Coronary Artery By-Pass Grafting in Patient With Paroxysmal Nocturnal Hemoglobinuria (Case Report)

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell disease that presents with haemolytic anaemia, thrombosis and bone marrow failure. We report a case of a 51-year-old male with a history of PNH in treatment with Eculizumab admitted to our Hospital for acute chest pain and dyspnoea. The diagnosis was a triple vessel disease and patient was scheduled for coronary artery bypass grafting surgery. To balance the risk between thrombosis and bleeding in this particular clinical setting, we decided to use thromboelastography (TEG) as point of care solution and we used the R parameter as the target of our anticoagulant therapy. The R parameter between 11 and 14 sec can be used as a target value to balance the risk; in addition, there was no evidence of acute hemolysis during the surgery and supplemental dose of Eculizumab was administered in order to minimize any potential exacerbation of intravascular hemolysis

Аортокоронарное шунтирование у пациента с пароксизмальной ночной гемоглобинурией (клиническое наблюдение)

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell disease that presents with haemolytic anaemia, thrombosis and bone marrow failure. We report a case of a 51-year-old male with a history of PNH in treatment with Eculizumab admitted to our Hospital for acute chest pain and dyspnoea. The diagnosis was a triple vessel disease and patient was scheduled for coronary artery bypass grafting surgery. To balance the risk between thrombosis and bleeding in this particular clinical setting, we decided to use thromboelastography (TEG) as point of care solution and we used the R parameter as the target of our anticoagulant therapy. The R parameter between 11 and 14 sec can be used as a target value to balance the risk; in addition, there was no evidence of acute hemolysis during the surgery and supplemental dose of Eculizumab was administered in order to minimize any potential exacerbation of intravascular hemolysis.Пароксизмальная ночная гемоглобинурия (ПНГ) — клональное заболевание гемопоэтических стволовых клеток, которое проявляется гемолитической анемией, тромбозами и недостаточностью функции костного мозга. Пациент мужского пола 51 года с ПНГ в анамнезе, по поводу которой он получал лечение экулизумабом, поступил в больницу с жалобами на острую боль в грудной клетке и одышку. Поставили диагноз трехсосудистого поражения коронарного русла, по поводу чего запланировали проведение аортокоронарного шунтирования. Для того, чтобы избежать развития как тромбоза, так и кровотечения, в данном сложном клиническом случае, решили провести пациенту тромбоэластографическое исследование и использовать параметр R в качестве целевого при проведении антикоагулянтной терапии. При поддержании значений данного параметра в рамках 11-14 сек можно достичь оптимального баланса между риском тромбоза и кровотечения. Кроме того, во время оперативного вмешательства не наблюдали острого гемолиза, а для уменьшения риска развития внутрисосудистого гемолиза дополнительно назначили экулизумаб

Acute dose-response curve of enalapril in renovascular hypertensives

We evaluated the acute blood pressure lowering effect of enalapril in terms of dose-response curve and compared this effect with that on humoral parameters. Eleven renovascular patients with acute angiotensin-converting enzyme (ACE) inhibition received (according to a randomized double-blind cross-over design) placebo, 10, 20, and 40 mg of enalapril with a 72-hour interval between each dose. Seated blood pressure and heart rate were measured every hour for 6 hours and then again at the twelfth and twenty-fourth hour, while venous blood samples for plasma renin activity, plasma aldosterone and serum ACE measurements were obtained at the fourth and twenty-fourth hour after receiving the placebo or drug. Blood pressure was significantly reduced by all three doses of enalapril at hour 4, while at hour 24 it was reduced only by the 20- and 40-mg doses. A significant correlation (r = 0.68; P less than 0.001) was found between percentage decrements of mean blood pressure and the log of the doses at hour 4 with a similar (although not significant) trend at hour 24. Plasma renin activity was significantly and to a similar extent increased by the three doses of enalapril at hour 4, while at hour 24 it was significantly increased only by the 40-mg dose. Serum ACE and plasma aldosterone were significantly reduced both at hours 4 and 24 without any difference between doses. No correlation was found between mean blood pressure changes and those of humoral factors.(ABSTRACT TRUNCATED AT 250 WORDS

