Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study.

BACKGROUND: There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3-5 days after loading doses of aspirin. METHODS: Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3-5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). RESULTS: Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3-5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. CONCLUSIONS: Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3-5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing.

The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.

BACKGROUND: Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention. METHODS: In a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy. RESULTS: 75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: d f (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G'GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in d f (p = 0.02), G'GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for d f (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values. CONCLUSION: Patients with ischaemic stroke have denser and stronger clot structure as detected by d f and G'GP. The effect of thrombolysis on clot microstructure (d f ) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.

Prospective evaluation of blood coagulability and effect of treatment in patients with stroke using rotational thromboelastometry.

BACKGROUND: Stroke is the second largest cause of death worldwide. Abnormalities in hemostasis play an important role in the pathophysiology of ischemic stroke (IS). These hemostatic defects can be detected using rotational thromboelastometry (ROTEM) as a global method of measuring coagulation. This study assessed the effects of IS on blood hypercoagulability using ROTEM method, before and subsequent to therapeutic interventions. METHODS: In a prospective observational cohort study, whole blood coagulation using ROTEM, along with full blood count and standard coagulation tests, were compared between patients with IS and an age-matched control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours in the stroke group after therapy to assess the effects of therapeutic intervention. RESULTS: Seventy-two patients with IS were age-matched to 71 healthy subjects. Clotting time (CT) INTEM (P = .01) and maximum clot firmness (MCF) INTEM (P = .02) were significantly different between stroke patients at baseline and healthy subjects, but this difference disappeared when controlled for by smoking status. There was no association between ROTEM parameters and time from stroke symptom onset or stroke severity as reflected in The National Institute of Health Stroke Scale score. Significant but small changes in the values of MCF-EXTEM, clot formation time (CFT) EXTEM, and alpha-EXTEM CT were observed after therapeutic intervention (thrombolysis or aspirin treatment). CONCLUSIONS: ROTEM testing does not seem to detect a hypercoagulable state in patients with IS. Nonetheless, some ROTEM parameters had a small change after antiplatelet therapy or thrombolysis.

Characterisation of clot microstructure properties in stable coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is associated with an increased prothrombotic tendency and is also linked to unfavourably altered clot microstructure. We have previously described a biomarker of clot microstructure (df) that is unfavourably altered in acute myocardial infarction. The df biomarker assesses whether the blood will form denser or looser microstructures when it clots. In this study we assessed in patients with stable chest pain whether df can differentiate between obstructed and unobstructed CAD. METHODS: A blood sample prior to angiography was obtained from 251 consecutive patients undergoing diagnostic coronary angiography. Patients were categorised based on angiographic findings as presence or absence of obstructive CAD (stenosis ≥50%). The blood sample was assessed using the df biomarker, standard laboratory markers and platelet aggregometry (Multiplate). RESULTS: A significant difference (p=0.028) in df was observed between obstructive CAD (1.748±0.057, n=83) and unobstructive CAD (1.732±0.052, n=168), where patients with significant CAD produce denser, more tightly packed clots. df was also raised in men with obstructive CAD compared with women (1.745±0.055 vs 1.723±0.052, p=0.007). Additionally df significantly correlated with the platelets response to arachidonic acid as measured by the ASPItest area under the curve readings from platelet aggregometry (correlation coefficient=0.166, p=0.008), a low value of the ASPItest indicating effective aspirin use was associated with looser, less dense clots. CONCLUSIONS: For the first time, we characterise clot microstructure, as measured by df, in patients with stable CAD. df can potentially be used to risk-stratify patients with stable CAD and assess the efficacy of therapeutic interventions by measuring changes in clot microstructure.

Step 8: encourages all mothers, families to touch, hold, breastfeed, care for their babies: the coalition for improving maternity services:.

Step 8 of the Ten Steps to Mother-Friendly Care encourages all mothers and families, including those with sick or premature newborns or infants with congenital problems, to touch, hold, breastfeed, and care for their babies to the extent compatible with their conditions. The rationales for compliance with the step and systematic review are presented.

Step 4: provides the birthing woman with freedom of movement to walk, move, assume positions of her choice: the coalition for improving maternity services:.

Step 4 of the Ten Steps of Mother-Friendly Care insures that women have the freedom to walk, move, and assume positions of their choice during labor and birth. The rationales and the evidence in support of this step are presented.

Step 1: offers all birthing mothers unrestricted access to birth companions, labor support, professional midwifery care: the coalition for improving maternity services:.

The first step of the Ten Steps of Mother-Friendly Care insures that women have access to a wide variety of support in labor and during the pregnancy and postpartum periods: unrestricted access to birth companions of their choice, including family and friends; unrestricted access to continuous emotional and physical support from a skilled woman such as a doula; and access to midwifery care. The rationales for the importance of each factor and the evidence to support those rationales are presented.