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Biomedical subjects

J Petäjä

Publications and source records attributed to J Petäjä.

At least 19 recordsLinked to original sources
PubMed2006

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig.

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.

Animals↗
PubMed2006

Thrombin generation during reperfusion after coronary artery bypass surgery associates with postoperative myocardial damage.

BACKGROUND: Cardiopulmonary bypass and coronary artery bypass grafting (CABG) result in significant thrombin generation and activation of fibrinolysis. Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in myocardial damage after CABG is unknown. OBJECTIVES: We measured thrombin generation and fibrin turnover during reperfusion after CABG to evaluate their associations with postoperative hemodynamic changes and myocardial damage. METHODS: One hundred patients undergoing primary, elective, on-pump CABG were prospectively enrolled. Plasma prothrombin fragment F(1+2) and D-dimer were measured preoperatively and at seven time points thereafter. Mass of the Mb fraction of creatine kinase (Ck-Mbm) and troponin T (TnT) were measured on the first postoperative day. RESULTS: Reperfusion induced an escalation of thrombin generation and fibrin turnover despite full heparinization. F(1+2) during early reperfusion associated with postoperative pulmonary vascular resistance index. F(1+2) at 6 h after protamine administration correlated with Ck-Mbm (r = 0.40, P < 0.001) and TnT (r = 0.44, P < 0.001) at 18 h postoperatively. Patients with evidence of myocardial damage (highest quintiles of plasma Ck-Mbm and TnT) had significantly higher F(1+2) during reperfusion than others (P < 0.002). Logistic regression models identified F(1+2) during reperfusion to independently associate with postoperative myocardial damage (odds ratios 2.5-4.4, 95% confidence intervals 1.04-15.7). CONCLUSIONS: Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.

Adult↗
PubMed2004

A simple automatized audit system for following and managing practices of platelet and plasma transfusions in a neonatal intensive care unit.

During neonatal intensive care, blood components are often used in clinical situations where both their efficacy and safety lack solid justification. A practical system to continuously analyse actual transfusion practices is a prerequisite for improvements of quality in transfusion therapy. We hypothesized that such a system would reveal inappropriate variations in clinical decision making and offer a means for staff education and quality improvement and assurance. The study consisted of three 120-152-day periods (P I, P II and P III) between January 2000 and October 2001 and involved 543 new patient admissions (141 patients with birth weight < 1501 g) and 6227 days of patient care at a single tertiary level NICU. P I was a control with no intervention, P II was after technically introducing the computer system and, the last period, P III was after presenting and discussing the results of P I and P II at a staff meeting. Upon an order of platelet or fresh frozen plasma (FFP) unit from the blood bank, a computer-based audit system compared the last platelet count or prothrombin time [expressed as percentage of normal clotting activity, prothrombin time (PT-%)] to predefined criteria. In the case of exceeding the preset thresholds, the system required additional information and recorded the pretransfusion laboratory values for later analysis. Thirty-two per cent of platelet transfusions were given with pretransfusion platelet count >49 x 10(9) L(-1), and 60% of these transfusions (19% of all platelet transfusions) could not be clinically justified in retrospective chart review. There was no significant change in this practice from P II to P III. FFP transfusions were given with significantly different pretransfusion PT-% values during P II and P III. The proportions of FFP transfusions with pretransfusion PT-% > 49% were 7.8% and 0.9% during P II and P III, respectively (P < 0.0001). In chart review, none of the FFP transfusions with pretransfusion PT-% > 49% could be justified by clinical grounds. Inappropriate transfusions of both platelets and plasma remain a significant challenge for quality assurance of neonatal intensive care. Automated recording of pretransfusion platelet count and prothrombin time reliably identified the poorly justified transfusions and thus offered a practical resource-saving tool for quality assurance of transfusion in the NICU. A significant shift towards more appropriate use of plasma was demonstrated after implementation of the audit system.

Automation↗
PubMed2003

Fresh frozen plasma reduces thrombin formation in newborn infants.

