Alessandro Pampana

The practical management of intracerebral hemorrhage associated with oral anticoagulant therapy.

Oral anticoagulant-associated intracerebral hemorrhage is increasing in incidence and is the most feared complication of therapy with vitamin K1 antagonists. Anticoagulant-associated intracerebral hemorrhage has a high risk of ongoing bleeding, death, or disability. The most important aspect of clinical management of anticoagulant-associated intracerebral hemorrhage is represented by urgent reversal of coagulopathy, decreasing as quickly as possible the international normalized ratio to values ≤1·4, preferably ≤1·2, together with life support and surgical therapy, when indicated. Protocols for anticoagulant-associated intracerebral hemorrhage emphasize the immediate discontinuation of anticoagulant medication and the immediate intravenous administration of vitamin K1 (mean dose: 10–20 mg), and the use of prothrombin complex concentrates (variable doses calculated estimate circulating functional prothrombin complex) or fresh-frozen plasma (15–30 ml/kg) or recombinant activated factor VII (15–120 μg/kg). Because of cost and availability, there is limited randomized evidence comparing different reversal strategies that support a specific treatment regimen. In this paper, we emphasize the growing importance of anticoagulant-associated intracerebral hemorrhage and describe options for acute coagulopathy reversal in this setting. Additionally, emphasis is placed on understanding current consensus-based guidelines for coagulopathy reversal and the challenges of determining best evidence for these treatments. On the basis of the available knowledge, inappropriate adherence to current consensus-based guidelines for coagulopathy reversal may expose the physician to medico-legal implications.

Spontaneous renal subcapsular hematoma in a very old patient presenting with shock and severe anemia: an uncommon oral anticoagulant treatment-related complication.

Bleeding represents the most feared complication of oral anticoagulant therapy (OAT) with vitamin K antagonists (VKA), one of the major classes of drugs used in cardiovascular medicine. Of the general population in developed countries, 1–1.5% is subject to OAT, with widespread use over the last two decades. Elderly patients represent the main group of patients treated with OAT, with a high prevalence in this group of diseases needing OAT, such as atrial fibrillation. But advanced age also represents one of the main risk factors for VKA-related bleeding, together with severe liver and kidney diseases, severe thrombocytopenia, history of previous bleeding, anemia, dementia and risk of falls. The incidence rate of major hemorrhage rises gradually with age from 1.5 per 100 patient-years for patients younger than 60 years to 4.2 per 100 patientyears for patients older than 80 years, yielding a hazard ratio of 2.7 (95% confidence interval, 1.7–4.4). Bleeding is classified as major if it leads directly to death, it occurs in critical organs (brain, retroperitoneum, peritoneum, chest, spinal cord, joints, gastrointestinal tract), if it results in hemorrhagic shock, a decrease of 2 g/dL in hemoglobin (Hb) levels, or if it requires surgical or invasive maneuvers. The remaining bleedings are classified as minor bleedings. Spontaneous and/or traumatic retroperitoneal bleedings represents a well-recognized OAT-related major complication, often related to a rupture of the iliopsoas muscle, whereas spontaneous renal hematoma (SRH) is a very uncommon example of OAT-related bleeding, diagnosis of it being often difficult and late, especially when signs such as macrohematuria are absent. Prothrombin complex concentrate (PCC) is now considered the first choice for urgent OAT reversal together with intravenous vitamin K1 (VK1) in VKA-related major bleedings. The cornerstone of OAT reversal is bringing the International Normalized Ratio (INR) to a value less than 1.5, to restore normal coagulation, in association with maneuvers to stop bleedings and/or resolve hemorrhagic shock. Recently, an 86-year-old man taking warfarin for chronic atrial fibrillation came to our attention for the abrupt onset of dyspnea and fatigue; he suffered from left sciatica for 3 days and left lumbar pain for a few hours. He denied fever, and macrohematuria was absent. Recent trauma was excluded. His past history revealed previous coronary artery bypass and prostatic cancer. Physical examination showed pallor and sweating. Systemic blood pressure (SBP) measured 75/50 mmHg, demonstrating a status of shock. Blood arterial gas analysis was substantially normal. A 12-lead electrocardiogram (ECG) revealed tachycardic atrial fibrillation (120 beats per minute) and complete right bundle branch block. Chest and abdominal radiographs and abdominal ultrasonography performed in the emergency department were unremarkable. Results of laboratory assays showed Hb levels of 10.6 g/dL, creatinine 1.41 mg/dL, normal values of brain natriuretic peptide (BNP) and troponin I. D-Dimer was 336 ng/mL (normal value <250). INR was 2.0. The patient was monitored by continuous ECG and he was treated with intravenous dopamine and digoxin with improvement in SBP and heart rate. Over the next hours Hb levels progressively fell to 8.9 g/dL and 6.8 g/ dL. We began urgent OAT reversal by using three PCC (Uman Complex, Kedrion, Castelvecchio Pascoli, Italy) S Gori et al.

