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Biomedical subjects

B Sørensen

Publications and source records attributed to B Sørensen.

At least 19 recordsLinked to original sources

Whole blood thrombelastographic coagulation profiles using minimal tissue factor activation can display hypercoagulation in thrombosis-prone patients.

OBJECTIVE: Recently, our laboratory devised a dynamic whole blood (WB) thrombelastographic coagulation model employing activation with minute amounts of tissue factor. A series of studies were conducted to validate the feasibility of the model to illustrate hypocoagulation in various bleeding disorders and its usefulness in detecting the haemostatic effect of pro-coagulants by ex vivo titration experiments. In this context, the present study hypothesized that the thrombelastographic model also can reveal hypercoagulation. Hence, the objective of the present study was to record dynamic WB coagulation profiles in a series of patients (n=76) who had previously suffered from a venous (n=34) or arterial (n=42) thrombo-embolic event and to compare the results with those of a group of healthy reference subjects (n=60). MATERIAL AND METHODS: Patients receiving vitamin K antagonist treatment were not enrolled in the study. Forty-four of the patients had no known thrombophilia risk factor and 32 patients had at least one thrombophilia risk factor. RESULTS: The most commonly found risk factors were mild hyperhomocysteinaemia and heterozygosity for the factor V Leiden polymorphism. The data showed that, as compared with the healthy controls, patients with a history of venous or arterial thromboembolism had a significantly greater hypercoagulant WB coagulation clot signature as defined by a shortened clotting time together with an accelerated maximum velocity of clot propagation. CONCLUSIONS: In future studies with ex vivo dose titration assessment of pro-coagulant components mixed with blood from a patient suffering from compromised haemostasis, observation of a significantly shortened clot initiation concomitant with a distinctly accelerated clot propagation is likely to indicate an increased risk of thrombosis.

Adolescent↗

Acquired haemophilia: dynamic whole blood coagulation utilized to guide haemostatic therapy.

Acquired haemophilia is a rare bleeding disorder caused by autoimmune antibodies interacting with factor VIII (FVIII) or factor IX. Anticipating a high degree of heterogeneity amongst cases, we recently initiated systematic recording of whole blood (WB) coagulation dynamic profiles using our recently developed thrombelastographic method employing very small amounts of tissue factor for activation. Six newly diagnosed patients with acquired haemophilia A in our University Hospital were investigated with the purpose to characterize the WB clotting phenotypes in each patient, as well as inspecting the ex vivo and in vivo response to supplementation with various haemostatic agents. Our results show a striking heterogeneity in patients WB clotting profiles, each patient having a particular pattern and an individual type of response to bypassing agents. Profiles in some of patients resembled severe haemophilia A, even if there was a measurable residual FVIII:C activity while others were more similar moderate-to-mild haemophilia. In one case the profile was very close to normal. Each patient seemed to respond individually to bypassing agents. WB clotting profiles assisted us in selecting an optimal treatment modality in each case and whenever possible, we compared the clinical effects of the treatment selected with the appearance of the WB clotting pattern. In one patient, the ex vivo response to FVIII looked promising, and a approximately 200 IU kg-1 per 24 h high-dose programme nearly normalized the clotting profile in 2-week time. Our preliminary small series of data should be concluded with caution. However, it seems that WB clotting profile studies at baseline, with ex vivo addition of haemostasis promoting agents, and during treatment may hold the potential to predict the success of treatment.

Adult↗

New approaches for measuring coagulation.

Although specific assays of coagulation factors are essential for diagnostic purposes they only give partial information about an individual's haemostatic state. This can be better assessed by various global tests, and recent developments and evaluations of five such tests are described in this symposium: the PFA-100; waveform analysis; thrombin generation; overall haemostasis potential; thrombelastography. Each test has advantages in various applications, but the thrombin generation test and waveform analysis have been found most useful in haemophilia, whilst the PFA-100 is helpful in von Willebrand's disease.

Blood Coagulation Disorders↗

Tailoring haemostatic treatment to patient requirements - an update on monitoring haemostatic response using thrombelastography.

