Background: Monitoring of antiplatelet therapy in patients at cardiovascular risk is difficult because existing platelet function tests are too sophisticated for clinical routine. The whole blood TEG Platelet Mapping assay measures clot strength as maximal amplitude (MA) and enables for quantification of platelet function, including the contribution of the adenosine diphosphate (ADP) and thromboxane A2 (TxA2) receptors to clot formation. Methods: In 43 healthy blood donors, the analytical (CVa) and inter-individual variability (CVg) of the TEG Platelet Mapping assay were determined together with platelet receptor inhibition in response to arachidonic acid (AA) and ADP. Results: The CVa of the assay for maximal platelet contribution to clot strength (MAThrombin) was 3.5%, for the fibrin contribution to clot strength (MAFibrin) 5.2%, for MAAA 4.5% and for MAADP it was 6.6%. The MAThrombin CVg was 2.8%, MAFibrin 4.7%, MAAA 6.6% and for MAADP it was 26.2%. Females had a higher MAThrombin compared to males (62.8 vs. 58.4 mm, p = 0.005). The platelet TxA2 receptor inhibition was 1.2% (range 0 10%) and lower than for the ADP receptor (18.6% (0 58%); p < 0.0001). Conclusion: The high variability in ADP receptor inhibition may explain both the differences in response to ADP receptor inhibitor therapy and why major bleeding sometimes develops during surgery in patients not treated with ADP receptor inhibitors. An analytical variation of ~5 % for the TEG enables, however, for routine monitoring of the variability in ADP receptor inhibition and of antiplatelet therapy.

Clinical Profile and Outcome of Conversion Disorder in Children in a Tertiary Hospital of North India
The clinical profile, commonly involved precipitating factors, comorbid conditions, treatment options and outcome of conversion disorder in 40 children in a tertiary level hospital in North India were studied, retrospectively. Majority of the patients were from rural India. Most common presenting symptom was psychogenic non-epileptic seizures; depression and anxiety were among the commonest comorbid conditions. Precipitating factors were predominantly scholastic problems. Treatment option included either psychotherapy only or combination of psychotherapy and pharmacotherapy. No significant difference was found in terms of outcome between the in-patient and out-patient treatment groups. This observation could be cost effective for developing countries like India, where the resources are very limited.

Benign intracranial hypertension associated to blood coagulation derangements
Background: Benign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors’ control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH.Patients and methodsThe incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background. Results: The number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p < .001; Fisher Exact Test). Moderate to high titers of anticardiolipin antibodies ( 2-Glycoprotein type I) were found in 8 out of 17 patients.Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated in patients group (5.7 1.15 nM vs 0.45 0.35 nM; 8.7 2.5 ng/mL vs 2.2 1.25 ng/mL; 45.7 12.5 ng/mL vs 8.5 6.7 ng/mL, respectively; p < .001; Fisher Exact Test). Gene polymorphisms for factor V Leiden mutation, prothrombin mutation 20210 A/G, MTHFR 677 C/T, PAI-1 4G/5G, ACE I/D were detected in 13 patients.DiscussionIn agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH.Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

Clopidogrel in Orthopaedic patients: a review of current practice in Scotland
Background: Clopidogrel bisulfate is an antiplatelet agent used to prevent ischaemic events in patients with vascular disease. Current guidelines recommend withholding clopidogrel for 7 days pre-operatively. However these are not based on orthopaedic patients. We therefore decided to survey current orthopaedic practice to see whether this complied with available clinical data.MethodA questionnaire was sent to all orthopaedic consultants in Scotland. Four haematology departments, and the manufacturers, were contacted to ask for their recommendations, and an internet search was performed. Results: 140 questionnaires were sent with a 60.7 % response. 84.7 % of respondents have encountered patients on clopidogrel. Of those, 13.9 % did not routinely stop it, and 86.1 % stopped it 5-21 days pre-operatively (47.2 % at 7 days). 45.9 % had a unit policy on stopping clopidogrel, and the majority (69.4 %) did not consult their haematology department prior to instituting their policy. Increased peri-operative bleeding was the most reported complication (22.6 %). However this was only noted in those who stopped clopidogrel greater-than 7 days pre-operatively. Haematology advice ranged from continuing clopidogrel peri-operatively to stopping it 7 days pre-operatively and starting low-molecular-weight-heparin for thrombo-prophylaxis. The manufacturers suggested stopping clopidogrel 7 days pre-operatively. An internet search did not reveal any data on the effect of clopidogrel peri-operatively in orthopaedic patients.DiscussionRecommendations on stopping clopidogrel have evolved from studies conducted on patients undergoing cardio-thoracic surgery. There is no data available on the effect of clopidogrel in orthopaedic practise. Our survey indicates that increased bleeding has not been found in patients who continue clopidogrel peri-operatively. Almost half of respondents complied with current recommendations, stopping clopidogrel 7 days pre-operatively. However there remains a lack of consensus amongst orthopaedic surgeons. Currently elective patients should stop clopidogrel 7 days pre-operatively, and emergency patients should stop clopidogrel on admission, however their operation should not be delayed due to clopidogrel usage.

