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Biomedical subjects

S Schulman

Publications and source records attributed to S Schulman.

At least 37 records · Page 2Linked to original sources
PubMed2003

Thrombosis in inherited factor VII deficiency.

Thrombosis in congenital factor (F) VII deficiency was investigated through extensive phenotypic and molecular-genetic studies. Patients with a history of thrombosis among 514 entries in the FVII Deficiency Study Group database were evaluated. Thrombotic events were arterial in one case, disseminated intravascular coagulation in another and venous in seven. Gene mutations were characterized in eight patients: three were homozygous, three compound heterozygous and two heterozygous. FXa and IIa generation assays were consistent with the genetic lesions. One patient was heterozygous for the FV Leiden and one for the FIIG20210A mutation. In seven patients, surgical interventions and/or replacement therapies had a close temporal relationship with thrombosis, while in the remaining, events were apparently spontaneous. Thromboses were not associated with any specific age, phenotype, mutation zygosity or thrombophilic abnormalities. In particular, severe FVII deficiency did not seem to offer protection from strong thrombosis risk factors such as surgery and replacement therapy.

Adolescent↗
PubMed2002

A randomized study of alpha-interferon plus ribavirin for 6 months or 12 months for the treatment of chronic hepatitis C in patients with bleeding disorders.

Little is known about the optimal treatment in patients with chronic hepatitis C virus (HCV) who were infected by pooled plasma products. The aim of our study was to compare the efficacy of 6 and 12 months of combination therapy with interferon alpha-2b and ribavirin in patients with bleeding disorders and chronic HCV. In a randomized open study, 61 patients with haemophilia or von Willebrand disease received treatment with a combination of interferon alpha-2b and ribavirin at standard dosage for 6 or 12 months. Follow-up was done with analysis of HCV RNA after an additional 6 months. The prevalence of HCV genotype 1 was 67%. Overall, sustained viral response was achieved in 41%; 13 of 30 patients (43%) treated for 6 months vs. 12 of 31 patients (39%) treated for 12 months. The rate of sustained response was 22% in those with HCV genotype 1 and 80% in other genotypes (100% in genotype 2), with no difference between the treatment durations. The number of early discontinuations due to side-effects was 3 and 9, respectively. The study was stopped prematurely due to introduction of a more effective regimen, and the numbers are not sufficient to state equality. We conclude that the efficacy and safety of combination therapy against chronic hepatitis C in patients infected by pooled plasma products is similar to that observed in other populations. Six months of therapy seems sufficient in the case of HCV genotype 2. For other genotypes, the decision regarding duration of therapy has to be based on the tolerance of the individual patient together with experiences from other studies.

Adolescent↗
PubMed2002

Acquired platelet dysfunction may be an aetiologic factor in Heyde's syndrome--normalization of bleeding time after aortic valve replacement.

BACKGROUND: There is a well-documented relationship, with unknown aetiology, between aortic valve stenosis and occult gastrointestinal bleeding in elderly patients. Despite several studies attempting to determine the prevalence and to discuss the aetiology, there are still many unanswered questions. METHODS: A total of 288 consecutive patients with valvular aortic stenosis--mean age 73 +/- 9 years aortic stenosis group (ASG)--were compared with 129 pacemaker-treated patients, mean age 73 +/- 9 years control group (CG). Screening for occult blood in stools was performed in both groups. Those with a positive Hemocult test or a history of gastrointestinal bleeding were scheduled for further examination including upper endoscopy and colonoscopy. Template bleeding time was performed on patients in both groups and in patients with a prolonged bleeding time with an extended coagulation evaluation was carried out. Patients referred to aortic valve replacement and with a preoperatively prolonged bleeding time were re-examined after surgery. RESULTS: There was a significant difference in the number of subjects with prolonged bleeding time between groups (ASG 19; CG 2; P = 0.028). Re-examination of the bleeding time after aortic valve surgery revealed normalized values in nine of 12 (P = 0.0003). The number of patients with positive Hemocult test did not differ between groups (ASG 29; CG 12; NS). Comparison of the pressure gradient over the aortic valve demonstrated a significantly higher maximal gradient amongst patients with a preoperatively prolonged bleeding time (113 mm HG vs. 90 mmHG; P = 0.005). CONCLUSION: Prolonged bleeding time is related to valvular aortic stenosis and seems to be caused by acquired platelet dysfunction. The normalization of the bleeding time after valve surgery supports the hypothesis that the calcified cusps may interact with the platelet function.