Currently, there is no single haemostasis laboratory test that has the capacity to accurately illustrate the clinical effects of procoagulant or anticoagulant interventions. Although the time course of thrombin generation in plasma and the endogenous thrombin potential (ETP) may be useful coagulation parameters, clotting involves components other than thrombin (e.g. platelets, fibrinogen). The continuous coagulation profiles of thrombelastography may provide a more accurate reflection of in vivo biology, covering initiation, development and final clot strength during whole blood clot formation. This method has helped to clarify the mechanism of action of whole blood clot formation, demonstrating the differences from clotting in plasma, and the importance of platelets and tissue factor titrations. It has also been used to investigate hypocoagulation (in haemophilia A, rare coagulation disorders, anticoagulant therapy and dilutional coagulopathy), hypercoagulation and the ex vivo testing of haemostatic interventions. Thrombelastography has been shown to reflect the clinical efficacy of activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) in patients with haemophilia A with inhibitors and in patients with acquired haemophilia. Overall, tailoring laboratory assays to illustrate and correlate with clinical phenotypes is essential for effective coagulation monitoring. Applying an algorithm of preoperative, perioperative and postoperative tests, including thrombelastography, may enable physicians to achieve this.

Algorithms↗

Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate.

BACKGROUND: Plasma substitutes such as hydroxyethyl starch (HES) and various dextrans may compromise the haemostatic system, thereby causing potentially dangerous bleeding. Whilst several mechanisms have been advanced to explain the nature of the coagulopathy induced by this colloid, there has been comparably little interest in devising ways to optimize haemostasis after a relative colloid overdose. METHODS: Real-time whole blood (WB) clot formation profiles were recorded using a thrombelastographic method employing activation with tissue factor. The coagulation tracings were transformed into dynamic velocity profiles of WB clot formation. WB from healthy individuals (n=20) was exposed to haemodilution of approximately 55% with isotonic saline, HES 200/0.5, HES 130/0.4, and dextran 70, respectively. Possible modalities for improvement of the induced coagulopathy were explored, in particular ex vivo addition of a fibrinogen concentrate. RESULTS: WB coagulation profiles changed significantly with decreased clot strength, and a compromised propagation phase of clot formation. The duration of the initiation phase of WB coagulation was unchanged. No statistical differences were detected amongst the HES solutions and dextran 70. However, dextran 70 returned a more suppressed clot development and strength compared with the HES solutions. Ex vivo haemostatic addition of washed platelets (75 x 10(9) litre(-1)) and factor VIII (0.6 IU ml(-1)) produced insignificant changes in clot initiation, propagation, and in the clot strength. In contrast, ex vivo addition of a fibrinogen concentrate (1 g litre(-1)) improved the coagulopathy induced by all of the three individual plasma expanders tested. CONCLUSION: Coagulopathy induced by haemodilution with either HES 200/0.5, HES 130/0.4, and dextran 70 may be improved by fibrinogen supplementation.

Adult↗

Thromboelastography and recombinant factor VIIa-hemophilia and beyond.

Thromboelastography (TEG), which records the continuous profiles of whole blood (WB) coagulation, can be used to evaluate the effects of hemostatic agents, such as recombinant factor VII (rFVIIa). Our group has developed a revised TEG model, involving activation with minute amounts of tissue factor and subsequent signal processing, and has used this method to evaluate the effects of rFVIIa both in patients with hemophilia and in those receiving vitamin K antagonist (VKA) thromboprophylaxis. We review the early results of our investigations, which suggest that, in clinical situations where rFVIIa has shown benefit, the changes in the profiles obtained by TEG recording appear to correlate with the clinical outcome.

Adult↗

Whole blood clot formation phenotypes in hemophilia A and rare coagulation disorders. Patterns of response to recombinant factor VIIa.

