Type II heparin-induced thrombocytopenia (HIT) is a potentially severe adverse effect of heparin treatment triggered by an immune response. Although most cases occur in patients receiving unfractioned heparin, HIT can also arise after low-molecular-weight heparin (LMWH). We report a case of HIT in a postoperative orthopedic 75-year-old woman in treatment with LMWH (nadroparin) complicated by pulmonary embolism and treated successfully with recombinant hirudin. Early recognition and proper treatment are fundamental for the management of this life-threatening disorder. Copyright (c) 2009 Wiley Periodicals, Inc. less...

In recent years in the Department of Neurotraumatology in Cracow it has been noticed the frequent connection between appearance of chronic subdural hematoma (CSDH) and treatment by anticoagulant medications. The aim of this study is to draw attention to the problem of insufficient control of anticoagulants consumption, especially by patients treated for cardiovascular system diseases that increases the risk of bleeding and CSDH development. The paper is based on data from questionnaires that was sent to patients with CSDH, cured in the Department of Neurotraumatology form 2004 to 2005. Analyzed was the group of 51 patients with chronic subdural hematoma; 37 individuals (72.5%) confirmed taking acetylsalicylic acid in the period of 3 months before admission to the Department, 9 (17.6%) patients answered that they were taking low-molecular weight heparin. One patient (1.9%) was taking chronically derivative of cumarin. The authors would inform that anticoagulant treatment might favour increase of chronic subdural hematoma incidence. It's especially important, because the average life expectancy has been prolonged in Poland and there are more people taking acetylsalicylic acid. This can be an epidemiological problem in future. less...

Heparin is known to possess anti-inflammatory properties that in many cases appear to be separable from its anticoagulant activity. Mast cells, located in tissue, are the sole source of endogenous heparin, which may be involved in control of the inflammatory response. The majority of studies of the effects of heparin on the inflammatory response, carried out to date, have involved systemic administration and the potential influence of heparin in the site of inflammation has been less clear. In the present study, the effects of locally administered heparin and a non-anticoagulant derivative were investigated on leucocyte accumulation in the inflamed peritoneal cavity and leucocyte-endothelial interactions in the mesenteric microcirculation of the rat. Heparin and non-anticoagulant heparin inhibited the influx of neutrophils to the site of inflammation, as well as leucocyte rolling and adhesion in post-capillary venules. These effects were apparent only while heparin was present in the peritoneal cavity and plasma and may reflect, in part, an action on resident peritoneal cells, as the heparins tested were found also to inhibit the expression of endothelial adhesion molecules in response to products of activated mononuclear cells, in vitro. Our data show that locally administered heparin has anti-inflammatory effects in an in vivo model of peritoneal inflammation whilst present at the site of inflammation. These non-anticoagulant properties may involve interaction with cells in the site of inflammation, in addition to inhibiting cell adhesion at the level of the microcirculation. less...

PURPOSE: Five cases of sound-alike, look-alike, neonatal medication-dispensing errors and their resolution are reviewed. SUMMARY: In 2008, there were five cases in which look-alike or sound-alike neonatal medication-dispensing errors occurred at our institution. A mix-up between neonatal and adult or pediatric products occurred in four of the five cases. Three of the five errors resulted in near misses with the potential to cause harm. The other two errors reached the patients but did not cause harm. The medication mix-ups involved adult and neonatal phytonadione injectable emulsion, sodium citrate injection and vancomycin-heparin combination injection, adult tetanus-diphtheria-acellular pertussis and infant diphtheria-tetanus-acellular pertussis (DTaP) vaccines, Haemophilus B and DTaP vaccines, and cisatracurium and vecuronium. Each error exposed weaknesses in the system of neonatal medication storage, labeling, delivery, knowledge, and administration documentation at our institution. Resolution of system problems was made possible by a collaborative approach and involved reorganizing shelving used to store neonatal medications; using a differently colored labeling scheme for products whose syringes were nearly identical; implementing changes to the infant vaccine ordering, storage, dispensing, and documentation systems; and instituting centralized and decentralized pharmacist review of pharmacy technician automated dispensing cabinet-filling activities. CONCLUSION: An institution providing services to both neonatal and adult patients experienced five cases of medication-dispensing errors with look-alike or sound-alike medications. Multidisciplinary collaboration within the system helped the pharmacy identify, resolve, and prevent errors related to medication storage, labeling, delivery, knowledge, and administration documentation. less...

