Beta-thromboglobulin Concentration Research Articles

Quality control of riboflavin-treated platelet concentrates using Mirasol® PRT system: Polish experience.

The quality of platelet concentrates (PCs) is affected by preparation, storage, the type of container, and pathogen reduction technology (PRT). The Mirasol® Pathogen Reduction Technology (PRT) system (Terumo BCT Inc., Lakewood, USA), which uses riboflavin and ultraviolet (UV) light, has recently been proven effective against bacteria, viruses, parasites, and leukocytes. The aim of the study was to evaluate the effect of the Mirasol® PRT system, based on riboflavin and UV light exposure, on the most common in vitro platelet quality parameters of PCs prepared from whole blood-derived buffy coats. The study included 15 trials (n = 15). For each trial, 2 PCs were used: 1 for treatment with the Mirasol® PRT system (M) and 1 for a control (C). In the M group, PCs were illuminated. In the C group, saline solution was added. PCs from groups M and C were stored at 20-24°C, with agitation. Samples were collected on days 1, 3 and 5 to determine platelet concentration, total platelet count/unit, mean platelet volume (MPV), power of hydrogen (pH), glucose and beta-thromboglobulin concentration (BTG), hypotonic shock response (HSR), aggregation, CD42b and CD62P expression, pCO2, and pO2. No significant differences in HSR or CD42b expression were observed between groups M and C. All pH values were stable during the whole storage period (7.1-7.5). On storage day 1, CD62P expression in group C was significantly higher than in group M. In the Mirasol® group, significantly higher glucose consumption was noted on storage days 3 and 5. On day 5, a 2-3-fold increase in BTG was observed in both groups as compared to day 1; on day 5, BTG concentration was 32% higher in group M than in group C. On all storage days, pCO2 was comparable in groups M and C; lower pO2 values were reported for group M. In vitro results demonstrated that pH, HSR, aggregation, CD42b antigen expression, and MPV and platelet count parameters were comparable in groups M and C.

Association between hemostatic markers, serum lipid fractions and progression of cerebral small vessel disease: A 2-year follow-up study

IntroductionLittle is known if hemostatic markers and serum lipid fractions can predict further radiological progression beyond vascular risk factors in cerebral small vessel disease (SVD). We investigated whether they are associated with SVD radiological progression and if they are related to different SVD clinical manifestations. MethodsA single-center, prospective, cohort study with 2 years of radiological follow-up was performed in consecutive patients with different SVD manifestations. The study group consisted of 123 patients: 49 with lacunar stroke (LS), 48 with vascular dementia (VaD) and 26 with vascular parkinsonism (VaP). We assessed SVD progression by a visual SVD scale. We determined the relationship between serum or plasma concentrations of tissue factor (TF), thrombomodulin, beta-thromboglobulin (BTG), fibrinogen, D-dimer and total cholesterol, HDL-C, LDL-C, triglycerides and SVD progression by logistic regression analysis. Results34.9% patients had SVD radiological progression: 43% had isolated WMLs progression, 23.2% had new lacunes, 34.8% had both WMLs progression and new lacunes. Fibrinogen [OR 1.02 (95% CI 1.006–1.011] was significantly associated with risk of new lacunes or WMLs progression regardless of the clinical SVD manifestation. While low HDL [OR 0.96 (0.93–1)] and TF [OR 1.07 (0.99–1.1)] were marginally associated with new lacunes, BTG [OR 1.005 (0.99–1.01)] was associated with WMLs progression. ConclusionWe found a relationship between fibrinogen and risk of radiological progression of SVD regardless of the clinical SVD manifestation. In addition, lower HDL and increased TF predicted development of new lacunes, and higher BTG was associated with risk of WMLs progression.

