二磷酸腺苷介导的血小板聚集抑制率对心律置入装置术后囊袋血肿的影响

目的研究二磷酸腺苷(adenosine diphosphate,ADP)介导的血小板聚集抑制率对心律置入装置(CIED)置入术后囊袋血肿的影响。方法回顾性分析2010年1月²013年6月接受持续双重抗血小板药物治疗,需要置入心律置入装置术后发生囊袋血肿的患者43例为血肿组,按照年龄11匹配入选术后未发生囊袋血肿的患者43例为无血肿组,分析围术期接受持续双重抗血小板药物治疗患者囊袋血肿的风险因素。结果与无血肿组比较,血肿组ADP介导的血小板聚集抑制率明显升高,差异有统计学意义[(71.33±12.16)%vs(49.81±14.96)%,P<0.05],血小板聚集抑制率ADP>80%患者比例明显升高,差异有统计学意义[37.21%vs 13.95%,P<0.05]。多因素二元logistic分析显示,ADP介导的血小板聚集抑制率>80%为囊袋血肿风险的独立危险因素(OR=0.264,95%CI:0.0822013年6月接受持续双重抗血小板药物治疗,需要置入心律置入装置术后发生囊袋血肿的患者43例为血肿组,按照年龄11匹配入选术后未发生囊袋血肿的患者43例为无血肿组,分析围术期接受持续双重抗血小板药物治疗患者囊袋血肿的风险因素。结果与无血肿组比较,血肿组ADP介导的血小板聚集抑制率明显升高,差异有统计学意义[(71.33±12.16)%vs(49.81±14.96)%,P<0.05],血小板聚集抑制率ADP>80%患者比例明显升高,差异有统计学意义[37.21%vs 13.95%,P<0.05]。多因素二元logistic分析显示,ADP介导的血小板聚集抑制率>80%为囊袋血肿风险的独立危险因素(OR=0.264,95%CI:0.082⁰.850,P=0.026)。结论增高的ADP介导的血小板聚集抑制率增加持续双重抗血小板药物治疗心律置入装置置入术后囊袋血肿的风险。     

Impact of body mass index on the development of pocket hematoma: A retrospective study in Chinese people

BackgroundPocket hematoma is one of the major complications associated with cardiovascular implantable electronic devices （CIEDs） implantation. The aim of this study is to evaluate the impact of body mass index （BMI） on the occurrence of pocket hematoma after CIEDs implantation.MethodsThe study is a retrospective review of 972 patients receiving CIEDs implantation between 2008 and 2012 in a tertiary hospital.ResultsTwenty two patients （2.2%） developed severe pocket hematoma requiring re-intervention. The hematoma rate （4.6%,n = 15） of patients with a BMI of 〈 23 kg/m2 was significantly higher compared with that of patients with a BMI of≥23 kg/m2 （1.1%, n = 7,P〈 0.001）. In multivariate regression analysis, a BMI 〈 23.0 kg/m2 may be associated with the development of severe pocket hema-toma. An increase of 1.0 kg/m2 in BMI was associated with lower incidence of hematoma formation （OR： 0.84; 95% CI： 0.74-0.95;P = 0.006）.ConclusionBMI 〈 23 kg/m2 was associated with a higher incidence of pocket hematoma, requiring re-intervention. The data sup-port that great care must be taken when patients were with a lower BMI received CIEDs implantation.     

Inconsistency of different methods for assessing ex vivo platelet function: relevance for the detection of aspirin resistance

Background

Assays to evaluate platelet function are often interchangeably used to assess “resistance” to aspirin. We compared different platelet function assays in patients treated or untreated with aspirin.

Design and Methods

Platelet function was evaluated in 162 subjects, 85 of whom were not being treated with any antiplatelet drug and 77 of whom were receiving chronic therapy with low-dose aspirin. Platelet Function Analyzer collagen/ADP- and collagen/epinephrine closure times, as well as light transmittance aggregometry in response to ADP, collagen and arachidonic acid (this last in 47 aspirin-treated patients) were determined. In 43 aspirin-treated patients, serum thromboxane B₂ levels were also measured.

