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Biomedical subjects

W Streif

Publications and source records attributed to W Streif.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.

BACKGROUND: This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. METHODS: In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. RESULTS: As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION: During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.

Animals↗
PubMed2005

Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem): an in vitro study.

BACKGROUND: Precise coagulation monitoring might help prevent heparin-protamine mismatch and thus decrease postoperative blood loss. We therefore measured coagulation time (CT) by modified thrombelastography (Rotem) as a possible differential monitor of the effects of heparin and protamine. METHODS: Undiluted and diluted blood samples from 26 healthy volunteers were spiked with increasing concentrations of heparin (0.1, 0.2, 0.4, 0.8 and 1 U ml(-1)). In addition, undiluted blood was spiked with protamine hydrochloride (0.1, 0.2, 0.4, 0.8 and 1.6 U ml(-1)), and we tested the effect of protamine on the reversal of heparin 0.4 U ml(-1). Heparin-containing samples were analysed using the heparin-sensitive INTEM test and the heparinase-containing HEPTEM test; protamine series were also analysed with the EXTEM test (tissue factor activation). RESULTS: CT by the INTEM test [CT-INTEM; median (min/max)] increased significantly and dose-dependently with increasing concentrations of heparin [control, 175 s (146/226); heparin, 1.0 U ml(-1) 1320 s (559/2100); P<0.001] and protamine [control, 172 s (150/255); protamine, 1.6 U ml(-1) 527 s (300/1345); P<0.0001]. Up to heparin concentrations of 0.4 U ml(-1), results were similar in undiluted and diluted blood samples. As expected, CT-HEPTEM remained within the normal range for all tested heparin concentrations (median 180-183 s), but increased similarly to CT-INTEM for increasing protamine concentrations. CONCLUSION: CT measurement using the Rotem technique appears to be a valuable tool for heparin-protamine management. For detection of heparin alone, protamine alone and the two combined, the ratio of CT-INTEM:CT-HEPTEM can be used to distinguish the effects of heparin excess (CT-INTEM:CT-HEPTEM>1) from those of protamine excess (CT-INTEM:CT-HEPTEM=1).

Adult↗
PubMed2005

Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model.

BACKGROUND: This study was conducted to determine whether replacement of fibrinogen is useful in reversing dilutional coagulopathy following severe haemorrhage and administration of colloids. METHODS: In 14 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of gelatin solution to achieve dilutional coagulopathy. Animals were randomized to receive either 250 mg kg(-1) fibrinogen (n=7) or normal saline (n=7). A standardized liver injury was then inflicted to induce uncontrolled haemorrhage. Modified thrombelastography and standard coagulation tests were performed at baseline, after blood withdrawal, after dilution, after injection of the study drugs, and on conclusion of the protocol. Further, electron microscopy imaging of the blood clots was performed and blood loss after liver injury was determined. RESULTS: Severely impaired haemostasis was observed after haemodilution with gelatin substitution. With administration of fibrinogen, clot firmness and dynamics of clot formation reached baseline values. Median blood loss following liver injury was significantly less (P=0.018) in the fibrinogen-treated animals (1100 ml; 800-1400 ml) than in the placebo group (2010 ml; 1800-2200 ml). CONCLUSIONS: Replacing 65% of the estimated blood volume with gelatin in swine resulted in dilutional coagulopathy; subsequent fibrinogen administration improved clot formation and reduced blood loss significantly.

Animals↗
PubMed2004

[Monitoring of Perioperative Dilutional Coagulopathy Using the ROTEM Analyzer: Basic Principles and Clinical Examples].

Recent changes in quality of transfusion supply, transfusion triggers as well as fluid therapy promote the development of dilutional coagulopathy. Nevertheless, up to now guidelines generally assume presence of hypocoagulability when more than one individual circulating blood volume is lost. This might be true for some patients under some conditions but is not necessarily true for every patient. Routine coagulation tests are insufficient in predicting increased bleeding and, moreover, available after an unacceptable time delay. Therefore the occurrence of diffuse microvascular bleeding is often used as clinical sign to start hemostatic therapy. However, such severe derangement of hemostasis might lead to the development of secondary tissue damage and frequently is unresponsive to conventional treatment. Coagulopathy occurring during extensive surgery or after polytrauma can be detected and treated early when using the ROTEM monitoring. Recent data showing a direct beneficial effect of hemostatic therapy on blood loss and final outcome are scarce. However, evidence exists that the amount of blood loss, presence of coagulopathy and number of transfusions needed are associated with poor outcome in bleeding patients. Although manifold articles have been published already using thrombelastography for various indications (medline research "thrombelastography", 2022 articles), further data are needed to confirm the clinical experience that this technique is an excellent tool for safe patient management.