LIPID LOWERING BY STATIN;

Objectives: To observe the effect of lipid lowering by atorvastatin administrationon platelet reactivity by measuring serum beta thromboglobulin concentration in male andfemale Sprague Dawley rats. Study Design: Randomized control trial (RCT). Place of study:The study was conducted at Physiology department, Army Medical College, Rawalpindi. Animalhandling, obesity induction, drug administration and sample collection were done at NationalInstitute of Health (NIH), Islamabad and biochemical assays were performed at Centre forResearch in Experimental and Applied Medicine (CREAM), Army Medical College, Rawalpindi.Period: 12 months. Material and Methods: Ninety healthy Sprague Dawley (male and female)rats were randomly selected and divided into three equal groups. Group I rats (normal control)were given normal chow diet for three weeks. Group II rats (obese control) were given high fatdiet for three weeks to induce obesity. Group III rats (obese treated) were given atorvastatinfor three weeks in a dose of 10 mg/kg/day orally by gavage method after obesity induction.Terminal blood sampling was done at the end of the study by intra-cardiac puncture. Bloodwas centrifuged to obtain serum and serum beta thromboglobulin was measured by usingEnzyme Linked Immunosorbant assay. Results: There was a significant (p < 0.05) increasein serum B-TG concentration in obese rats as compared to normal control rats. Atorvastatinadministration to obese rats significantly (p < 0.05) reduced serum B-TG concentration.Conclusions: Obesity increases and statin administration decreases platelet reactivity in highfat diet induced obese Sprague Dawley rats as reflected by serum B-TG concentration.

Effect of sublingual immunotherapy on platelet activity in children with allergic rhinitis

IntroductionThe role of platelet activation in allergic inflammation is receiving increasing attention. Sublingual immunotherapy for allergic rhinitis can modify the immunological process to an allergen, rather than simply treating symptoms. ObjectiveThe aim of this study was to explore the role of platelet activation during sublingual immunotherapy in children with allergic rhinitis. MethodsForty-two House Dust Mite – sensitized children with allergic rhinitis were enrolled and received House Dust Mite allergen extract for sublingual immunotherapy or placebo. Serum of different time points during treatment was collected and used for detection of Platelet Factor-4 and Beta-Thromboglobulin concentration by Enzyme-Linked Immuno Sorbent Assay. ResultsOur data showed decreased expression of Platelet Factor-4 and Beta-Thromboglobulin protein after one year's sublingual immunotherapy. In addition, the decrease of symptom scores and serum Platelet Factor-4 and Beta-Thromboglobulin protein concentrations was positively related. ConclusionDuring sublingual immunotherapy, platelet activation was inhibited significantly. Our results might indicate that inhibition of platelet activation within the systemic circulation is an important mechanism during sublingual immunotherapy.

Significantly reduced adsorption and activation of blood components in a membrane oxygenator system coated with crosslinkable zwitterionic copolymer

A crosslinkable zwitterionic copolymer PMBT was coated onto the surfaces of polypropylene hollow fiber membrane (PP-HFM) oxygenator and its connecting tubes. The PMBT copolymer coating on the oxygenator circuit formed a cell outer membrane mimetic surface with excellent stability. The hemocompatibility of the PMBT copolymer coated PP-HFM oxygenator circuit was evaluated by animal extracorporeal circulation. The concentrations of clotting components fibrinogen and platelet in the blood were almost unchanged during the circulation through the PMBT copolymer coated oxygenator circuits. By contrast, the concentrations of fibrinogen and platelet were significantly reduced to 52% and 56% respectively in the uncoated oxygenator group due to adsorption and thrombogenesis of the blood during 2h circulation. Moreover, concentration of activation marker beta-thromboglobulin for platelet in the blood was remarkably lower in the PMBT group than the uncoated control group (p<0.01). All the results strongly supported that the hemocompatibility of the PP-HFM oxygenator circuit could be improved significantly by coating a stable and densely assembled zwitterionic polymer film. This simple, stable and highly effective cell membrane mimetic coating strategy may be applicable in developing advanced oxygenator systems and other artificial organs. Statement of SignificanceAlthough a number of studies have reported the fabrication of zwitterionic phosphorylcholine coated oxygenators to resist the adsorption and activation of blood components and eliminate heparin-induced thrombocytopenia, none of them have fabricated stable and densely assembled film, especially with crosslinkable amphiphilic random copolymer described in our manuscript. The novel features of our work include:•The first study of fabricating crosslinked and densely assembled zwitterionic copolymer coating on surfaces of a commercial oxygenator system.•The first study on hemocompatibility of both the PMBT coated and the bare commercial PP-HFM oxygenator circuits by animal extracorporeal circulation.•Much better hemocompatibility was measured on the PMBT coated oxygenator circuit compared with the bare and other polymer coated oxygenator systems.

