A journey through anticoagulant therapies in the treatment of left ventricular thrombus in post-COVID-19 heparin-induced thrombocytopenia: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis. CASE PRESENTATION: A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 109/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date. CONCLUSION: The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.

Spontaneous massive pectoral hematoma induced by vitamin K antagonist therapy: a case report.

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.

Selecting the right anticoagulant for stroke prevention in atrial fibrillation.

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.

Acute myocardial infarction in a 41-year-old woman due to elevated factor VIII: a case report.

Myocardial infarction is a life-threatening emergency with a high mortality rate. A high plasma level of factor VIII is an established risk for both arterial and venous thrombotic events. In this mini-review, we report the case of a 41-year-old woman without cardiovascular risk factors or a previous history of thrombotic events, admitted for ST-elevation myocardial infarction, in whom coronary angiography showed a thrombotic occlusion in the left anterior descending artery. The patient underwent primary percutaneous coronary intervention (PCI), with GPIIB-IIIA antagonist, then, a pre-dilation with a semi-compliant balloon-catheter, followed by implantation of 2 stents. The etiological assessment revealed a high level of coagulation factor VIII (FVIII). She underwent anticoagulation therapy (with acenocoumarol) with well-controlled international normalised ratio (INR).

Cost-effectiveness of direct oral anticoagulants versus vitamin K antagonist in atrial fibrillation: A study protocol using Real-World Data from Catalonia (FantasTIC Study).

BACKGROUND: Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut. METHODS: Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate ('one-way') deterministic sensitivity analysis. DISCUSSION: We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.

Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.

Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p < 0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p < 0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.

[Intravenous thrombolysis after reversion of acenocoumarol anticoagulation. Report of one case]. / Trombolisis endovenosa post reversión de acenocumarol con complejo de protrombina. Caso clínico.

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.

Cianosis en una paciente portadora de prótesis tricúspide: cuando unas puertas se cierran, otras se abren / Cyanosis in a woman with a prosthetic tricuspid valve: when one door closes another opens

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Oral anticoagulation therapy using acenocoumarol during the month of ramadan: a comparative study between fasting and non-fasting patients.

BACKGROUND AND OBJECTIVES: The effect of Ramadan fasting on anticoagulation by vitamin K antagonists has been previously investigated in small scale studies with controversial results. From this perspective, this study aimed to compare the fluctuations of anticoagulation in fasting and nonfasting patients taking Acenocoumarol and to identify the factors associated with such fluctuations. METHODS: The study, conducted between May and August 2018, was a comparative one. Three study periods were defined: before Ramadan (BR), Ramadan and after Ramadan (AR). Enrolment involved ambulatory patients aged over eighteen, without medical contraindications to fasting (for the fasting group) and whom international normalized ratio (INR) was within the therapeutic target range during the last three months BR. Anticoagulation monitoring consisted in five consecutive INR assays; INR0 (during the 14 days BR), INR1 (between the 1st and the 14th day of Ramadan), INR2 (between the 15th and the 28th day of Ramadan), INR3 (28 days after INR2) and INR4 (28 days after INR3). INR stability was assessed by calculating four percentages of time in therapeutic range (TTR); TTR0 (between INR0 and INR1), TTR1 (between INR0 and INR2), TTR2 (between INR2 and INR3) and TTR3 (between INR3 and INR4). The null hypothesis was the occurrence of an anticoagulation imbalance (evaluated by TTR) in fasting patients in comparison with non-fasting ones. RESULTS: One hundred and twenty-two patients (84 fasting patients), aged 60 ± 19 years, were included. In fasting patients, the average differences of INR1, 2, 3 and 4 compared with INR0 were statistically non-significant and accounted for +0.46, +0.34, +0.28 and +0.30 respectively. Among the three TTRs, only TTR2 significantly decreased in comparison with TTR0 in fasting group (50.3 ± 37.4 vs. 63.6 ± 39.3%, p=0.004). TTR1, 2 and 3 were comparable between fasting and non-fasting patients. CONCLUSIONS: The fluctuations of anticoagulation balance, assessed by TTR, were comparable between fasting and non-fasting patients taking Acenocoumarol.

