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Biomedical subjects

L M Aledort

Publications and source records attributed to L M Aledort.

At least 19 recordsLinked to original sources
PubMed2004

The economic impact of factor VIII inhibitors in patients with haemophilia.

The impact on the cost of care for haemophilia patients with inhibitors is not well defined. To quantify the effect on health care expenditures associated with inhibitors to factor VIII (FVIII) or FIX, we conducted a retrospective cohort study examining product use and outcomes in adult and paediatric haemophilia patients with and without inhibitors. Twelve patients with inhibitors to FVIII or FIX (cases) identified in the haemophilia surveillance system (HSS) at two centres were matched on age, severity of haemophilia, and treatment centre to haemophilia patients without inhibitors. Patients with HIV or significant liver disease were excluded from the study. All eligible non-inhibitor control patients were selected for inclusion in the study, resulting in a total of 28 controls. We then tracked product usage and hospitalizations from programme entry until 1998 or loss to follow-up, producing a total database of 184 person-years of experience. A descriptive matched analysis was conducted to examine annual differences in the cost of product used and hospitalizations. We found that the median cost for factor products among haemophilia patients with inhibitors was $55,853/year, $2,760 less than comparable haemophilia patients without inhibitors. The median number of hospitalizations per year was 1.0 for both inhibitor and non-inhibitor patients and the median number of days hospitalized was virtually the same. Although these findings do not appear to support the belief that there is a substantial increase in the cost of care for haemophilia patients with inhibitors, it does document that a few outlier patients can drive the cost of treatment for this disease. As the largest component of the cost of care is that of factor concentrate, it becomes imperative in the current health care environment to better define the true costs and benefits of treatments designed to eradicate or manage inhibitors. A careful cost accounting of immune tolerance induction (ITI) and other therapeutic strategies, taking into account successes and failures and duration and intensity of therapy, should help to better define the costs and benefits of such approaches. Methods to identify high cost inhibitor patients should be developed so that these strategies may be targeted to appropriate candidates.

Adolescent↗
PubMed2002

The role of porcine factor VIII in the management of unexpected bleeding episodes.

The introduction of porcine factor VIII (pFVIII) has been an important addition to our armamentarium in the management of patients with inhibitors to FVIII. Case studies will be presented that offer important differential diagnoses. The prevalence and indications for the use of this biological replacement therapy will be discussed.

Adult↗
PubMed2002

Factors predictive of death among HIV-uninfected persons with haemophilia and other congenital coagulation disorders.

Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.

Adult↗
PubMed2001

Leukemia after liver transplant.

INTRODUCTION: Acute leukemia is rare after solid organ transplantation. METHODS: Review of data on 3 patients with acute leukemia identified among 1365 who underwent liver transplantation at our center, and a review of the literature. RESULTS: In patient 1, AML-M4 developed 19 months after transplant for cryptogenic cirrhosis. In patient 2, B cell acute lymphoid leukemia was diagnosed 10 months after liver transplant for fulminant hepatitis. Both patients had normal cytogenetics, and achieved complete remission with chemotherapy. In patient 3, acute monocytic leukemia-M3 with t(15;17) arose 18 months after transplant for hepatitis C cirrhosis. This patient received treatment with retinoic acid and chemotherapy, but developed a disseminated intravascular coagulation and died before completing therapy. No patient presented with chromosomal abnormalities commonly seen in secondary leukemia. The latency period to diagnosis after transplant was 10-19 months. CONCLUSIONS: Acute leukemia, although rare after liver transplantation, should be considered in the differential diagnosis of hematological complications.

Adolescent↗
PubMed2001

Hemophilia.

Explore the source record for details and available documents.

Blood Coagulation Factors↗
PubMed2001

Therapeutic choices for patients with hemophilia and high-titer inhibitors.

Effective treatment of bleeding episodes in hemophilia with high titer inhibitors (HTI) remains a challenge, despite the fact that the therapeutic armamentarium has expanded considerably over the past few years. Treatment safety has improved with the availability of porcine factor VIII (FVIII) and bypassing products such as recombinant factor VIIa (rFVIIa), and plasma-derived activated Prothrombin Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, and the risk of thrombosis. The proceedings of a one-day workshop of physicians who specialized in treating patients with hemophilia held in Vienna on May 13, 2000 have been summarized. In making a decision regarding the choice of product, physicians often consider the type of bleeding episode (life or limb threatening), age of the patient, volume of the reconstituted product, previous exposure to plasma derived products, cost, efficacy, and safety. For plasma naïve patients, to achieve rapid hemostasis a majority of the panelists used porcine FVIII (for patients who lack porcine inhibitory antibodies) or rFVIIa. For patients previously treated with plasma derived factors, in addition to the above concentrates, aPCCs were recommended. Although no data exists regarding safety and efficacy, switching products was routinely practiced either because of availability or cost. Furthermore, the panelists were uncertain about the efficacy of bypassing agents in the prevention of joint disease in inhibitor patients. The workshop participants felt that future research offers the best solution to resolve some of the dilemmas faced by clinicians and may help individualise treatment in a hemophilia patient with a high titer inhibitor.

Animals↗
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↗