Acute agranulocytosis after oral administration of dabigatran: a rare case report and a short review of literature.

This case report describes agranulocytosis immediately after oral administration of dabigatran in a 68 years old man with atrial fibrillation (AF). Dabigatran is an oral, reversible and competitive thrombin inhibitor that has shown promising results. In patients with atrial fibrillation of RE-LY study (Randomized Evaluation of Long-Term Anticoagulant Therapy), dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. Dabigatran is administered as a prodrug and the peak of the plasma concentrations occurs within 2 h of ingestion. Agranulocytosis is characterized by a severe decrease or lack of circulating granulocytes. This rare event can be found among people taking dabigratan, especially for people who are female, over the age of 60, who took the drug for < 1 month. Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. The patient's white blood cell count increased abruptly after discontinuation of the drug, suggesting an immune response caused by dabigatran. Although anticoagulant drugs are commonly used to treat atrial fibrillation, attention should be paid to this aspect and possible drug interactions.

Use of bivalirudin for heparin-induced thrombocytopaenia after thrombolysis in massive pulmonary embolism: a case report.

A 68-year-old man was referred to the emergency department 6 h after onset of sudden acute dyspnoea. Immediate ECG showed sinus tachycardia with the typical S1-Q3-T3 pattern and incomplete right bundle branch block. The echocardiogram showed the presence of mobile thrombus in the right atrium, a distended right ventricle with free wall hypokinesia and displacement of the interventricular septum towards the left ventricle. Lung spiral computed tomography (CT) showed bilateral pulmonary involvement and confirmed the picture of a thrombotic system in the right atrium and caval vein. Thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) and heparin (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Six hours after thrombolysis bleeding gums and significant reduction in platelet count (around 50,000) were observed. Heparin was discontinued and bivalirudin (0.1 mg/kg bolus and 1.75 mg/kg per h infusion) plus warfarin was initiated and continued for 5 days until the international normalised ratio (INR) was within the therapeutic range (2.0-3.0) for 2 consecutive days, with concomitant platelet count normalisation. Lung spiral and lower abdominal CT before discharge did not show the presence of clots in the pulmonary arteries of the right and left lung. This case suggests that bivalirudin could offer promise for use in patients with heparin-induced thrombocytopaenia (HIT) after thrombolysis for massive pulmonary embolism.

Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects. Findings after follow-up of six years.

BACKGROUND: An increasing number of studies with conflicting results regarding the association between angiotensin-converting enzyme (ACE) gene deletion polymorphism and cardiovascular disease has recently been published. The present prospective long-term study was conducted to evaluate whether the DD genotype could also be associated with a higher prevalence of hypertension in healthy subjects over 6 years of follow-up. We also investigated the effects of the ACE-I/D genotypes on diastolic function by echocardiography in healthy subjects without any risk factors and any events after 6 years of follow-up. POPULATION: 684 healthy volunteers (aged 25-55 years) normotensive and free of cardiovascular diseases, with acceptable echocardiographic window were enrolled. All subjects had to have a normal electrocardiogram (ECG) and echocardiogram (ECHO) at entry. All subjects have undergone a complete physical examination, 12-lead ECG and ECHO; DNA analysis and serum cholesterol have been performed on venous blood samples. All subjects underwent a clinical evaluation each year for the 6-year duration of the study. In addition, 275 subjects without any risk factors underwent an ECHO every year of the follow-up, to check the influence of genotypes on myocardial diastolic performances. RESULTS: All 684 subjects completed 6 years of follow-up. We obtained 3 genetically distinct groups: I) the ACE-DD group (n = 225, 80 F/ 145 M, mean age 43.4 +/- 7.6 years) with 42 hypertensive subjects (18.3%), 5 heart failure (HF) subjects and 6 subjects with acute coronary syndromes (ACS). There was no association between family history, smoking habit, hypercholesterolaemia and events. 2) the ACE-ID group (n = 335, 116 F/2 19 M, mean age 43.6 +/- 7 years) with 16 hypertensive subjects (4.7%) and 3 subjects with ACS. 3) the ACE-II group (n = 124, 45 F/79 M, mean age 42.5 +/- 6.9 years) with 2 hypertensive subjects (1.6%) and I HF subject. The incidence of hypertension and cardiovascular events, was significantly higher in the ACE-DD (53 cases, 23%) than in the ACE-ID and ACE-II groups (20 and 3 cases, 5.9% and 2.4%, respectively), p = 0.0001. The higher incidence of hypertension was observed in the older age groups (36-45 and 46-55 years) with ACE-DD and ACE-ID genotypes. Moreover, ACE-DD significantly and early affected myocardial diastolic properties in the total group examined, also when stratified for age. There was a reduction of E/A ratio and it was more evident in subjects aged 36-45 and 46-55 years, p = 0.0001. CONCLUSION: Our data suggest that ACE-DD polymorphism is associated with a higher incidence of hypertension in baseline healthy subjects, irrespective of other risk factors, and appears to affect the diastolic function. These effects were apparent predominantly in the older age groups.