Results

In untreated patients, collagen/ADP- and collagen/epinephrine-closure times were correlated with each other (r=0.5, P=0.0001), but did not correlate with ADP- or collagen-induced aggregation. In patients treated with aspirin, collagen/ADP-closure time values were not different from those in untreated patients, while the collagen/epinephrine-closure time was prolonged. ADP-induced aggregation was unaffected by aspirin, while collagen-induced aggregation was reduced. Arachidonic acid-induced aggregation was almost completely suppressed (% maximum light transmittance aggregometry=5±13%). There was, however, no correlation between the various platelet function tests. Serum thromboxane B₂, an index of platelet cyclooxygenase-1 activity, was almost completely suppressed (down to 8±17 ng/mL) in treated patients, and was not correlated with arachidonic acid-, ADP- and collagen-induced aggregation or with collagen/ADP-closure time, but was inversely correlated with collagen/epinephrine-closure time.

Conclusions

There is a high heterogeneity of results of tests evaluating inhibition of platelet function by aspirin, and the results of functional tests do not match biochemical measurement of cyclooxygenase-1 activity. Extreme caution should, therefore, be used in defining “resistance” to aspirin on the basis of the results of these tests.     

Thrombocytopenia,Dual Antiplatelet Therapy,and Heparin Bridging Strategy Increase Pocket Hematoma Complications in Patients Undergoing Cardiac Rhythm Device Implantation

Background

Pocket hematoma is a troublesome complication associated with the implantation of cardiac implantable electronic devices (CIEDs). This study aims to determinate the risk factors of pocket hematoma complications in relation to different antithrombotic strategies and severity of thrombocytopenia in Chinese patients.

Methods

We conducted a retrospective study of 1093 consecutive patients undergoing implantation of CIEDs and divided them into 3 groups: no antithrombotic group (n = 512), continuing antiplatelet group (n = 477), and temporarily discontinuing warfarin with or without heparin bridging strategy (n = 104).

Results

A pocket hematoma developed in 40 patients (3.7%). The temporarily discontinuing warfarin group (7.7%) had a higher incidence of pocket hematoma than no oral antithrombotic group (2.1%) and continuing antiplatelet group (4.4%) (P = 0.012). The dual antiplatelet group (16.2%) and the heparin bridging strategy group (14.0%) had significantly higher incidence of pocket hematoma compared with the no antithrombotic group (2.1%; P < 0.001, both). Patients having aspirin or clopidogrel alone had low incidence of pocket hematoma (3.9% and 1.2%, respectively), similar to the no antithrombotic group (P = not significant). Multivariate analysis revealed that dual antiplatelet agents (P = 0.004), heparin bridging strategy (P < 0.001), and moderate to severe thrombocytopenia (P = 0.007) were independent predictors for pocket hematoma complications.

Conclusions

The use of dual antiplatelet agents, heparin bridging strategy, and the presence of moderate to severe thrombocytopenia significantly increased the risk of pocket hematoma complications in the periprocedural period of CIED implant. Aspirin or clopidogrel alone did not increase the risk of pocket hematoma complications.     

Very late drug-eluting stent thrombosis after nonsteroidal anti-inflammatory drug treatment despite dual antiplatelet therapy

BACKGROUND:

Drug-eluting coronary stent implantation emerged as a safe and effective therapeutic approach by preventing coronary restenosis and reducing the need for further revascularization. However, in contrast to bare metal stents, recent data suggest a unique underlying pathology, namely late coronary stent thrombosis and delayed endothelial healing.

OBJECTIVE:

To report a case of very late coronary stent thrombosis (834 days after implantation) requiring repeat urgent target-vessel revascularization. Importantly, six days before the acute coronary event, combined nonsteroidal anti-inflammatory drug therapy was initiated.

RESULTS:

Although a dual antiplatelet regimen was continuously maintained, aggregation measurements indicated only partial antiplatelet effect, which returned to the expected range when nonsteroidal anti-inflammatory drugs were omitted.

CONCLUSIONS:

The observation indicates that, even 834 days after drug-eluting stent implantation, effective combined antiplatelet therapy might be crucial in certain individuals and the possible impact of drug interactions should not be underestimated. Further efforts should focus on the challenging task of identifying patients or medical situations with prolonged, increased risk of stent thrombosis.     

Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome: the role of hyperglycemia and obesity

Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease (CAD), CAD patients with metabolic syndrome (MS) still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention (PCI). Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography (CAG) were enrolled in our study. MS was defined by modified Adult Treatment Panel III criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry (LTA) and thrombelastography (TEG). Clopidogrel resistance was defined as more than 50% adenosine diphosphate (ADP) induced platelet aggregation as measured by TEG. Results Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG (55% ± 31% vs. 68% ± 32%; P < 0.001) and LTA (29% ± 23% vs. 42% ± 29%; P < 0.001). In the multivariate analysis, elderly [OR (95% CI): 1.483 (1.047–6.248); P = 0.002], obesity [OR (95% CI): 3.608 (1.241–10.488); P = 0.018], high fasting plasma glucose level [OR (95% CI): 2.717 (1.176–6.277); P = 0.019] and hyperuricemia [OR (95% CI): 2.583 (1.095–6.094); P = 0.030] were all statistically risk factors for clopidogrel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without diabetes and obesity [75% (61/81) vs. 43% (67/156); P < 0.001]. Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopidogrel resistance.     

Clinical and genetic aspects of Bernard-Soulier syndrome: searching for genotype/phenotype correlations

Background

Bernard-Soulier syndrome is a severe bleeding disease due to a defect of GPIb/IX/V, a platelet complex that binds the von Willebrand factor. Due to the rarity of the disease, there are reports only on a few cases compromising any attempt to establish correlations between genotype and phenotype. In order to identify any associations, we describe the largest case series ever reported, which was evaluated systematically at the same center.

Design and Methods

Thirteen patients with the disease and seven obligate carriers were enrolled. We collected clinical aspects and determined platelet features, including number and size, expression of membrane glycoproteins, and ristocetin induced platelet aggregation. Mutations were identified by direct sequencing of the GP1BA, GP1BB, and GP9 genes and their effect was shown by molecular modeling analyses.

Results

Patients all had a moderate thrombocytopenia with giant platelets and a bleeding tendency whose severity varied among individuals. Consistent with expression levels of GPIbα always lower than 10% of control values, platelet aggregation was absent or severely reduced. Homozygous mutations were identified in the GP1BA, GP1BB and GP9 genes; six were novel alterations expected to destabilize the conformation of the respective protein. Except for obligate carriers of a GP9 mutation with a reduced GPIb/IX/V expression and defective aggregation, all the other carriers had no obvious anomalies.

Conclusions

Regardless of mutations identified, the patients’ bleeding diathesis did not correlate with thrombocytopenia, which was always moderate, and platelet GPIbα expression, which was always severely impaired. Obligate carriers had features similar to controls though their GPIb/IX/V expression showed discrepancies. Aware of the limitations of our cohort, we cannot define any correlations. However, further investigations should be encouraged to better understand the causes of this rare and underestimated disease.     

Recombinant tissue plasminogen activator plus heparin compared with heparin alone for patients with acute submassive pulmonary embolism: one-year outcome

Objective To evaluate the long-term effects of thrombolysis on patients with submassive pulmonary embolism (PE). Methods Data of 136 patients with acute submassive PE and low risk of bleeding were prospectively collected from January 2005 to October 2011 in a single medical center. Patients received recombinant tissue plasminogen activator (r-tPA) plus low molecular weight heparin (LMWH, TT group, n = 79) or LMWH alone (AT group, n = 57), depending on treating physician’s recommendation and patient’s preference. Echocardiography was performed at admission, 24 h, 6 and 12 months to evaluate right ventricular function. Computed tomography pulmonary angiography (CTPA) and lung perfusion scan were performed on admission, at 7 days, 6 and 12 months to evaluate clot burden. Results Seventy-nine patients received r-tPA plus LMWH (TT group) while 57 received LMWH alone (AT group). The baseline characteristics and risk factors did not differ between the two groups. Respiratory rate, heart rate, and systolic blood pressure improved within two hours in both groups. Systolic pulmonary arterial pressure and tricuspid regurgitation improved to a greater extent in the TT group at 24 h, and at 12 months (P < 0.001), as compared to those in the AT group. At one week, and 12 months, clot burden decreased more in AT group, as compared to that in AT group (P < 0.001). There was no death due to bleeding in both groups. Recurrent PE were similar in both groups (2.5% in TT vs. 1.8% in AT). The rates of minor hemorrhages were 6.3% in TT group and 1.8% in AT group (P < 0.05). Conclusion In submassive PE patient who has low risk of bleeding, thrombolysis plus anticoagulation can lead to greater improvement of right ventricular dysfunction and clot burden reduction as compared to anticoagulation therapy alone.     

