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S Lethagen

Publications and source records attributed to S Lethagen.

At least 37 records · Page 2Linked to original sources
PubMed2001

[New in vitro analysis tested: bleeding time is still the best method for evaluation of primary hemostasis].

The need is great for a simple, cheap and readily accessible method for the evaluation of primary hemostasis in work-ups at both out-patient clinics and units caring for surgical or intensive care patients. PFA-100 is a recently introduced instrument for in vitro testing of platelet function. We report experiences from Stockholm, Gothenburg and Malmo of PFA-100 measurements performed on samples from healthy controls and from patients with von Willebrand disease or platelet disorders. It is shown that the PFA-100 system has a high sensitivity for von Willebrands disease, while the sensitivity for hereditary platelet dysfunction is low. In its present design this new device could not replace the template bleeding time as a screening test for primary hemostasis.

Bleeding Time↗
PubMed2001

Platelet activation by Shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome.

Thrombocytopenia caused by platelet consumption in thrombi is a major manifestation of hemolytic uremic syndrome (HUS) associated with Shiga toxin (Stx) producing Escherichia coli. Platelets have glycosphingolipid receptors capable of binding Stx, but a direct interaction between the toxin and platelets, leading to platelet activation, has not been reported. In this study, it is shown that Stx1 and its B (binding) subunit (Stx1B), at 10 pg/mL to 10 ng/mL, bound to platelets. Toxin was internalized in platelets within 2 hours. This led to increased platelet aggregation, as demonstrated by confocal microscopy. Preincubation of Stx1B with anti-Stx1 antibody inhibited this reaction. Stx1 induced morphologic changes in platelets seen on scanning electron microscopy. In the presence of platelets and tumor necrosis factor-pretreated human umbilical vein endothelial cells (HUVEC), Stx1 and Stx1B induced the binding of platelets to the endothelial cell membrane and were present at this binding site. Incubation of Stx1 and Stx1B with whole blood increased fibrinogen binding to platelets detected by flow cytometry. Fibrinogen binding was partially inhibited by preincubation with anti-Stx1. Stx1 increased platelet retention measured in a glass bead assay. In addition, plasma from 17 patients with HUS, taken during the acute phase of the disease, increased the retention of normal platelets and normalized after recovery. Taken together, the results of this investigation show that Stx1, Stx1B, and a factor or factors in the plasma of patients with HUS activate platelets. The presence of Stx1 at the binding site of platelets to HUVEC suggests that Stx may be directly involved in the prothrombotic state seen in HUS.

Adolescent↗
PubMed2001

Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.

Coagulants↗
PubMed2001

Clinical spectrum of hepatitis C-related liver disease and response to treatment with interferon and ribavirin in haemophilia or von Willebrand disease.

Our aim was to evaluate the severity of liver disease resulting from chronic hepatitis C in haemophilia or von Willebrand disease and the efficacy of 6 months treatment with interferon alpha and ribavirin. Fifty-five liver biopsies were performed in 43 patients without any bleeding complications, as seen with ultrasound immediately after the biopsy and 48 h thereafter. Histological changes were mild, with low scores for both inflammation and fibrosis, in spite of long exposure to blood products (mean 27 years). Two patients had compensated cirrhosis. Thirty-five out of 39 included patients completed study treatment. Hepatitis C virus (HCV)-RNA was negative in 77% (30/39) of patients at the end of treatment, and 36% (14/39) achieved a complete sustained response at follow-up 6 months after treatment. Treatment failure was more frequent in patients with virus genotype 1 compared with non-1 (P = 0.0003). The response rate correlated well with that of non-haemophilic patients. In summary: (1) liver biopsy was safe with our regimen; (2) liver disease in our patients was usually mild and had a slow progress; (3) only HCV genotype 1 predicted treatment failure; (4) our treatment results agreed with those from non-haemophilic patients.

Adolescent↗
PubMed2000

[Use the entire "analysis package" when investigating patients with venous thrombosis! Don't forget the relatives...].

During the last few years several genetic markers have been discovered that contribute to an increased risk of venous thrombosis. Patients who have several genetic markers are at a considerably higher risk of being affected than patients with only one marker. Recommendations are made as to which patients should be investigated, with appropriate laboratory analyses, when an increased risk of venous thrombosis is suspected. Most of the analyses can be done even if the patient is undergoing warfarin treatment.

Activated Protein C Resistance↗
PubMed2000

Correlation between different intensities of anti-vitamin K treatment and coagulation parameters.