Autoanalysis↗
PubMed2004

[Dilutional coagulopathy, an underestimated problem?].

When no fresh frozen plasma is available, acute major blood loss is compensated above all with crystalloids, colloids and erythrocyte concentrates, meaning that all plasma clotting factors are diluted. Consumption coagulopathy is almost always accompanied by dilutional coagulopathy. Formulas for calculating critical blood loss and standard coagulation tests are often not helpful in the case of massive transfusion. On the other hand, systems suitable for point of care, such as thrombelastography, have important advantages. In the case of consumption and dilutional coagulopathy plasma coagulation is disturbed and critical values are first seen for fibrinogen. Not only is fibrin polymerization impaired by the bleeding-induced loss and dilution of fibrinogen, but also by interaction with artificial colloids, particularly hydroxyethyl starch preparations. Therapy of consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is not available in sufficient quantity or within a reasonable time, coagulation factor concentrates must be used. Neither fresh frozen plasma therapy nor treatment with coagulation factor concentrates has been the subject of detailed clinical study. Further studies are needed to work out guidelines for coagulation management in the case of massive blood loss.

Blood Coagulation↗
PubMed2003

Remifentanil and nitrous oxide reduce changes in cerebral blood flow velocity in the middle cerebral artery caused by pain.

BACKGROUND: Cerebral blood flow is affected by painful stimuli, and analgesic agents may alter the response of cerebral blood flow to pain. We set out to quantify the effects of remifentanil and nitrous oxide on blood flow changes caused by experimental pain. METHODS: We simulated surgical pain in 10 conscious volunteers using increasing mechanical pressure to the tibia. We measured changes in cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)) caused by the pain, using transcranial Doppler sonography. We gave increasing doses of remifentanil (0.025, 0.05 and 0.1 micro g kg(-1) min(-1)) or nitrous oxide [20%, 35% and 50% end-tidal concentration (FE'(N(2)O))] and compared these effects on blood flow changes. RESULTS: Nitrous oxide increased CBFV(MCA) only when given at 50% FE'(N(2)O). Remifentanil did not affect CBFV(MCA). Pain increased CBFV(MCA). Both agents attenuated this pain-induced change in CBFV(MCA) with the exception of nitrous oxide at 20% FE'(N(2)O). CONCLUSIONS: Inhalation of nitrous oxide or adminstration of remifentanil attenuated pain-induced changes in CBFV(MCA).

Adolescent↗
PubMed2003

Use of low molecular mass heparin (enoxaparin) in newborn infants: a prospective cohort study of 62 patients.

OBJECTIVE: To detail low molecular mass heparin (enoxaparin) use in the first few months of life. DESIGN: Prospective, consecutive cohort of unselected newborn infants. METHODS: Newborn infants were divided into groups by gestational age, underlying condition, hepatic and renal function, thrombocytopenia, and prothrombin time (PT/INR). Groups were analysed with respect to many aspects of enoxaparin treatment using multivariate methods. RESULTS: Sixty two newborn infants received enoxaparin representing 5.39 treatment years. Thromboembolic events (TEs) occurred predominantly in the lower and upper venous system in the presence of indwelling catheters (69%). Preterm infants required longer than full term infants to achieve an anti-(factor Xa) level in the target range (six versus two days). Preterm infants required higher doses of enoxaparin than full term infants to maintain anti-(factor Xa) levels in the target range (2.1 v 1.7 mg/kg/12 h). Infants with congenital heart disease (CHD) required less enoxaparin than those without CHD to maintain an anti-(factor Xa) level in the target range (1.7 v 2.1 mg/kg/12 h). Impaired renal and liver function influenced the number of dose changes needed (three versus one a month). Complete or partial resolution of TE was accomplished in 59% of newborn infants. Four infants developed major bleeds (1.2% per patient year). Recurrent TE and clot extension occurred in three infants (0.9% per patient year). CONCLUSIONS: Preterm infants are more difficult to treat with enoxaparin than full term infants. Enoxaparin appears to be an alternative to treatment with standard heparin or no treatment.

Anticoagulants↗
PubMed2000

[Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in 13 children: a case series].