BACKGROUND: Newborn infants undergoing intensive care are at risk of bleeding and thrombotic complications. Fresh frozen plasma (FFP) is used in hope of preventing these complications, despite poorly defined effects on the coagulation system and lack of proven clinical efficacy. OBJECTIVES AND METHODS: We prospectively evaluated coagulopathy and the effect of standardized amount of FFP transfusion (10 mL kg-1 + 4 mL in 2 h) on various coagulation markers in 33 newborn infants during the first 24 h of intensive care. RESULTS: Increased levels of prothrombin fragment F1+2, thrombin-antithrombin complexes (TAT), and d-dimer were found prior to the transfusion in 97%, 81%, and 100% of the patients, respectively. FFP transfusion was associated with a decrease in F1+2 level in 26/32 (81%) of the patients. The extent of F1+2 decrease correlated with the pretransfusion F1+2 level (R = 0.65, P < 0.0001). The patient series was divided into two groups according to increasing pretransfusional F1+2 level: Group 1 (preFFP F1+2 > or = 2.35 nm, n = 16), Group 2 (F1+2 <2.35 nm, n = 16). In Group 1, F1+2 decreased on average 1.58 nm (P < 0.01) from the baseline during FFP transfusion but no significant change in the level of F1+2 during the transfusion was observed in Group 2. Pretransfusional levels of individual factors or prothrombin time (PT) did not correlate with the FFP-associated decrease in F1+2 level. CONCLUSIONS: In the patients with the highest pretransfusional thrombin formation, FFP had an acute thrombin-reducing effect. Pretransfusion thrombin generation markers, rather than PT or individual pro- and anticoagulants, may be helpful in identifying the patient who will have measurable coagulational effects induced by FFP.

Biomarkers↗
PubMed2001

Activated protein C and inflammation in human myocardium after heart surgery.

To assess possible interactions between inflammation and activation of the anticoagulant protein C system during post-ischemic reperfusion protein C, APC, neutrophil L-selectin expression and myocardial myeloperoxidase activity (MPO) were measured in 19 patients undergoing cardiopulmonary bypass. After reperfusion for 10 min, APC to protein C ratio (APC/PC) increased from pre-reperfusion value 1.43 +/- 0.12 (mean +/- SEM) to 2.25 +/- 0.29, p = 0.015. Negative correlations were observed between APC/PC and MPO activity (Spearman r -0.64, p = 0.007) and APC/PC and neutrophil L-selectin expression (r = -0.7, p = 0.007, demonstrating that post-ishemic protein C activation was associated with decreased neutrophil tissue sequestration. Thus, physiological protein C activation may be involved in regulation of the inflammatory injury during reperfusion of human ischemic coronary circulation.

Adult↗
PubMed2001

Perforation complications of percutaneous central venous catheters in very low birthweight infants.

OBJECTIVE: To prospectively survey perforation complications of consecutively inserted percutaneous central venous catheters (PCVC) in very low birthweight (VLBW) infants over a 2 year period. METHODOLOGY AND RESULTS: Three serious perforation complications were encountered in a series of 100 consecutive PCVC. One infant (birthweight 685 g) developed pericardial effusion and fatal cardiac tamponade during the use of a polyurethane PCVC. At autopsy, the pericardial sac contained 8 mL fluid with a glucose concentration of 109 mmol/L and the catheter tip was embedded in the right ventricular wall. The second infant (birthweight 1380 g) showed pleural effusion and transient immobility of the right diaphragmatic leaf after perforation of a similar PCVC into the right pleural cavity. The third perforation, causing subcutaneous oedema, occurred in a 655 g infant who had a silastic PCVC. CONCLUSIONS: The data suggest a 3% incidence for PCVC-associated symptomatic perforation complications and a 1% incidence for fatal perforations, despite a policy of careful placement. The data also indicate that perforation complications occur regardless of the size or material of the PCVC. Proper visualization of the PCVC and vigilant attention to its location is required to prevent these rare but potentially fatal complications.

Autopsy↗
PubMed2001

Increased risk of intraventricular hemorrhage in preterm infants with thrombophilia.

The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may involve coagulation disturbances and venous infarction. We tested whether coagulation abnormalities associated with adult venous thrombosis would constitute a risk factor for IVH in newborn infants. In 22 infants (gestational age 24.3--39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the frequencies of congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin gene (G20210A-FII) were assessed and compared with those observed in 29 premature newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506-FV in the general population, the odds ratio for being a carrier of Gln506-FV for patients with IVH was 5.9 (95% confidence interval 1.7--20.3, p = 0.013) and for patients without IVH 0.9 (95% confidence interval 0.1--7.6, p > 0.99). The absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born before 30 wk of gestation was estimated at 80%, whereas the corresponding risk for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn infants with IVH than in the general population, whereas there was no difference in the frequencies of Gln506-FV in infants without IVH and in the general population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a premature infant with Gln506-FV or other established thrombophilic coagulation abnormality may be considerable.

Case-Control Studies↗
PubMed2000

Cardiolipin enhances protein C pathway anticoagulant activity.

