Factor for felons: how can we provide haemophilia care to the incarcerated?

OBJECTIVES: In 2011, 6.98-million offenders were documented in the adult correctional system, with state operating costs designated 12% towards medical care ($11.97 day per inmate) for the general population. Common co-existing health problems identified are: arthritis (13%), hypertension (11%), asthma (10%) and heart problems (6%). Less than 5% of inmates have health issues related to cancer, diabetes, liver or renal problems and communicable diseases. The leading cause of death is suicide (33.2%), followed by heart disease (26.1%). Despite these statistics quality is lacking. Given these statistics, one would expect that a small proportion of patients from Hemophilia Treatment Center (HTC) will spend some time within the justice system. Currently there are no data addressing haemophilia care needs while incarcerated. METHODS: This article will review the current health care issues in the adult correctional system. Additionally, six case reports of incarcerated haemophiliacs will be highlighted exploring the successes and challenges with maintaining haemophilia care addressing the priority of meeting the haemophilia care needs verses the penal system regulations. SUMMARY: It can be expected that at some point, the HTC will experience a patient incarcerated for some period of time. The HTC will continue to advocate for their patient within this system, despite the many challenges faced. CONCLUSIONS: Despite the challenges outlined, ongoing communication and education with the correctional system, education of the medical personnel and prison personnel remains the priority as we advocate for our patients. Continued strategies in these areas are paramount.

Analyzing multiple risk factors in patients with sarcomas. A case-control study.

CONTEXT: Sarcomas are a rare group of malignancies. Very little is known about their risk factors. AIMS: The aim was to evaluate different risk factors in patients with sarcomas and to determine the median age at diagnosis, differences in race, gender, histological grades and staging in sarcoma patients. SETTINGS AND DESIGN: A retrospective case-control study was conducted in a tertiary care hospital in the USA. This included patients diagnosed with sarcomas from year 2000 to 2010. MATERIALS AND METHODS: Data were extracted with the help of electronic medical records using International Classification of Diseases, Ninth revision codes. Healthy, matched controls were randomly selected from the same tertiary care hospital database. STATISTICAL ANALYSIS: Univariate comparisons between cases and controls were done using a two-group independent t-test for age and using Chi-square tests for the categorical variables. In order to identify possible independent predictors of sarcomas, a multiple logistic regression model was constructed using sarcoma status as the dependent variable and using, initially, all variables with a univariate P < 0.2 as independent variables. Variables were reduced in a manual stepwise manner to arrive at a final model. Statistical significance was set at P < 0.05. All analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: A total of 425 sarcoma patients and 429 age, sex and race matched healthy controls were analyzed in this study. We found that a history of smoking and alcoholism was significantly associated with sarcomas. We also found that the history of cancer in first-degree relatives had a significant relationship. In addition, patients with sarcomas are more likely to have a history of another malignancy when compared with controls. CONCLUSIONS: Smoking and alcohol are potential risk factors for sarcomas. In addition, a history of cancer in the first-degree relative is also a potential risk factor. Patients with sarcomas are likely to have a history of another malignancy when compared with controls.

Infection risk and stability of a continuous 8-h 250 mL rFVIII infusion.

This study seeks to identify the delivery method of continuous infusion using a 250 cc IV bag via pump, change every 8 h. Additionally, the study will examine the infection risk with the use of 8 h infusions. Ten hemophilia A patients were identified for the study. Each patient received a bolus factorVIII (FVIII) infusion with a pre FVIII level and 1 h post FVIII level to determine recovery levels for optimal dosing. On the day of 8-h continuous infusion, the pt received a bolus VIII (Kogenate FS (™)) for correction to 100% followed by individually calculated continuous infusion (Kogenate FS (™)) FVIII. FVIII levels were drawn from the IV bag and peripherally from the patient in the opposite arm at time points: pre infusion, 1, 2, 3, 4, 5, 6 and 8 h. Additionally, blood cultures were drawn from the IV bag and from the IV tubing at time points pre infusion, 4 and 8 h. Fourteen subjects agreed to participate in the study; 4 failed to follow up, hence 10 subjects were included in the analysis of data; 7 severe, 2 moderate, and 1 mild hemophilia A. Age range was 26-62 years. Ethnic breakdown included 5 African American, 4 Caucasian, 1 Hispanic. With all infusions, the range of FVIII was 65-135% (blood) and 62-200% (bag). After the start of infusion, there were no significant differences noted between the hourly FVIII levels in the subjects and the IV values (P-value range 0.36-0.9). Additionally, given three time points with six cultures per patient, totaling 60 points of cultures drawn for the study, all cultures from the IV bag and patient were negative. The effective delivery method and safety of an 8-h continuous infusion of FVIII (Kogenate FS (™)) has been confirmed. This method can be helpful given that many hospitals may not carry the required mini-pumps, allowing a standard safe delivery of FVIII (Kogenate FS (™)) continuous infusion by available means.