Effects of alcohol ingestion post-exercise on platelet aggregation

The present study examined the influence of ingesting a moderate dose of alcohol on platelet count and platelet aggregation during recovery following exercise. Nineteen subjects (11 male and 8 female) were studied immediately after a standardised cycle ergometer test and during the 24-h period of recovery. In random order, alcohol (0.7 g/kg body mass) was given 1 h after exercise on one test occasion, while an equal volume of alcohol-free solution was administered on the other. Venous blood samples were obtained at baseline, post-exercise, and at 1, 5, and 22 h post-alcohol ingestion. Blood alcohol level increased significantly 1 h after the ingestion of alcohol, but decreased and returned to the resting baseline level at 5 h during recovery. Males and females subjects exhibited similar mean values of platelet count, platelet aggregation, and beta-thromboglobulin concentration at rest and following exercise and recovery. A significant increase in platelet count and a decrease in platelet aggregation using adenosine diphosphate (ADP) was found following exercise. Although plasma beta-thromboglobulin level (pooled data for males and females) showed an increase by 26.0% (from a mean pre-exercise value of 22.3–28.1 IU/ml), this rise was not significant ( P>.05). The post-exercise increase in platelet count was mainly due to exercise-induced plasma volume loss. During recovery, while the increase in platelet count post-exercise returned to the baseline level in control and alcohol trials, the optical density of platelet aggregation remained significantly depressed at 5-h during recovery in the alcohol trial but not in the normal control condition. It is concluded that exercise induces significant reduction in platelet aggregation and the consumption of alcohol after physical exercise delays the normal return of platelet aggregation to the resting baseline levels during recovery.

Relationships between thrombohemorrhagic complications and platelet function in patients with essential thrombocythaemia.

Three subgroups have been distinguished in essential thrombocythaemia (ET) patients, on the basis of clinical and laboratory findings. ET patients with bleeding incidents had smaller platelet volume, lower concentrations of beta-thromboglobulin and platelet factor 4 in their plasma, 10%, 26%, and 26% lower compared to patients without complications, respectively. ATP secretion from platelets of bleeders, clotters, and "no-complications" ET patients was found to be 75%, 36%, and 45%, respectively, lower than in healthy people. Spontaneous platelet aggregation appeared to be normal in about 90% of ET patients with no complications and in all bleeders but only in 35% patients with clotting incidents. All bleeders had abnormal agonist-evoked aggregation assays. Among remaining ET patients 30%-60% displayed normal values of different evoked aggregation tests. Thus, clinically distinguished group of bleeding ET patients may be differentiated from other subgroups on the basis of laboratory findings.

Changes in platelet ATP secretion and aggregation during pregnancy and in preeclampsia.

Platelet secretion plays an important role in the aggregation of platelets. However, the quantitative relationship between platelet aggregation and secretion of ATP during pregnancy and in pre-eclampsia has yet to be clarified. This study is designed to determine whether platelet count, volume, aggregation, and the amount of secreted ATP change in healthy, nonpregnant women, nonpreeclamptic pregnant women, and preeclamptic pregnant women and whether beta-thromboglobulin (BTG) and platelet factor 4 (PF-4) concentrations alter in nonpreeclamptic and pre-eclamptic women. Peripheral blood was collected from 114 women. Nonpreeclamptic pregnant women were divided into four groups (gestational weeks 10, 20, 30, and 35). Platelet aggregation and ATP secretion were investigated with the use of a lumi-aggregometer. BTG and PF-4 concentrations in peripheral blood were determined in 12 pregnant and 11 preeclamptic women. The amount of secreted ATP upon induction by 5 microM ADP increased significantly (P < 0.05-0.01) with gestational age. On the other hand, the amount of secreted ATP induced by 5 microg/mL collagen reached the maximal value from gestational weeks 20 to 35 in nonpreeclamptic women. Significantly more platelet aggregation was induced by the ADP and collagen in nonpreeclamptic women in gestational weeks 20 and 30 than in the gestational weeks 10 or 35 (P < 0.05-0.005). The amount of secreted ATP and platelet count were significantly lower (P < 0.05) in preeclampsia than in normal pregnancy. The BTG and PF-4 concentrations were significantly higher (P < 0.05) in preeclampsia than in normal pregnancy. The sensitivity of platelets for ATP secretion may intensify with progression of pregnancy. In normal pregnancy, around gestational week 35, the platelets may exhibit weaker ability to aggregate but maintain the capacity to secrete ATP. In preeclampsia, secreted ATP decreased because platelets may be stimulated to undergo a partial secretion.

