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The Neurologist Nov 2021Protein S deficiency and coronavirus disease 2019 (COVID-19) are rare etiologies of ischemic stroke. We describe a case of an ischemic stroke revealing severe acute...
INTRODUCTION
Protein S deficiency and coronavirus disease 2019 (COVID-19) are rare etiologies of ischemic stroke. We describe a case of an ischemic stroke revealing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a patient with a history of protein S deficiency and cerebral imaging suggestive of vasculitis.
CASE REPORT
A 52-year-old woman, with history of protein S deficiency, was admitted for right hemiparesis and aphasia that happened 6 hours before her consultation. Her National Institutes of Health Stroke Scale (NIHSS) was 11. She had hypoxia (SpO2 93%). COVID-19 polymerase chain reaction was positive. Cerebral computed tomography scan showed an ischemic stroke in the territory of the superficial left middle cerebral artery. The recommended time period for thrombolysis was exceeded and we did not dispose of sufficient resources to deliver thrombectomy. She was treated with aspirin, statins, antibiotic therapy, and oxygen. Considering the high risk of thromboembolic complications and the history of protein S deficiency, anticoagulation treatment with heparin followed by acenocoumarol was started. Evolution was marked by the appearance of 24 hours regressive, acute symptoms of confusion. Brain magnetic resonance imaging showed new ischemic strokes in both anterior cerebral arteries and on magnetic resonance angiography narrowing of the left internal carotid artery and both anterior cerebral arteries suggestive of vasculitis was seen. We maintained anticoagulation and prescribed methylprednisolone 500 mg daily for 3 days. Evolution was marked by improvement of clinical deficit and respiratory status.
CONCLUSIONS
SARS-CoV-2 infection potentializes the prothrombotic effect and vascular inflammation by accentuating protein S deficit. The place of steroids seems justifiable in the presence of symptoms of vasculitis in brain imaging.
Topics: Brain Ischemia; COVID-19; Female; Humans; Middle Aged; Protein S Deficiency; SARS-CoV-2; Stroke
PubMed: 34734908
DOI: 10.1097/NRL.0000000000000367 -
Biomedica : Revista Del Instituto... Sep 2021We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of...
We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2),a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient’s genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.
Topics: Anticoagulants; Child; Female; Genotype; Humans; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Retrospective Studies; Vitamin K Epoxide Reductases
PubMed: 34559488
DOI: 10.7705/biomedica.5840 -
FEMS Microbiology Letters Oct 2021The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties...
The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties could be modified. In this context, these studies are relevant for drugs such as acenocoumarol, whose dosage must be controlled due to, among other factors, food-drug interactions. Acenocoumarol is an oral anticoagulant with a narrow therapeutic range. The aim of the present research is to evaluate, in vitro, the effect of bifidobacteria on acenocoumarol. The drug was incubated with Bifidobacterium bifidum CIDCA 5310 or Bifidobacterium adolescentis CIDCA 5317 in MRS broth at 37°C for 24 h in anaerobic conditions. The effect of incubation with sterilized spent culture supernatants (SSCS) was also evaluated. Analysis by RP-HPLC showed that both bifidobacterial strains reduced the area of the acenocoumarol peak and two new peaks were evidenced. In addition, a decrease in the intensity of the bands at 1650, 1390 and 1110/cm was observed in the FTIR spectroscopic determinations. Moreover, a new band appeared at 1720/cm. No effect on the drug was observed when incubation was performed with SSCS. The present study showed a significant change in the concentration of the anticoagulant after incubation with bifidobacteria and results are compatible with biomodification of the drug due to enzymatic activity of bifidobacteria.
Topics: Acenocoumarol; Anticoagulants; Bifidobacterium; Drug Interactions; Probiotics
PubMed: 34529059
DOI: 10.1093/femsle/fnab125 -
Nederlands Tijdschrift Voor Geneeskunde Sep 2021Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent...
Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.
Topics: Acenocoumarol; Anticoagulants; Blood Coagulation; Humans; International Normalized Ratio; Phenprocoumon
PubMed: 34523845
DOI: No ID Found -
International Journal of Clinical... Oct 2021
Topics: Acenocoumarol; Drug Interactions; Enzyme Inhibitors; Humans; Omeprazole; Pharmaceutical Preparations; Proton Pump Inhibitors
PubMed: 34423773
DOI: 10.5414/CP203997 -
Annals of the Rheumatic Diseases May 2021Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may...
OBJECTIVES
Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.
METHODS
We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of and single nucleotide variants on this association.
RESULTS
Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94-3.20), both for knee (OR=2.34, 95% CI=1.67-3.22) and hip OA (OR=2.74, 95% CI=1.82-4.11). Among acenocoumarol users, carriers of the high ) expression haplotype together with the OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69-6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78-1.33).
CONCLUSIONS
These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.
Topics: 4-Hydroxycoumarins; Acenocoumarol; Aged; Alleles; Anticoagulants; Calcium-Binding Proteins; Disease Progression; Extracellular Matrix Proteins; Female; Humans; Incidence; Indenes; Male; Middle Aged; Osteoarthritis; Polymorphism, Single Nucleotide; Prospective Studies; Vitamin K; Vitamin K Epoxide Reductases; Matrix Gla Protein
PubMed: 34412027
DOI: 10.1136/annrheumdis-2020-219483 -
Revista Medica Del Instituto Mexicano... Aug 2021Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by arterial or venous thrombosis and/or obstetric events in the presence of...