The challenges of the homeless haemophilia patient.

The current economic hardships within the United States can increase the risk of persons becoming homeless. In 2001, it was estimated that between 0.1% and 2.1% of the population were homeless every night and that 2.3 - 3.5 million persons could become homeless every year [1]. Many issues can increase the risk of homelessness including: home foreclosure, declining work force due to declining wages, low-wage opportunities and less secure jobs, decline in public assistance, lack of affordable housing with limited housing assistance programs, poverty, lack of affordable health care, domestic violence, mental illness, and addiction disorders. Many on the streets may suffer from mental illness, developmental disabilities, and or chronic physical illness [6]. Given these issues, the Hemophilia Treatment Center (HTC) can expect to experience the issue of homelessness within their own population of persons with hemophilia. Currently, there are no studies that address the issue of the person with hemophilia who may become homeless. This presents unique challenges that this population may encounter to survive in addition to managing bleeding issues related to the diagnosis of hemophilia. This article will review the issues related to homelessness in the general population. Two case studies of persons with hemophilia who became homeless will be discussed outlining the strategies utilized to assist the patient during this crisis.

Frequency and predictors of venous thromboembolism in orthotopic liver transplant recipients: a single-center retrospective review.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of major abdominal operations. Liver transplantation is carried out as a treatment for end-stage liver disease (ESLD). It is not well studied whether this population is at increased or decreased risk of a VTE event after a liver transplantation. This study was to determine the frequency of VTE in this population and identify possible predictors. METHODS: Retrospective review of 917 patients over 15 years at a single tertiary center was conducted. Liver transplant recipients with symptomatic VTE occurring up to 1 year after liver transplantation were included. Upper and lower extremities deep vein thrombosis (DVT) was identified. The diagnosis of DVT and pulmonary embolism (PE) was made by appropriate diagnostic imaging. Data regarding known risk factors of VTE such as thrombophilia, recent hospitalization, malignancy, and other comorbid conditions were collected. RESULTS: Among 917 patients, a total of 45 events occurred in 42 (4.58%) patients. Twelve had PE and 33 had DVT events. On Cox regression analysis the absence of an alcoholism diagnosis (Hazard Ratio [HR], -0.33; 95% confidence interval [CI], 0.13-0.83), the presence of diabetes (HR, -3.36; 95% CI, 1.76-6.42), a history of VTE (HR, -8.06; 95% CI, 3.37-19.3), and the presence of end-stage renal disease (ESRD; HR, 3.68; 95% CI, 1.34-10.01) were significant predictors of a VTE outcome. No particular diagnosis, history of malignancy, or presence of thrombophilia were associated with increased risk of VTE. CONCLUSION: The 4.58 % incidence of VTE is comparable with the reported incidence after major abdominal procedures (5%-10%). This data also shows that there is increased risk of VTE in transplant recipients with comorbid conditions of diabetes, previous VTE, and ESRD. This study suggests that a more aggressive strategy for prophylaxis of VTE should be used in liver transplant recipients as with other major abdominal procedures.

Congenital von Willebrand's disease and clinical hypothyroidism.