BACKGROUND AND PURPOSE: The purpose of this study was to assess the prevalence of embolic signals (ES) in acute coronary syndromes (ACS) and their association with stroke. METHODS: From December 2004 to October 2006, 209 consecutive patients with ACS (without prosthetic heart valves or previous stroke) were studied within 72 hours of symptom onset. Patients underwent ES monitoring in both middle cerebral arteries by transcranial Doppler for 30 minutes. Median follow-up was 14 months after discharge. RESULTS: Patients were treated according to current European Society Cardiology guidelines. Specifically, 92% of patients received heparin(s), 100% aspirin, 92% clopidogrel, 67% intravenous glycoprotein IIb/IIIa inhibitors, 9% fibrinolysis, and 67% underwent angioplasty. ES were detected in 7 patients (prevalence 3.4%; 95% CI, 1.4 to 6.8). Except for a higher prevalence of ES in patients with unstable angina versus other ACS categories (8.5% versus 1.9%, P=0.047), none of the factors among baseline characteristics, clinical features, ACS treatment, and cardiac findings were associated with the presence of ES. During hospitalization, 3 patients without ES had cerebrovascular events (one stroke and 2 transient ischemic attacks), whereas no cerebrovascular events occurred in patients with ES. CONCLUSIONS: The prevalence of ES among hospitalized patients with ACS is currently low, possibly because of improvement in ACS treatment. In this ACS sample, ES did not appear associated with short-term risk of cerebrovascular events. less...

The National Institute for Clinical Excellence (NICE) produces recommendations on appropriate treatment within the National Health Service (NHS) in England and Wales. The NICE guidelines on prophylaxis for venous thromboembolism in orthopaedic surgery recommend that all patients be offered a low molecular weight heparin (LMWH). The linked hospital episode statistics of 219 602 patients were examined to determine the rates of complications following lower limb arthroplasty for the 12-month periods prior to and following the publication of these guidelines. These were compared with data from the National Joint Registry (England and Wales) regarding the use of LMWH during the same periods. There was a significant increase in the reported use of LMWH (59.5% to 67.6%, p < 0.001) following the publication of the guidelines. However, the 90-day venous thromboembolism events actually increased slightly following total hip replacement (THR, 1.69% to 1.84%, p = 0.06) and remained unchanged following total knee replacement (TKR, 1.99% to 2.04%). Return to theatre in the first 30 days for infection did not show significant changes. There was an increase in the number of patients diagnosed with thrombocytopenia, which was significant following THR (0.11% to 0.16%, p = 0.04). The recommendations from NICE are based on predicted reductions in venous thromboembolism events, reducing morbidity, mortality and costs to the NHS. The early results in orthopaedic patients do not support these predictions, but do show an increase in complications. less...

Rosetting of erythrocytes infected with Plasmodium falciparum is frequently observed in children with severe malaria. This adhesion phenomenon has been linked to the DBL1alpha domain of P. falciparum erythrocyte membrane protein 1 (PfEMP1) in three laboratory clones: FCR3S1.2, IT4R29 and Palo Alto varO. Here, we compare the soluble recombinant NTS-DBL1alpha(1)-varO domain (NTS: N-terminal segment) obtained from E. coli, Pichia pastoris and baculovirus/insect cell expression systems. In each case, the presence of NTS was necessary for obtaining a soluble product. Successful expression in E. coli required maltose-binding protein as an N-terminal fusion partner. Each expression system produced an identical, correctly folded protein, as judged by biochemical and biophysical characterisations, and by the capacity to elicit antibodies that react with the surface of VarOinfected erythrocytes and disrupt VarO rosettes. Binding studies using surface plasmon resonance (SPR) techniques showed that NTS-DBL1alpha(1) produced in E. coli binds to heparin with micromolar affinity. IC(50) constants for other sulphated oligosaccharides were determined using SPR by measuring their competitive binding to the soluble protein in the presence of immobilised heparin. The affinity to NTS-DBL1alpha(1) was related to the degree of sulphation of the oligosaccharide, although the position of the sulphate groups on the sugar rings was also important. VarO rosettes could be disrupted by sulphated oligosaccharides with an efficacy that correlated with their binding affinity to recombinant NTS-DBL1alpha(1). Thus high yields of soluble NTS-DBL1alpha(1) with native conformation have been produced, opening novel perspectives for both structure-function studies and vaccine development. less...

