Acquired haemophilia in cancer: A systematic and critical literature review.

AIM: There is a paucity of data on the clinical presentation and management of cancer patients with acquired haemophilia (AH), we here report a systematic literature review on acquired haemophilia in the context of cancer. METHODS: Treatment outcomes of AH were defined as complete response (CR), partial response (PR) or no response (NR), based on inhibitor eradication, coagulation factor VIII levels and bleeding control. Reported deaths were either related to cancer or bleeding. RESULTS: Overall, 105 cases were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age was 68 years for both males (range 37-86 years) and females (range 43-89 years), 39 patients were female subjects and 66 were males. A solid cancer was diagnosed in 60 subjects, while 45 patients suffered a haematological malignancy. Solid cancers affected mainly males; however, the incidence of solid tumours vs haematological malignancies was not statistically significant (P = .09). Not all patients were treated for their underlying cancer, bleeding and/or inhibitor, in two cases outcome is unavailable. CR was reported in 62.1% (64/103) cases, PR in 9.7% (10/103) cases, NR with or without death was reported in 28.1% (29/103) cases. CONCLUSION: CR was best achieved when successful and complete elimination of autoantibodies occurred contemporaneously with the successful treatment of the underlying malignancy. In some cases, recurrent autoantibodies were harbingers of relapsed cancer. Type of cancer, inhibitor titer, treatments administered for bleeding control and inhibitor eradication did not significantly affect clinical outcome of analyzed cases.

Methodologies for data collection in congenital haemophilia with inhibitors (CHwI): critical assessment of the literature and lessons learned from recombinant factor VIIa.

AIMS: To systematically review the effectiveness of on-demand treatment with recombinant coagulation factor VIIa (rFVIIa) in congenital haemophilia with inhibitors and, if feasible, perform a meta-analysis of the data. MATERIALS AND METHODS: Publications from Embase® , MEDLINE® , MEDLINE® In-Process and the Cochrane Central Register of Controlled Trials were searched. Selected publications were reviewed for inclusion by two independent expert reviewers. Discrepancies were reconciled by a third independent reviewer. Data from selected studies were extracted using a predefined grid to ensure uniform and comparable results were captured. RESULTS: A systematic search (cut-off date of 2 May 2016) identified 20 studies (13 observational; seven randomized controlled trials). All studies were of sufficient quality to include in this analysis and comprised 1221 participants, with 5981 bleeds in 746 individuals treated with rFVIIa. Haemostatic overall effectiveness of the individual studies identified ranged from 68% to 100% at ≤12 hours, 86% to 96% at 13-24 hours and 76% to 99% at 24-48 hours with rFVIIa <100 µg/kg, with similar rates reported for the ≥250 µg/kg dose. However, heterogeneity between the studies precluded pooling of results. CONCLUSIONS: Data from the individual studies confirmed that rFVIIa is an effective therapy for the on-demand treatment of bleeds in congenital haemophilia with inhibitors. However, the high levels of heterogeneity between studies precluded pooling of results for a valid, reliable or precise summary measure. There remains a need to implement standardized clinical definitions and measurements for the effectiveness and safety of haemophilia therapies in future clinical trials.

Lenalidomide as a novel therapy for gastrointestinal angiodysplasia in von Willebrand disease.

INTRODUCTION: Lenalidomide is a thalidomide analog with anti-angiogenic properties. Previous case reports suggest its efficacy in preventing gastrointestinal bleeding (GIB) secondary to angiodysplasia (AD) in hereditary haemorrhagic telangiectasia and potentially in reversing AD. We present the first case series to explore lenalidomide as a treatment for AD-related GIB in patients with von Willebrand disease (VWD). METHODS: A retrospective chart review was conducted to include patients with VWD, who were evaluated from 2010 to 2013 and who had received lenalidomide to treat recurrent GIB secondary to AD. All patients had failed single-agent use of antifibrinolytic agents. Patients were observed for at least 2 years on therapy. RESULTS: Five patients (3 males; 68.2 ± 4.9 years) with VWD (3 with type 3 and 1 each with types 1 and 2a) and AD were found. Sites of AD included the stomach, duodenum, jejunum and colon. Lenalidomide was started at 5 mg oral daily. Uptitration to 10 and 15 mg in 1 patient each was necessary due to recurrence of GIB. The mean number of endoscopies performed for control of GIB post lenalidomide was significantly lower compared to pretherapy (0.25 vs 5.50; P = .001). Mean bleed-free duration on lenalidomide was 12.6 ± 4.7 months. Three patients have reported no GIB on lenalidomide. CONCLUSION: This case series demonstrates significantly reduced number of endoscopies and increased bleed-free duration with lenalidomide treatment in selected patients with VWD and recurrent GIB from AD. Prospective multicenter trials are needed to further define the role of lenalidomide in the management of GIB from angiodysplasia and VWD.