In vitro evaluation of new surface coatings for extracorporeal circulation.

Cardiopulmonary bypass (CPB) exposes blood to large, foreign surfaces. This exposure may activate the cellular and humoral inflammatory systems, resulting in inflammatory reactions and organ dysfunction. Coating the inner surfaces of the bypass circuit may help alleviate these side-effects. The objective of this study was to determine the influence of two new surface treatments on blood cell and complement activation. Oxygenator and tubing sets coated with synthetic polymers (n = 7) or heparin (n = 7) were compared to uncoated sets (n = 7) in an in vitro model of CPB. The circuits were run at 4 l/min and recirculated for 120 min. The inflammatory response was assessed at regular intervals by platelet counts, and activation of complement, leucocytes and platelets. We found that the median platelet counts decreased from 127 to 122 x 10(9)/l (not significant, NS) in the synthetic polymer sets, from 96 to 88 x 10(9)/l (NS) in the heparin-coated sets, and from 93 to 54 x 10(9)/l (p < 0.01) in the uncoated sets after 2 h of recirculation. There were significant differences in platelet counts between the coated sets and the uncoated set at end of experiments (p < 0.05). Beta-thromboglobulin (BTG) concentrations increased in the synthetic polymer sets from 166 to 352 ng/ml (p < 0.01), in the heparin coated sets from 336 to 1168 ng/ml (p < 0.01), and in the uncoated sets from 301 to 3149 ng/ml (p < 0.01) after 2 h of recirculation. The differences in BTG at termination of the experiments were significant among all three sets (p < 0.05). Myeloperoxidase (MPO) concentrations in the synthetic polymer sets increased from 63 to 86 micrograms/l (p < 0.01), in the heparin-coated sets from 90 to 208 micrograms/l (p < 0.01), and in the uncoated sets from 122 to 513 micrograms/l (p < 0.01) after 2 h of recirculation. The differences in MPO at termination of the experiments were significant among all three groups (p < 0.01). There were no significant differences at termination of the experiments among the three sets regarding complement activation as measured by C3 activation products and the terminal complement complex. We conclude that in the current in vitro model of a CPB circuit, the synthetic polymer coating and the heparin coating caused significantly less platelet loss and granulocyte and platelet activation than the uncoated surface (p < 0.05). The synthetic polymer coating caused significantly less granulocyte and platelet activation than the heparin coating (p < 0.05). There was moderate complement activation within each group, but no significant differences among the three groups.

Association between carotid atherosclerosis and hemostatic markers in patients with cerebral small artery disease.

The purposes of this study were to investigate the association between carotid atherosclerosis and hemostatic markers, and to elucidate the difference in hemostatic markers between intima-media thickening and plaque formation in patients with cerebral small artery disease. We investigated carotid atherosclerosis by assessing diffuse intima-media thickness measurements and localized plaque using B-mode ultrasonography, and we measured the concentrations of plasma fibrinogen, beta-thromboglobulin and platelet factor 4 as markers for platelet activation, and the activity of plasma von Willebrand factor as a marker for endothelial damage. The intima-media thickness was significantly associated with age, male sex, the concentrations of plasma beta-thromboglobulin and platelet factor 4, and the activity of plasma von Willebrand factor. The plaque score showed a significant association with male sex, the concentration of fibrinogen, and the activity of plasma von Willebrand factor. These results may indicate that underlying mechanisms are not the same between the intima-media thickness and plaque formation. We suggest that hemostatic markers could reflect the severity of carotid atherosclerosis in patients with cerebral small artery disease, and that preventive antiplatelet therapies against brain infarction might be necessary for patients with severe carotid atherosclerosis.

Effects of ionic and non-ionic contrast media on platelet function as evaluated by plasma concentration of beta-thromboglobulin.

The aim of the study was to evaluate the effects of ionic and non-ionic contrast media on platelet function. In 44 patients who underwent angiography, the plasma concentration of beta-thromboglobulin (beta TG) was measured before and after ionic contrast medium (diatrizoate) administration in 22 patients and non-ionic contrast medium (iopromide) in the other 22 patients. A significant decrease in the plasma beta TG levels after intraarterial contrast medium injection occurred in both groups of patients. No significant beta TG level changes occurred in patients with normal pre-examination beta TG levels in both groups. In patients with elevated beta TG levels before arteriography, beta TG returned to normal values after contrast medium injection in both groups. There was no significant correlation between the amount of administered contrast medium and beta TG concentration after angiography. These results suggest that platelet function is not affected by either ionic or non-ionic contrast medium in patients with normal platelet activation. In patients with enhanced platelet activation, the activation became normal after contrast medium administration.

