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Biomedical subjects

M Felfernig

Publications and source records attributed to M Felfernig.

At least 19 recordsLinked to original sources

Stability of coagulation factors in thawed, solvent/detergent-treated plasma during storage at 4 degrees C for 6 days.

BACKGROUND AND OBJECTIVES: Transfusion of fresh-frozen plasma is still a pillar in emergency medicine for using to prevent dilutional coagulopathy or disseminated intravascular coagulation after severe blood loss, but thawing procedures can delay its availability. On the other hand, the wastage of plasma, once thawed and not transfused within a defined time-period, represents an inefficient handling of economic resources and is contradictory to blood donor intentions. In this study we investigated the stability of coagulation factor activities and plasma protein levels during 6 days of storage of thawed solvent/detergent (S/D)-treated plasma at +4 degrees C. Our results may form the basis for reconsideration of expiry times of thawed S/D-treated plasma. MATERIALS AND METHODS: Five units of S/D-treated plasma (Octaplas) were thawed and warmed to 20 degrees C, then recooled and stored at +4 degrees C for 6 days. The activities of coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen, antithrombin (AT), protein C, protein S and von Willebrand factor antigen (vWF:Ag) were measured on days 0, 1, 2, 3 and 6. RESULTS: Except for protein S, the activities of all coagulation factors and inhibitors were at least 0.5 U/ml during storage at 4 degrees C for 6 days. The mean levels, during storage, of factors IX, X, XI and XII, vWF:Ag, fibrinogen and protein C were at least 94%, and of factors II, V and VIII, and AT at least 78%, of the levels immediately after thawing; the activity of factor VII decreased to 83% and of protein S to 43% of the baseline values. CONCLUSIONS: Thawed S/D-treated plasma stored at +4 degrees C for up to 6 days still contains sufficient coagulation activities and plasma proteins to be regarded as suitable for transfusion in the established indications.

Blood Coagulation Factors↗

The effects of hydroxyethyl starch solutions on thromboelastography in preoperative male patients.

BACKGROUND: Hydroxyethyl starches (HES) have been shown to decrease clot strength and to increase coagulation times assessed by thromboelastography (TEG). HES with minimal anticoagulant side-effects is beneficial for plasma volume expansion in the perioperative setting. A comparison of the in vivo effects of high, middle and low molecular weight HES solutions on TEG variables has not been performed so far. METHODS: Blood was obtained before and after intravenous infusion (10 ml kg-1) of either saline, HES 70/0.5/4 (molecular weight in kDa/degree of substitution/C2:C6 ratio), HES 130/0.4/9, HES 200/0.6/9.4, or HES 450/0.7/4.6 in 50 otherwise healthy patients. Thromboelastography was performed in 360 micro l of 1% celite activated citrated whole blood after recalcification. RESULTS: HES 450/0.7/4.6 prolonged reaction time indicating impairment of the plasmatic coagulation system. TEG parameters indicative for platelet function, including angle alpha, maximum amplitude and coagulation time, deteriorated after infusion of HES 450/0.7/4.6 and HES 70/0.5/4. HES 200/0.6/9.4 and HES 130/0.4/9 impaired platelet contribution to hemostasis only partially, decreasing two or one TEG platelet parameters, respectively. CONCLUSION: Infusion of HES 450/0.7/4.6 compromises TEG parameters more than the other solutions tested, whereas HES 130/0.4/9 has the smallest effect. Further outcome-related studies are needed in order to assess the clinical relevance of our findings.

Adult↗

Influence of hypotensive and normotensive anesthesia on platelet aggregability and hemostatic markers in orthognathic surgery.

