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ED visits by males with hemophilia
ED Visits by Males With Hemophilia RACHELLE NUSS, MD, RICHARD HOFFMAN, MD, AND LUCINDA HAMMOND, MSPH Hemophilia is a rare disorder affecting 1 in 5,000 males. Because hemophilia-associated hemorrhage may occur at anytime, affected males frequently seek care in the ED. We studied the epidemiology of ED visits by males with hemophilia. The medical records of all identified Coloradan males with hemophilia who sought care in Colorado EDs in 1998 were reviewed. Fifty-one males with hemophilia had a total of 125 ED visits; hemorrhage accounted for 64.8% of visits (95% CIⴝ55.6, 73.1). On 13.0% (95% CIⴝ6.4, 22.6) of visits for hemorrhage, treatment was warranted, but not given. On 12.3% (95% CIⴝ5.5, 22.8) of visits when treatment was given, there were errors in product choice or dose. Documentation of factor concentrate brand and lot number was present for just 13.9% (95% CIⴝ6.5, 24.7) and 24.6% (95% CIⴝ14.8, 36.9) of visits, respectively. There is substantial room for improvement in the prescribing practices and documentation related to hemophilia care in the ED. Available resources should be utilized by ED physicians. (Am J Emerg Med 2002;20:74-78. Copyright 2002, Elsevier Science (USA). All rights reserved.)
Hemophilia is an X-linked genetically transmitted disorder which affects one in 5,000 males.1 The term hemophilia is used to describe people with a significantly reduced coagulation protein factor VIII or factor IX activity level. Because the disorder is X-linked most affected people are males. Males with hemophilia experience excessive hemorrhage into joints, skin, soft tissue, muscle, and solid organs.2 Given the rarity and complexity of hemophilia, there have been extensive efforts to localize care to specialized hemophilia treatment centers. Hemophilia patient satisfaction with hemophilia treatment centers has been shown to be high.3 Mortality is decreased in people with hemophilia who receive hemophilia comprehensive care.4 However, most centers are in urban areas, there are a limited number of centers, hours of operation are restricted, and one-third of males with hemophilia do not receive care at these centers.1 Thus, many males with hemophilia seek care in the ED (ED). However, we previously found that more than 50% of people with hemophilia who sought care in Colorado EDs were not or only somewhat satisfied with care received in that setting.3 A primary complaint was lack of hemophilia knowledge on the part of the ED staff.3 This is consistent with the emergency medicine literature which states, “Hemophiliac patients represent a challenge to ED physicians”
From the Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado Health Sciences Center and the Colorado Department of Public Health and Environment, Denver, CO. Supported by the Centers for Disease Control and Prevention, Contract grant no. U27/CCU809781. Manuscript received February 26, 2001, returned May 1, 2001, revision received June 26, 2001, accepted June 30, 2001. Address reprint requests to Rachelle Nuss, MD, P.O. Box 6507, Mail-Stop F416, Aurora, CO 80045-0507. E-mail: rachelle.nuss@ uchsc.edu Key Words: Hemophilia, ED, medical errors. Copyright 2002, Elsevier Science (USA). All rights reserved. 0735-6757/02/2002-0002$35.00/0 doi:10.1053/ajem.2002.30098 74
because they are “particularly well-educated and experienced in their disease and its treatment, whereas ED doctors may have little experience with management.”5 This conundrum prompted us to study the descriptive epidemiology of ED visits by males with hemophilia. The study findings are discussed. METHODS To design and evaluate appropriate prevention programs for the morbidities associated with hemophilia, the Centers for Disease Control and Prevention (CDC) funded a Hemophilia Surveillance Study (HSS). Data were collected for this study by medical chart review to determine the prevalence of hemophilia, assess the demographics and determine the primary morbidities of hemophilia. In 1992 six state health departments (Colorado, Georgia, Louisiana, Massachusetts, Oklahoma, and New York) were funded to