Aged↗
PubMed2001

Total thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and pro-TAFI in patients with haemophilia A.

Pro-thrombin-activatable fibrinolysis inhibitor (pro-TAFI), also known as TAFI, procarboxypeptidase U, or procarboxypeptidase B, is a relatively recently described plasma glycoprotein synthesized in the liver. It can be catalysed into its active form, TAFI (TAFIa, carboxypeptidase U or B) by a complex of thrombin/thrombomodulin. TAFI can potentially inhibit fibrinolysis by removing carboxyterminal lysine residues from partially degraded fibrin, decreasing plasminogen binding on the surface of fibrin, which thereby results in a decrease of the fibrinolytic activity. As TAFI represents a connection between coagulation and fibrinolysis, it can be expected that TAFI levels are altered in different thrombotic and haemorrhagic diseases, such as haemophilia A. Total TAFI antigen (including pro-TAFI, TAFI and the inactive form of TAFI [TAFIi]) and pro-TAFI were determined in 17 patients with haemophilia A. Thirteen healthy age-matched volunteers served as controls. No significant difference in levels of total TAFI antigen was observed between controls and patients with haemophilia, although it was slightly decreased in patients with haemophilia. Pro-TAFI was significantly reduced in haemophilia patients compared to controls (P=0.0113). TAFI antigen levels similar to controls have already been described in different clinical conditions, including haemophilia A. Decrease of pro-TAFI in haemophilia A can be an additional factor, together with decrease in thrombin generation, which induces impaired activation of pro-TAFI to TAFI, and could cause accelerated fibrinolysis. This supports the validity of usage of antifibrinolytics in the treatment of haemophilia A. In this paper we use new nomenclature for TAFI, and we believe that this recommended terminology for different forms of TAFI can simplify further standardization in TAFI investigation.

Adult↗
PubMed2001

Nocturnal enuresis in pediatric sickle cell disease.

To assess the prevalence of nocturnal enuresis in children and adolescents with sickle cell disease (SCD) and associated factors, structured telephone interviews were conducted with primary caregivers of 217 children and adolescents with SCD aged 5 years or older. Prevalence, perceived causes, interventions undertaken, and emotional impact were assessed. Nocturnal enuresis was significantly higher for males (28.2% of males) than for females (11% of females), p = .002, and compared with cited population prevalence rates, nocturnal enuresis was significantly higher for children with SCD, p < .01. SCD was the most common reason given by primary caregivers for enuresis. Primary caregivers used a wide range of interventions for nocturnal enuresis, but few used empirically supported treatments for enuresis or spoke with their health care team about the enuresis. These data suggest that systematic assessment and intervention for nocturnal enuresis must be implemented in the follow-up care of children and adolescents with SCD.

Adolescent↗
PubMed2000

Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial.

BACKGROUND: The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial. METHODS: In a prospective, randomized study of the duration of oral anticoagulation (six weeks or six months) after a first episode of venous thromboembolism, patients were questioned annually about any newly diagnosed cancer. After a mean follow-up of 8.1 years, we used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population. The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates, and the standardized incidence ratios were calculated. RESULTS: A first cancer was diagnosed in 111 of 854 patients (13.0 percent) during follow-up. The standardized incidence ratio for newly diagnosed cancer was 3.4 (95 percent confidence interval, 2.2 to 4.6) during the first year after the thromboembolic event and remained between 1.3 and 2.2 for the following five years. Cancer was diagnosed in 66 of 419 patients (15.8 percent) who were treated for six weeks with oral anticoagulants, as compared with 45 of 435 patients (10.3 percent) who were treated for six months (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The difference was mainly due to the occurrence of new urogenital cancers, of which there were 28 cases in the six-week group (6.7 percent) and 12 cases in the six-month group (2.8 percent) (odds ratio, 2.5; 95 percent confidence interval, 1.3 to 5.0). The difference in the incidence of cancer between the treatment groups became evident only after two years of follow-up, and it remained significant after adjustment for sex, age, and whether the thromboembolism was idiopathic or nonidiopathic. Older age at the time of the venous thrombosis and an idiopathic thromboembolism were also independent risk factors for a diagnosis of cancer. No difference in the incidence of cancer-related deaths was detected. CONCLUSIONS: The risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following two years. Subsequently, the risk seems to be lower among patients treated with oral anticoagulants for six months than among those treated for six weeks.