This prospective randomized study investigated the influence of normotensive and hypotensive general anesthesia on platelet aggregability, intraoperative blood loss and parameters of plasmatic coagulation during extensive orthognathic surgery. A total of 30 patients were randomly allocated for either normotensive anesthesia maintained by continuous infusion of propofol and remifentanil (NORMO, n=10) or hypotensive anesthesia, whereby hypotension was induced by increasing the infusion rate of remifentanil (HYPO-R, n=10) or by administration of nitroglycerin (HYPO-N, n=10). Whole blood platelet aggregability was significantly reduced during hypotension compared to normotensive anesthesia (P<.01, HYPO-N and HYPO-R vs. NORMO). Mean arterial blood pressure during hypotension correlated well with adenosinediphosphate- (R=.712, P<.001) and collagen-induced platelet aggregability (R=.685, P<.001). Within hypotensive study groups, postoperative fibrinogen levels were significantly different, whereas intraoperative platelet aggregability, postoperative platelet count, prothrombin time, activated partial thromboplastin time and antithrombin levels were not different. Normotensive anesthesia, however, caused significant decreases in platelet count (-29%), prothrombin time (-24%), fibrinogen (-41%) and antithrombin (-28%) and a significant prolongation in activated partial thromboplastin time (+21%) and thrombin time (+18%). There was a trend to reduced intraoperative blood loss in hypotensive study groups; however, differences were not significant. In conclusion, induced hypotension--independent of substances used for induction of hypotension--reduces intraoperative platelet aggregability, subsequently protecting the coagulation system against subclinical consumption coagulopathy. Induced hypotension-caused platelet dysfunction does not lead to an increased intraoperative blood loss, but quite on the contrary shows a trend to reduced intraoperative blood loss, possibly by preventing platelet-induced subclinical consumption coagulopathy.

Adult↗

Impact of early high caloric duodenal feeding on the oxygen balance of the splanchnic region after severe burn injury.

Early enteral nutrition is recommended in burned patients. Depending on the amount administered, enteral feeding causes an increase of intestinal oxygen-demand. Although early moderate enteral nutrition has been shown to be beneficial, early high calorie enteral nutrition might lead to an imbalance of the O(2)-balance of the gut since intestinal perfusion is decreased after major burns. In 20 severely burned patients during the first 48 h of early high caloric duodenal feeding an assessment of the CO(2)-gap between the arterial and the gastric CO(2), as parameter for the intestinal O(2)-balance, was performed. Time points were prior to starting the enteral nutrition (BASE) subsequently every 30 min after increasing the amount of nutrition administered and from the 11th to the 48th h after beginning of nutrition in intervals of 6 h. In none of the patients was the CO(2)-gap increased during the rapid increase of enteral nutrition. On the contrary the CO(2)-gap decreased significantly. We conclude that high caloric duodenal feeding in the early hypodynamic postburn phase does not have adverse effects on the oxygen balance of the intestine.

Adult↗

Effects of temperature on partial thromboplastin time in heparinized plasma in vitro.

BACKGROUND AND OBJECTIVE: Perioperative hypothermia has been found to impair the coagulation cascade and to increase blood loss and transfusion requirements. The effect of concomitant in vitro heparinization on coagulation during hypo- and hyperthermic conditions has not been well defined. METHODS: In the present study, activated partial thromboplastin time was examined in vitro at 33 degrees C, 35 degrees C, 37 degrees C, 39 degrees C and 41 degrees C in normal human plasma in response to unfractionated heparin. RESULTS: Hypothermia <or= 35 degrees C prolonged activated partial thromboplastin time by 10% compared with test temperatures at 37 degrees C (P < 0.05). Hyperthermia alone had no effect. Unfractionated heparin (0.1-0.4 IU mL(-1)) increased activated partial thromboplastin time in a dose-dependent manner (by 189% at 0.4 IU mL(-1), P < 0.05). Test temperatures of 33 degrees C and 41 degrees C increased heparin-induced prolongation of activated partial thromboplastin time. At a heparin concentration of 0.4 IU mL(-1), hypothermia (33 degrees C) and hyperthermia (41 degrees C) prolonged partial thromboplastin time by 12% and 22%, respectively, compared with normothermic test temperature of 37 degrees C within the heparin group (P < 0.05). CONCLUSIONS: These observations suggest that both hypo- and hyperthermia increase the response to heparin in vitro. Further studies are needed to identify the effect of patient's body temperature on heparin activity and bleeding tendency in vivo.

Adult↗

The effects of hydroxyethyl starches of varying molecular weights on platelet function.

