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Biomedical subjects

L M Aledort

Publications and source records attributed to L M Aledort.

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

Making a therapeutic choice: human versus recombinant fractions - can we do it?

New manufacturing methods have resulted in production of higher purity human-derived products and recombinant factors with less human- or animal-derived reagents or stabilizers for the treatment of congenital coagulation disorders. In addition, new viral inactivation processes are being used to reduce the chance of viral contamination. Preferred treatment approaches are moving toward using newer-generation agents. At the same time, rationale exists for continuing fractionation of all types of products, based on considerations including cost, product availability, safety issues, and specific clinical situations for which a recombinant or high-purity product is not available. These issues and others are reviewed in the context of making a therapeutic choice.

Blood Coagulation Factors↗
PubMed2001

Unexpected bleeding disorders.

Patients with known coagulation deficiencies, either congenital or acquired, may bleed spontaneously with trauma or with surgical intervention. In contrast, however, are the unchallenged patients who bleed in a variety of clinical settings that demand rapid diagnosis so that appropriate therapy can be instituted. In the first section Dr. Louis M. Aledort demonstrates a series of vignettes of actual cases who presented with unexpected bleeding or a screening laboratory abnormality prior to a needed surgical intervention. Settings include dental, oral surgical, obstetrical, surgical and gynecological. The differential diagnoses of these cases are discussed. In the second section Dr. David Green also uses vignettes to demonstrate how the laboratory is used to differentiate the various clinical entities. The choice and priority of required tests indicated by the settings, history, site and type of bleeding, and the syllogisms used to define the abnormality are stressed. In the third section, Dr. Jerome Teitel reviews in detail the therapeutic armamentarium available to the clinician and presents algorithms for the management of these bleeding disorders.

Adult↗
PubMed2000

Obstetrical and gynaecological bleeding: a common presenting symptom.

Excessive haemorrhage is one of the commonest symptom when women present to obstetricians and gynaecologists. In the majority of cases the cause is related to the primary obstetric and gynaecological pathology and is easily identified. However, less commonly, the bleeding is unexpected and due to an undiagnosed underlying coagulation defect, the commonest of which is von Willebrand (vWD) disease. Menorrhagia is a common, and may be the only, clinical manifestation of an inherited bleeding disorder. Screening 150 women with menorrhagia, vWD was diagnosed in 13% of patients and other hereditary haemorrhagic disorders in another 4%. Menorrhagia with onset at the menarche was predictive of an inherited bleeding disorder in 65% of vWD and 67% of FXI deficient patients. Therefore, testing for bleeding disorders should be considered in women with menorrhagia especially those with early onset and no obvious pelvic pathology. Childbirth and puerperium present a special risk for excessive haemorrhage. The risk of postpartum haemorrhage is very high in women with inherited bleeding disorders. In our centre, the incidence of primary and secondary postpartum haemorrhage was 22% and 11% in carriers of haemophilia 18.5% and 20% in vWD and 16% and 24% in FXI deficient women, respectively. Acquired haemophilia can be an unusual cause of severe and unexpected postpartum haemorrhage with a very high mortality rate. Unexplained postpartum and postoperative haemorrhage that does not respond to general measures should alert clinicians to the possibility of bleeding disorders as a causative factor. In addition, increased awareness among obstetricians and gynaecologists of these less common causes and close collaboration with the local haemophilia centre and availability of management guidelines are essential for optimal outcome.

Adult↗
PubMed2000

Factor VIII inhibitors. Immune tolerance induction: is it cost effective? We know too little.

The development of an inhibitor in a hemophiliac is a serious clinical problem. Many inhibitors have high titers, and thus one cannot guarantee hemostasis. The prevalence of this transfusion-transmitted disease reaches as high as 35%, even with newer products. The costs of product use for inhibitor patients are significantly higher than for those without an inhibitor. For more than 20 years, using the concept of antigen overload, several regimens have existed for the induction of immune tolerance to eradicate these inhibitors. Registries exist reviewing the results of these regimens in the United States and internationally. Although much has been garnered about predictors of outcomes, we have much to learn about who the ideal candidates are, what optimal regimens are, and when to stop, as well as how to maintain a success. The costs of managing an inhibitor patient with and without human immunodeficiency virus (HIV) have caused managed care programs to seriously challenge the use of these regimens. Data are needed to provide the cost benefit of immune tolerance.