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by arterial or venous thrombosis and/or obstetric events in the presence of antiphospholipid antibodies (aPL). It is usually diagnosed in patients between the ages of 15 and 50 years, and there are 5 new cases per 100,000 people per year. It is reported a case of APS, which it is present in an older adult with an unusual clinical manifestation.
CLINICAL CASE
Female patient without history of autoimmune diseases, at age 70 presented hemolytic anemia, Coombs direct positive, classified as autoimmune hemolytic anemia (AHAI) Coombs+, and severe thrombocytopenia. Other immunological, infectious, and lymphoid proliferative disorders and solid tumors were ruled out. Fisher-Evans syndrome (FES) was diagnosed with good response to treatment. Three months later, the patient presented deep venous thrombosis in the left pelvic limb, positive antiphospholipid antibodies (aPL) and positive aloantibodies were determined, establishing the diagnosis of primary APS and FES as its initial manifestation. Since then, the patient has been in treatment with acenocoumarol and prednisone without new recurrences of thrombosis, with persistence of moderate thrombocytopenia, without adding another clinical manifestation in 15 years of follow-up.
CONCLUSION
The unusual presentation of this disease in older adults with comorbidities should not rule out the possibility of the development of a primary autoimmune disease, so it should be considered for diagnosis in this age group.
Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Middle Aged; Pregnancy; Thrombocytopenia; Thrombosis; Young Adult
PubMed: 34374754
DOI: No ID Found -
Revista de Neurologia Sep 2021Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal... (Observational Study)
Observational Study
INTRODUCTION
Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity.
OBJECTIVES
The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis.
PATIENTS AND METHODS
A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables.
RESULTS
Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031).
CONCLUSIONS
ICH-OAC has a high mortality rate, related to the use of acenocoumarol and regardless of the initial clinical situation. A lower rate of early mortality was found among patients who received ART.
Topics: Aged; Aged, 80 and over; Anticoagulants; Anticoagulation Reversal; Antidotes; Cerebral Hemorrhage; Clinical Protocols; Factor Xa Inhibitors; Female; Follow-Up Studies; Hospital Mortality; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Neuroimaging; Prospective Studies; Severity of Illness Index; Tertiary Care Centers; Thromboembolism; Tomography, X-Ray Computed; Treatment Outcome; Vitamin K
PubMed: 34328205
DOI: 10.33588/rn.7305.2020565 -
European Review For Medical and... Jul 2021The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic... (Comparative Study)
Comparative Study
OBJECTIVE
The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic stroke is the most frequent embolic event associated with AF, embolization to other sites in the pulmonary and systemic circulations may occasionally occur. To avert the risk of embolization, long-term oral anticoagulation therapy is recommended for all AF patients if the CHA2DS2-VASC score is at least 1 for men and at least 2 for women. Since anticoagulant therapy is associated with an increased risk of bleeding, the choice of oral anticoagulant agent should be made by careful consideration of the benefit-to-risk ratio. The use of a newer class of direct oral anticoagulants (DOACs) as an alternative to the anti-vitamin K (AVK) anticoagulants (warfarin, acenocumarol, etc.) can help mitigate the need for periodic monitoring of International Normalized Ratio (INR) and adverse bleeding events that are commonly associated with the use of AVK anticoagulants. Though the use of DOACs (dabigatran, rivaroxaban, edoxaban, apixaban, etc.) is gaining ground due to their relative safety profile and the low overall cost, quite a few clinicians remain skeptical about their use.
PATIENTS AND METHODS
Our objective was to evaluate the risk of thromboembolism, stroke, neuropsychiatric illness, depression, and dementia, in patients with non-valvular atrial fibrillation who have been treated with either acenocumarol or apixaban, as well as to see the inflammatory status (ESR) and levels of fibrinogen. Our team at Municipal Emergency University Hospital, Timisoara, Romania, conducted a retrospective study using the medical records of AF patients who were treated with either apixaban or acenocumarol between 2016-2019. We divided the patients into two groups and compared the groups for the aforementioned outcomes.
RESULTS
AF patients who were prescribed apixaban had a lower rate of stroke and psychiatric illness compared to those on acenocumarol. No significant correlation was found in terms of risk of developing depression or dementia between the groups.
CONCLUSIONS
Non-valvular AF patients on apixaban had lower rates of thromboembolic events than the patients on acenocumarol. This article will serve as a reminder of the positive health and financial outcomes of apixaban use, especially to those healthcare systems that are still oblivious to the decrease in economic burden and gain in quality-adjusted life years (QALY) by the long-term use of NOACS/ DOACS instead of the AVK anticoagulants.
Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Retrospective Studies; Risk Assessment; Romania; Stroke
PubMed: 34286492
DOI: 10.26355/eurrev_202107_26241 -
The Pan African Medical Journal 2021Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy...
Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy is bleeding, and sometimes it can occur in unsuspected areas. Spontaneous pectoral hematoma is one of the rare complications due to over anticoagulation by VKA therapy, with only a few cases reported in the literature. Concomitant use of this therapy with commonly used antibiotic, especially in the elderly with multiple comorbidities, can increase the risk of bleeding. Herein, we report a case of a 72-year-old woman under VKA for the treatment of atrial fibrillation, who presented with a spontaneous massive pectoral hematoma, while using antibiotic to treat a respiratory tract infection, who was successfully managed.
Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Female; Hematoma; Hemorrhage; Humans; Thromboembolism; Vitamin K
PubMed: 34285747
DOI: 10.11604/pamj.2021.38.324.28454