In order to study the effect of different intensities of anti-vitamin K treatment on coagulation parameters, 23 patients with venous thromboembolism were given, after the initial treatment period, warfarin at doses giving an International Normalised Ratio of 1.3-2.0 for 4 weeks, and of 1.1-1.3 for another 4 weeks. Blood samples were taken at the end of each of these periods and 4 weeks after the end of warfarin treatment. The vitamin K-dependent coagulation factors VII, IX, and X, as well as the inhibitor protein C and its cofactor protein S, all showed a highly significant correlation with treatment intensity. This was to some extent also true for the coagulation activation markers, prothrombin fragment 1+2 and thrombin-antithrombin complex. Ratios of pro- and anticoagulant factors in some instances showed a decrease at therapeutical (International Normalised Ratio) levels, and also sometimes with reduced warfarin treatment intensity. Taken together, our results encourage further research addressing issues of varying treatment intensity with warfarin and alternative methods for monitoring of anti-vitamin K treatment.

Adult↗
PubMed2000

Effect kinetics of desmopressin-induced platelet retention in healthy volunteers treated with aspirin or placebo.

Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16-27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery.

Adult↗
PubMed2000

The Malmö model for immune tolerance induction: impact of previous treatment on outcome.

Ten patients, who had been treated according to the Malmö model for immune tolerance induction (ITI), were analysed regarding treatment with clotting factors and chemotherapy during the time period between inhibitor detection and ITI. Of the patients who were successfully rendered tolerant (n=6) all but one had received treatment with FVIII, either alone (n=1), or combined with cyclophosphamide (n=4). Of the patients who did not become tolerant, three of four had received treatment with FVIII during the inhibitor period but only one with FVIII and chemotherapy. The total amount of treatment received was in general much lower in the group that did not become tolerant. In individual cases, it appeared very clear that the inhibitor level and anamnestic response was substantially reduced prior to the ITI using the Malmö treatment model. We conclude that treatment of acute bleeds during the inhibitor period may be of importance for ITI and that the different response rates published for different immune tolerance regimens most likely do not reflect the true response rate for the respective regimen.

Adult↗
PubMed2000

Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty.

We performed a randomized double-blind study on the effect of tranexamic acid on postoperative blood loss and blood transfusions in 39 primary THR operations. Tranexamic acid was given at the end of the operation and 3 hours later. Ultrasound examination 1 week later was performed to measure the occurrence of deep hematomas. In contrast to previous findings in knee arthroplasty, the administration of tranexamic acid failed to give a significant reduction in the postoperative blood loss. This lack of effect was possibly related to the fact that the drug was administered too late. In 11 of the 20 patients receiving tranexamic acid, blood transfusion was not necessary, this being the case in 4/19 in the placebo group (p = 0.05). The occurrence of postoperative deep venous thromboses was similar in the tranexamic acid and placebo groups.

Aged↗
PubMed2000

Platelet retention in coronary artery bypass surgery with and without a heart-lung machine. Cause of thrombosis in coronary artery bypass surgery.

The aim of this study was to examine platelet function after coronary artery bypass grafting (CABG) with and without the use of extracorporeal circulation (ECC). Sixteen male patients scheduled for CABG with (n = 8) and without (n = 8) ECC were included in the study. Platelet retention, as measured with a glass-bead retention test, was examined daily during the first postoperative week. Von Willebrand factor (vWF), ristocetin co-factor (Rcof) and prothrombin fragment (PF 1 + 2) were analyzed the day after the operation. We found a significant increase (p < 0.0001) in platelet retention during the first postoperative week after CABG. There was a tendency (not statistically significant) towards a more pronounced increase in the group operated on without ECC. This increase occurred despite the fact that all patients were treated with aspirin (75 mg daily) from the first postoperative day. The median time to maximal postoperative platelet retention was 2 days. In 3 patients platelet retention increased to more than 6 times the basal level.

Adult↗
PubMed2000

NovoSeven in warfarin-treated patients.

Haemorrhages represent a major complication of treatment with vitamin K antagonists. In cases of severe bleeding, a prompt effect on the increased International Normalized Ratio value is vital to achieve haemostasis. As conventional treatment, that is plasma or plasma-derived concentrates, carries the risk of blood-borne virus transmission, new treatments are needed. An open, multicentre pilot trial is currently under way to determine the effect of recombinant activated factor VII (rFVIIa; NovoSeven) administered to patients experiencing a bleeding episode after receiving vitamin K antagonists. When rFVIIa was given to a patient with a warfarin-induced nosebleed, it had an immediate haemostatic effect and the International Normalized Ratio value virtually normalized.

Anticoagulants↗
PubMed1999

[Centralized care is the basis of care programs for hemophilia patients].

