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Cureus Apr 2023A common complication of anticoagulation therapy is bleeding, especially in patients receiving long-term vitamin K antagonists. Spontaneous intramural hematoma is a rare...
A common complication of anticoagulation therapy is bleeding, especially in patients receiving long-term vitamin K antagonists. Spontaneous intramural hematoma is a rare etiology among life-threatening major bleeds. An 80-year-old female patient presented with diffuse abdominal pain. Her history included ischemic heart disease and chronic atrial fibrillation treated with 3 mg of acenocoumarol per day. Three days before her admission, she developed diffuse abdominal pain with fecaloid vomiting, bloating, and not passing gas. Palpation of the abdomen revealed asymmetrical distension and pain, with no signs of peritoneal irritation or bleeding. Investigations showed anemia with a hemoglobin level of 9.2 g/dL, a white blood cell count of 14200/mm, a C-reactive protein of 112.6 mg/L, and a prothrombin time of 75.1 seconds with an international normalized ratio (INR) of 8.5. Abdominal contrast-enhanced computed tomography (CT) showed segmental parietal thickening, luminal narrowing, and partial small bowel obstruction secondary to an intramural jejunum hematoma responsible for a gallbladder occlusion with infiltration of the mesenteric fat in front. The patient recovered two days after conservative treatment. In this case, we report an unusual small bowel intramural hematoma of the jejunum secondary to anticoagulant therapy. Physicians should be aware of this unusual cause of abdominal pain. Early diagnosis may avoid unnecessary surgical exploration.
PubMed: 37162778
DOI: 10.7759/cureus.37257 -
Cureus Mar 2023Coumarin derivatives are the most used class of oral anticoagulants, and almost 1-2% of adults worldwide take it in the form of warfarin (WA) or acenocoumarol (AC)....
Coumarin derivatives are the most used class of oral anticoagulants, and almost 1-2% of adults worldwide take it in the form of warfarin (WA) or acenocoumarol (AC). Cutaneous necrosis is a rare and severe complication of oral anticoagulant therapy. Most commonly, it occurs in the first 10 days, and the incidence peaks between the third and sixth day of starting treatment. Cutaneous necrosis due to AC therapy is underreported in the literature, and studies refer to this condition as "coumarin-induced skin necrosis"; however, this term is not totally accurate, as coumarin itself has no anticoagulant properties. We report a case of a 78-year-old female patient with AC-induced skin necrosis, who presented with cutaneous ecchymosis purpura over her face, arms, and lower extremities 3 hours after AC intake.
PubMed: 37131576
DOI: 10.7759/cureus.36960 -
Cureus Mar 2023Spontaneous renal rupture (SRR) with retroperitoneal hemorrhage is an extremely rare medical emergency and is rather challenging for the surgical team. Management of SRR...
Spontaneous renal rupture (SRR) with retroperitoneal hemorrhage is an extremely rare medical emergency and is rather challenging for the surgical team. Management of SRR often requires surgical intervention and nephrectomy as it is life-threatening. Antiphospholipid syndrome (APLS) is an autoimmune disease that affects several organs, including kidneys, causing significant abnormalities. Current data suggest that APLS can result in renal artery stenosis, renal vein thrombosis, arterial hypertension, thrombotic microangiopathy, and antiphospholipid syndrome nephropathy where there is renal involvement. Here, we report the case of a 49-year-old man who presented to the Emergency Department with sudden-onset abdominal pain in the context of retroperitoneal bleeding due to SRR. The patient developed hemodynamic instability and underwent a total nephrectomy. The surgical specimen revealed APLS-related lesions. Serological tests confirmed the diagnosis of APLS, which was managed with acenocoumarol and hydroxychloroquine. Since then, he has not experienced any thromboembolic or hemorrhagic episodes. This article aims to present for the first time a case of SRR as the first presentation of APLS as well as to analyze the possible associated mechanisms.
PubMed: 37123758
DOI: 10.7759/cureus.36839 -
Pharmaceuticals (Basel, Switzerland) Apr 2023Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and...
Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and café-au-lait spots (flat brown spots). Thus, there is an increasing need for the development of depigmenting agents. We aimed to repurpose an anticoagulant drug as an effective ingredient against hyperpigmentation and apply cosmeceutical agents. In the present study, the anti-melanogenic effects of two anticoagulant drugs, acenocoumarol and warfarin, were investigated. The results showed that both acenocoumarol and warfarin did not cause any cytotoxicity and resulted in a significant reduction in intracellular tyrosinase activity and melanin content in B16F10 melanoma cells. Additionally, acenocoumarol inhibits the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, suppressing melanin synthesis through a cAMP-dependent, protein kinase (PKA)-dependent downregulation of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Furthermore, anti-melanogenic effects were exerted by acenocoumarol through downregulation of the p38 and JNK signaling pathway and upregulation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades. In addition, the β-catenin content in the cell cytoplasm and nucleus was increased by acenocoumarol through a reduction in the phosphorylated β-catenin (p-β-catenin content). Finally, we tested the potential of acenocoumarol for topical applications by conducting primary human skin irritation tests. Acenocoumarol did not induce any adverse reactions during these tests. Based on the results, it can be concluded that acenocoumarol regulates melanogenesis through various signaling pathways such as PKA, MAPKs, PI3K/Akt/GSK-3β, and β-catenin. These findings suggest that acenocoumarol has the potential to be repurposed as a drug for treating hyperpigmentation symptoms and could provide new insights into the development of therapeutic approaches for hyperpigmentation disorders.
PubMed: 37111361
DOI: 10.3390/ph16040604 -
Medicina Clinica Jul 2023The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid... (Review)
Review
The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.
Topics: Humans; Antiphospholipid Syndrome; Anticoagulants; Factor Xa Inhibitors; Warfarin; Thrombosis; Administration, Oral
PubMed: 37105842
DOI: 10.1016/j.medcli.2023.03.011 -
Cureus Mar 2023Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous... (Review)
Review
Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous thromboembolism (VTE) and arterial thromboembolism (ATE). Twenty percent of COVID-19 patients suffer from coagulation abnormalities like pulmonary embolism, myocardial infarction, stroke, deep vein thrombosis, etc. Ovarian vein thrombosis (OVT) has been previously linked to post-partum period, pregnancy, hypercoagulable state, or malignancy. We analyzed PubMed and Google Scholar databases for research and publications regarding OVT in patients with COVID-19. The search yielded nine case reports. These case reports were found to implicate COVID-associated coagulopathy (CAC) as an additional risk factor for ovarian vein thrombosis (OVT). OVT most commonly presents with abdominal pain and fever, making it difficult to diagnose, owing to the similarity in presentation with multiple other pathologies. OVT can be diagnosed radiologically with ultrasound, magnetic resonance imaging (MRI) scan, or CT scan with IV contrast. CT has been used as the modality of choice for diagnosing OVT. Although rare, OVT can cause life-endangering complications by extension of thrombus into systemic veins or pulmonary artery embolization. Therefore, early diagnosis and treatment are vital. There is no official guideline for the treatment of OVT post-COVID. However, the literature supports the use of apixaban or enoxaparin/acenocoumarol.
PubMed: 37090373
DOI: 10.7759/cureus.36437 -
Reumatologia Clinica Apr 2023Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency,...
Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency, which may present with severe haemorrhagic manifestations. LAHPS is usually associated with systemic lupus erythematosus (SLE), or infections and it is more frequent in the paediatric population and female gender. We describe a 42-year-old man with thrombotic antiphospholipid syndrome (APS) on chronic anticoagulation treatment with acenocoumarol who presented with spontaneous intracranial bleeding, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and low factor II levels (after optimal anticoagulation reversal) as a debut of SLE.
Topics: Male; Child; Female; Humans; Adult; Antiphospholipid Syndrome; Lupus Coagulation Inhibitor; Hypoprothrombinemias; Lupus Erythematosus, Systemic; Prothrombin; Hemorrhage
PubMed: 37061283
DOI: 10.1016/j.reumae.2022.02.008 -
Molecules (Basel, Switzerland) Feb 2023The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic...