Platelet adhesion onto immobilized fibrinogen under arterial and venous in-vitro flow conditions does not significantly differ between men and women
Background: Gender-related differences in incidence of arterial thrombosis have been a focus of interest for years. The platelet integrin IIb 3 is primarily responsible for the interaction between platelets and fibrinogen and consecutive thrombus growth. In this study, we evaluated platelet adhesion onto immobilized fibrinogen under venous and arterial flow conditions in men and women. Methods: Platelets in whole anticoagulated blood were labelled with the fluorescence dye Mepacrine and perfused through the rectangular flow chamber over glass cover slips coated with fibrinogen (shear rates of 50 s-1, 500 s-1 and 1500 s-1). A fluorescence laser-scan microscope was used for visualisation and quantification of platelet adhesion at 15 seconds, 1 and 5 minutes after the start of perfusion. Results: During perfusion, the platelet adhesion linearly increased in regard to exposition time and shear rate. After five minutes of perfusion the platelet adhesion onto immobilized fibrinogen showed no significant gender related difference, neither at 50 s-1 nor at 500 s-1 and 1500 s-1 (p > 0.05), respectively. No significant difference in platelet adhesion onto immobilized fibrinogen, in regard to the menopausal status, was either observed (p > 0.05). Conclusion: In our in vitro experimental system, hormonal differences between men and women did not influence platelet adhesion onto immobilized fibrinogen, neither under venous nor under arterial rheological conditions.

HPA-1 polymorphism of IIb 3 modulates platelet adhesion onto immobilized fibrinogen in an in-vitro flow system
Background: Platelet adhesion and subsequent thrombus formation on a subendothelial matrix at the site of vascular damage play a crucial role in the arrest of posttraumatic bleeding but also in different pathological thrombotic events, such as acute coronary syndrome and stroke. Recently published studies have clearly demonstrated that platelet integri IIb 3 is intimately involved in the occlusive thrombus formation at the site of endothelial damage. Therefore, any genetic variation in the expression of this receptor may lead to an excessive bleeding or excessive thrombus formation. In this study, we evaluated the influence of HPA-1 polymorphism of integrin IIb 3 on platelet adhesion onto immobilized fibrinogen using an in vitro system simulating blood flow. Methods: Platelets in anticoagulated whole blood [49 healthy previously genotyped blood donors) were labelled with fluorescence dye and perfused through a rectangular flow chamber (shear rates of 50 s-1, 500 s-1 and 1500 s-1). A fluorescence laser-scan microscope was used for visualisation and quantification of platelet adhesion at 15 sec, 1 and 5 minutes after start of perfusion. Results: During perfusion, the platelet adhesion linearly increased with regard to exposition time and shear rate. Perfusion of blood preincubated with Abciximab over fibrinogen-coated cover-slips showed reduced platelet adherence (absolute fluorescence: 168 35 U vs. 53000 19000 at control experiments, p < 0.05), as well as by perfusion over BSA-coated glass coverslips. Platelet with HPA-1a/1a genotype exhibited initial better adhesion but they also exhibited higher detachment under arterial flow conditions compared to the HPA-1b/1b platelets. Analysis of stable adhesion rate indicate that the platelets carrying the HPA-1b/1b genotype have a higher reactivity threshold for initial interaction with fibrinogen but under the higher shear rate (in regard to time of perfusion) also realize more stable bonds with fibrinogen than platelets with the HPA-1a/1a genotype. Conclusion: Our data support the contention that genetically determined variants of platelet integrins IIb 3 could play a role in arterial thrombogenesis and thus confirm the hypothesis derived from epidemiological studies.

Evidence behind the WHO Guidelines: Hospital Care for Children: What is the Appropriate Empiric Antibiotic Therapy in Uncomplicated Urinary Tract Infections in Children in Developing Countries?

Choosing the right Vitamin C supplement
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