Menorrhagia, Tranexamic Acid and False Negative D-Dimer in Patients with Venous Thromboembolism Case Report and Systematic Literature Review

A 56 years-old woman came to our attention for abrupt onset of shortness of breath. Pulmonary embolism was firstly ru led out due to negative D -Dimer and unlikely probability. On second day, the patient presented with heavy menorrhagia and treated with tranexamic acid (TA). She informed that similar episode happened some months ago, so she had been treated with cycles of

Clinical management of spontaneous intracranial haemorrhage associated with oral anticoagulants: a case series

Introduction: Intracranial haemorrhage (ICH) is associated with high mortality and morbidity, and for this reason it is the most feared complication of oral anticoagulant therapy (OAT). Recommendations are available for the immediate reversal of OAT, but these measures are not always used uniformly and rapidly. The aim of this study was to critically review the treatment of spontaneous OAT-related ICH in our hospital. Materials and methods: We retrospectively analyzed the medical records of patients admitted to our ward between January 2006 and January 2010 for spontaneous OAT-related ICH. Results: In the analyzed period, 15 patients were hospitalized for OAT-related ICH (supratentorial in 66.5%, infratentorial in 20%, acute subdural hematoma in 13.5%). In 66.5% of the patients, the INR on arrival was within the therapeutic range. In 60% of the cases, the Glasgow Coma Scale (GCS) on arrival was > 8/15. Three-factor prothrombin complex concentrate (PCC) was administered in 80% of the cases, and 30% of patients received fresh frozen plasma (FFP) and recombinant activated factor VII (FVIIra). One patient received PCC plus PFC, and another received PCC with FVIIra. FFP alone was used in 13.5% of the patients. All of the patients received intravenously administered vitamin K1. Treatment was started in the Emergency Room in 33.5% of the cases; in the other 66.5% it began on our ward. In 66.5% of the patients, the treatment was effective in reversing OATwithin 8 hours. In 2 cases, the hematoma was surgically evacuated, and the patients survived. Total mortality for OAT-related ICH was 46.5% (32.9% in non-OAT-related ICH). In 71.5% of the patients with OAT-related haemorrhages, death occurred within 48 hours of arrival. Sixty percent of the patients with ICH > 60 cm3 (20% in patients with ICH < 60 cm3) and 100% of those with GCS < 7/15 died. For survivors, the median modified Rankin Scale at discharge was 3. All survivors were still alive at 3 months after discharge. Conclusions: Our study shows that in ICH associated with OAT, mortality is related to the size of the hematoma and to the GCS. Our study confirms that treatment of OAT-related ICH varies and is sometimes delayed. Management protocols for ICH-OATshould be implemented in clinical settings.

Impatto ospedaliero e management pratico delle emorragie cerebrali intraparenchimali spontanee associate a terapia anticoagulante orale nel corso degli anni