Effect of Clopidogrel vs Ticagrelor on Platelet Aggregation and Inflammation Markers After Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction

Background

Patients with acute coronary syndrome show an inflammatory response that is known to affect platelet aggregation. We aimed to clarify the relationship between the inflammation severity and the effect of antiplatelet therapy after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).

Effect of enoxaparin on peak and trough levels of antifactor Xa in patients with a creatinine clearance of less than 30 mL/min

AIM:

To assess whether there was an increased risk of bleeding with enoxaparin in patients with a creatinine clearance (CCT) of less than 30 mL/min.

METHODS:

Patients with a CCT of less than 30 mL/min who were given enoxaparin 1 mg/kg/day were included. Antifactor Xa levels (peak and trough) were measured after three doses (days) of enoxaparin. The peak antifactor Xa levels were measured 4 h after the third enoxaparin dose, and the trough levels of antifactor Xa were measured 12 h and 24 h after the third enoxaparin dose. Basic demographic data such as age, sex, race, diagnosis and creatinine values were assessed at baseline. Adverse events were monitored and recorded. Domain-specific review board approval was obtained before the present study began.

RESULTS:

A total of 15 patients were recruited for the present study. Three patients dropped out of the study; therefore, 12 patients were analyzed. The mean age of the 12 patients was 69.25 years (range 41 to 89 years). There were six men and an equal number of women. There were eight Chinese patients, three Malay patients and one Indian patient. The indication for anticoagulation was deep vein thrombosis in seven patients, non-ST elevation myocardial infarction in four patients and atrial fibrillation in one patient. There were no adverse events noted in any patient.

CONCLUSION:

It is safe to administer enoxaparin once a day to patients with renal impairment and a CCT of less than 30 mL/min.     

Risk factors and complications following percutaneous endoscopic gastrostomy: a case series of 1041 patients

BACKGROUND:

Most studies exclude patients with severe coagulation disorders or those taking anticoagulants when evaluating the outcomes of percutaneous endoscopic gastrostomy (PEG).

OBJECTIVE:

To investigate complications and risk factors of PEG in a large clinical series including patients undergoing antiplatelet and anticoagulant therapy.

METHODS:

During a six-year period, 1057 patients referred for PEG placement were prospectively audited for clinical outcome. Exclusion criteria and follow-up care were defined. Complications were defined as minor or severe. Uni- and multivariate analyses were used to evaluate 14 risk factors. No standardized antibiotic prophylaxis was given.

RESULTS:

A total of 1041 patients (66% male, 34% female) with the following conditions underwent PEG: neurogenic dysphagia (n=450), cancer (n=385) and others (n=206). No anticoagulants were administered to 351 patients, thrombosis prophylaxis was given to 348 while full therapeutic anticoagulation was received by 313. No increased bleeding risk was associated with patients who had above-normal international normalized ratio values (OR 0.79 [95% CI 0.08 to 7.64]; P=1.00). The total infection rate was 20.5% in patients with malignant disease, and 5.5% in those with nonmalignant disease. Severe complications occurred in 19 patients (bleeding 0.5%, peritonitis 1.3%). Cirrhosis (OR 2.91 [95% CI 1.31 to 6.54]; P=0.008), cancer (OR 2.34 [95% CI 1.33 to 4.12]; P=0.003) and radiation therapy (OR 2.34 [95% CI 1.35 to 4.05]; P=0.002) were significant predictors of post-PEG infection. The 30-day mortality rate was 5.8%. There were no procedure-related deaths.

CONCLUSIONS:

Cancer, cirrhosis and radiation therapy were predictors of infection. Post-PEG bleeding and other complications were rare events. Collectively, the data suggested that patients taking concurrent anticoagulants had no elevated risk of post-PEG bleeding.     

Fiducial Placement for Stereotactic Body Radiation Therapy under Only Endoscopic Ultrasonography Guidance in Pancreatic and Hepatic Malignancy: Practical Feasibility and Safety

Background/Aims

Stereotactic body radiation therapy (SBRT) for gastrointestinal malignancies requires the placement of fiducials to guide treatment delivery. This study aimed to determine the safety and technical feasibility of endoscopic ultrasonography (EUS)-guided fiducial placement for SBRT.