Since thromboembolic events (TE) are rare among children there is only limited information on the optimal choice of antithrombotic agents, dose and duration of antithrombotic therapy. Recombinant tissue plasminogen activator (rt-PA) is increasingly used for thrombolytic therapy of organ- and limb threatening thrombosis in children. We investigated retrospectively the efficacy and safety of rt-PA in 13 children treated consecutively between 1996-1999, following the same protocol. The median age was 3.9 years (3 days to 16 years). All children suffered from underlying diseases. In addition, 7 children had cardiac catheters and central venous catheters and two children suffered from Factor V Leiden mutation. Seven children presented with a TE in the arterial system, 6 with one in the venous system. All children were treated with continuous infusion of rt-PA (median dose 0.05; 0.0125-0.2 mg/kg/h) together with low-dose standard heparin (median dose 8; 5-15 IU/kg/h). Thrombolysis was performed for a median time period of 102 hours (6 hours to 16 days). Treatment effects on the thrombus were regularly confirmed by ultrasound. Plasma levels of fibrinogen and haemoglobin decreased moderately during treatment. No cumulative effect or increased dose requirement of rt-PA was detected during extended treatment. Patency of obstructed vessels was achieved in all children. One child developed severe gastrointestinal bleeding. Six children (46%) developed minor bleeding at the site of catheter puncture. One child developed rethrombosis at the site of the previous thrombus 2 weeks after completion of rt-PA treatment. Under rigorous laboratory and ultrasound control, our protocol using low dose rt-PA over a prolonged period of time was effective and safe.

Adolescent↗
PubMed2000

Influence of exogenous factor VIIa on thrombin generation in cord plasma of full-term and pre-term newborns.

Factor (F) VIIa has been used to treat adults and children with a variety of bleeding disorders. The results from these studies cannot be extrapolated to newborns because their hemostatic system differs significantly from adults, which may influence the effects of FVIIa on thrombin (IIa) generation. We compared the effects of FVIIa concentrates on IIa generation in plasmas from adults, full-term newborns and pre-term newborns. Defibrinated plasma (using arvin) from adults, or umbilical cords from full-term or pre-term deliveries was supplemented with FVIIa (Novo Nordisk, Bagsvaerd, Denmark), mixed with dilute thromboplastin reagent, and the resultant reaction mixture subsampled periodically into ethylenediamine tetraacetic acid, followed by measurement of total IIa activity (S-2238). Thrombin-alpha2 macroglobulin complexes, determined as residual activity after neutralization with heparin and antithrombin, were subtracted from total IIa to give free IIa. Prothrombin (FII) and inhibitor complexes were measured by enzyme-linked immunosorbent assays. Addition of FVIIa caused a reduction in the lag phase for the appearance of free IIa and consumption of FII, which was more pronounced in newborn plasma. There was no increase in peak IIa levels regardless of the amount of FVIIa added. Final inhibitor complex concentrations were increased in plasmas from adults compared with newborns, likely reflecting higher plasma concentrations of FII in adults. Generation of IIa was more rapid in pre-term plasma compared with that in adult and full-term cord plasmas due to increased endogenous tissue factor (TF). In summary, FVIIa enhanced IIa generation in plasma from different age groups, with the effect being more pronounced in plasma from pre-term newborns, possibly due to increased levels of plasma TF.

Adult↗
PubMed1999

Analysis of warfarin therapy in pediatric patients: A prospective cohort study of 319 patients.

This study details warfarin use in a large pediatric population followed in a central anticoagulation clinic. A prospective, consecutive cohort of nonselected children were studied. Patients were divided into groups by age, target international normalized ratio (INR) range, disease, medications, and vitamin K supplemented enteral nutrition use. Groups were analyzed on multiple aspects of warfarin therapy using multivariate methods. A total of 319 patients received 352 warfarin courses representing 391 treatment years. Age independently influenced all aspects of therapy. When compared with all older children, the </=1 year of age group required increased warfarin doses, longer overlap with heparin, longer time to achieve target INR ranges, more frequent INR testing and dose adjustments, and fewer INR values in the target range. Although significantly different than children </=1 year, children 1 to 6 years of age showed the same findings when compared with 7- to 18-year-olds. Fontan patients required 25% decreased dosage as compared with other congenital heart disease patients. Children on corticosteroids had less INRs in the target range and children on phenobarbital/carbamazepine required increased maintenance dosages of warfarin. Also, patients receiving enteral nutrition required increased dosages of warfarin. Serious bleeding occurred in 2 children (0.5% per patient year). Recurrent thromboembolic events (TEs) occurred in 8 children. Two children had recurrences while receiving warfarin (1.3% per patient year). This study outlines the profound effect of age and relative complexity of clinical management of warfarin therapy in children.

Adolescent↗
PubMed1999

Spontaneous arterial thrombosis in children.

Spontaneous peripheral artery thrombosis in children is rare. We present 2 cases, in both of which the diagnosis was delayed. Acute arterial insufficiency should be considered in children who have clinical symptoms of leg pain, pallor, and reduced pulses. Angiography is the gold standard to confirm or exclude the diagnosis.

Aspirin↗
PubMed1999

Antithrombotic therapy in children.