We evaluated the effect of various hydroxyethyl starch (HES) solutions on platelet function. Blood was obtained before and after the IV infusion (10 mL/kg) of saline (n = 10), HES 70/0.5--0.55 (molecular weight in kD/degree of substitution; n = 10), HES 130/0.38--0.45 (n = 10), HES 200/0.6--0.66 (n = 10), or HES 450/0.7--0.8 (n = 10) in otherwise healthy patients scheduled for elective surgery. Collagen and epinephrine were used as agonists for assessment of platelet function analyzer closure times. Flow cytometry was used to assess agonist-induced expression of activated glycoprotein IIb/IIIa complex and P-selectin. Infusion of HES 450/0.7--0.8, HES 200/0.6--0.66, and HES 70/0.5--0.55 prolonged closure times and reduced glycoprotein IIb/IIIa expression, whereas saline and HES 130/0.38--0.45 had no significant effect on platelet variables. P selectin expression was not affected by any solution tested. In vitro experiments demonstrated a less inhibiting effect of HES 130/0.38--0.45 on closure times when compared with other HES solutions. This study shows that HES 450/0.7--0.8, HES 200/0.6--0.66, and HES 70/0.5--0.55 inhibit platelet function by reducing the availability of the functional receptor for fibrinogen on the platelet surface. Our data indicate that fluid resuscitation with HES 130/0.38--0.45 may reduce the risk of bleeding associated with synthetic colloids of higher molecular weight and degree of substitution.

Adult↗

Early detection of preeclampsia by determination of platelet aggregability.

Preeclampsia is still a leading cause of maternal and fetal morbidity and mortality. There is evidence for the involvement of platelets. Therefore, we investigated the suitability of corrected whole blood impedance aggregometry as an early predictor of preeclampsia in 71 consecutive, high-risk pregnancies. According to the occurrence of preeclampsia, defined postpartum by an independent investigator, and the stage of pregnancy (early and late, cutoff: 25 weeks of gestation), four study groups were defined. Platelet aggregation data were corrected for the influence of hematocrit and platelet count by a special purpose software package. Women developing preeclampsia showed significantly higher platelet aggregation response compared to controls in early and late pregnancy. In early pregnancy, all women developing preeclampsia had aggregation responses to collagen higher than the highest responses among the controls. Hence, this test had a 100% positive predictive value of subsequent preeclampsia. Despite being significantly increased, platelet aggregability was of minor predictive value in late pregnancy. We conclude that preeclampsia is accompanied by exaggerated platelet aggregability, particularly perceptible early in the course of pregnancy. We propose collagen-induced whole blood platelet aggregation with correction for the influence of hematocrit and platelet count for early detection of preeclampsia.

Adenosine Diphosphate↗

Propofol without muscle relaxants for conventional or fiberoptic nasotracheal intubation: a dose-finding study.

UNLABELLED: Endotracheal intubation has been performed during the administration of propofol anesthesia without neuromuscular blockade. In this study, we determined the propofol dose required for conventional nasotracheal or for fiberoptic nasotracheal intubation of all patients. Thirty-two patients undergoing maxillofacial surgery were randomly assigned to the conventional (n = 16) or to the fiberoptic (n = 16) intubation group. In both groups, anesthesia was induced by using IV fentanyl and IV titrated propofol according to clinical need (spontaneous respiration rate, verbal response). An endotracheal tube was placed nasally in the pharynx and the vocal cords visualized by using a fiberscope inserted via the tube. In the conventional group, the larynx was visualized additionally with a laryngoscope blade (Miller). In both groups propofol was titrated until the vocal cords opened. Patients were tracheally intubated, and the propofol dose was recorded. In all patients, the trachea could be intubated without the use of muscle relaxants. Considerable interindividual differences of dose requirements were observed. The amount of propofol required in the conventional group was significantly (P < 0.0001) larger (median +/- SD: 2.74 +/- 1.59 mg/kg; range 1.95-7.07 mg/kg) than in the fiberoptic group (1.37 +/- 0.59 mg/kg; 0.72-2.86 mg/kg). Hemodynamics remained stable in all patients. Postintubational hoarseness occurred in three patients of each group. Fiberoptic nasal intubation without a muscle relaxant can be facilitated with significantly smaller and more predictable dosages of propofol than conventional nasal endotracheal intubation. The possibility of titrating the propofol dose under assisted ventilation until the vocal cords open during fiberoptic nasotracheal intubation and the better predictability of the required dose favors the fiberoptic approach. IMPLICATIONS: In this study, contrary to all preceding studies using predefined doses of propofol and opioids, we determined the minimal required propofol dose in combination with fentanyl for conventional or fiberoptic nasotracheal intubation without muscle relaxants.