[A rare and severe complication related to acenocoumarol therapy: intra-alveolar bleeding]. / Une complication rare et grave du traitement par l'acénocoumarol: l'hémorragie intra-alvéolaire.

Intra-alveolar bleeding is a rare and severe medical emergency due to numerous causes. We report the clinical case of a patient who could contribute to extend the literature on this subject. The study included a 62-year old man, with a history of a trial fibrillation, under anti-vitamins K antagonist admitted with dyspnoea of sudden onset associated with haemoptysis and practising self-medication using non-steroidal anti-inflammatory drugs. X-rays and chest scan showed diffuse bilateral alveolar opacities. Haemostatic screening tests on admission showed non-coagulable INR. The diagnosis of intra-alveolar bleeding was clinically and radiologically suspected and then confirmed by bronchial endoscopy with broncho-alveolar lavage (BAL) which detected uniformly hemorrhagic liquid. Previous studies of similar complications occurring after anti-vitamins K antagonists assumption are rare. In conclusion, it seems very important to emphasize the interest of strict and optimal clinico-biological monitoring of patients treated in anti-vitamins K antagonists to avoid an overdose which could contribute to a life-threatening severe haemorrhagic event.

Síndrome de Lemierre por Klebsiella pneumoniae / Lemierre syndrome due to Klebsiella pneumoniae

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Trombolisis endovenosa post reversión de acenocumarol con complejo de protrombina: caso clínico / Intravenous thrombolysis after reversion of acenocoumarol anticoagulation: report of one case

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.

Extremely low therapeutic doses of acenocoumarol in a patient with CYP2C9*3/*3 and VKORC1-1639A/A genotype.

Vitamin-K antagonists (VKAs) have remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. The management of treatment with VKAs is challenging due to their narrow therapeutic index and the wide interindividual variation in response to therapy. Variants of the CYP2C9 and the VKORC1 gene account for 30-50% of the variability in dosing requirements, and it has been proposed that genotyping of these loci could facilitate management of VKA therapy and minimize risk of overanticoagulation, even in very low doses. We present the first reported case of a patient with the compounded genotype CYP2C9*3*3 and VKORC1-1639A/A under treatment with acenocoumarol, and review of other reported cases with analogous genotypic profiles but under treatment with warfarin.

Experiencia en manejo anestésico para cirugía no cardiaca en pacientes con asistencias ventriculares / Experience in anaesthetic management of non-cardiac surgery in patients with ventricular assist devices

La insuficiencia cardiaca constituye un cuadro sindrómico de elevada incidencia en la medicina actual. Cuando los síntomas de la insuficiencia cardiaca progresan y se convierten en refractarios, la indicación de trasplante cardiaco es la mejor opción terapéutica. Sin embargo, debido a la escasez de donantes y a las largas listas de espera, muchos de estos pacientes necesitan la implantación de dispositivos de asistencia ventricular como puente a este trasplante, o en algunos casos, cuando el trasplante no es una opción, como terapia definitiva. En este artículo se presenta una serie de 4 casos clínicos en pacientes portadores de dispositivos de asistencia ventricular que precisaron intervención quirúrgica. Tres de ellos estaban asistidos con asistencias de larga duración: 2 EXCOR (pulsátiles y paracorpórea) y un HEARTWARE (no pulsátil e intracorpórea) y el último con una asistencia de corta duración; CentriMag Levitronix biventricular. No existe bibliografía significativa sobre las implicaciones perioperatorias de estos pacientes cuando son sometidos a cirugía urgente o programada. La experiencia en nuestro centro nos lleva a plantear la necesidad de conocer una serie de aspectos: funcionamiento de cada dispositivo, recalcando la correcta colocación de las cánulas durante la cirugía; el manejo apropiado de la medicación, recalcando la importancia de las terapias anticoagulantes y antiagregantes; los cambios fisiopatológicos a nivel cardiopulmonar debidos a la implantación de estos dispositivos; y la importancia de la administración de una correcta antibioterapia. Ante la complejidad que presentan estos casos, la escasa experiencia en este campo y los pocos casos que existen de estas situaciones se recomienda la creación de protocolos para garantizar un manejo correcto de estos