Data from case reports and systematic reviews suggest an association of Hypothyroidism and Acquired von Willebrand's syndrome. It is not known if congenital von Willebrand's disease is associated with hypothyroidism in a similar way. The aim of this study was to identify the association of congenital von Willebrand's disease (VWD) with clinical hypothyroidism. A total of 350 cases of congenital VWD were initially screened from our institution database from 1985 to 2010. A careful review of patient records was carried out to see if patients truly had congenital VWD and coexisting clinical hypothyroidism. Patients with uncertain diagnoses or other bleeding disorders were excluded, leading to 197 patients remaining in the final sample. A random age- and sex-matched parallel control group was also obtained from the hospital database. Of 197 patients (mean age 43.8 ± 17.5 years, women 72%) of congenital VWD, 32/197 (16%) were diagnosed with clinical hypothyroidism, while only 11/197 (5.6%) of the matched controls were clinically hypothyroid. Univariate and multivariate analysis demonstrated that VWD was an independent predictor of developing clinical hypothyroidism (OR 3.45; 95% CI 1.65-7.22, P = 0.001). The proportion of patients diagnosed with clinical hypothyroidism was more in the VWD group (P < 0.0001). Our analysis shows a strong association of clinical hypothyroidism in patients with congenital VWD, but future studies will be required to delineate a pathological mechanism. In our opinion, clinicians should consider checking thyroid function in the newly diagnosed and established cases of congenital VWD.

Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII, in subjects with haemophilia A.

OBI-1 is a recombinant B-domain deleted porcine factor VIII (FVIII). FVIII treatment in those with haemophilia A may be complicated by the development of anti-FVIII antibodies (inhibitors) leading to a failure to respond to treatment with human FVIII. To compare the pharmacokinetics and safety of a single dose of OBI-1 with Hyate:C in subjects with haemophilia A and inhibitors, subjects were randomized to receive either Hyate:C followed by placebo or placebo followed by OBI-1 in a double-blind fashion. FVIII levels were assayed using both a one-stage coagulation assay (OSCA) and chromogenic assay. Pharmacokinetic parameters for FVIII were calculated for 6/9 subjects randomized; in three subjects baseline anti-porcine FVIII inhibitors led to a lack of measurable FVIII activity. Mean C(max) appeared higher for OBI-1 (OSCA: 176.00 U dL(-1), standard deviation ± 88.00; chromogenic: 151.00 ± 31.51 U dL(-1)) than Hyate:C (OSCA: 82.3 ± 19.22 U dL(-1); chromogenic: 52.67 ± 13.8 U dL(-1)). Mean AUC also appeared higher for OBI-1 (OSCA: 2082.87 ± 1323.43 U h(-1) dL(-1) ; chromogenic: 1817.28 ± 625.14 U h(-1) dL(-1)) than Hyate:C (OSCA: 1177.8 ± 469.49 U h(-1) dL(-1); chromogenic: 707.61 ± 420.05 U h(-1) dL(-1)). Two infusion-related events occurred: one with Hyate:C, one with placebo. Four of five subjects without anti-porcine FVIII inhibitors at baseline remained porcine FVIII inhibitor negative 29 days after infusion. A single dose of OBI-1 appears to have higher bioavailability than Hyate:C in subjects with haemophilia A without measurable anti-porcine FVIII inhibitors, and is well tolerated. These results should be confirmed in a larger phase 2/3 study.

Liver transplantation in the haemophilia patient.

Summary. Hepatitis C is a chronic condition that many persons with haemophilia contracted in the 1980s due to the infusion of factor concentrates that did not have viral inactivation processes in place. Many patients with haemophilia are now living longer lives, well into their eighties due to the improvement of their care. The effects of the hepatitis C virus on the liver over time are now being realized as this population ages. Although the new treatments for hepatitis C have a prolonged response, as demonstrated by a persistent negative viral load, many haemophilia patients have either not responded to the therapy or had significant side effects to treatment, which prevented continued therapy. Of these infected haemophiliacs with liver disease, many have demonstrated a slow progressive decline resulting in liver failure, cirrhosis or liver cancer. Liver transplant then becomes their only option. This article will review liver transplantation in the haemophilia patient highlighting three case studies demonstrating the effectiveness of specific short-term factor infusions and other haemostatic support to minimize bleeding during the surgical period. These cases confirm the opportunity for successful liver transplantation for haemophilia patients utilizing specific factor recommendations with minimal bleeding risk.

Liver transplantation in the haemophilia patient.