Hypercoagulability in heart failure.

Thromboembolism is an important complication in patients with heart failure. A variety of factors associated with heart failure predispose to thrombosis. These include vascular pathology, increased coagulability, and impaired flow. The focus of this review is to summarize data on platelet function and coagulation indices in heart failure. Several studies have shown that patients with heart failure have increased plasma concentrations of beta-thromboglobulin, a marker of platelet activation. Increased plasma concentrations of fibrinopeptide A and thrombin activation have also been demonstrated. In addition, plasma concentrations of endothelial procoagulants, von Willebrand factor, fibrinolytic products, and D-dimer are also increased during heart failure. If platelet activation and hypercoagulability are a surrogate for clinical events, treatment with antiplatelet or anticoagulant therapy can potentially reduce thromboembolism and mortality in heart failure.

Premature coronary heart disease: the influence of positive family history on platelet activity in vivo in children and adolescents (family study).

Hypercoagulative disturbances are an integral part of atherosclerosis. The estimation of beta-thromboglobulin (BTG) concentrations in the offspring of parents suffering from premature coronary heart disease (CHD) makes it possible to evaluate platelet activity in vivo in this high-risk group. The study included 292 individuals. BTG concentrations in platelet-poor plasma were estimated in 90 offspring (60 boys and 30 girls, aged 7-18 years) of fathers who had experienced a premature infarct (aged 45 years or younger) and in their parents (the main group, n = 185). All the participants were tested under their usual living conditions. Fifty-nine healthy children and adolescents of the same age with no family history of vascular events, diabetes or hypertension, together with their parents, formed the control group (n = 107). The mean BTG level in the main group was significantly elevated (86.04 +/- 8.14 ng/ml in the boys and 75.57 +/- 8.55 ng/ml in the girls), when compared with the values for their respective controls (49.30 +/- 3.54 ng/ml and 52.56 +/- 3.42 ng/ml, P < 0.001 and P < 0.005). High BTG levels (higher than the 95th percentile in the controls) were observed in 33.3 +/- 6.1% of the boys and in 23.3 +/- 7.7% of the girls in the main group. Twelve months later, a follow-up study of 16 offspring from the main group and 12 from the control group demonstrated that the increase in BTG levels in children and adolescents with infarction heredity over those observed in children without such a background was sustained (85.86 +/- 16.88 ng/ml compared with 75.90 +/- 14.02 ng/ml, P > 0.5). Significantly raised levels of BTG were also detected in the wives of men who had experienced premature infarcts, when these women were compared with respective controls (86.13 +/- 9.85 ng/ml and 45.04 +/- 4.82 ng/ml, P < 0.0001). Spontaneous platelet activation in vivo under normal living conditions was observed in a considerable proportion of children and adolescents with a family history of premature CHD. This activation is expected to constitute an endogenous risk-factor and is probably one of the mechanisms by which atherosclerosis advances before it becomes clinically apparent.

Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility

Centrifugal pumps are being used increasingly for short-term extracorporeal circulation purposes such as during heart operations. Whether the centrifugal pump improves the cardiopulmonary bypass biocompatibility has not been fully documented. A roller pump (n = 20) was compared in vivo with a centrifugal pump (n = 20) in groups of patients in which cardiopulmonary bypass circuits that were either totally heparin coated (Carmeda BioActive Surface; n = 20) or uncoated (n = 20) were used. We expected the heparin coating to attenuate blood activation, thus possibly making the comparison of the two pumps easier with respect to their different blood activation potentials. Samples of blood plasma, obtained during cardiopulmonary bypass from low-risk coronary artery bypass grafting patients, were analyzed for hemolysis (plasma haemoglobin), complement activation (C3bc and the terminal complement complex), a complement lytic inhibitor (vitronectin), coagulation activation (fibrinopeptide A), granulocyte activation (lactoferrin), and platelet activation (beta-thromboglobulin). The concentrations of terminal complement complex, lactoferrin, and beta-thromboglobulin were significantly lower in association with heparin-coated surfaces. The concentration of plasma hemoglobin was significantly lower in association with the centrifugal pump. In uncoated circuits, the beta-thromboglobulin level was significantly higher in association with the roller pump than with the centrifugal pump, but this significant reduction in the beta-thromboglobulin level did not hold true for the heparin-coated circuit group. A heparin-coated cardiopulmonary bypass surface reduces the blood activation potential during cardiopulmonary bypass, and the centrifugal pump causes less hemolysis than the roller pump.

Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin‐coated Equipment

The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 +/- 632 ng/ml) and C4a (1088 +/- 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 +/- 1045 ng/ml and 1494 +/- 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 +/- 177 micrograms/L) and 10 min after the administration of protamine (676 +/- 314 micrograms/L) were significantly (p < 0.05) lower than in the other 2 groups (820 +/- 341 and 893 +/- 303 micrograms/L and 1365 +/- 595 and 1,258 +/- 622 micrograms/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma beta-thromboglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.

Magnesium Inhibits Platelet Activity - an Infusion Study in Healthy Volunteers

Magnesium (Mg) has shown the ability to inhibit arterial thrombus formation in some experimental animal studies. This effect may be due to an inhibition of platelet reactivity as in vitro studies have demonstrated that Mg inhibits platelet aggregation. In order to evaluate the in vivo effect of Mg in humans measurements of platelet activity, fibrinolytic activity, as well as measurements of prostacyclin (PGI2), and nitric oxide (NO) release were performed after infusion of magnesium sulphate (MgSO4) in healthy volunteers. In a placebo controlled, cross-over study in 14 healthy male subjects, 8 mmol MgSO4 was given as an intravenous bolus over 15 min followed by 3 mmol MgSO4/h. The mean S-Mg concentration increased from 0.85 to 1.50 mM during the Mg infusion period. A transient decrease in blood pressure was observed during the initial bolus infusion of Mg. Haemodynamic parameters were otherwise unstable. The bleeding time increased by 48% during the Mg infusion (p < 0.005), and in accordance with this, ex vivo platelet aggregation in platelet rich plasma was significantly inhibited, both following collagen (p = 0.02) and ADP (p = 0.04) stimulation. There were no significant changes in plasma beta-thromboglobulin concentration or the excretion of 2,3-dinor-thromboxane B2 in the urine. Neither tissue plasminogen activator (t-PA)activity, tissue plasminogen activator (t-PA)antigen nor plasminogen activator inhibitor (PAI)antigen changed during the Mg infusion period. There was no sign of increased release of PGI2 from the vessel wall as judged by urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha. Nor was there any sustained increase in the release of NO, measured as nitrate concentration in urine. However, a transient increase in NO release was observed during one sample period. In conclusion a reduced platelet activity and increased bleeding time, was found during Mg infusion in healthy volunteers. Fibrinolytic activity showed no changes. An anti-platelet effect may in part be responsible for the beneficial effect of Mg, described in patients with acute myocardial infarction (MI) and preeclampsia.

Completely heparinized cardiopulmonary bypass and reduced systemic heparin: Clinical and hemostatic effects

When heparinized circuits are used for cardiopulmonary bypass, the amounts of heparin and protamine administered systemically can be reduced. However, it is not entirely known what effects this reduction in systemic anticoagulation has on clinical performance and on the coagulation and fibrinolytic systems. Two hundred three patients undergoing first-time elective myocardial revascularization were prospectively randomized either to a group in which a completely heparin-coated circuit was used for perfusion (group H; n = 101 patients) and in which a reduced heparin dose was given (activated clotting time, > 250 seconds) or to a control group (group C; n = 102 patients) in which an uncoated, but otherwise identical, circuit was used and in which full systemic heparinization was induced (activated clotting time, > 480 seconds). Indicators of thrombin generation, platelet activation, and fibrinolytic activity were studied in a subset of 34 patients. The total amount of postoperative mediastinal drainage was significantly reduced in group H (median, 575 mL) compared with that in group C (median, 635 mL; p = 0.002). Two patients in group C but none in group H received homologous red blood cell transfusions (p = not significant). The loss of hemoglobin in group H was a median of 21 g/L, and this was significantly lower than the 25 g/L noted in the control group (p = 0.006). During cardiopulmonary bypass, the plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in both groups. At the end of cardiopulmonary bypass the plasma levels of these markers of thrombin formation were significantly higher in group H, although the increase was modest compared with the major increase observed 2 hours after operation in both groups. There were no significant intergroup differences in the platelet counts, the concentration of beta-thromboglobulin, or the plasma levels of fibrinogen and D-dimer. No differences in perioperative morbidity, the postoperative kidney function, or the intubation time were observed, and there were no hospital deaths. The combination of complete heparin-coated cardiopulmonary bypass circuits and low systemic heparinization is safe for patients undergoing elective coronary artery bypass procedures and reduces the perioperative blood loss. There was no evidence of increased thrombogenicity, fibrinolytic activity, or consumption of coagulation factors. No clinical or technical side effects were observed.