Angiotensin-converting enzyme inhibitors in hypertension: a review. Int

Angiotensin-converting enzyme (ACE) inhibitors are a new class of drugs, whose main indications are the treatment of hypertension and of heart failure. Data obtained with captopril, the first orally active ACE inhibitor, affords an understanding of the rationale of their therapeutic use based on the knowledge of their mechanisms of action, efficacy, contraindications and precautions, dosage and frequency of administration, side-effects, interactions and advantages. ACE inhibitors appear to exert their haemodynamic effect mainly by inhibiting the renin-angiotensin-aldosterone system, but also by modulating sympathetic nervous system activity and by increasing prostaglandin synthesis. Therefore they act both on vasoconstrictor and volume factors, since they cause vasodilation (the main effect) and mild natriuresis without affecting the heart rate and contractility and, probably, favourably influencing renal, coronary and cerebral circulation. So far it appears that ACE inhibitors can be usefully employed in the treatment of heart failure, in which they reduce both pre- and after-load, and mainly of hypertension. In the past captopril has been used to treat only severe and or resistant hypertension and some secondary forms, like renal parenchymal and renovascular hypertension, but now it seems that captopril is useful also to treat mild to moderate essential hypertension. Their efficacy in reducing blood pressure is similar to that of thiazide diuretics and of beta-blockers, the two drugs now considered of first choice and they exert their hypotensive action without the development of pseudotolerance or tolerance. ACE inhibitors seem, at the moment, contraindicated in pregnancy and in hyperkalaemic syndromes and must be used with caution in patients with collagen disease (mainly associated with renal failure), with severe bilateral renal artery stenosis (and with severe artery stenosis of a solitary kidney) and with severe sodium depletion. It is now established that captopril has a flat dose response curve and that it must be given (twice daily) at a dose not exceeding 150 mg/day. The same pharmacological approach must be used with future ACE inhibitors in order to establish the right posology and the frequency of administration. In this respect enalapril seems to be a promising ACE inhibitor with a prolonged action (at least 24 hours). The exact posology of ACE inhibitors might be crucial, since it has been shown that the side-effects of captopril (skin rashes, fever, taste disturbances, proteinuria and neutropenia) are dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS

Expression of ABCC6 gene in Acute Myeloid Leukemia

Multidrug resistance (MDR) is a major impediment to the successful treatment of acute myeloid leukemia (AML). One of the known MDR mechanisms is the over expression of efflux pumps belonging to the superfamily of ABC transporters, such as P-glycoprotein (ABCB1), BCRP (ABCG2) and MRP1 (ABCC1) [1]. At present, little is known about the clinical relevance of other ABC-transporters in AML. However it was observed that patients with acute lymphoblastic leukemia presenting high MRPs expression, including MRP6, have unfavorable prognosis [2]. In this study, we investigated the expression of ABCB1, ABCC1, ABCG2 and ABCC6 genes in six healthy controls and in thirteen patients with AML, at diagnosis, after chemotherapy, at refractory disease and at relapse. Real-time PCR results showed that at diagnosis, compared to healthy subjects, all patients, except one, presented at least one among ABCB1/ABCC1/ABCC6 genes up-regulated; instead ABCG2 was always down-regulated. Moreover, we interestingly observed that three patients with poor prognosis exhibited higher level of ABCC6 mRNA after treatment compared to diagnosis and that in these patients also BCRP was up-regulated, sign of chemoresistance. We also observed that ninety percent of treated patients presented ABCG2 expression significantly higher after treatment than at diagnosis; thirty percent presented over expression of ABCB1 and only two patients showed ABCC1 up-regulation. In conclusion, our results showed a possible involvement of MRP6 in the development of MDR in AML and that BCRP has, more than MDR1 and MRP1, a relevant role in this mechanism. ABCC6 resulted up-regulated in thirty percent of treated AML patients, but further studies on a larger number of patients are necessary to establish if MRP6 may be involved in the treatment failure of AML and if co-expression of these ABC-transporters may have prognostic significance. REFERENCES 1. Brian C. Shaffer et al. Drug Resist Updat. 2012; 15(1-2): 62–69. 2. Plasschaert SL et al. Clin Cancer Res. 2005; 15;11(24 Pt 1):8661-8