference Population ◽  
Matrix Gla Protein ◽  
Control Group ◽  
Adverse Side Effect ◽  
Dependent Protein ◽  
Local Expression

SummaryMatrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 ± 123.1 nM) compared to the control group (571.6 ± 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.

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