Cost-Benefit Analysis↗
PubMed1999

Phenotypic expressions of CCR5-delta32/delta32 homozygosity.

OBJECTIVE: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-delta32/delta32 homozygous genotype has phenotypic expressions other than those related to HIV-1. DESIGN: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-delta32/delta32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-delta32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. RESULTS: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-delta32/delta32 study subjects. Based on blood pressure measurement and treatment history, CCR5-delta32/delta32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were approximately 20% higher in CCR5-delta32/delta32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-delta32/delta32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-delta32 genotype. CCR5-delta32/delta32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. CONCLUSIONS: CCR5-delta32/delta32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-delta32/delta32 homozygosity does not provide broad protection against viral infections.

Adult↗
PubMed1998

Unsolved problems in haemophilia.

Diagnosis and therapy for the vast majority of haemophiliacs in the world remain beyond their reach. Health care costs for hemophilia replacement products keep rising. Global inequities for financing health care result in most hemophiliacs being undertreated. The transfusion-transmitted disease, factor VIII inhibitors, is common. Its predictability escapes detection. Management has progressed substantially and offers many therapeutic modalities. Programs for prophylaxis or immune tolerance induction are impossible for most patients. Thus, the challenge for haemophiliacs is to attain these goals.

Costs and Cost Analysis↗
PubMed1998

Prophylactic use of factor VIII: an economic evaluation.

BACKGROUND: Since the introduction of exogenous factor VIII therapy, several studies have explored the clinical benefits of prophylactic use of factor VIII. Little research, though, has focused on the economic aspects of this regimen. We conducted a cost analysis using data from the Orthopedic Outcomes Study, a prospective, cross-national study of the clinical outcomes associated with different patterns of factor VIII utilization to examine the health care costs incurred and expenditures averted in patients receiving on-demand versus prophylactic use of factor VIII in hemophilia. METHODS AND ANALYSIS: 831 patients with severe hemophilia aged 1 to 31 years, from 19 centers around the world were included in the cost analysis. Patients were categorized into three groups according to the number of weeks during the study years in which they received prophylactic regimens of factor VIII. For each subject, we estimated the costs of hospitalization, surgery, days lost from school or work, and factor VIII utilization. Costs were then stratified by age and by joint score to assess confounding, and a multivariate model developed to determine the relationship between use of factor VIII prophylaxis and total costs, while controlling for potential confounders. RESULTS: Patients who received factor VIII episodically incurred substantially greater disability-related costs (days lost from school or work, days hospitalized due to hemophilia, surgery) than patients who received factor VIII prophylactically for some or all of the study period. For all treatment regimens, most disability-related costs were accounted for by hospitalization for hemophilia-related conditions. The cost of factor VIII itself was substantial in all treatment categories but was highest among patients who received year-round prophylaxis, exceeding the savings resulting from reduced disability and other health care expenditures. CONCLUSIONS: Reductions in non-factor health care costs and disability associated with prophylactic use of factor VIII in hemophilia were substantial and helped somewhat to offset the much higher costs of this regimen. For certain subgroups, frequent episodic treatment may be more expensive than full-time prophylaxis. However, because of the very high cost of year-round prophylactic use of factor VIII, total health care expenditures were highest among patients receiving this therapeutic regimen. However, because prophylaxis clearly offers important clinical benefits, this approach may be warranted on medical rather than economic grounds.

Adolescent↗
PubMed1998

Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors.

OBJECTIVE: To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN: Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered. RESULTS: Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported. CONCLUSION: rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.

Adolescent↗