participate in this study in conjunction with their local Hemophilia Diagnostic and Treatment centers. Details of the HSS have been reported extensively.1 A brief summary of study definitions and treatment follows. Hemophilia disease severity was determined by the factor VIII or IX activity level.2 Males with a factor VIII or IX activity ⬍1% were considered severely affected. Moderately affected males have a factor VIII or IX activity of 1% to 5%. Males with ⬎5% to 30% factor VIII or IX activity level have mild hemophilia. The frequency of hemorrhage is determined by disease severity. Treatment is generally administered for confirmed or suspected acute bleeding events. Males with moderate or severe factor VIII deficiency are treated with intravenous factor VIII concentrates, either recombinant or human pooled plasma-derived. Males with mild factor VIII deficiency receive a synthetic compound, DDAVP, if they are proven responsive to it. Males with factor IX deficiency require treatment with either recombinant or pooled plasma derived concentrates. After exposure to factor concentrate, 15-33 % of males with severe factor VIII deficiency and 1% to 3% of factor IX deficient develop an inhibitor or antibody to the factor for which they are deficient.2 In general, routine factor concentrates are no longer effective when an inhibitor develops. Males with an inhibitor require treatment with alternative factor concentrates often referred to as bypassing concentrates.2 For the HSS project, hemophilia was made a reportable condition in Colorado so that all males with hemophilia could be identified and relevant records reviewed. When the Colorado data abstractor was reviewing the medical record for every identified hemophiliac person in Colorado, in addition to the data to be collected for the HSS, we requested the abstractor review and record ED visit data for the substudy reported here. There were 185 males with hemophilia identified in Colorado in 1998. Data were abstracted from all 144 medical
NUSS, HOFFMAN, AND HAMMOND ■ ED VISITS BY MALES WITH HEMOPHILIA
records of Colorado males with hemophilia who visited an ED from January 1 to December 31, 1998. Of these, 7 visits to out of state hospitals and 10 nursing visits for factor concentrate infusion only were excluded. Two visits by a single individual were also excluded, as he did not inform the ED that he had severe hemophilia. The remaining 125 ED visits by 51 males who were evaluated by a physician are the basis of this report. Data were collected directly from the ED report and recorded onto a data collection sheet designed specifically for this study. Variables included demographics, type and severity of disorder, time of visit, referral to the ED, HIV status, and types of treatment received. Missing information was supplemented using the Colorado Hemophilia registry from the HSS project. The reason for the visit was reviewed and grouped into hemophilia and nonhemophilia-related categories. The need for any blood tests and radiographs performed was reviewed by one of the authors, a hematologist with 15 years experience in hemophilia care (R.N.). The administration of factor concentrate to treat bleeding episodes was reviewed for appropriate indication and correct dose according to published guidelines.2,6 Administration of intravenous DDAVP was also reviewed and assessed according to published guidelines.2,6 The ED records were studied to determine whether follow-up instructions relevant to hemophilia-associated complications were given. DATA ANALYSIS All data were entered into a Microsoft Access database and analyzed using SAS system for Windows, version 7 (Cary, NC). Descriptive demographics are reported as percentages or proportion of the total Coloradan hemophilia population and as percentages or proportion of the ED visits. Confidence intervals around these percentages and proportions were calculated using the exact method for binomial proportions.7 RESULTS There were 125 visits by 51 males to 25 hospitals in Colorado in 1998. The data are shown in Table 1. The distribution of race/ethnicity for emergency visits is heavily skewed because of one black individual