This study evaluates the sensitivity of a new in vitro high frequency ultrasound test of the whole blood coagulation process. A rat model of anticoagulant treatment is reported. Many recent studies of the role of red blood cells in the whole blood coagulation process have revealed an increasing demand for global tests of the coagulation process performed on whole blood instead of plasma samples In contrast to existing optical tests, high frequency ultrasound presents the advantages of characterizing the mechanical properties of whole blood clotting. Ultrasound longitudinal wave velocity and integrated attenuation coefficient (IAC) were simultaneously assessed in a 10 to 30MHz frequency range during the whole blood coagulation process in vitro in rats under anticoagulant therapy. Differences between humans and rats were also clearly emphasized in non-clotting blood and in clotting blood using specific criteria deduced from acoustic parameters (ultrasound velocity for non-clotting blood:=1574+/-2m/s for rats and 1583+/-3m/s for humans and IAC=2.25+/-0.14 dB/cm for rats and 1.5+/-0.23 dB/cm for humans). We also measured the coagulation time t(0) from the acoustic velocity (t(0) =11.15+/-7min for control rat blood and 43.3+/-11.4min for human blood). Different doses of heparin were administered to rats. The sensitivity of the ultrasound device to the effects of heparin was evaluated. Differences between non-treated rats and chronically and acutely treated rats were recorded and quantified. We particularly noted that the slope S and the amplitude I of the variations in acoustic velocity were linked to clot retraction, which is a good indicator of the platelet function. The amplitude of the variations in S was between (20+/-8)x10(-3) m/s(2) for control group rats, and (0.92+/-0.35)x10(-3) m/s(2) for chronic heparin-treated group rats. The values of I were 15 times higher for control group rats than for chronic heparin-treated group rats. (E-mail: rachel.libgot@univ-tours.fr). less...

OBJECTIVES: Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. METHODS: We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. RESULTS: Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. CONCLUSION: Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke, or death, in this large, contemporary registry. In light of significant complications referable to bleeding, liberal use of protamine during CEA appears warranted. less...

OBJECTIVE: To describe the outcome of pregnancy in women with inherited antithrombin (AT) deficiency. STUDY DESIGN: A descriptive retrospective study was performed. Medical records were reviewed in order to collect data about maternal thrombotic complications and pregnancy outcomes. All women with known inherited AT deficiency and at least one pregnancy looked after at the Vall d'Hebron University Hospital were included. Relatives with known AT deficiency but no pregnancies looked after in our institution were excluded. Eighteen pregnancies were registered among nine AT-deficient women during 1991-2005. This cohort included women without antithrombotic treatment because AT deficiency was not known at the time of their pregnancies. RESULTS: In 12 pregnancies (66.7%) anticoagulant therapy with low-molecular weight heparin was given, while not in the other six (33.3%) because AT deficiency was not known at this time. Three episodes of venous thromboembolism were recorded (16.7%). Among all pregnancies 10 suffered an adverse outcome (55.6%), including miscarriage (11.1%), stillbirth (11.1%), intrauterine growth restriction (33.3%), placental abruption (6.7%), preeclampsia (6.7%) and intrapartum fetal distress (23.1%). No relation between AT activity and pregnancy complications was found. A lower incidence of pregnancy complications was observed among women with antithrombotic treatment. CONCLUSIONS: Inherited antithrombin deficiency is associated with a high risk of venous thromboembolism during pregnancy and the puerperium. We also observed a high incidence of poor pregnancy outcome among AT-deficient women. less...