Until now, no routinely used clotting assay has demonstrated the power to reflect significantly a patient's response to recombinant factor (rF)VIIa. Adopting a thrombelastographic principle, profiles of continuous whole blood (WB) coagulation were studied in minimally altered WB activated with a small amount of tissue factor (TF). Investigation of the WB clotting profile was performed before and after ex vivo addition of rFVIIa 20 nm to WB from 26 patients with hemophilia A, two patients with severe hemophilia B, and individuals with deficiencies of FV, FX, FXI, and FXIII. In five patients with hemophilia plus inhibitors, the response to ex vivo added rFVIIa and to activated complex concentrate (APCC) was studied. Patients with severe and moderate hemophilia A demonstrated remarkable variance in the hemostatic characteristics at baseline, even in groups with the same FVIII:C activity levels. The response to rFVIIa at 20 nm also varied extensively, the effect correlating with the continuous WB coagulation phenotype at baseline. This indicates that the efficacy of rFVIIa may be optimized by tailoring the dose according to the hemostatic response to varying doses tested prior to in vivo administration. In patients with inhibitors against FVIII and factor IX, rFVIIa and APCC substitution resulted in quite similar response patterns that appeared to be dose dependent. In severe FV, FX, and FXIII-deficient WB, rFVIIa addition induced minor changes only. In FXI deficiency, rFVIIa normalized the dynamic properties of clotting, although a reduced clot firmness remained unchanged. In conclusion, the thrombelastographic analysis of WB clotting, as activated with a minute amount of TF, seems an interesting method that detects phenotypic variation amongst hemophilia patients. The method appears useful for assessment of the hemostatic capacity and it seems a promising tool for evaluation of the individual response to rFVIIa or APCC before and during in vivo administration.

Adult↗

Current treatment of von Willebrand's disease.

During the last couple of decades improved pathophysiological insight, use of improved diagnostic tools, and improved understanding of treatment requirements, have converged on an improved safety of treatment and quality of life for the patient suffering VWD. The scientific development in this area has elucidated a vast heterogeneity in VWD now appreciated as a vastly heterogeneous group of bleeding disorders. In some subtypes, dysfunctional VWF protein characteristics are clarified and logically linked with the distinct site of the VWF gene mutation abolishing specific functions of VWF, while in other subtypes such relationships have not yet been established. With the most frequently occurring variant, designated type 1, the quantitative loss in VWF seems to correlate with its reduced function. However, we are only at the beginning of the era of molecular genetics of this specific variant. Medical evidence based guidelines by ordinary standards for treatment of VWD do not exist. Therefore, treatment is based on a mechanistic approach and empirical knowledge. The review presented here focuses on the management of bleeding in VWD. Its basis is a mixture of data reported to literature and the authors' personal clinical observations. Our intention is the presentation and discussion of current issues related to VWD as well as the various pharmaceutical treatment options available for patients afflicted with von Willebrand's disease, together with some theoretical thoughts on possible future modalities.

Blood Platelets↗

Potential role of the dynamic properties of whole blood coagulation in assessment of dosage requirements in haemophilia.

In the clinical setting, patients suffering from haemophilia are classified according to the residual level of the deficient coagulation factor. Patients suffering from the severe form of haemophilia (critical factor level <0.01 IU mL-1) display some heterogeneity in their tendency to bleeding despite the uniform factor level. Utilizing a new thrombelastographic method in which coagulation is activated by very small amounts of tissue factor and where resulting data are processed with new software, we studied the whole blood coagulation profile in 11 patients with severe haemophilia A and 11 patients with moderate haemophilia. In both groups of patients, we found a considerable degree of heterogeneity in the coagulation signal. In moderate haemophilia with factor VIII (FVIII):C levels between 0.01 and 0.05 IU mL-1, variance was expected, whereas a quite substantial diversity had not been forecasted in patterns of the whole blood coagulation profiles in patients with the severe form of haemophilia A. Ex vivo substitution to patient's blood to reach various theoretical levels of recombinant factor VIII (rFVIII) revealed that the coagulation response to FVIII supplementation varied substantially. In some severely affected patients levels of FVIII:C close to 0.05 IU mL-1 was sufficient to normalize the coagulation profile, while others required a dose giving >0.50 IU mL-1 of FVIII to achieve a normal whole blood clotting profile. In conclusion, our study revealed that severe haemophilia A seems not to be a single entity, but rather several different clinical and biochemical phenotypes, and that the response to added FVIII varies amongst patients.

Blood Coagulation↗

Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women.