Methods

From November 2010 to August 2012, 32 consecutive patients who were scheduled to receive SBRT for pancreatic and hepatic malignancies were referred for EUS-guided fiducial placement. Primary outcome measurements included technical success, the fiducial migration rate, and procedural complications.

Results

All 32 patients had successful fiducial placement under EUS guidance. The mean number of fiducials placed per patient was 2.94±0.24 (range, 2 to 3 seeds). Spontaneous fiducial migration was noted in one patient (3.1%). Of the 32 patients with fiducials placed, 29 patients (90.6%) successfully underwent SBRT. One patient (3.1%) developed mild pancreatitis, requiring a 2-day prolonged hospitalization after fiducial placement. Five patients (15.6%) underwent same-session, EUS-guided fine needle aspiration for histologic confirmation at the time of fiducial placement, without any procedure-related complication.

Conclusions

EUS-guided fiducial placement is a safe and technically feasible technique for preparing patients with both pancreatic and hepatic malignancies for SBRT. The fiducial markers facilitate safe and accurate targeting of the tumor during SBRT.     

Percutaneous tracheostomy in patients on anticoagulants

Aims:

To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies.

Settings and Design:

Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU).

Materials and Methods:

Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved.

Results:

Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred.

Conclusions:

PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings.     

Cost-effectiveness of enoxaparin compared with unfractionated heparin in ST elevation myocardial infarction patients undergoing pharmacological reperfusion: A Canadian analysis of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment – Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial

OBJECTIVE:

To evaluate the cost-effectiveness of enoxaparin versus unfractionated heparin in conjunction with fibrinolysis in ST elevation myocardial infarction patients within Canada.

DESIGN:

Based on the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment – Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial, a model was created to analyze the cost-effectiveness of enoxaparin compared with unfractionated heparin in conjunction with fibrinolysis among ST elevation myocardial infarction patients within Canada. Clinical outcomes were derived from published results of the main trial. Resource use costs were first assessed based on United States Diagnosis-Related Group values for hospitalizations and Current Procedural Terminology codes for outpatient visits and tests. Both were then converted using Canadian local costs. Survival and life expectancy were estimated from Framingham survival data. The incremental cost-effectiveness ratio was expressed as cost per life year gained.

RESULTS:

Through 30 days after random assignment, the primary composite end point favoured the enoxaparin group over the unfractionated heparin group (death or recurrent myocardial infarction rate 9.9% versus 12.0%, P<0.001), and was associated with a modest increased cost of $169.50 ($8,757.00 versus $8,587.50, respectively). Life years gained as a result of treatment with enoxaparin was increased by 0.11 years (P<0.05). Enoxaparin was found to be cost-effective, as indicated by an incremental cost-effectiveness ratio of $4,930 with a 99% probability of costing less than $20,000.

CONCLUSIONS:

Although associated with modest increased direct medication costs, enoxaparin following fibrinolysis improved the clinical efficacy in STEMI patients and increased the life years gained.     

Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization

Summary

Background and objectives

Soluble CD40 ligand (sCD40L) is a marker of platelet activation; whether platelet activation occurs in the setting of renal artery stenosis and stenting is unknown. Additionally, the effect of embolic protection devices and glycoprotein IIb/IIIa inhibitors on platelet activation during renal artery intervention is unknown.

Design, setting, participants, & measurements

Plasma levels of sCD40L were measured in healthy controls, patients with atherosclerosis without renal stenosis, and patients with renal artery stenosis before, immediately after, and 24 hours after renal artery stenting.

Results

Soluble CD40L levels were higher in renal artery stenosis patients than normal controls (347.5 ± 27.0 versus 65.2 ± 1.4 pg/ml, P < 0.001), but were similar to patients with atherosclerosis without renal artery stenosis. Platelet-rich emboli were captured in 26% (9 of 35) of embolic protection device patients, and in these patients sCD40L was elevated before the procedure. Embolic protection device use was associated with a nonsignificant increase in sCD40L, whereas sCD40L declined with abciximab after the procedure (324.9 ± 42.5 versus 188.7 ± 31.0 pg/ml, P = 0.003) and at 24 hours.