The anticoagulant activity of activated protein C (APC) was studied using factor Xa-1-stage assays of both the procoagulant and anticoagulant activities of phospholipid vesicles containing phosphatidylserine or cardiolipin as active phospholipids. In the absence of APC, phosphatidylserine vesicles showed higher procoagulant activity than cardiolipin vesicles whereas cardiolipin vesicles supported APC-dependent anticoagulant activity better than phosphatidylserine vesicles. Enhancement of APC anticoagulant activity in plasma by cardiolipin was markedly stimulated by the APC cofactor protein S. In purified reaction mixtures, cardiolipin in phospholipid vesicles dose-dependently enhanced APC anticoagulant activity. This effect of cardiolipin was partially dependent on protein S, and immunoblotting studies showed that cardiolipin enhanced the APC-mediated cleavage of the factor Va heavy chain at Arg506 and Arg306. In solid-phase binding assays, increasing amounts of cardiolipin in multicomponent phospholipid vesicles increased the affinity for protein S and to a lesser extent APC. These data are consistent with the hypothesis that cardiolipin stimulates the anticoagulant protein C pathway by increasing the affinity of phospholipid surfaces for protein S:APC and by enhancing inactivation of factor Va by APC due to cleavages at Arg506 and Arg306 in factor Va. Based on this, it is further hypothesized that anti-cardiolipin or anti-oxidized cardiolipin antibodies may be thrombogenic because they inhibit phospholipid-dependent expression of the anticoagulant protein C pathway.

Blood Coagulation↗
PubMed2000

Serum tumor marker CA 125 is an early and sensitive indicator of veno-occlusive disease in children undergoing bone marrow transplantation.

Veno-occlusive disease (VOD) is a potentially lethal complication of patients undergoing bone marrow transplantation (BMT). The diagnosis of VOD is currently based on clinical signs and unspecific laboratory findings. CA 125 is an oncofetal antigen used as a tumor marker in various malignancies, especially in those originating from the female reproductive tract or gastrointestinal organs, whereas serum CA 125 levels are not increased in hematological malignancies. Several pathophysiological alterations occurring in VOD may lead to elevations in serum CA 125 levels. Therefore, we explored the behavior of this marker as a diagnostic tool in VOD. Twenty-nine pediatric transplant patients were studied. Eight patients (28%) developed clinical VOD, and a significant increase in serum CA 125 was noted in all of them. During the 7 days preceding the diagnosis of VOD, an increase of at least 57% in serum CA 125 from the pre-BMT value was observed in 6 (86%) of 7 of the evaluable patients with VOD. In contrast, a similar increase was noted in only 6 of the 21 non-VOD patients during the post-BMT period of 30 days. Accordingly, the sensitivity and specificity of serum CA 125 for predicting or detecting VOD were 86% and 71%, respectively. The serum levels of CA 125 were not affected by the presence of Graft-versus-Host Disease (GvHD) or a septic infection. In conclusion, serum CA 125 is of value as an early marker of VOD in children undergoing BMT.

Adolescent↗
PubMed1999

Cardiopulmonary bypass and activation of antithrombotic plasma protein C.

OBJECTIVE: We hypothesized that antithrombotic plasma-activated protein C plays a defensive antithrombotic role during coronary ischemia and postischemic reperfusion. METHODS AND RESULTS: We evaluated protein C activation during cardiopulmonary bypass and coronary reperfusion in 20 patients undergoing coronary bypass surgery. During cardiopulmonary bypass and during the 10 minutes after aortic unclamping, the plasma levels of protein C (mean +/- standard error of the mean) decreased from 123% +/- 7% to 74% +/- 5% of normal mean. In contrast, the levels of activated protein C in plasma increased from 122% +/- 8% to 159% +/- 21%, and the activated protein C/protein C ratio increased from 1.04 +/- 0.08 to 2.29 +/- 0. 31 (P =.006, 2-tailed Wilcoxon signed rank test). Patients were stratified on the basis of the increase in activated protein C in the coronary sinus plasma at 10 minutes after reperfusion by means of the arbitrary value of 1.5 for the activated protein C/protein C ratio. Within 24 hours, the patients with low increases in activated protein C (ratio < 1.5, n = 8) had a significantly (P <.05) lower cardiac output and mean pulmonary artery pressure, as well as a higher systemic vascular resistance, than patients (n = 11) with high increases in activated protein C (ratio > 1.5). The rapid increase in activated protein C during the first 10 minutes after aortic unclamping indicated protein C activation in the reperfused vascular beds. CONCLUSIONS: The antithrombotic protein C pathway was significantly activated during cardiopulmonary bypass mainly during the minutes after aortic unclamping in the ischemic vascular beds. Suboptimal protein C activation during ischemia may impair the postischemic recovery of human heart and circulation.