with 22 ED visits in 1998. This individual was 47 years old, HIV and hepatitis C infected, had severe factor VIII deficiency, was severely mentally ill, and was living in a nursing home where caregivers were unable to administer factor concentrate. The demographics of all males identified with hemophilia in Colorado in 1998 (n⫽185) are shown in Table 2 for comparison with the demographics of the subset of males with hemophilia who visited the ED any time that year (n⫽51). The median age, race/ethnicity, hemophilia type, hemophilia severity, percent inhibitor positive and HIVinfected is comparable between the groups. The 4 inhibitorpositive males who visited the ED had a total of 16 visits giving them a rate of 3.75 per person versus 2.3 visits per person in the remaining 47 inhibitor-negative males. Medical records revealed that males contacted their physician before 56% (95% CI⫽46.8, 64.9) of ED visits (n⫽70). This included 48.8% (95% CI⫽33.3, 64.5) of visits by boys younger than 21 years of age (n⫽21) and 59.8%
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TABLE 1. Demographics of ED Visits by Coloradans With Hemophilia During 1998
Variable Age ⬍21 years ⱖ21 years Race/ethnicity White Black Hispanic Hemophilia type VIII deficient IX deficient Hemophilia severity Mild Moderate Severe Inhibitor Positive Negative HIV-infected Yes No
No. Visits (n ⫽ 125)
Percentage of Visits (95% CI)
43 82
34.4 (26.1, 43.4) 65.6 (56.6, 73.9)
84 28 13
67.2 (58.2, 75.3) 22.4 (15.4, 30.7) 10.4 (5.7, 17.1)
103 22
82.4 (74.6, 88.6) 17.6 (11.4, 25.4)
36 33 56
28.8 (21.1, 37.6) 26.4 (18.9, 35.0) 44.8 (35.9, 54.0)
16 109
12.8 (7.5, 20.0) 87.2 (80.1, 92.5)
53 72
42.4 (33.6, 51.6) 57.6 (48.4, 66.4)
(95% CI⫽48.3, 70.4) of visits by men 21 years or more (n⫽49). The majority of ED visits were between 5:00 PM and 8:00 AM (n⫽81, 64.8%, 95% CI⫽55.8, 73.1). This finding remained consistent when stratified by age (⬍21 years n⫽25, 58.1%, 95% CI⫽42.1, 73.0; 21 years or older, n⫽56, 68.3%, 95% CI⫽57.1, 78.1) although visits after midnight up to 8AM were more frequently by males 21 years old or more (22.0%, 95% CI⫽13.6, 32.4 and 7.0%, 95% CI⫽1.5, 19.1 respectively). Diagnoses made during the ED visits relative to hemophilia severity are shown in Table 3. When stratified by age, the most common reason for an ED visit in those younger than 21 years of age, was traumatic hemorrhage in males with mild hemophilia (n⫽11, 25.6%, 95% CI⫽13.5, 41.2). In males 21 years of age or older, the most common reason was hemorrhage without a recognized precipitating event in those with severe hemophilia (n⫽20, 24.4%, 95% CI⫽15.6, 35.1). Eighty-one (64.8%, 95% CI⫽55.8, 73.1) of the 125 ED visits were for hemorrhage as shown in Table 3. Factor concentrate or DDAVP was indicated for 77 of these visits and administered on 65 visits (84.4%, 95% CI⫽74.4,91.7). After evaluation, it was recognized on 2 of the 12 visits where treatment was omitted but not prescribed, and individuals were immediately referred to an alternative hospital that stocked factor concentrate. Information about the remaining 10 visits where treatment was omitted but not prescribed is shown in Table 4. The decision not to treat was discussed with the primary hemophilia-care provider on 2 of these 10 visits. The untreated 2-year-old child returned to the ED the next day with an elbow hemarthrosis and was then treated with factor concentrate. Of the 65 factor concentrate infusions, there were errors in administration for 5 (7.7%, 95% CI⫽2.6, 17.1); Two individuals received a concentrate other than that ordered and three individuals received one-half the appropriate dose
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TABLE 2. Demographics of Coloradans With Hemophilia who Visited the ED Compared With all Coloradans With Hemophilia
Variable Age ⬍21 years ⱖ21 years Race/ethnicity White Black Hispanic Unknown Hemophilia type VIII deficient IX deficient Hemophilia severity Mild Moderate Severe Inhibitor Positive Negative HIV-infected Yes No Unknown
TABLE 3.
Coloradans With Hemophilia who Visited the ED N ⫽ 51 N, (%; 95% CI)
All Coloradans With Hemophilia N ⫽ 185 N, (%; 95% CI)
24 (47.1; 32.9, 61.5) 27 (52.9; 38.5, 67.1)