Adult↗

The effect of hydroxyethyl starch 200 kD on platelet function.

We evaluated the effects of hydroxyethyl starch with a molecular weight of 200 kD (HES 200 kD) on platelets to gain insight into the potential mechanisms involved in the anticoagulant effects of HES 200 kD. Blood was obtained before and after an IV infusion (10 mL/kg) of either saline (n = 15) or HES 200 kD (n = 15) in otherwise healthy patients scheduled for minor elective surgery. Flow cytometry was used to assess the expression of glycoprotein (GP) IIb-IIIa, GP Ib, and P-selectin on agonist-activated platelets. Overall platelet function was evaluated by assessing thromboelastographic maximum amplitude (MA) in celite-activated blood and platelet function analyzer-closure times by using collagen/adenosine diphosphate cartridges. Saline infusion had no effects on platelet variables, whereas HES 200 kD reduced GP IIb-IIIa expression and MA and prolonged platelet function analyzer-closure times, without affecting the expression of P-selectin and GP Ib. In vitro experiments extended these observations by a concentration-related inhibiting effect of HES 200 kD on GP IIb-IIIa expression. This study demonstrates that cellular abnormalities with decreased availability of platelet GP IIb-IIIa are involved in the anticoagulant effects of HES 200 kD.

Adenosine Diphosphate↗

The axillary vein central venous catheter in severely burned patients.

In severely burned patients the approach to the central vein is often difficult due to concomitant edema, but also due to the fact that the skin area, where commonly used approaches are performed, is burned as well, whereas the axillary region is often not involved. In order to perform an axillary approach to the central vein as an alternative to the commonly used approaches in patients, an anatomical dissection in fresh human cadavers was carried out. Considering the anatomical landmarks which were found during dissection of the axillary region, the axillary approach to the central vein was used in 35 patients in our intensive burn care unit with unaffected axillary skin. In three cases the only complication observed was an occasional puncture of the axillary artery without major hematoma. The infection rate of the catheters was similar to the commonly used puncture sites. This approach to the central venous line in severely burned patients can be recommended.

Adult↗

Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation.

UNLABELLED: Orthotopic liver transplantation (OLT) is associated with severe bleeding, especially after reperfusion of the grafted liver. Heparin released from the liver graft contributes to postreperfusion coagulopathy. Although patients with liver cirrhosis have increased levels of endogenous heparinoids, the role of these substances during liver transplantation is unclear. Therefore, we performed native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping of the vena cava, 10 min before and 10 min after graft perfusion, and at the end of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin activity. In contrast to other investigations, we found significant heparin effects before reperfusion, although patients received no exogenous heparin. These heparin effects were greater in patients with cirrhosis compared with patients with cancer as the underlying disease leading to OLT. Administration of coagulation factors is the usual treatment of coagulopathies during OLT. The comparison of native versus heparinase-modified TEG can distinguish between heparin activity or coagulation factor deficiency as a cause of bleeding complications and provides a rational approach to the treatment of bleeding during OLT. IMPLICATIONS: Impaired coagulation function, contributed to by heparin or heparin-like substances, is frequently observed after reperfusion of a transplanted liver. This study demonstrates that a heparinase-modified thrombelastography can identify significant heparin effects in the absence of exogenous heparin administration in patients undergoing liver transplantation.

Anticoagulants↗

The effect of hydroxyethyl starch on platelet aggregation in vitro.