AIMS: To study if established diagnostic threshold values for gestational diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by maternal and perinatal outcomes. METHODS: Historical cohort study of 3260 pregnant women examined for gestational diabetes on the basis of risk indicators. Information on oral glucose tolerance test results and clinical outcomes were collected from medical records. RESULTS: There was an increased risk of delivering a macrosomic infant in women with 2-h capillary blood glucose of 7.8-8.9 mmol/l compared with women with 2-h glucose < 7.8 mmol/l. Despite treatment, 2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with increased rates of macrosomia, spontaneous preterm delivery, hypertensive complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more frequent in women with 2-h glucose > or = 11.1 mmol/l than in women with 2-h glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and perinatal complications increased with the diagnostic threshold for 2-h glucose. Large-scale blinded studies are needed to clarify the question of a clinically meaningful diagnosis of gestational diabetes mellitus. Until these results are available, a 2-h threshold level of 9.0 mmol/l after a 75-g oral glucose tolerance test seems acceptable.

Adult↗

Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation.

We investigated whole blood coagulation by thrombelastography (TEG) employing activation with minute amounts of tissue factor (TF). Continuous raw data captured were transformed into novel parameters, such as the maximum velocity (MaxVel) and the time to maximum velocity (t,MaxVel) of whole blood clot formation. The courses of the whole blood clot development were very similar to thrombin generation curves reported in plasma. In this assay healthy women (n = 30) showed an earlier onset and an increased coagulation velocity compared to healthy men (n = 30). In patients with severe hemophilia, and persons undergoing thromboprophylaxis, distinctly abnormal coagulation profiles were observed with a decrease in the MaxVel, as well as a prolonged t,MaxVel. Changes appeared to be dependent on the nature and severity of the hemostatic deficit. Preliminary studies in patients substituted with recombinant factor VIIa demonstrated a marked change in the coagulation profile, in which the MaxVel and t,MaxVel shifted towards normal in a dose-dependent way. Data suggest that the whole blood coagulation TEG profile, following activation with minute amounts of TF, may reflect the hemostatic potential in patients suspected of impaired hemostasis.

Adult↗

Natural carbon isotopes used to study methane consumption and production in soil.

Changes in the isotopic composition of carbon can be used to reveal simultaneous occurrence of methane production and oxidation in soil. The method is conducted in laboratory jar experiments as well as in the field by using flux chambers. Simultaneous occurrence of production and oxidation of methane was suggested.

Carbon Isotopes↗

Clinical impact of mild carbohydrate intolerance in pregnancy: a study of 2904 nondiabetic Danish women with risk factors for gestational diabetes mellitus.

OBJECTIVE: The objective was to study the clinical impact of mild carbohydrate intolerance in pregnant women with risk factors for gestational diabetes mellitus. STUDY DESIGN: This was a historical cohort study of 2904 pregnant women examined for gestational diabetes on the basis of risk factors. Information on oral glucose tolerance test results and clinical outcomes was collected from laboratory charts and medical records. RESULTS: The following outcomes increased significantly with increasing glucose values during the oral glucose tolerance test: shoulder dystocia, macrosomia, emergency cesarean section, assisted delivery, hypertension, and induction of labor. However, when corrections were made for other risk factors, hypertension and induction of labor were only marginally associated with glucose levels. CONCLUSION: In a group of nondiabetic pregnant women with risk factors for gestational diabetes, there was a graded increase in the frequency of shoulder dystocia and other maternal-fetal complications with increasing glucose levels during an oral glucose tolerance test.

Adult↗

[Occurrence of Enterobius vermicularis in children hospitalized at a central hospital].

The aim of the study was to determine the prevalence of EV among hospitalized children and to estimate if abdominal pain is related to EV-infestation. A perianal tape-test for identification of eggs of EV was done on 186 children, aged 1-17, hospitalized in the period 8.3.1996 to 31.12.1997. The children were separated into two groups: 123 children with abdominal pain, and 63 children with symptoms thought not to be related to EV (trauma, testicular retention and hernia). Clinical data were collected from case records. Altogether 40 children (22%) were infested with EV. Among 111 children aged 5-12 the prevalence was 32 (29%). No association was found between abdominal pain and infestation with EV. In conclusion, EV is a common disease among hospitalized children. According to this study there is no indication for routine perianal tape-test of children hospitalized for abdominal pain.

Abdominal Pain↗