Efficacy and safety of Nuwiq® (human-cl rhFVIII) in patients with severe haemophilia A undergoing surgical procedures.

INTRODUCTION: Haemophilia A patients are at a high risk of excess bleeding during surgeries. The aim of haemostatic therapy during the perioperative period is to normalize FVIII level perioperatively and postoperatively to maintain normal haemostasis until wound healing is complete. AIMS/METHODS: To examine the efficacy of Nuwiq® (simoctocog alfa, human-cl rhFVIII), a 4th generation recombinant FVIII produced in a human cell line, for surgical prophylaxis in patients with severe haemophilia A. This analysis assessed the efficacy of Nuwiq® during surgical procedures and in the postoperative period in seven clinical studies of previously treated patients (PTPs) with severe haemophilia A. RESULTS: Thirty-six patients, aged 3-55 years, received surgical prophylaxis with Nuwiq® for 60 surgeries (28 major and 32 minor). Efficacy was evaluated for 52 surgeries (25 major and 27 minor). The success rate of Nuwiq® treatment was 98.1% (51 of 52 evaluated surgeries); haemostatic efficacy was assessed as "excellent" or "good" in all but one major surgery (assessed as "moderate"). The number of infusions ranged from 1 to 19 for minor surgeries and from 3 to 76 for major surgeries. The median (range) daily doses were 42.0 (28.2-100.9) IU kg-1 for minor surgeries and 69.3 (43.3-135.6) IU kg-1 for major surgeries. There were no serious treatment-related adverse events, and none of the patients developed FVIII inhibitors. CONCLUSIONS: The results of this pooled analysis show that Nuwiq® was efficacious in maintaining haemostasis during and after major and minor surgical procedures in PTPs with severe haemophilia A.

Efficacy and safety of a VWF/FVIII concentrate (wilate® ) in inherited von Willebrand disease patients undergoing surgical procedures.

INTRODUCTION: Surgical procedures in von Willebrand disease (VWD) patients may require prophylactic treatment with exogenous von Willebrand factor (VWF) and coagulation factor VIII (FVIII) to prevent excessive bleeding. Wilate® is a plasma-derived, double virus-inactivated, highly purified, freeze-dried VWF/FVIII concentrate, containing both factors in a physiological activity ratio of 1:1. AIM: To investigate the efficacy and safety of wilate® in maintaining haemostasis in VWD patients undergoing surgical procedures. METHODS: This prospective, open-label multinational clinical study documents 28 individuals who underwent 30 surgical procedures managed with wilate® . Twenty-one patients had VWD Type 3, and 21 surgeries were major. Efficacy was assessed intra- and postoperatively by the surgeon and investigator, respectively, and adjudicated by an Independent Data Monitoring Committee, using an objective scale based on blood loss, transfusion requirements and postoperative bleeding and oozing. Treatment success (primary endpoint) was determined using a composite assessment algorithm and was formally assessed. RESULTS: Surgical prophylaxis with wilate® was successful in 29 of 30 procedures. The overall rate of success was 96.7% (98.75% CI: 0.784, 1.000). All 21 surgeries in patients with VWD Type 3 were managed successfully. There was no accumulation of VWF or FVIII after multiple dosing, and no thromboembolic events or inhibitors to VWF or FVIII were observed. CONCLUSIONS: Wilate® demonstrated effective prevention and treatment of bleeding in inherited VWD patients undergoing surgery, with no clinically significant safety concerns.

Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

INTRODUCTION: Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain. AIM: To assess self-reported prevalence, description and management of pain in adult males with mild-to-severe haemophilia and history of joint pain/bleeding. METHODS: Participants completed a pain survey and five patient-reported outcome instruments assessing pain, functional impairment and health-related quality of life (HRQoL). RESULTS: Of 381 participants enrolled, median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65% were overweight/obese. Many (56%) were not receiving routine infusions; 30% never received routine infusions. During the prior 6 months, 20% experienced acute pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed (30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti-inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice (65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common opioid for both acute/chronic pain (30%); other long-acting opioids were infrequently used specifically for chronic but not acute pain (morphine, 7%; methadone, 6%; fentanyl patch, 2%). CONCLUSION: Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused.

US experience with recombinant factor VIIa for surgery and other invasive procedures in acquired haemophilia: analysis from the Hemostasis and Thrombosis Research Society Registry.

INTRODUCTION: Acquired haemophilia (AH) is a rare disorder caused by autoantibodies against factor VIII. AIM: The Hemostasis & Thrombosis Research Society (HTRS) Registry was used to monitor the safety of recombinant FVII (rFVIIa). This study aims to report data from the HTRS Registry regarding safety and efficacy of rFVIIa for haemostatic management of surgeries and other invasive procedures in patients with AH. METHODS: For each rFVIIa-treated procedure, the initial dose, total dose, average infused dose, number of doses and treatment duration were calculated. Efficacy was assessed on a 4-point scale. RESULTS: Of 166 registered patients with AH, 37 patients underwent 58 procedures [30 (51%) rFVIIa-treated]. The median (range) age of all patients undergoing procedures was 70 (13-93) years; for rFVIIa-treated patients, 74 (28-89) years. Approximately 67% (39/58) of all procedures were elective. Overall, the most common procedures were endoscopy (12) and central venous access device (10); rFVIIa was used preoperatively (11), postoperatively (13) and during six follow-up procedures during ongoing postoperative rFVIIa treatment. The median (range) initial dose was 90.0 (44-187) µg kg(-1) preoperatively and 106.0 (56-270) µg kg(-1) postoperatively. For rFVIIa-treated episodes with a reported outcome, 20 (91%) were rated excellent/good or no additional agents used and 2 (9%) were rated as poor/ineffective requiring a switch to another bypassing agent. No thromboembolic events were reported. CONCLUSIONS: Adequate haemostasis was provided for 91% of rFVIIa-treated procedures at doses largely conforming to the package insert. No safety concerns were reported.

Von Willebrand factor for menorrhagia: a survey and literature review.

BACKGROUND: von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. METHODS: We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. RESULTS: Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg(-1) on day 1-6 of menstrual cycle. CONCLUSIONS: This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings.

Managing chronic pain in adults with haemophilia: current status and call to action.

Haemophilic arthroses are associated with acute pain during bleeding episodes and with chronic pain caused by arthritic complications of repeated bleeding into joints. Unlike other conditions (e.g. osteoarthritis, rheumatoid arthritis, sickle cell disease), there are limited data on pain management in haemophilia. Management of arthritic individuals and those with sickle cell disease relies heavily on administration of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. In haemophilia, acetaminophen often has limited efficacy at therapeutic doses, offering a narrow dosing range in those with liver disease due to chronic hepatitis C. NSAIDs can effectively manage pain in patients with haemophilia, but these agents are potentially associated with a significant risk of precipitating or exacerbating bleeding complications in an already coagulopathic population. Opioids have proven effective in osteoarthritis and sickle cell disease, but outcomes data in those with haemophilia are virtually non-existent. Patients with haemophilia are at least as vulnerable as other chronic pain populations to opioid-related adverse events and to developing abusive behaviours and addiction. Despite pain management strategies for patients with haemophilia being far from optimal, the predominant precept of haemophilia management still applies. As such, it is critically important to aggressively reverse or prevent acute symptomatic bleeding in a timely and effective manner to at least minimize pain and progressive joint damage. This review should serve as a call to action to prioritize pain management in haemophilia care and spur interest in the development, improvement and standardization of tools to assess and manage acute and chronic pain in haemophilia.