UNLABELLED: The effect of hydroxyethyl starch (HES) on hemostasis seems to be minimal when it is used in recommended amounts. A number of studies have investigated the effect of HES on platelet function when administered in vivo, but there has been no study investigating the effect on the isolated platelet function when administered in vitro. A photometrical method to assess platelet function in platelet-rich plasma (approximately 250 x 10(9) platelets/L) was used with platelet aggregation induced using either collagen, epinephrine, adenosine diphosphate, or ristocetin. We found a dose-dependent decrease of platelet aggregation in vitro with either collagen or epinephrine, but not with adenosine diphosphate or ristocetin. However, the changes of HES on platelet aggregation were detected only in doses larger than those routinely used in the clinical setting. Therefore, we conclude that the influence of HES at the recommended doses on initial platelet aggregation may not be clinically relevant. IMPLICATIONS: The effect of hydroxyethyl starch on platelet function and coagulation is discussed. This study showed no influence on platelets in clinically relevant doses in an in vitro model.

Adenosine Diphosphate↗

Does reoperation for abdominal sepsis enhance the inflammatory host response?

OBJECTIVE: To determine the effect of reoperation for severe abdominal sepsis on the course of proinflammatory mediators and hemodynamic factors. DESIGN: Inception cohort. SETTING: A university hospital and a secondary care hospital. PATIENTS AND METHODS: Fifteen patients suffering from severe peritonitis due to intestinal perforation or infected necrotizing pancreatitis were studied following 19 subsequent operations. Plasma samples were obtained immediately before and after reoperation, as well as at 1, 3, 6, 12, and 24 hours after operation to determine endotoxin, tumor necrosis factor alpha, and interleukin-6 levels. Clinical factors and therapeutic support were recorded at the corresponding times. MAIN OUTCOME MEASURES: Postoperative hemodynamic instability as defined by changes of the mean arterial pressure, pulmonary capillary wedge pressure, and vasopressor support. Courses of proinflammatory mediators were correlated to the hemodynamic findings. RESULTS: Mean arterial pressure decreased from 94 mm Hg postoperatively to 80 mm Hg at 3 hours (P = .006) and 81 mm Hg at 6 hours postoperatively (P = .005). Pulmonary capillary wedge pressure dropped from 14 mm Hg postoperatively to 12 mm Hg at 1 hour (P = .05). Vasopressor support significantly increased from 1 to 6 hours postoperatively (P = .02). Neither endotoxin nor tumor necrosis factor alpha levels showed significant changes in the postoperative course. Interleukin-6 levels continously increased from 586 pg/mL preoperatively to 910 pg/mL at 1 hour (P = .02) and 931 pg/mL at 3 hours postoperatively (P = .04). Overall interleukin-6 levels (R = -0.38, P = .003) and especially early postoperative interleukin-6 levels inversely correlated with postoperative mean arterial pressure. CONCLUSIONS: Reoperation for abdominal sepsis frequently causes substantial hypotension, and is, thus, potentially harmful to the patient. Reoperative trauma may induce an early postoperative increase in interleukin-6 levels. Because this increase occurs before the development of hypotension, a relationship between the kinetics of this cytokine and the observed hemodynamic instability may be present.

Adult↗

Platelet disorders in uraemia before and after haemodialysis under the influence of low dose aspirin.

Thrombocyte dysfunction and increased bleeding time (BT) are well documented in uraemic patients. However, these patients are frequently medicated with low dose aspirin (ASA) in order to maintain shunt patency and prevent cardiovascular events. Recently, life- threatening gastrointestinal haemorrhage in an uraemic subject taking low dose aspirin has been reported. In this work ASA related bleeding risk in uraemic patients and the effect of haemodialysis on their bleeding tendency was studied by measuring in vitro bleeding time (BT) using the Thrombostat 4000 in 34 uraemic patients on chronic haemodialysis compared to 50 healthy subjects. Our results indicate that low dose aspirin does not influence uraemic thrombopathia 8 to 10h after ingestion but seems to increase bleeding risk shortly after ingestion. Moreover, haemodialysis alters uraemic in vitro BT with regard to the time after ingestion of ASA.

Adult↗