Hepatitis C is a chronic condition that many persons with haemophilia contracted in the 1980s due to the infusion of factor concentrates which did not have viral inactivation processes in place. Many patients with haemophilia are now living longer lives, well into 80 years of age, due to the improvement of their care. The effects of the HCV on the liver over time are now being realized as this population ages. Although the new treatments for hepatitis C have a prolonged response, as demonstrated by a persistent negative viral load, many haemophilia patients have either not responded to the therapy or had significant side-effects to the treatment, preventing continued therapy. Of these infected haemophiliacs with liver disease, many have demonstrated a slow progressive decline resulting in liver failure, cirrhosis or liver cancer. Liver transplant then becomes their only option. This article will review liver transplantation in the haemophilia patient highlighting three case studies demonstrating the effectiveness of specific short-term factor infusions and other haemostatic support to minimize bleeding during the surgical period. These cases confirm the opportunity for successful liver transplantation for haemophilia patients utilizing specific factor recommendations with minimal bleeding risk.

Dialysis in the haemophilia patient: a practical approach to care.

The major focus of care for patients with haemophilia is to ensure health with minimal joint dysfunction. As this population ages, additional coexisting conditions can develop including rare instances of nephrotic syndrome in haemophilia B inhibitor patients undergoing immune tolerance, hypertension, diabetes, and coronary artery disease, all of which can adversely affect the renal system over time. In haemophilia patients, co-infected with HIV and hepatitis C, these conditions can also increase the risk of renal problems resulting in the need for dialysis. This article provides a practical approach for the haemophilia patient who requires dialysis and outlines the decision making process to ensure a positive outcome. The goal of care is to optimize dialysis treatment without increasing the bleeding risk.

Pulmonary artery sarcoma mimicking a pulmonary embolism.

Sarcomas involving the lung are a rare occurrence, often a result of metastatic disease from primary malignancies involving the skin, liver, breast or heart. Primary pulmonary artery sarcomas are rarer still, with limited cases reported world-wide and consequently data regarding treatment modalities are sparse and largely experimental. These tumors are often mistaken for a pulmonary embolism and seemingly supported by radiological findings. Patients will often present without symptom resolution despite therapeutic anticoagulation. The following case illustrates how a soft tissue sarcoma of the pulmonary artery can mimic a pulmonary embolism, thus, resulting in both a diagnostic and therapeutic dilemma. A positron emission tomography scan was an invaluable tool in this case, showing increased radiotracer uptake and placing neoplasm at the top of the differential diagnosis. This ultimately led to a biopsy that was vimentin positive, cytokeratin negative and CD117 negative, thus consistent with soft tissue sarcoma.

Hypercoagulability risks among adult living liver donors.

BACKGROUND: Review of the literature is limited with respect to thrombotic risk in the living liver donor. This study examines inherent coagulable changes that occur as a result of the surgery. MATERIALS AND METHODS: At our center, we have performed 353 orthotopic adult liver transplants in the past 4 years. Of these, 20 were adult-adult right lobe living donor transplants. All living donors are alive and doing well. Of these, eight living donors were followed preoperatively and postoperatively monitoring protein C, protein S, antithrombin III, and factor VIII levels. Levels were checked at 48 hours postoperatively, as well as at 2, 4, and 6 weeks. RESULTS: All eight patients had normal levels preoperatively, although significantly low levels were identified postoperatively of these coagulation markers: protein C decreased to as low as 0%, (range 0-29; normal 50-150) within 48 hours postoperatively; protein S decreased to 3% to 40% during the same time frame (normal 50-150), and antithrombin III levels decreased to 47% to 55% (normal range 50-150%). Factor VIII levels significantly increased to >200% (normal 50- 150). All coagulation levels returned to the normal range within 4 to 6 weeks. None of the patients developed a thromboembolic event. CONCLUSIONS: We observed an imbalance of low protein C, S, and antithrombin III and elevated factor VIII levels, which have been documented as thrombotic risks in adults. Our findings suggest that the imbalance in the coagulation profile after surgery may be an independent risk factor for thrombosis beyond the surgical event, a phenomenon that requires further exploration.

Bone marrow morphology in multiple myeloma.

This study was undertaken at the Christian Medical College and Hospital, Ludhiana, encompassing all patients of multiple myeloma presenting between January 01, 1982 and December 31, 1991. In all, 89 patients were included. The may Grunwald Giemsa stained bone marrow aspiration slides of each patient was examined under oil- immersion and a morphological grading made as mature (12 patients), immature (53) and plasmablastic (24). The estimated median survival for the mature category was 55 months, for immature 23 months and for plasmablastic two months. The estimated median survival on combining the mature of immature groups was 52 months, and on comparing this with the plasmablastic group, the difference in survival was found to be statistically significant (p < 0.05).