Conclusions

Atherosclerotic renal artery stenosis is associated with platelet activation, but this appears to be related to atherosclerosis, not renal artery stenosis specifically. Embolization of platelet-rich thrombi is common in renal artery stenting and is inhibited with abciximab.     

Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children

Background

Genome-wide association studies are currently identifying new loci with potential roles in thrombosis and hemostasis: these loci include novel polymorphisms associated with platelet function traits and count. However, no genome-wide study performed on children has been reported to date, in spite of the potential that these subjects have in genetic studies, when compared to adults, given the minimal degree of confounders, i.e., acquired and environmental factors, such as smoking, physical activity, diet, and drug or hormone intake, which are particularly important in platelet function.

Design and Methods

To identify new genetic variants involved in platelet reactivity and count, we performed a genome-wide association study on 75 children (8.5±1.8 years) using the Illumina Sentrix Human CNV370-Quad BeadChip containing 320,610 single nucleotide polymorphisms. Functional analyses included assessment of platelet aggregation and granule secretion triggered by different agonists (arachidonic acid, collagen, epinephrine, ADP), as well as platelet count. Associations were selected based on statistical significance and physiological relevance for a subsequent replication study in a similar sample of 286 children.

Results

We confirmed previously established associations with plasma levels of factors XII, VII and VIII as well as associations with platelet responses to ADP. Additionally, we identified 82 associations with platelet reactivity and count with a P value less than 10⁻⁵. From the associations selected for further replication, we validated two single nucleotide polymorphisms with mildly increased platelet reactivity (rs4366150 and rs1787566) on the LPAR1 and MYO5B genes, encoding lisophosphatidic acid receptor-1 and myosin VB, respectively; and rs1937970, located on the NRG3 gene coding neuroregulin-3, associated with platelet count.

Conclusions

Our genome-wide association study performed in children, followed by a validation analysis, led us to the identification of new genes potentially relevant in platelet function and biogenesis.     

Comparison of in vitro responses to fresh whole blood and reconstituted whole blood after collagen stimulation

Background

In patients who have large bleeds, there is a tendency to transfuse more plasma and platelets than recommended in earlier guidelines, and accordingly many hospitals now provide “transfusion packages” with an intended red cell:platelet:plasma ratio of 1:1:1. The purpose of this study was to investigate in vitro functions of transfusion packs compared with fresh whole blood.

Material and methods

“Reconstituted whole blood” was prepared with the same ratio of red cells, platelets and plasma as used in local transfusion packages. The aggregation and thrombin-antithrombin complex formation responses to collagen stimulation of this reconstituted whole blood were compared with those of fresh whole blood. The storage time of red cells and platelets was varied in a systematic manner, giving nine different compositions of reconstituted whole blood that simulated transfusion packs.

Results

The responses varied significantly between whole blood and reconstituted whole blood -and between the reconstituted whole blood of different compositions. A significant decrease (p<0.005) in collagen-induced platelet count reduction was seen with increasing platelet and red blood cell age. Thrombin-antithrombin complex formation peaked in studies with platelets stored for 5 days. The red cells stored for the longest time induced the greatest thrombin-antithrombin complex formation. Fresh whole blood gives more consistent responses, and the aggregation response to collagen is stronger than in reconstituted whole blood.

Discussion

Our results indicate that in vitro responses of reconstituted whole blood vary substantially according to how long the red cells and platelets are stored for. As the responses obtained by testing whole blood are more consistent and usually stronger, the alternative use fresh whole blood in special conditions should not be excluded without further consideration.     

The use of retrievable inferior vena cava filters in the trauma population

OBJECTIVE:

To determine if the use of retrievable filters resulted in an increase in the placement of inferior vena cava (IVC) filters in trauma patients.

DESIGN:

All patients who underwent IVC filter placement at Yale-New Haven Hospital, New Haven, Connecticut, USA between the years 1999 and 2004.

SETTING:

Academic, level 1 trauma centre.

PATIENTS:

Included in the present study were 202 trauma patients and 676 nontrauma patients.

INTERVENTION:

IVC filter placement.

MAIN OUTCOME MEASURE:

Demographics, indications, complication rates and type of IVC filters placed in trauma patients versus nontrauma patients were evaluated.