Thromboembolic events are an increasingly common secondary complication in children who are successfully treated for serious, life-threatening primary diseases. In contrast to adults, thromboembolic events are rare enough in children to hinder clinical trials assessing optimal use of antithrombotic agents. Currently, pediatric patients are treated according to guidelines extrapolated from adults. However, optimal prevention and treatment of thromboembolic events in children likely differs from such treatment for adults. The following review summarizes the available information on commonly used antithrombotic agents in children, which include standard heparin, low molecular heparin, oral anticoagulants, thrombolytic therapy, antiplatelet agents, antithrombin concentrates, and protein C concentrates. The mechanisms, dosing, monitoring, therapeutic range, factors influencing dose-response relationship, and side effects are discussed.

Anticoagulants↗
PubMed1998

Venous thromboembolic events in pediatric patients. Diagnosis and management.

Venous thromboembolism is a rapidly increasing secondary complication in children being treated for serious, life-threatening, primary diseases. Most current management guidelines and recommendations for imaging techniques have been extrapolated from the results of trials in adults. This may be less than optimal for children as there are important differences. The purpose of this article is to summarize the information on venous thromboembolism in children, and offer some guidelines for diagnosis, prophylaxis, and therapeutic intervention based on the best available evidence.

Adolescent↗
PubMed1998

Factor V Leiden and prothrombin gene G 20210 A variant in children with ischemic stroke.

OBJECTIVE: To investigate if the factor V Leiden mutation (F-V-LM) and/or the prothrombin gene G 20210 A variant (P-G20210A-V) are risk factors for acute stroke in Austrian children. PATIENTS: 33 children with acute ischemic stroke documented by computer tomography and/or magnetic resonance imaging of the brain were enrolled in an open multicenter survey. RESULTS: 6/33 children had F-V-LM (5 heterozygous, 1 homozygous). This represents 18% (95% CI: 6.7-39.9%) of our pediatric stroke population and thus exceeds the expected prevalence in the Austrian population of 4,6% (Fischer's exact test, p = 0.01). F-V-LM was not found in 11 children with neonatal stroke but in 6/22 children with stroke after the neonatal period. 5/6 children with F-V-LM had an underlying disorder that is a risk factor for stroke in children. The P-G20210A-V was detected in 1/26 (3.85%; 95% CI: 0.1-21.4%) patients. Comparison of the prevalence of P-G20210A-V in our study with that in the general population of Austria of 1% revealed no statistical significance (Fischer's exact test, p = 0.38). CONCLUSION: Our data suggest that the F-V-LM is a risk factor for acute stroke in Austrian children beyond the neonatal period. The P-G20210A-V apparently does not represent a risk factor for stroke in Austrian children.

Activated Protein C Resistance↗
PubMed1997

Partial nephrectomy in a cystic partially differentiated nephroblastoma.

Cystic partially differentiated nephroblastoma (CPDN) is a rare neoplastic disorder consisting of a well-demarcated cystic lesion of the kidney where blastemal or other embryonic cells are present in the septa of the cysts. Magnetic resonance imaging can detect the cystic character of the lesion and will produce imaging features that are highly suggestive of either CPDN or cystic nephroma (CN) (synonym: multilocular cyst of the kidney), a benign entity. Although malignant potential exists in CPDN, all cases reported to date have had a favorable prognosis after surgery alone. Partial nephrectomy is considered safe, and the treatment of choice in the newborn period. We report a case of CPDN in a newborn that was successfully treated with partial nephrectomy. More than five years after nephron sparing surgery, the involved kidney shows normal anatomical structure except for a diminished upper pole, no evidence of tumor recurrence and good renal function.

Cysts↗
PubMed1997

Fibromuscular dysplasia of the internal carotid artery in a child with alpha-1-antitrypsin deficiency.

Fibromuscular dysplasia (FMD) is a non-inflammatory segmental arteriopathy of unknown origin. Most often the renal arteries are affected, however, also mesenteric, lumbar, vertebral, or carotid arteries may be involved. FMD has frequently been reported as a cause of stroke in adults, but very rarely in children. We report the case of an 11-year-old boy who presented with an ischaemic infarction in the anterior part of the territory of the left middle cerebral artery. Angiography demonstrated a 'string of beads' lesion suggestive of FMD causing occlusion at the origin of the middle artery. Laboratory analyses revealed the protease inhibitor (Pi) phenotype SZ (PiSZ) of alpha-1-antitrypsin deficiency as well as decreased antioxidants and signs of enhanced lipid peroxidation. Such an imbalance may be associated with diminished resistance to oxidation, possibly causing direct cellular and tissue injury. Whether alpha-1-antitrypsin deficiency and an impaired status of antioxidants, as seen in our patient, might play a role in the pathogenesis of FMD is presently unclear.

Antioxidants↗