RiassuntoPremesseL’emorragia cerebrale intraparenchimale spontanea (sICH) rappresenta la forma più temuta di ictus cerebrale. Nonostante il rischio di sanguinamento intracerebrale associato alla terapia anticoagulante orale (TAO) con farmaci vitamina K antagonisti (VKA) sia rimasto costante, il più ampio uso dei VKA negli ultimi 20 anni ha comportato un incremento delle sICH TAO associate (sICH-TAO).Scopo dello studioValutare se la percentuale di sICHTAO è aumentata nel nostro ospedale nel corso degli anni e quale è stato e se è cambiato il management pratico del reverse urgente della TAO nel corso degli anni.MetodiAbbiamo analizzato retrospettivamente i dati clinici, strumentali e di laboratorio dei pazienti consecutivamente ricoverati nel reparto di Medicina Interna del nostro Ospedale dal 2006 con lo scopo di valutare la severità clinica della sICH, la terapia antitrombotica assunta prima dell’arrivo in Ospedale, i valori di INR all’arrivo in Ospedale nei pazienti con sICH-TAO e dopo il trattamento di reverse urgente e l’impatto sulla mortalità totale delle sICH-TAO.RisultatiNel periodo analizzato 122 pazienti, 56 maschi, di età media±DS 79,8±9,6 anni, sono stati ricoverati per sICH. 25 pazienti (20,4%) assumevano TAO e 44 (36%) antiaggreganti piastrinici prima dell’evento. La percentuale di sICH-TAO è aumentata dal 9% del 2006 al 31,5% dei primi 10 mesi del 2011. 39 pazienti (31,96%) sono deceduti. La mortalità è risultata del 56% nei pazienti con sICH-TAO, del 40,9% nei pazienti in terapia antiaggregante e del 12,8% nei pazienti che non assumevano terapia antitrombotica. I valori medi di INR all’arrivo in Ospedale sono risultati 3,55±2,39. Un paziente (4%) è risultato avere valori di INR <2,0, il 48% dei pazienti erano in range terapeutico (2,0–3,0), il 28% aveva valori di INR compresi tra 3,0 e 4,0, il 8% 4,0–5,0, il 12% valori di INR >5,0 (8% ≥9,0). Il reverse urgente della TAO è stato effettuato nel 80% dei casi con concentrato di complesso protrombinico (CCP), nel 12% dei casi è stato somministrato plasma fresco congelato e nel 16% dei casi fattore VII ricombinante attivato. Il 96% dei pazienti ha ricevuto l’infusione di vitamina K1. Alla fine della prima infusione di CCP i valori medi di INR sono risultati 1,61±0,76. La mediana di dosaggi dell’INR fino alla dimostrazione della neutralizzazione della TAO è stata 3.ConclusioniLe sICH-TAO sono un’emergenza medica in incremento e ciò è dovuto alla più ampia diffusione dei farmaci VKA. I Medici di Laboratorio sono chiamati a dare risposte rapide dei valori di INR dal momento che il reverse urgente della TAO è imperativa in questo contesto. La stretta collaborazione tra Medici dell’emergenza e di Laboratorio è fondamentale.SummaryBackgroundSpontaneous intracerebral hemorrhage (sICH) represents the most feared subtype of stroke. Despite the intracranial bleeding risk associated to oral anticoagulant (OAT) with vitamin K antagonists (VKA) has remained constant, the wider use of VKA over the last 20 years has proven the increasing of OAT related ICH (OAT-sICH).Aim of the studyTo evaluate whether the percentage of OAT-sICH is increased in our hospital and which has been the practical management of OAT urgent reverse and whether this management has changed over the years.MethodsWe retrospectively analyzed data records of patients consecutively admitted in the Internal Medicine ward of our hospital for ICH since 2006. Of these patients we retrieved clinical, radiological and laboratory findings aimed to investigate the severity of sICH, the antithrombotic drugs used before admission, the INR values in OAT-sICH patients at hospital arrival and after OAT reverse and the mortality burden.ResultsIn the analyzed period 122 patients, 56 males, with mean age 79.8±9.6 years, were admitted. 25 patients (20.4%) were on OAT, whereas 44 (36%) were treated by antiplatelets agents. The percentage of OATsICH increased from 9% in 2006 to 31.5% in the first ten months of 2011. 39 patients (31.96%) died. Mortality was 56% in OAT-sICH patients, 40.9% in antiplatelets related sICH, while mortality was 12.8% in patients not treated with antithrombotic drugs. Mean values of INR at hospital arrival were 3.55±2.39. One patient (4%) presented INR value <2.0, 48% of patients was in therapeutic range (2.0–3.0), 28% had INR values between 3.0 and 4.0, 8% 4.0–5.0, 12% INR values >5.0 (8%–9.0). OAT reverse was performed by using prothrombin complex concentrate (CCP) in 80% of patients, whereas 12% was treated with fresh frozen plasm. 96% of patients received intravenous vitamin K1. At the end of first dose of CCP mean values of INR were 1.61±0.76. Median number of INR assays until demonstration of OAT reversal was 3.ConclusionOAT-sICH is an increasing emergency due to wider use of VKA. Laboratory physicians are called to give quick results of INR as the urgent OAT reverse is imperative. Therefore close collaboration between emergency and laboratory physicians is fundamental.