RESULTS:

The present study determined 45.4% (n=92) of trauma patients undergoing IVC filter placement were younger than 40 years of age, compared with 7.8% (n=53) of nontrauma patients. The most common indication for IVC filter placement in trauma patients was prophylaxis (n=162, 80.2%), while in the nontrauma patients only 11.4% (n=77) of patients underwent prophylactic filter placement. The number of retrievable filters used in trauma patients increased from 46.7% in 2001, the year they became available, to 78.9% in 2004. The use of retrievable filters similarly increased in the nontrauma population from 35.9% in 2001 to 78.3% in 2004. Approximately 24% of the patients that underwent IVC filter placement at Yale-New Haven Hospital were categorized as trauma patients. The complication rate for this time period was 0.5% (n=1) in the trauma population versus 3.7% (n=26) in the nontrauma population.

CONCLUSION:

The overall number of IVC filters placed in trauma patients did not dramatically increase with the introduction of retrievable filters, suggesting that the indications for the use of IVC filters have not changed.     

Bleeding complications associated with glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older undergoing percutaneous coronary intervention

BACKGROUND:

Treatment of symptomatic coronary artery disease with percutaneous intervention requires antithrombotic therapy. Patients with elevated thromboembolic risk benefit from therapy with glycoprotein IIb/IIIa inhibitors. The safety and effectiveness of glycoprotein IIb/IIIa inhibition have been well documented in clinical trials. Drug-induced bleeding complications in elderly patients have not been specifically addressed.

METHODS:

Between 2006 and 2009, a total of 439 unselected patients 80 years of age and older undergoing percutaneous intervention for symptomatic coronary artery disease were included in the present nonrandomized retrospective study. In one-half of the patients, glycoprotein IIb/IIIa inhibitors were administered peri-interventionally. The in-hospital occurrence of bleeding complications (access site, gastrointestinal and cerebral) were analyzed in the groups with and without glycoprotein IIb/IIIa inhibitors.

RESULTS:

The mean age of the patients was 84 years. Nearly all patients (95%) received dual antiplatelet therapy. Patients treated with glycoprotein IIb/IIIa inhibitors had more complex coronary lesions and bypass graft interventions, and a tendency toward more access site bleeding complications than patients without inhibitors, which included femoral hematomas (4.6% versus 2.3%, respectively; P not significant) and femoral pseudoaneurysms (6% versus 3.2%, respectively; P not significant). The rate of blood transfusion was equal in both groups (0.9%). Major hemorrhagic events did not occur. Vessel closure devices were used more often in patients without glycoprotein inhibition.

CONCLUSIONS:

An increase in minor bleedings must be expected when using glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older. However, this issue must not prevent this treatment option from being offered to elderly patients. There appears to be no elevated risk for major bleeding complications. Broadened use of vascular closure devices in this specific patient population may lower the rate of access site complications.     

Evaluation of platelet cross-matching in the management of patients refractory to platelet transfusions

Background

Cross-match-compatible platelets are used to support thrombocytopenic patients who are refractory to randomly selected platelets. However, few studies have addressed the efficacy of using this strategy for patients requiring intensive platelet transfusion therapy. The aim of this study was to determine the effectiveness of cross-match-compatible platelets in an unselected group of patients refractory to platelets from random donors.

Materials and methods

A total of 406 cross-match-compatible platelet components were administered to 40 evaluable patients who were refractory to random-donor platelets. A solid-phase red cell adherence method was used for platelet cross-matching. The corrected count increment was used to monitor the effectiveness of each platelet transfusion. Multivariate analysis was performed to detect whether any variables could predict the response to transfusion.

Results

Statistically significant improvements were found in the mean corrected count increment when comparing cross-match-compatible platelets with randomly selected and incompatible platelets (p<0.001 for each). Compatible platelet transfusions were associated with a good response in 72.9% of cases while incompatible platelets were associated with a poor response in 66.7% of transfusion events (p<0.001). In the presence of clinical factors or alloimmunisation, compatible platelets were associated with good responses in 67.9% and 28.0% respectively vs 100% and 93.3% in their absence (p=0.009, p<0.001). Multivariate analysis revealed that cross-matching and alloimmunisation were the strongest predictors of transfusion response at 1 hour, while ABO compatibility, type of units received, followed by alloimmunisation then clinical factors were predictors at 24 hours.

Discussion

Platelet cross-matching using the solid-phase red cell adherence technique is an effective and rapid first-line approach for the management of patients refractory to platelet transfusions.