Search PubMed⌕ Search

Biomedical subjects

S Schulman

Publications and source records attributed to S Schulman.

At least 19 recordsLinked to original sources
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↗
PubMed1999

Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized.

The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10. 75 of the patients started before the age of 3, 31 at the age of 3-5 and 15 at the age of 6-9. Each subgroup was evaluated separately. In addition, a regimen of one infusion weekly was compared with that of two (haemophilia B) or three (haemophilia A) infusions weekly in each patient. A significant decrease in the overall number of joint bleeds per year was found after shortening the infusion interval (P<0.005), but the individual bleeding pattern varied. In survival analysis of the first pathologic joint score event, those who started prophylaxis before the age of 3 had a better outcome overall than those starting at later ages (P=0.001). However, in subgroup analysis, no significant difference was seen in the annual number of joint bleeds and the development of arthropathy between those starting with, or shifting to, the more intensive regimen before the age of 3 and those that were put on this regimen at the age of 3-5. Age at start of prophylaxis was found to be an independent predictor for the development of arthropathy (P=0.0002), whereas dose and infusion interval at start were not. Our data emphasize the importance of starting replacement therapy during the first years of life. However, it seems that when beginning the regimen it can be individualized and adjusted according to the bleeding pattern. In this way, the need for a venous access system may be assessed on an individual basis.

Age Factors↗
PubMed1999

Efficacy of a high purity, chemically treated and nanofiltered factor IX concentrate for continuous infusion in haemophilia patients undergoing surgery.

We have evaluated the haemostatic efficacy of plasma derived, highly purified, solvent-detergent treated factor IX concentrate (Nanotiv), to which a nanofiltration step has recently been added to improve safety with regard to parvovirus B19, hepatitis A and other nonlipid enveloped viruses. Thirteen surgical procedures, including eight orthopaedic operations, were carried out using continuous infusion of Nanotiv in 10 haemophilia B patients (nine severe and one mild). Tranexamic acid was used for 11 of the 13 procedures. The mean factor IX levels on the day of surgery and postoperative days 1-3 were 0.77, 0.89, 0.80 and 0.73 IU mL(-1), respectively. The haemostatic effect was rated as normal or excellent and no blood transfusions were needed. One patient had thrombophlebitis twice at the infusion site. The remaining cases received heparin, 5 units per 100 IU of Nanotiv, and had neither superficial nor deep venous thromboembolic complications. The requirement for factor IX in the four joint replacement operations was 663 IU kg(-1) during the first 9 days, which compares favourably with previous materials. Thus, continuous infusion with this highly purified factor IX concentrate with improved viral safety is effective for surgery in haemophilia B.

Adolescent↗
PubMed1999

Oral anticoagulation in venous thromboembolism: decisions based on more than mere feelings.

Although there is a very limited scientific basis for the recommendation to target the intensity of oral anticoagulation after venous thromboembolism at an international normalized ratio (INR) of 2.0-3.0, this has been widely adopted. It seems possible from the DURAC I and II trials that a slight lowering of the upper limit could further reduce the risk of major haemorrhage. The optimal duration of anticoagulation in this group of patients has been extensively investigated. For the majority of patients a treatment duration of 6 months eliminates the high risk of relatively early recurrences without yielding an increase in the incidence of major haemorrhages. Patients with a distal deep vein thrombosis and a temporary risk factor or those with poor compliance should have a shorter treatment duration, whereas further prolongation is warranted in patients with certain biochemical abnormalities or recurrent thromboembolic episodes. The optimal treatment regimen is individualized, taking into account a variety of risk factors, and re-evaluated regularly in case of prolonged therapy.

Administration, Oral↗
PubMed1999

Characteristics of septic arthritis in human immunodeficiency virus-infected haemophiliacs versus other risk groups.