Factor VIII alloantibody inhibitors: cost analysis of immune tolerance induction vs. prophylaxis and on-demand with bypass treatment.

Development of inhibitors (alloantibodies to exogenous factor VIII) is the most significant treatment complication in patients with haemophilia A. The only proven way to eradicate inhibitors is through immune tolerance induction (ITI), while bypassing agents are typically employed to treat or prevent bleeds in patients with high titre inhibitors. Costs of these approaches have not been well studied. The aim of this study was to compare lifetime costs of treating patients with severe haemophilia A with inhibitors using on-demand or prophylaxis treatment with bypassing agents and ITI. A decision-analytic model was developed to compare the treatment costs and outcomes. Quantitation of the reduction in bleeding events for patients on prophylaxis and after eradication of inhibitors when on ITI and relapse of inhibitors was derived from published studies. Costs were obtained from standard US costing sources and are reported in 2014 US dollars. Costs and outcomes were discounted 3% per annum. Lifetime costs of treating patients with inhibitors are lower for ITI vs. on-demand or prophylaxis. Patients are also projected to live longer, have greater quality-adjusted life-years, and have fewer bleeding events than patients treated on-demand. Treating patients via ITI to eradicate inhibitors may result in lower lifetime costs and greater life-years and quality-adjusted life-years than treating with bypassing agents.

ITI choice for the optimal management of inhibitor patients - from a clinical and pharmacoeconomic perspective.

The development of alloantibody inhibitors against factor VIII (FVIII) represents the most significant complication of haemophilia care. Inhibitors tend to develop early in the course of treatment in about 20-30% of patients with severe haemophilia who receive on-demand or prophylactic FVIII therapy. Many factors are associated with inhibitor formation, including disease severity, major FVIII gene defects, family history and non-Caucasian race, as well as age at first treatment, intensity of early treatment, use of prophylaxis and product choice. As these latter treatment-related variables are modifiable, they provide opportunity to minimize inhibitor incidence at the clinical level. Data from the Bonn Centre in Germany have indicated an overall success rate of 78% for immune tolerance induction (ITI) therapy, with a failure rate of 15% and with some treatments either ongoing (3%) or withdrawn (4%). Similarly, data from the G-ITI study, the largest international multicentre ITI study using a single plasma-derived (pd) FVIII/von Willebrand factor (VWF) product, have demonstrated success rates (complete and partial) in primary and rescue ITI of 87% and 74%, respectively, with 85% of poor prognosis patients achieving success. Favourable clinical results based on success rates and time to tolerization continue to be reported for use of pdFVIII/VWF in ITI, with pdFVIII/VWF having a particular role in patients who require rescue ITI and those with a poor prognosis for success. Data from prospective, randomized, controlled clinical studies, such as RES.I.ST (Rescue Immune Tolerance Study), are eagerly awaited. Another factor to consider with ITI therapy is cost; preliminary data from an updated decision analytic model have provided early evidence that ITI has an economic advantage compared with on-demand or prophylactic therapy.

Prophylaxis in real life scenarios.

Prophylaxis has become the standard mantra of care for those individuals with severe haemophilia A and B. Primary prophylaxis is advocated to prevent the occurrence of symptomatic acute spontaneous haemarthroses and to preserve joint structure and function. Typically, twice or thrice weekly infusions of factor VIII or IX concentrates are integral to this treatment approach. Secondary prophylaxis is initiated after the relentless cycle of progressive joint damage has been triggered by prior haemarthroses and is intended to preserve existing joint health by preventing additional spontaneous bleeding events. Event-driven prophylaxis involves the administration of clotting factor concentrates to prevent acute traumatic bleeds, which are anticipated to occur in association with surgical or physical trauma. This regimen enhances the effectiveness of primary or secondary prophylaxis protocols or on-demand approaches to replacement therapy. Besides the marked reduction in the so-called annual bleed rate, prophylaxis regimens frequently increase personal self-confidence to embark on a more active and physical lifestyle; however, in reality, prophylaxis must be individualized in accordance with bleeding phenotypes, with the unique pharmacokinetic profile of administered replacement clotting factor concentrates, with the specific clinical scenario, and with the degree of intensity anticipated for any physical activity. The introduction of extended half-life replacement products will also influence how these prophylaxis regimens will be accomplished. The following scenarios will discuss how prophylaxis regimens can be implemented to protect the individual from developing spontaneous and activity-induced acute bleeding complications and to maintain an improved quality of life.

