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Biomedical subjects

S Schulman

Publications and source records attributed to S Schulman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1999

The effect of the duration of anticoagulation and other risk factors on the recurrence of venous thromboembolisms. Duration of Anticoagulation Study Group.

BACKGROUND: In order to find the optimal balance of anticoagulation, avoiding recurrent events as well as major hemorrhage, it is important to know the impact of different risk factors over time. METHODS: Based on a randomized, multicenter trial on different durations of anticoagulation after a first episode of venous thromboembolism, the probability of recurrence over 6 years of follow-up was analyzed. The contribution of the site of the thrombus, the nature of the triggering risk factor and the presence of cardiolipin antibodies to the risk of recurrence was also calculated. RESULTS: There is a cumulative risk of recurrence of 4 to 5% per year, which continues through year 6 after the index event, independent of the initial duration of anticoagulation. Deep vein thrombosis proximal to the knee joint or symptomatic pulmonary embolism confers a risk of recurrence that is higher than of distal thrombosis but equal to the risk when the triggering factor is permanent or unknown. The combination of proximal deep vein thrombosis or symptomatic pulmonary embolism and permanent/unknown triggering factor increases the risk, and the presence of cardiolipin antibodies generates an additional risk in all subgroups. CONCLUSION: It is necessary to tailor the duration of anticoagulation individually, according to the presence of different risk factors.

Antibodies, Anticardiolipin↗
PubMed1998

Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Duration of Anticoagulation Study Group.

PURPOSE: To compare the risk of recurrent venous thromboembolism in patients with and without antiphospholipid antibodies. PATIENTS AND METHODS: Anticardiolipin antibodies were tested 6 months after a first or second episode of venous thromboembolism. Of the patients with a first episode of venous thromboembolism only the 412 who received 6 months of anticoagulation were studied. Two hundred and eleven patients with a second episode received oral anticoagulation for 6 months or indefinitely. The therapy was targeted at an international normalized ratio (INR) of 2.0 to 2.85. All patients were followed up for 4 years after enrollment. RESULTS: Among the 412 patients with a first episode of venous thromboembolism the risk of recurrence was 29% in patients with anticardiolipin antibodies and 14% in those without antibodies (P = 0.0013). In those with antibodies, there was an increased risk during the first 6 months after cessation of anticoagulation. The risk of recurrence increased with the titer of the antibodies. Four-year mortality rate was 15% in those with antibodies and 6% in those without (P = 0.01). Among 34 patients with a second event of venous thromboembolism and anticardiolipin antibodies, there were no recurrences during anticoagulant therapy versus 20% in those who received only 6 months of treatment (P = 0.08). CONCLUSIONS: The presence of elevated titers of anticardiolipin antibodies 6 months after an episode of venous thromboembolism is a predictor for an increased risk of recurrence and of death. Patients with anticardiolipin antibodies and venous thromboembolism seem to benefit from prolonged oral anticoagulation.

Aged↗
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↗
PubMed1998

Safety, efficacy and lessons from continuous infusion with rFVIIa. rFVIIa-CI Group.

Continuous infusion with coagulation factor concentrates has only been widely adopted during the last decade and with recombinant activated factor VII (rFVIIa) only during the last 2 years. Still the accumulated number of days on continuous infusion with this product amounts by now to more than one year, 35 patients and 26 surgical procedures. The experience is reviewed here and compared with data from the conventional bolus dose regimen.

Factor VIIa↗
PubMed1998

Hepatitis C virus-infected, HCV-RNA-negative patients with bleeding disorders--relationship to age, HIV and treatment.

All 155 anti-hepatitis C-virus (HCV) positive patients with haemostatic disorders at our unit were tested for HCV-RNA in order to determine the prevalence of a negative result. The patients were also characterized in order to find predictors for a negative HCV-RNA test. The prevalence of a negative HCV-RNA test was 15.5% (24 of 155) and this was similar among anti-HIV positive and negative patients. A common denominator for the 4 HIV-infected, HCV-RNA negative haemophiliacs was treatment with azidothymidin prior to the first test. Among the anti-HIV negative patients, those < 40 y of age had a significantly greater chance of being HCV-RNA-negative than the older ones (27.3 vs 3.6%). They also had a lower consumption of plasma products than age-matched HCV-RNA positive cases. Absence of co-infection with hepatitis B was not correlated with a negative HCV-RNA test. Young age and a low requirement for factor concentrates thus seem to be predictors for a negative HCV-RNA test in patients with bleeding disorders.