Relationship between ACE-DD polymorphism and diastolic performance in healthy subjects.

BACKGROUND: The ACE-D allele has been associated with cardiovascular disease. The study evaluates the relationship between the ACE-ID genotypes and diastolic function in healthy subjects after 6 years of follow-up. METHODS: Two hundred and seventy-five healthy volunteers aged 25-55 years had normal physical examination, 12-lead ECG, acceptable echocardiographic windows and echocardiogram at entry. Venous blood was drawn for DNA analysis. RESULTS: Two hundred and forty-two subjects completed 6 years of follow-up. Three genetically distinct groups were obtained: ACE-DD group (n=71, 26F/45M, mean age 48 +/- 7 years); ACE-ID (n=115, 39F/76M, mean age 40 +/- 7 years); and ACE-II (n=56, 20F/36M, mean age 47 +/- 6 years). Significant differences in E/A ratio were found between ACE-DD and ACE-ID, and ACE II (p=0.028, <0.0001, 0.0001), respectively. After 6 years, echocardiography showed a significant reduction of E/A ratio in the ACE-DD group, p=0.0001. CONCLUSION: The data suggest that ACE-DD is associated with deteriorating myocardial diastolic properties.

Safety and tolerability of abciximab in patients with acute myocardial infarction and failed thrombolysis.

AIM: The aim of this study was to evaluate glycoprotein IIb/IIIa receptor inhibitor effectiveness in AMI patients with unsuccessful thrombolysis. METHODS: Eighty-four patients hospitalised within 4 h of symptom onset were randomised (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa inhibitors were administered to patients who did not present with reperfusion signs 30 min after starting thrombolysis and 30-60 min after the end of full thrombolysis in patients with pain recurrence and ST-segment elevation. Reperfusion was assessed by the creatine kinase peak occurring within 12 h, by the observation of rapid ST-segment reduction (50-70% within 1 h) in 12-lead ECG continuous monitoring, by the rapid regression of pain and by the development of early ventricular arrhythmias. Group 1 (GP IIb/IIIa) (42 patients) received treatment with GP IIb/IIIa inhibitors i.v., heparin according to TIMI-14 trial and aspirin during failed thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence and ST segment elevation. Group 2 (placebo) (42 patients) received a full dose of rtpA (100 mg) and placebo either during failed thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence and ST segment elevation and standard heparin treatment and aspirin. RESULTS: Thirty-nine group 1 (GP IIb/IIIa) patients showed rapid reperfusion (6 +/- 4 min) after abciximab treatment; 22 patients received rtpA 65 mg and 20 patients received rtpA 100 mg and subsequent GP IIb/IIIa inhibitor treatment. Coronarography, performed after 3-12 h, showed patency of infarct related artery (IRA) in 39 patients whose clinical picture was suggestive of rapid reperfusion during administration of a bolus of GP IIb/IIIa inhibitors. No group 2 (placebo) patients showed reperfusion and they were submitted to rescue PTCA. SIDE EFFECTS: Four cases in the GP IIb/IIIa group and two cases in placebo group (major bleeding). Patients receiving GIIb/IIIa inhibitors showed a reduced incidence of stent treatment (ns) and a significant reduction of events (angina) within 30 days of treatment. CONCLUSION: Our data suggest the possibility of using IIb/IIIa glycoprotein receptor inhibitors in patients with AMI and failed thrombolysis. The increased risk of bleeding was acceptable. The most important results were the safety of this combination.

Cardiovascular glycoside-like intoxication following ingestion of Thevetia nereifolia/peruviana seeds: a case report.

Some plants contain glycoside compounds which determine cardiovascular symptoms similar to those observed after acute toxic digoxin administration. The present case report involves a patient who showed important cardiovascular symptoms following the ingestion of Thevetia nereifolia/peruviana seeds. About 30 min after ingestion, a 65-year-old man presented with dizziness, giddiness, numbness and a burning sensation, diarrhea, sweating, vomiting and ECG changes. At the time of admission he presented with tremors; his body temperature was 37 degrees C, and blood analysis gave the following results: K 5.6 mEq/l, myoglobin 176 IU, troponin T 0.10 ng/ml, PO2 69 mmHg, PCO2 37.4 mmHg, pH 7.33, HCO3- 19.9 mEq/l, hemoglobin 14.8 g/dl, saturation 92.5%. Echocardiography showed a left ventricle with normal global and segmentary contractility. The following days, the patient showed a reduction, until total resolution, of the atrioventricular block and of the alterations of the ST segment. The ectopic beats also resolved; K value before discharge was 4.4 mEq/l. On the third day, the serum levels of digoxin were 0.15 ng/ml. This case report is important because it describes all the cardiovascular and non-cardiovascular signs of glycoside toxicity in an adult patient who accidentally swallowed only two seeds (non-fatal dose) of Thevetia.