The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic inflammatory diseases (e.g., atopic dermatitis and psoriasis) and investigate the potential underlying mechanisms. For this purpose, we used murine macrophage RAW 264.7 as a model in experiments aimed at investigating the anti-inflammatory effects of acenocoumarol in inhibiting the production of pro-inflammatory mediators and cytokines. We demonstrate that acenocoumarol significantly decreases nitric oxide (NO), prostaglandin (PG)E, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Acenocoumarol also inhibits the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2, potentially explaining the acenocoumarol-induced decrease in NO and PGE production. In addition, acenocoumarol inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun N terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), in addition to decreasing the subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicates that acenocoumarol attenuates the macrophage secretion of TNF-α, IL-6, IL-1β, and NO, inducing iNOS and COX-2 expression via the inhibition of the NF-κB and MAPK signaling pathways. In conclusion, our results demonstrate that acenocoumarol can effectively attenuate the activation of macrophages, suggesting that acenocoumarol is a potential candidate for drug repurposing as an anti-inflammatory agent.
Topics: Animals; Mice; Acenocoumarol; Anti-Inflammatory Agents; Cyclooxygenase 2; Extracellular Signal-Regulated MAP Kinases; Interleukin-6; Lipopolysaccharides; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Tumor Necrosis Factor-alpha
PubMed: 36903321
DOI: 10.3390/molecules28052075 -
Current Drug Safety 2024Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events.
BACKGROUND
Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events.
CASE PRESENTATION
A 90-year-old female was admitted to our hospital with tonic-clonic seizures, possibly due to dementia syndrome. Valproic acid (VPA) was prescribed for the treatment of seizures. VPA is an inhibitor of cytochrome P450 (CYP) 2C9 enzymes. A pharmacokinetic interaction with phenprocoumon occurred, which is a substrate for CYP2C9 enzymes. The interaction resulted in a strong INR increase and subsequent clinically relevant bleeding in our patient. Valproic acid is not specifically mentioned in the phenprocoumon drug label as a CYP2C9 inhibitor, and in the Dutch medication surveillance database, no medication alert is shown when prescribing this combination, and no interaction with phenprocoumon has been reported so far.
CONCLUSION
When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.
Topics: Female; Humans; Aged, 80 and over; Phenprocoumon; Valproic Acid; Acenocoumarol; Cytochrome P-450 CYP2C9; Aryl Hydrocarbon Hydroxylases; Anticoagulants
PubMed: 36896908
DOI: 10.2174/1574886318666230310104322 -
Medical Cannabis and Cannabinoids 2023Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different...
INTRODUCTION
Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment of their Cytochrome P450 (CYP)-mediated herb-drug interaction profiles.
METHODS
Plant extracts were either commercially obtained or prepared using ethanol as solvent, followed by overnight decarboxylation in a reflux condenser system. The extracts were characterized for their cannabinoid content using NMR and HPLC-PDA-ELSD-ESIMS. CYP inhibition studies with the cannabis extracts and pure cannabinoids (tetrahydrocannabinol [THC] and cannabidiol [CBD]) were performed using pooled, mixed gender human liver microsomes. Tolbutamide and testosterone were used as specific substrates to assess the inhibitory potential of the extracts on CYP2C9 and CYP3A4, and the coumarinic oral anticoagulants warfarin, phenprocoumon, and acenocoumarol were studied as model compounds since in vivo herb-drug interactions have previously been reported for this compound class.
RESULTS
In accordance with the plant chemotypes, two extracts were rich in THC and CBD (at different proportions); one extract contained mostly CBD and the other mostly cannabigerol (CBG). Residual amounts of the corresponding acids were found in all extracts. The extracts with a single major cannabinoid (CBD or CBG) inhibited CYP2C9- and CYP3A4-mediated metabolism stronger than the extracts containing both major cannabinoids (THC and CBD). The inhibition of CYP3A4 and CYP2C9 by the extract containing mostly CBD was comparable to their inhibition by pure CBD. In contrast, the inhibitory potency of extracts containing both THC and CBD did not correspond to the combined inhibitory potency of pure THC and CBD. Although being structural analogs, the three coumarin derivatives displayed major differences in their herb-drug interaction profiles with the cannabis extracts and the pure cannabinoids.
CONCLUSION
Despite the fact that cannabinoids are the major components in ethanolic, decarboxylated cannabis extracts, it is difficult to foresee their herb-drug interaction profiles. Our in vitro data and the literature-based evidence on in vivo interactions indicate that cannabis extracts should be used cautiously when co-administered with drugs exhibiting a narrow therapeutic window, such as coumarinic anticoagulants, regardless of the cannabis chemotype used for extract preparation.
PubMed: 36814687
DOI: 10.1159/000528465