Heart failure (HF) is a syndromic condition with a high incidence in current medicine. When the symptoms of HF progress, and become refractory, cardiac transplant is the best therapeutic option. However, due to the shortage of donors and the long waiting lists, many of those patients are candidates for implantation of ventricular assist devices as a bridge to the cardiac transplant, or when this is not an option, as a definitive therapy. A series of four clinical cases of patients with ventricular assist devices that required surgical intervention, is presented. Three of them were assisted with long-term care: two EXCOR (pulsatile and para-corporeal) and one HEARTWARE (non-pulsatile and intra-corporeal), and the last one with short-term assistance; CentriMag biventricular Levitronix. There is no significant literature on the peri-operative implications of these patients when they undergo urgent or scheduled surgery. The experience in our centre leads us to raise the need to determine a series of aspects: operation of each device, emphasising the correct placement of the cannulas during the surgery; the proper management of any medication, emphasising the importance of anticoagulant and anti-platelet therapies; the Pathophysiological changes at cardiopulmonary level due to the implantation of these devices; and the importance of the administration of a correct antibiotic therapy. Given the complexity of these cases, the limited experience in this field, and the few cases that exist in these situations, it is recommended to create protocols to ensure their proper management

Programa de autocontrol del tratamiento anticoagulante oral con antagonistas de la vitamina K en pacientes pediátricos / Self-monitoring treatment program with oral vitamin K antagonists in paediatric patients

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Factores asociados al mal control de la anticoagulación con antivitaminaK en pacientes con fibrilación auricular no valvular atendidos en consultas de Medicina Interna y Neurología. Estudio ALADIN / Factors associated with poor anticoagulation control with vitaminK antagonists among outpatients attended in Internal Medicine and Neurology. The ALADIN study

Objetivo: Identificar los factores asociados con el mal control de la anticoagulación con antagonistas de la vitaminaK (AVK) en pacientes con fibrilación auricular no valvular (FANV) atendidos en consultas de Neurología y Medicina Interna de España. Métodos: Estudio transversal, multicéntrico, anidado en el estudio ALADIN, de sujetos con FANV, tratados con AVK, atendidos en consultas de Medicina Interna o Neurología de España. El grado de control de la anticoagulación se estudió mediante el método directo y el de Rosendaal, considerando los 6meses previos a la inclusión. Resultados: De los 1.337 pacientes incluidos en ALADIN, 750 estaban tratados con AVK, con información completa sobre el INR de los últimos 6meses en 383 pacientes. Las puntuaciones medias del índice de Charlson, CHADS2, CHA2DS2-VASc y HAS-BLED fueron 1,94±1,54; 3,10±1,26; 4,63±1,54 y 2,20±0,90, respectivamente. El 46,2% y el 47,0% de los pacientes presentaban un control adecuado de la anticoagulación por los métodos directo y Rosendaal, respectivamente. El control inadecuado de la anticoagulación se asoció por el método directo con diabetes (OR: 2,511; IC95%: 1,144-5,659), antecedentes de INR inestable (OR: 35,371; IC95%: 15,058-83,083) y la realización de >6 controles en los últimos 6meses (OR: 4,747; IC95%: 2,094-10,759), y por el método de Rosendaal, con los antecedentes de INR inestable (p<0,001) y con HAS-BLED (OR: 3,991; IC95%: 2,520-6,319). Conclusiones: Pese al alto riesgo tromboembólico, sólo estaban bien controlados algo más de la mitad. Los factores asociados al mal control de la anticoagulación fueron la diabetes, INR inestable, >6 controles de INR y el HAS-BLED

Objective: To identify factors associated with poor anticoagulation control with vitaminK antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. Methods: Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6months before the inclusion. Results: Out of 1,337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94±1.54; 3.10±1.26; 4.63±1.54, and 2.20±0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95%CI: 1.144-5.659), prior labile INR (OR: 35.371; 95%CI: 15.058-83.083) and the determination of >6INR controls in the last 6months (OR: 4.747; 95%CI: 2.094-10.759), and according to the Rosendaal method, with prior labile INR (P<.001) and HAS-BLED score (OR: 3.991; 95%CI: 2.520-6.319). Conclusions: Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6INR controls and HAS-BLED