Cardiovascular comorbidities are increased in U.S. patients with haemophilia A: a retrospective database analysis.

There is conflicting evidence in the literature on whether individuals with haemophilia in the USA have greater, reduced, or similar risks for cardiovascular disease as the general population. This study evaluated the prevalence of cardiovascular comorbidities among USA males with haemophilia A, relative to an unaffected general male population with similar characteristics. Males with haemophilia A and continuous insurance coverage were identified by ICD-9-CM code 286.0 (1 January 2007-31 December 2009) using the MarketScan Commercial and Medicare Research Databases. Individuals with haemophilia A were exact matched 1:3 with males without a diagnosis of haemophilia A. The prevalence of cardiovascular comorbidities identified by ICD-9-CM code was determined for matched cohorts. Of the study population, 2506 were grouped in the haemophilia A cohort and 7518 in the general cohort. Proportions of individuals with haemorrhagic stroke (2.0% vs. 0.5%, P < 0.001), ischemic stroke (4.7% vs. 2.7%, P < 0.001), coronary artery disease (10.7% vs. 5.8%, P < 0.001), myocardial infarction (0.8% vs. 0.3%, P = 0.003), hypertension (22.6% vs. 15.5%, P < 0.001), hyperlipidaemia (15.9% vs. 11.9%, P < 0.001), arterial thrombosis (12.1% vs. 5.9%, P < 0.001), and venous thrombosis (4.4% vs. 1.1%, P < 0.001) were significantly greater for the haemophilia A cohort. Results were consistent across most age groups, and comorbidities appeared at an earlier age in those with haemophilia A than in the general population. Among the USA haemophilia A population cardiovascular comorbidities are more prevalent and they appear earlier in life in comparison to the general male population, suggesting the need for earlier, enhanced screening for age-related comorbidities in the haemophilia community.

The challenge of pain evaluation in haemophilia: can pain evaluation and quantification be improved by using pain instruments from other clinical situations?

Pain is a critical aspect in the lives of individuals with congenital haemophilia A or B. Initially, pain serves as a warning sign for an active bleeding event; however, after multiple bleeding episodes, pain may become chronic, debilitating, and distracting. It is essential that pain instruments be developed and validated for use in persons with haemophilia, especially in paediatric cohorts, so that new therapies to treat acute bleeds can be assessed in a standardized manner. This review evaluates the existing pain instruments utilized in the English language haemophilia literature and compares their features and practicality with instruments published for other clinical pain scenarios associated with non-coagulopathic disease states, such as cancer and surgical convalescence, in paediatric, adolescent, and adult populations. In clinical trials involving haemophilia cohorts, few pain instruments have been validated. Only one instrument has addressed pain specifically in individuals less than 16 years of age. In contrast, multiple instruments have been applied extensively to other pain situations, especially in the paediatric oncology area, where the age range extends to less than 3 years. We conclude that trials quantifying pain in haemophilia would benefit from the addition and validation of instruments in use in other pain situations. Suggestions for modifying the pain instruments currently used in haemophilia are presented, specifically to address paediatric haemophilia cohorts.

MASAC Consensus Conference: impediments to conducting clinical research in persons with haemophilia, von Willebrand's disease and rare bleeding disorders.

A consensus conference conducted by the Medical and Scientific Advisory Council of the National Hemophilia Foundation was held in New Orleans, LA, on November 11, 2010, to discuss the impediments to conducting clinical research in persons with haemophilia, von Willebrand's disease and rare bleeding disorders. The conference combined presentations providing academic, non-profit and industry perspectives with periods of open discussion. The objective of this conference was to identify the many challenges involved in facilitating U.S. Food and Drug Administration approval of innovative products for these patient populations.

Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE).

Recent data from the Dosing Observational Study in Hemophilia diary study has described home treatment with recombinant activated factor VII (rFVIIa) in congenital haemophilia with inhibitors (CHwI). The current analysis compares prescribed and patient/caregiver-reported rFVIIa administration in paediatric and adult CHwI patients in this study. Patients with ≥ 4 bleeding episodes within a 3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were eligible. Patients/caregivers completed a diary for ≥ 90 days or until the patient experienced four bleeds. Initial, total and mean rFVIIa doses reported for each bleeding episode were calculated and compared with the physician-prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%) completed the study. Children and adults had similar mean durations of bleeding episodes. Both patient groups were administered higher initial rFVIIa doses for joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs. 200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs. 123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but children received significantly more doses per joint bleed than adults (median 6.5 vs. 3.0). The median total dose per joint bleed was higher in children than adults (1248.7 vs. 441.6). For children and adults, both initial and additional doses administered for bleeds were higher than prescribed. Children received higher total doses per bleed due to an increased number of infusions per bleed.

Health care expenditures for Medicaid-covered males with haemophilia in the United States, 2008.

Although haemophilia is an expensive disorder, no studies have estimated health care costs for Americans with haemophilia enrolled in Medicaid as distinct from those with employer-sponsored insurance (ESI). The objective of this study is to provide information on health care utilization and expenditures for publicly insured people with haemophilia in the United States in comparison with people with haemophilia who have ESI. Data from the MarketScan Medicaid Multi-State, Commercial and Medicare Supplemental databases were used for the period 2004-2008 to identify cases of haemophilia and to estimate medical expenditures during 2008. A total of 511 Medicaid-enrolled males with haemophilia were identified, 435 of whom were enrolled in Medicaid for at least 11 months during 2008. Most people with haemophilia qualified for Medicaid based on 'disability'. Average Medicaid expenditures in 2008 were $142,987 [median, $46,737], similar to findings for people with ESI. Average costs for males with haemophilia A and an inhibitor were 3.6 times higher than those for individuals without an inhibitor. Average costs for 56 adult Medicaid enrollees with HCV or HIV infection were not statistically different from those for adults without the infection, but median costs were 1.6 times higher for those treated for blood-borne infections. Haemophilia treatment can lead to high costs for payers. Further research is needed to understand the effects of public health insurance on haemophilia care and expenditures, to evaluate treatment strategies and to implement strategies that may improve outcomes and reduce costs of care.

Healthcare expenditures for males with haemophilia and employer-sponsored insurance in the United States, 2008.

Although hemophilia has a potentially high economic impact, published estimates of health care costs for Americans with hemophilia are sparse and non-specific as to the non-bleeding complications of the disease. The objective of this study is to estimate average annual health care expenditures for people with hemophilia covered by employer-sponsored insurance, stratified according to the influence of age, type of hemophilia [A (factor VIII deficiency) versus B (factor IX)], presence of neutralizing alloantibody inhibitors and exposure to blood-borne viral infections. Data from the MarketScan Commercial and Medicare Research Databases were used for the period 2002-2008 to identify cases of hemophilia and to estimate mean and median medical expenditures during 2008. A total of 1,164 males with hemophilia were identified with continuous enrollment during 2008, 933 with hemophilia A and 231 with hemophilia B. Mean health care expenditures were $155,136 [median $73,548]. Mean costs for 30 (3%) males with an inhibitor were 5 times higher than for males without an inhibitor, approximately $697,000 [median $330,835] and $144,000 [median $73,321], respectively. Clotting factor concentrate accounted for 70%-82% of total costs. Average costs for 207 adults with HCV or HIV infection were 1.5 times higher than those for adults without infection. Hemophilia treatment is costly, particularly for individuals with neutralizing alloantibody inhibitors who require bypassing agents. Efforts to understand the cause of inhibitors are needed so that prevention strategies can be implemented and the excess costs resulting from this serious complication of hemophilia care can be avoided.