Adolescent↗
PubMed1998

Long-term prophylaxis in venous thromboembolism: LMWH or oral anticoagulation?

Warfarin remains the standard drug for secondary prophylaxis following venous thromboembolism, however this treatment is not ideal. In patients for whom monitoring is problematic or who have a high risk of bleeding complications, other possible solutions have been explored. Unfractionated heparin has been used to a limited extent in these situations and requires dose adjustment in order to achieve an acceptable efficacy. Low-molecular-weight heparin (LMWH) is a valuable alternative to warfarin for these patients and for thromboprophylaxis during pregnancy. In several subgroups of patients with venous thromboembolism the use of a LMWH instead of warfarin could offer specific advantages. The combination of warfarin and LMWH is warranted in patients for whom it is predicted that warfarin treatment alone may fail. The optimal dose of LMWH in long-term prophylaxis has not been evaluated in a properly designed study and the optimal duration of prophylaxis with LMWH is thought to be similar to that for warfarin.

Administration, Oral↗
PubMed1998

Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study.

PURPOSE: Prior studies show that increased levels of the DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT), also referred to as O6-alkylguanine-DNA alkyltransferase (AGT) correlate with the resistance of glioma cell lines to nitrosoureas. The observed nitrosourea sensitivity of MGMT-deficient lines (methyl excision repair negative [MER-]) and those repair-proficient lines pretreated with MGMT-specific inhibitors (eg, O6 benzylguanine) has raised the possibility that tumor MGMT levels may be an important predictor of survival in patients with gliomas. PATIENTS AND METHODS: We correlated the MGMT level in malignant astrocytoma tissues, obtained from patients treated with radiotherapy and bis-chloroethylnitrosourea (BCNU) on a prior prospective trial (Southwest Oncology Group [SWOG] 8737), with overall and failure-free survival. RESULTS: Of 64 assessable patients with malignant astrocytoma (63% glioblastoma, 37% anaplastic astrocytoma), 64% had high (> 60,000 molecules/nucleus) MGMT levels. The overall median survival for patients with high versus low MGMT levels was 8 and 29 months, respectively (P=.0002), and median failure-free survival 3 and 6 months, respectively (P=.008). Subset analysis by histology (high v low MGMT levels) for anaplastic astrocytoma was 14 versus 62 months (n=24) and for glioblastoma was 7 versus 12 months (n=40). The overall hazards ratio (risk for death) for high versus low MGMT levels was 3.41; in young patients, the hazards ratio was higher (age 18 to 40 years, 4.19; age 41 to 60 years, 3.08) but became equal by MGMT level at age older than 60 years (1.11). Multivariate analysis showed that MGMT was independent of other known prognostic factors (age, performance status, histology). CONCLUSION: The MGMT level in tumor tissue specimens may be a predictive marker of survival in patients with malignant astrocytoma that is independent of other previously described prognostic variables.

Adult↗
PubMed1998

Experiences with continuous infusion of recombinant activated factor VII.

A questionnaire was sent to 28 haemophilia treatment centres known to have used recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), to collect data on continuous infusion of this product. This mode of administration was recently introduced for rFVIIa but there are several questions which remain to be answered in order to optimize this technique. Of the 26 responding centres, 14 had used rFVIIa in continuous infusion for 40 treatment episodes over a total of 283 days. In most of the cases the treatment was targeted at a factor VII level of 10 IU/ml, monitored by the one-stage clotting assay. This seemed to be adequate for most of the haemorrhagic and surgical procedures. Pretreatment pharmacokinetic evaluation was performed in only a minority of the cases but is probably of great importance given the wide variation observed in the clearance values. A strategy was necessary to prevent local thrombophlebitis, at least for infusions in peripheral veins; parallel infusion of heparin, saline or dextrose-saline proved effective. The question of optimal monitoring needs further attention. Haemorrhagic complications were significantly less frequent when treatment was combined with the antifibrinolytic tranexamic acid.

Drug Monitoring↗