Novel autologous, high concentrated fibrin as advanced hemostatic agent for coronary surgery.

BACKGROUND: Variability in transfusion outcomes and excessive postoperative bleeding represents a significant problem in cardiac surgery. The effort to reduce bleeding complications and transfusion outcomes is desirable. Our study investigated the feasibility of reducing bleeding complications and transfusion requirements by applying perioperatively prepared autologous bio-regenerative fibrin sealant. METHODS: A prospective, case-control study enrolled 74 patients undergoing coronary artery bypass grafting by a single surgeon. Patients in the control group (N = 43), received traditional methods of hemostasis, while patients in the experimental group (N = 31) were treated additionally with autologous bio-regenerative fibrin. RESULTS: Patients were well-matched with regard to basic demographic, laboratory and procedural data. Allogeneic blood transfusion requirement in control group was 39.5 % (17 of 43 patients), compared to 6.5 % (2 of 31 patients) in treated group (p < 0,001). The lower infection rate in the experimental group was also noted. No safety issues were identified during the preparation and application process. CONCLUSION: Autologous bio-regenerative fibrin can be safely prepared, with no time consuming, and was demonstrated to be a useful tool to decrease allogeneic blood transfusion requirements following elective coronary artery bypass grafting surgery. A prospective randomized trial is needed to confirm these findings.

Scoring system to predict early carotid restenosis after eversion endarterectomy by analysis of inflammatory markers.

BACKGROUND: Inflammation is one of the mechanisms that leads to carotid restenosis (CR). The aim of this study was to examine the influence of increased values of inflammation markers (high-sensitivity C-reactive protein [hs-CRP], C3 complement, and fibrinogen) on CR development after eversion carotid endarterectomy (CEA). METHODS: A consecutive 300 patients were included in the study, in which eversion CEA was performed between March 1 and August 1, 2010. Demographic data, atherosclerosis risk factors, comorbidities, and ultrasound plaque characteristics were listed in relation to potential risk factors for CR. Serum concentrations of hs-CRP, fibrinogen, and C3 complement were taken just before surgery (6 hours); 48 hours after CEA; and during regular checkups at 1 month, 6 months, 1 year, and 2 years. An "inflammatory score" was also created, which consisted of six predictive values of inflammatory markers (hs-CRP just before and just after CEA, fibrinogen just before and just after CEA, and C3 complement just before and just after CEA) with a maximum score of 6 and a minimum score of 0. At every follow-up visit to the outpatient clinic, ultrasound assessment of the carotid artery for restenosis was done. RESULTS: Our results showed an increased risk of early CR within 1 year in patients with increased hs-CRP before CEA (6 hours) and increased fibrinogen 48 hours after surgery and in patients not taking aspirin after CEA. Sex was determined to be an independent predictor of CR, with female patients having a higher risk (P = .002). Male patients taking aspirin with an inflammatory score >2 had an increased risk for restenosis compared with male patients with inflammatory score <2. Not taking aspirin after CEA and fibrinogen (48 hours) were the strongest predictors, and the Fisher equation incorporating these predictors was used to predict CR. A computer program was created to calculate whether the patient was at high or low risk for CR by selecting whether the patient was taking aspirin (yes or no) and whether fibrinogen was increased 48 hours after CEA (yes or no) and to display the recommended therapeutic algorithm consisting of aspirin, clopidogrel, cilostazol, and statins. CONCLUSIONS: Increased hs-CRP before CEA, increased fibrinogen 48 hours after CEA, and not taking aspirin were the main predictors of early CR. With the clinical implementation of the Fisher equation, it is possible to identify patients at high risk for early CR and to apply an aggressive therapeutic algorithm, finally leading to a decreased CR rate.

Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study.

OBJECTIVES: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). METHODS: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. RESULTS: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p<0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. CONCLUSION: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel- HTPR in patients with carotid artery stenosis undergoing CEA.

Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis.

BACKGROUND: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. METHODS: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). RESULTS: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01). CONCLUSIONS: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.

Low On-Treatment Platelet Reactivity Predicts Long-Term Risk of Bleeding After Elective PCI.

BACKGROUND: Bleeding after percutaneous coronary interventions (PCI) is an important complication with impact on prognosis. AIM: To evaluate the predictive value of enhanced platelet responsiveness to dual antiplatelet therapy with aspirin and clopidogrel, for bleeding, after elective PCI. METHODS AND RESULTS: We performed multiple electrode aggregometry (MAE) platelet functional tests induced by arachidonic acid (ASPI) and adenosine-diphosphate (ADP) before PCI, and 24 hours after PCI, in 481 elective PCI patients who were followed-up for an average of 15.34 ± 7.19 months. Primary end point was the occurrence of any bleeding, while ischemic major adverse cardiovascular event (MACE) was a secondary endpoint. The incidence of total, BARC ≤ 2, and BARC ≥ 3 bleeding, according to BARC classification, was 19, 18, and 1%, respectively. Groups with any, and BARC ≤ 2 bleeding, had a lower average value of MAE ADP test after 24 hours, compared to the group without bleeding: 45.30 ± 18.63 U versus 50.99 ± 19.01 U; P = 0.005; and 45.75 ± 18.96 U versus 50.99 ± 18.99 U; P = 0.01; respectively. Female gender (HR 2.11; CI 1.37-3.25; P = 0.001), previous myocardial infarction (HR 0.56; CI 0.37-0.85; P = 0.006), lower body mass (HR 0.78; CI 0.62-0.98; P = 0.03), and MAE ADP test after 24 hours (HR 0.75; CI 0.61-0.93; P = 0.009) were the independent predictors for any bleeding by Cox univariate analysis. After adjustment, MAE ADP test after 24 hours, was the only independent predictor for any (HR 0.7; CI 0.56-0.87; P = 0.002), and BARC ≤ 2 (HR 0.71; CI 0.56-0.89; P = 0.003) bleeding, by Cox multivariate analysis. CONCLUSION: MAE ADP test before and after PCI, was associated with any, and BARC ≤ 2 bleeding after elective PCI.

Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia.

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

Primary PCI for acute myocardial infarction in a patient with idiopathic thrombocytopenic purpura. A case report and review of the literature.

BACKGROUND AND PURPOSE: The occurrence of acute myocardial infarction (AMI) in patients with idiopathic thrombocytopenic purpura (ITP) is rare, especially when the platelet count is low. Since only few case reports have been published, there are no recommendations for the management of thrombocytopenic patients with AMI. The aim of the present study is to discuss different aspects of this challenging issue and to review limited data available in the literature. CASE STUDY: An 80-year-old patient with ITP (platelet count 5 . 10(9)/l) is presented who developed an AMI (ST segment elevation myocardial infarction) and was successfully treated by primary percutaneous coronary intervention (PCI). CONCLUSION: Considering the high bleeding risk in patients with ITP and AMI, careful balance between usual anticoagulation and antiplatelet therapy on the one hand, and efforts to raise platelet count on the other hand are needed.

[Recombinant activated factor VII and intraoperative use of cell saver in neurosurgical treatment of arteriovenous malformation].

INTRODUCTION: Arteriovenous (AV) malformation of brain causes abundant intraoperative bleedings, because of increased blood flow, which complicates operative treatment. The use of cell saver for intraoperative salvage of blood and recombinant activated factor VII (rFVIIa) significantly reduces complications during operative treatment. CASE OUTLINE: We present a 29-year old male patient with AV malformation of the 4th degree on Spetzler-Martin scale. Because of the possibility of abundant bleeding, a cell saver (Sequestra 1000 Metronic, USA) was used, and to achieve and control adequate haemostasis, we used rFVIIa. CONCLUSION: The use of cell saver for intraoperative blood salvage and rFVIIa proved successful in operative treatment of AV malformation of 4th degree.

[Recombinant factor VII (NovoSeven) in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation].

BACKGROUND: Cerebral arteriovenous (AV) malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven) significantly reduce complications during surgical treatment. CASE REPORT: We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scale, in the brain. Due to a possible heavy bleeding we used a apparatus for intrasurgical blood recovery, Cell Saver, Sequestra 1 000, Medtronic, U.S.A., and recombinant human factor VIIa (rFVIIa--NovoSeven, NovoNordisk, Denmark) to control bleeding and restore an adequate hemostasis. CONCLUSION: The use of an apparatus for intraoperative blood saving, as well as the NovoSeven preparation in the management of AV malformation of IV stage, showed to be successful.

Salvage late plasmapheresis in a patient with pulmonary embolism caused by heparin-induced thrombocytopenia primarily resistant to danaparoid sodium and lepirudin.

We report the case of 64-year-old female patient with pulmonary embolism and bilateral femoropopliteal deep vein thrombosis caused by heparin-induced thrombocytopenia type II (HIT II) resistant to danaparoid sodium and subsequently administered lepirudin in whom a single late plasmapheresis performed on day 6 of the initiation of treatment of HIT reversed the course of the disease, preventing its highly potential fatal outcome. Primarily administered lepirudin was not only ineffective but even led to further aggravation of the patient's clinical state and platelet count drop in the first stage of the HIT treatment. The improvement of the patient's clinical state was not achieved before therapeutic plasma exchange (TPE) had removed the greatest part of pathogenetic circulating substrate. Only after TPE, lepirudin, introduced again, led to the platelet count recovery. In the subsequent course of the treatment, lepirudin was combined with an overlapping oral anticoagulant. Previously positive heparin aggregation test and fast particle gel heparin-platelet factor 4 immunoassay were normalized as well as the patient's clinical status. Early plasmapheresis, administered within 4 days of the onset of thrombocytopenia in HIT, as a beneficial therapeutic measure in certain individual cases, is indisputable. However, our results do not concur with previously reported findings of the so far most comprehensive study on plasmapheresis performed in the management of HIT with thrombosis, discrediting late plasmapheresis administered 4 days after the onset of the disease not only as ineffective, but even as an aggravating factor. Our results suggest the possible beneficial impact of late plasmapheresis as a method that may reverse a prothrombotic process and lead to a fast improvement in the patient's platelet count, especially in cases initially resistant to thrombin inhibitors.

The use of acute normovolemic hemodilution in patients undergoing cardiac surgery.

Avoiding allogeneic blood transfusion during cardiac surgery and during the post-operative period is of great importance. Acute normovolemic hemodilution (ANH) is one of the options for blood salvage. We have prospectively analyzed 310 consecutive patients (pts) after different open heart procedures, operated on during April-May, 2000. ANH was possible in 226 pts (73%) with hemoglobin level over 125 g/l and hematocrit over 36%. Of those, one unit of blood was withdrawn in 128 pts (70%), while two to five units of blood were taken in 68 pts (30%). Total number of autologous blood units taken was 296, for the average of 1.31 units/pt. Predictors of increased intra- and post-operative blood loss were hematocrit (Hct) <39% (76% vs. 24%, p<0.001), age over 65 (p=0.028), female sex (p=0.006), CPB duration over 90 min (63% vs. 37%; p<0.001) and preoperative left ventricular ejection fraction (LVEF) <35% (63% vs. 37%; p<0.001). All pts with the above-mentioned characteristics were in need for allogeneic blood transfusion. During their hospital stay, 142 pts did not get allogeneic blood (142/310, 46%), and all were in the ANH group (142/226, 62%).