The cases are presented of four haemophiliacs infected with human immunodeficiency virus (HIV) and with septic arthritis among the 340 patients followed at our centre. The data of these cases and 39 additional HIV-infected haemophiliacs with septic arthritis, identified in a literature search, are reviewed. The spectrum of bacterial pathogens is limited and somewhat different from that in other risk groups. The localization is exclusively to joints affected by haemophilic arthropathy. The laboratory picture is characterized by the absence of peripheral leucocytosis, varying CD4-helper cell counts, a high erythrocyte sedimentation rate and fever. The clinical picture mimics that of haemarthrosis, often causing a delay in diagnosis. Treatment with systemic antibiotics is often sufficient, obviating the need for arthrotomy and open drainage. Prognosis related to the joint function is relatively good, but poor when related to the medium- to long-term survival of the patient.

Adult↗
PubMed1999

For how long should the treatment with vitamin K antagonists be maintained?

Studies have shown that in most patients with venous thromboembolism (VTE), continuation of treatment with vitamin K antagonists for up to 27 months significantly reduces the probability of recurrence. Likewise, prolongation of oral anticoagulation beyond 6 months is believed to be of benefit in patients with certain forms of hereditary thrombophilia. Very prolonged periods of treatment with vitamin K antagonists at standard doses, although conferring benefit regarding the risk of recurrence of VTE, are associated with an increased incidence of major bleeds and require intensive monitoring. Use of a lower intensity of anticoagulation may reduce these negative aspects and enable anticoagulation to be carried out for longer.

Administration, Oral↗
PubMed1999

Safety and efficacy of continuous infusion of a combined factor VIII-von Willebrand factor (vWF) concentrate (Haemate-P) in patients with von Willebrand disease.

We studied the safety and efficacy of treatment with continuous infusion of a von Willebrand factor (vWF) concentrate Haemate-P in patients with von Willebrand disease (vWD). Three patients with mild and 5 patients with severe forms of vWD, were treated with continuous infusion of Haemate-P by minipump. The indications for treatment were: to prevent bleeding during 9 surgical procedures or 1 vaginal delivery in 6 patients and to treat 2 bleeding episodes in 2 patients. The patients were monitored daily for factor VIII (FVIII:C) and ristocetin cofactor (vWF: RCo) levels and the infusion rate was adjusted to maintain the desired therapeutic level of vWF:RCo. The treatment was effective in preventing surgical bleeding and controlling bleeding episodes. All factor VIII:C and most of the vWF:RCo levels measured during the study period were above the target therapeutic levels. A significant decrease in clearance of FVIII:C and vWF:RCo was observed over the treatment period. Haemate-P consumption averaged 24.3+/-7.9 vWF:RCo U/kg/day which is approximately half the expected dose had intermittent bolus injections been used. We suggest that continuous Haemate-P infusion is superior to intermittent bolus injections for the treatment of vWD patients by virtue of its efficiency, simplicity and considerable savings.

Adolescent↗
PubMed1999

The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. DURAC Trial Study Group. Duration of Anticoagulation.

The results concerning the risk of recurrent venous thromboembolism (VTE) in carriers of the G1691A mutation in the coagulation factor V gene are not consistent and this risk in carriers of the G20210A polymorphism in the prothrombin gene has hitherto not been reported. We followed 534 patients for 48 months after their first episode of objectively documented VTE. The prevalence of the G1691A allele in 467 (87.5%) of the patients and in 207 controls was 25.3% and 8.2%, respectively, in heterozygote form and 2.4% and 0.5%, respectively, in homozygote form. The adjusted odds ratio (OR) for the first VTE was 4.4 (95% CI 2.6-7.8). The risk of recurrent VTE in heterozygotes was not statistically different from non-carriers (17.8% vs 17.6%), with 85% power to detect a hazard ratio of 2.35. Homozygotes had a significantly increased risk (p = 0.036) of recurrent VTE. The prevalence of the G20210A allele in 456 patients and 207 controls was 6.1% and 1.4%, respectively. The adjusted OR was 4.6 (95% CI 1.6-19.3) for the first VTE in 28 carriers of this polymorphism. The risk of recurrent VTE for these was not statistically different from non-carriers with an OR of 0.9 (95% CI 0.2-2.9).

Adolescent↗