Hemocompatibility in Hemodialysis and Erythropoietin Therapy

Two studies designed to investigate the effect of recombinant human erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on hemocompatibility were conducted. Study 1, whose main aim was to establish whether treatment with rHuEPO enhances coagulation activation during dialysis, included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3% and then during therapy at a HCT of 29.3%. The plasma concentrations of the thrombin-antithrombin III complex were not higher during rHuEPO therapy than before it when performing hemodialysis with a Cuprophan membrane. No significant difference was demonstrated either in the values of activated clotting times (Hemochron), thrombocyte or white blood cell counts (Coulter S+II), or in plasma C5a concentrations (ELISA) established during dialysis sessions before and during rHuEPO therapy. In Study 2, which focused primarily on the question of whether or not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8 patients on chronic dialysis were examined both before therapy at a mean HCT value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the examinations made during rHuEPO and before rHuEPO therapy; however, statistically significant differences were found between dialysis sessions involving Cuprophan and AN69HF membranes. No significant difference between examination before and during rHuEPO was demonstrated in activated clotting time nor thrombocyte and white blood cell counts in this study either. The authors conclude that rHuEPO therapy does not enhance coagulation activation during hemodialysis, does not have an effect on thrombocyte activation, and does not influence complement activation and changes in white blood cell counts.

The Laboratory Evaluation of Hypertensive Gravidas

A number of laboratory tests are available for the evaluation of the hypertensive gravida. These tests can be used to either predict and/or prognosticate between preeclampsia and other hypertensive disorders of pregnancy. These laboratory tests were evaluated based on published experience with special attention to its ability to facilitate identification of the patient with preeclampsia apart from other hypertensive disorders that co-exist with and occur as a complication of pregnancy. Hypocalciuria and increased cellular plasma fibronectin seem to be good tests to differentiate preeclampsia from chronic hypertension. The management of preeclampsia with its increased risk of perinatal morbidity and mortality renders this differentiation clinically very important. Hyperuricemia, proteinuria, increased serum beta-thromboglobulin concentration, abnormal red blood cell morphology with increased hemoglobin/hematocrit, and increased serum iron individually and collectively reflect the severity of preeclampsia. Platelets and total serum lactate dehydrogenase are the best tests to reflect the severity of HELLP syndrome. Circulating hCG and serum thromboglobulin seem to be the most promising future predictors for preeclampsia.

Antiplatelet Effect of Nifedipine depending on its Action on Red Cell Deformability in Essential Hypertension.

In patients with essential hypertension, increased level of platelet activity expressed as the concentrations of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were observed. Elevation of the levels of both beta-TG and PF4 correlated with the increase in platelet aggregability in platelet-rich plasma (PRP) and the decrease in red blood cell deformability, which were considered as being the possible factors for the platelet intravascular activation. After 2 weeks of monotherapy with nifedipine (40 mg daily), a decrease in platelet aggregability in PRP was observed in 35 of the 75 patients and an increase in red cell deformability in 37 of the 75 patients. Using cluster analysis, all cases were divided into several groups based on nifedipine effects on red cell deformability and platelet aggregability in PRP. It was revealed that the statistically significant decrease in the levels of platelet markers took place only in patients in whom nifedipine simultaneously decreased platelet aggregability and increased red cell deformability. Analysis of variance showed a high power of influence for combined changes in these parameters for reducing intravascular platelet activation by nifedipine. It is suggested that nifedipine reduces platelet activity by direct action on platelets and indirectly due to its capacity to increase red cell deformability, resulting in elimination of platelet stimulation by red blood cells.