Administration, Oral↗
PubMed2000

Molecular genetic analysis of severe protein C deficiency.

Severe protein C deficiency is a rare, early onset, venous thrombotic condition that is inherited as an autosomal recessive trait. The protein C (PROC) genes of nine unrelated individuals with severe protein C deficiency were sequenced yielding a total of 13 different lesions. Eight of these were novel, including a gross gene deletion, three missense mutations, two micro-deletions, a splicing mutation and a single base-pair substitution in the HNF-3 binding site in the PROC gene promoter. Evidence for the pathogenicity of the mutations detected was obtained by molecular modelling, in vitro splicing assay and reporter gene assay. Neither the plasma protein C activity level nor the nature of the PROC gene lesions detected were found to be a good prognostic indicator of the age of onset or clinical severity of thrombotic symptoms. Other factors may thus complicate the relationship between genotype and clinical phenotype. Indeed, in two patients, the inheritance of either one or two Factor V Leiden alleles in addition to two PROC gene lesions could have served to precipitate the thrombotic events. No association was however apparent between clinical severity and the possession of a particular promoter polymorphism genotype. Despite the absence of a clear genotype-phenotype relationship, the molecular genetic analysis of the severe recessive form of protein C deficiency potentiates both the counselling of affected families and the provision of antenatal exclusion diagnosis.

Alternative Splicing↗
PubMed2000

The risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg. The DURAC Trial Study Group.

OBJECTIVES: To investigate the risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg. DESIGN: An open prospective long term follow-up multicentre trial. Patients were followed by frequent outpatient visits at each centre during the first 12 months after inclusion and thereafter annually. SETTING: Sixteen hospitals in central Sweden. SUBJECTS: A total of 790 consecutive patients with objectively verified first episode of acute deep vein thrombosis and without diagnosed malignant disease were recruited from a randomized study comparing 6 weeks with 6 months of oral antivitamin K therapy as secondary thromboprophylaxis. MAIN OUTCOME MEASURES: Deep vein thrombosis in the contralateral leg was confirmed by venography or ultrasound. With regard to the ipsilateral leg, venography was required. RESULTS: A recurrent episode of venous thromboembolism was documented in 192 patients after a mean (+/-SD) period of 31(+/-29) months. In 26 additional patients with ipsilateral symptoms the diagnostic critera were not fulfilled. One hundred and eleven patients have deceased and 69 patients withdrew from the study. The 392 patients without recurrent episodes were followed for a median of 96 months with 90% for at least 48 months. An objectively verified recurrent contralateral and ipsilateral deep vein thrombosis occurred in 95 and 54 cases, respectively, and in 41 patients pulmonary embolism was documented. In two patients thromboses with unusual locations were registered. The risk of contralateral versus ipsilateral recurrence was significantly increased with a risk ratio of 1.6 (95% confidence interval 1.4-1.9) in a time to event model. In a multivariate analysis none of the investigated variables were significantly associated with the side of recurrent thrombosis. CONCLUSIONS: The risk of a recurrent deep vein thrombosis is increased in the contralateral leg. This brings into question the importance of an impaired venous flow for recurrent episodes of thrombosis.

Aged↗
PubMed2000

Continuous infusion of recombinant factor VIIa in hemophilic patients with inhibitors: safety, monitoring, and cost effectiveness.

The continuous infusion of recombinant activated factor VII (rFVIIa) was first described in 1996. Because of the significant benefits in convenience and cost that can be achieved with this mode of administration compared with bolus doses, the method was quickly adopted, albeit with many local variations. Some of those have been less favorable, resulting in hemorrhagic complications. The potential pitfalls and experiences from a large number of cases collected in an international registry of continuous infusion with rFVIIa are reviewed. The only indications discussed here are hemophilia A or B with inhibitors or acquired hemophilia. Different recommendations may apply for other indications.

Autoantibodies↗
PubMed2000

Duration of anticoagulants in acute or recurrent venous thromboembolism.

While the most recent trend in secondary prophylaxis after venous thromboembolism has been toward a prolonged duration, it has become obvious that individualization according to risk factors is crucial. Subgroup analyses in a long-term follow-up of a previous trial, as well as new trials on patients with idiopathic thromboembolism, have now improved our base of evidence. Many studies on the influence of biochemical factors in the risk of recurrence have also been published recently. This review should be helpful in-the individual decision on how to tailor the duration of anticoagulation.

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↗