Adult↗
PubMed1999

Dermatan sulfate and LMW heparin enhance the anticoagulant action of activated protein C.

Unfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

Animals↗
PubMed1997

Anticoagulant synergism of heparin and activated protein C in vitro. Role of a novel anticoagulant mechanism of heparin, enhancement of inactivation of factor V by activated protein C.

Interactions between standard heparin and the physiological anticoagulant plasma protein, activated protein C (APC) were studied. The ability of heparin to prolong the activated partial thromboplastin time and the factor Xa- one-stage clotting time of normal plasma was markedly enhanced by addition of purified APC to the assays. Experiments using purified clotting factors showed that heparin enhanced by fourfold the phospholipid-dependent inactivation of factor V by APC. In contrast to factor V, there was no effect of heparin on inactivation of thrombin-activated factor Va by APC. Based on SDS-PAGE analysis, heparin enhanced the rate of proteolysis of factor V but not factor Va by APC. Coagulation assays using immunodepleted plasmas showed that the enhancement of heparin action by APC was independent of antithrombin III, heparin cofactor II, and protein S. Experiments using purified proteins showed that heparin did not inhibit factor V activation by thrombin. In summary, heparin and APC showed significant anticoagulant synergy in plasma due to three mechanisms that simultaneously decreased thrombin generation by the prothrombinase complex. These mechanisms include: first, heparin enhancement of antithrombin III-dependent inhibition of factor V activation by thrombin; second, the inactivation of membrane-bound FVa by APC; and third, the proteolytic inactivation of membrane-bound factor V by APC, which is enhanced by heparin.

Animals↗
PubMed1997

Activated protein C correlates inversely with thrombin levels in resting healthy individuals.

To study whether the circulating anticoagulant, activated protein C (APC), could be a regulator of thrombin activity in basal physiological conditions, fibrinopeptide A and activated protein C levels were determined in samples from 40 healthy individuals. There was a significant inverse correlation between the fibrinopeptide A and APC levels (Spearman rank correlation R = -0.487; P = 0.0023). Because of well-known mechanisms by which decreasing APC levels could cause increased thrombin formation, we suggest that APC may downregulate thrombin activity in subjects with normal protein C levels. Regulation of thrombin formation in health is likely significant for maintaining vascular patency but its molecular mechanisms are poorly understood. The current data suggest that a single physiological anticoagulant, namely APC, may be a significant regulator of procoagulant thrombin activity.

Adult↗
PubMed1996

Central venous thrombosis after cardiac operations in children.

To evaluate the incidence, mortality, late outcome, and cause of central venous thrombosis after pediatric heart operations and other operations performed with cardiopulmonary bypass, we identified patients with postoperative central venous thrombosis during a 10-year period at a single pediatric hospital. There had been 1591 open heart (with bypass) and 1086 closed heart (no bypass) procedures and 13 operations with cardiopulmonary bypass for extracardiac indications. There were 20 patients with central venous thrombosis, yielding incidences of 1.1% and 0.2% after cardiopulmonary bypass and after closed heart operations, respectively. When neonates were compared with older children (1 to 119 months of age) undergoing heart procedures, a tenfold increase (5.8% vs 0.6%) (p < 0.001) in the incidence of central venous thrombosis was observed. The mortality was eight of 20 (40%). Central venous thrombosis contributed to seven deaths and it was a direct cause of one death. Ten patients were reinvestigated 5 to 108 months after central venous thrombosis. The outcome of surgery was excellent in eight. Two had residual thrombosis, but this was not hemodynamically significant to the cardiorespiratory condition of the patients. During or preceding thrombosis, low levels of antithrombin III and/or protein C and high levels of the plasminogen activator inhibitor were observed in five of the patients. A congenital thrombotic risk factor, "resistance to activated protein C," was found in two of 12 tested patients with central venous thrombosis (17%). In conclusion, central venous thrombosis, especially in neonates, is an important cause of morbidity and mortality after cardiac operations. The cause is multifactorial, with contributions from multiple acquired thrombophilic coagulation abnormalities, and resistance to activated protein C may act as a risk factor for thrombosis already during neonatal period.

Blood Coagulation Tests↗