Haemophilia is a rare and potentially life-threatening disease. In Sweden, with a population of approximately 8.5 million, about 350 people suffer from the more severe forms of haemophilia or von Willebrand disease. Meticulous management is important if the patients are to be spared chronic disability and serious treatment complications. The disease is lifelong and affects psychosocial aspects of life among patients and their families. With the help of a grant from the Swedish Board of Halth and Welfare, a care programme has been designed to guarantee Swedish haemophiliacs comparable and optimal care. The programme has been drawn up by representatives of the three haemophilia centres in Sweden (at University Hospital, Malmö, Sahlgrenska University Hospital, Gothenburg, and Karolinska Hospital, Stockholm) in co-operation with the World Federation of National Haemophilia Organisations. To ensure optimal individual application of the programme, individualised management strategies and patient information leaflets have been prepared.

Centralized Hospital Services↗
PubMed1999

Desmopressin in the treatment of women's bleeding disorders.

Bleeding disorders in women are an underestimated problem that deserves increased attention. About 9%-14% of females have menorrhagia and, amongst them, there is a significant over-representation of von Willebrand disease (VWD), with a prevalence of 13% in this group as compared with about 1% in the general population. The bleeding disorder has not been diagnosed in most of these women and they may therefore be withheld from treatment with desmopressin, which is effective in most cases of VWD and also in platelet dysfunctions and mild factor VIII deficiency. This paper is a review of the haemostatic use of desmopressin with special reference to women's bleeding disorders, the mechanisms of action, modes of administration, clinical indications, dosage recommendations, and hospital or home treatment. Desmopressin stimulates endogenous release of FVIII and von Willebrand factor (VWF), it increases platelet adhesiveness and shortens bleeding time. It can be given as intravenous or subcutaneous injection, but the intranasal spray is probably the most practical mode of administration for females with bleeding disorders as it is simple to administer and suitable for home treatment. The spray has been used successfully in connection with menorrhagia and other bleeding symptoms.

Blood Loss, Surgical↗
PubMed1998

Antidiuretic effect of desmopressin given in hemostatic dosages to healthy volunteers.

The aim of this study was to characterize the magnitude and duration of the antidiuretic effects elicited by desmopressin given in hemostatic dosage intravenously (i.v.) (0.3 microg/kg) or intranasally (i.n.) (300 microg) both as single or repeated doses (four i.n. doses with 12-hr intervals) to healthy volunteers. Urine osmolality increased to a maximum median value of 1,087 mOsmol/kg after the single i.v. dose, 1,065 after the single i.n. dose, and 1,071 during the repeated i.n. dosing schedule, and did not differ significantly between the three dosage schedules. The increase lasted for 24 hr after single doses, and 12 hr after the last of the repeated i.n. doses. Serum sodium did not decrease more than normal diurnal variation after single doses, but decreased marginally below the normal reference range in three volunteers after repeated doses. Lowest median serum sodium concentrations after single i.v. and i.n. doses were 140 and 141 mmol/l, respectively, and 139 after repeated i.n. doses. Body weight changed only marginally after single doses, but increased 1.3 kg during repeated dosing. In adult healthy volunteers, single desmopressin doses give an antidiuretic effect lasting for about 24 hr. There is no difference in magnitude or duration between i.v. or i.n. doses. The effect is prolonged as long as the doses are repeated. Serum sodium is only marginally affected by single doses, but tends to decrease after four repeated doses with 12-hr intervals. If desmopressin is repeated for a period of up to 48 hr, fluid intake should be restricted to 2 liters per day in adults.

Administration, Intranasal↗
PubMed1998

Major surgery seems not to influence HIV disease progression in haemophilia patients.

The influence of major surgery on HIV disease progression and decline in CD4+ cell count was evaluated in 23 seropositive haemophilia patients. 24 HIV-infected patients served as non-operated controls. In addition, 32 age-matched seronegative subjects were included. The follow-up time was up to 5 years. During the course of the study, eight of the operated (35%) and 11 of the non-operated (48%) subjects developed HIV-related symptoms (P=0.267). The relative risk for developing HIV-related symptoms after surgery was 0.60 (95% CI 0.25; 1.48). A significant decline in CD4+ cell counts was observed in both the surgery (4.0 x 10(6)/l/month, 95% CI 2.0; 6.0 x 10(6), P=0.001) and the non-surgery (4.0 x 10(6)/l/month, 95% CI 2.0; 6.0 x 10(6), P=0.004) seropositive subgroup, but no difference between the two subgroups was seen (P=0.793). HIV (6.0 x 10(6)/l/month, 95% CI 2.1; 9.9 x 10(6), P=0.0005) but not surgery (-1.0 x 10(6)/l/ month, 95% CI -3.0; 0.96 x 10(6), P=0.647) was an independent predictor for the decline in CD34+ cell count. No interaction effect was observed between HIV infection and surgery (P=0.361). The annual amount of factor concentrate used for regular replacement therapy did not influence the decline in CD4+ cell count (P=0.492). We conclude that major surgery may be considered in symptom-free HIV-seropositive haemophilia patients, with CD4+ cell counts > or = 0.20 x 10(9)/l under similar premises as for seronegative subjects.

Adolescent↗