75 (40.9; 33.4, 48.0) 110 (59.1; 52.0, 66.6)
42 (82.4; 69.1, 91.6) 3 (5.9; 1.2, 16.2) 6 (11.8; 4.4, 23.9) 0
149 (80.5; 74.1, 86.0) 7 (3.7; 1.5, 7.6) 21 (11.4; 7.2, 16.8) 8 (4.4; 1.9, 8.3)
39 (76.5; 62.5, 87.2) 12 (23.5; 12.8, 37.5)
142 (76.6; 70.0, 82.6) 43 (23.4; 17.4, 30.0)
23 (45.1; 31.1, 59.7) 13 (25.5; 14.3, 39.6) 15 (29.4; 17.5, 43.8)
78 (42.2; 35.0, 49.6) 49 (26.5; 20.3, 33.5) 58 (31.3; 24.7, 38.6)
4 (8.0; 2.2, 18.9) 46 (92.0; 78.6, 96.7)
5 (2.7; 0.8, 6.2) 180 (97.3; 93.8, 99.1)
12 (23.5; 12.8, 37.5) 39 (76.5; 62.5, 87.2) 0
32 (17.3; 12.1, 23.5) 143 (77.3; 70.6, 83.1) 10 (5.4; 2.6, 9.7)
Diagnoses Made at ED Visits
Reason by Severity:
N (N ⫽ 125)
Percentage of Total (95% CI)
Traumatic hemorrhage Severe hemophilia Moderate hemophilia Mild hemophilia Hemorrhage (no known trauma) Severe hemophilia Moderate hemophilia Mild hemophilia HIV-associated problem* Severe hemophilia Moderate hemophilia Mild hemophilia Trauma (not bleeding) Severe hemophilia Moderate hemophilia Mild hemophilia Other† Severe hemophilia Moderate hemophilia Mild hemophilia Unknown
47 17 11 19 34 23 8 3 11 6 5 0 11 2 0 9 22 7 9 5 1
37.6 (48.4, 66.4) 13.6 (8.1, 20.9) 8.8 (4.5, 15.2) 15.2 (9.4, 22.7) 27.2 (19.6, 35.9) 18.4 (12.0, 26.3) 6.4 (2.8, 12.2) 2.4 (0.5, 6.9) 8.8 (4.5, 15.2) 4.8 (1.8, 10.2) 4.0 (1.3, 9.1) 0 8.8 (4.5, 15.2) 1.6 (0.2, 5.7) 0 7.2 (3.3, 13.2) 16.8 (11.4, 25.4) 5.6 (2.3, 11.2) 7.2 (3.3, 13.2) 4.0 (1.3, 9.1) 0.8 (0.0, 4.4)
*All males with HIV-associated problems were ⬎18 years old. †The “Other” category is comprised of the following complaints: Pulmonary/Cardiac/Upper Respiratory Infections (n ⫽ 8), Nonhemophilia related pain (n ⫽ 6), Abdominal complaint/pain (n ⫽ 5), Hemophilia related infusion only (n ⫽ 1), Hemophilia related pain (n ⫽ 1).
TABLE 4. ED Visits Resulting in Discharge Without Appropriate Treatment
Age (years)
Diagnosis (deficiency)
2 11 13
Mild IX Severe IX Mild IX
22
Mild VIII
22 31
Mild VIII Mild VIII
34 43
Mild VIII Mild IX
49
Moderate IX
78
Moderate VIII
Problem Elbow trauma Abdominal pain Traumatic elbow hemarthrosis Thigh trauma Forearm hemorrhage Hematemesis/infiltrate on chest x-ray film Hematemesis Abdominal pain/blood in stool Shoulder/epigastric pain Bleeding foot
Reason for no Treatment With DDAVP or Factor Concentrate None None None No factor concentrate at hospital No DDAVP in hospital None None None None None
of factor concentrate. The primary hemophilia-care provider was contacted for one of these visits. On 5 visits (7.7%, 95% CI⫽2.6, 17.1) when factor concentrate was administered, the dose given was not recorded; 4 of the 5 visits were by one child to the same ED. The primary hemophilia-care provider was contacted just once. The frequency of factor concentrate infusions for which the brand name and lot number were recorded is shown in Table 5. Overall, the brand name of concentrate was recorded on 13.9% (95% CI⫽6.5, 24.7) of the records. Whether recombinant or pooled human plasma-derived concentrate had been administered could be discerned for 40% (95% CI⫽28.0, 52.9) of the infusions. The lot number administered was indicated on 24.6% (95% CI⫽14.8, 36.9) of records. DDAVP was prescribed on 8 visits. This includes one visit by an individual who was not a candidate for DDAVP. The DDAVP dose was recorded as milligrams per kilogram on 2 records although the correct dose is on a microgram per kilogram basis. One record had no dose for DDAVP recorded. The primary hemophilia care provider was contacted for just one of the visits. Narcotics were prescribed to 6 males (11.8%, 95% CI⫽4.4, 23.9) who visited the ED. They received narcotics on 19 of their 21 ED visits (15.2%, 95% CI⫽9.4, 22.7 of all ED visits). Five of the 6 males were 21 years of age or older. Three of the 6 males had an inhibitor. The primary need for narcotics was to treat hemophilia-associated bleeding pain. Ten coagulation blood tests were obtained on 6 males presenting to the ED with known hemophilia in their steady TABLE 5. Infused
Frequency of Documentation for Factor Concentrates VIII Concentrate N (%; 95% CI)
Brand name Generic Recombinant Intermediate Lot number Total
IX Concentrate N (%; 95% CI)
6 (13.3; 5.1, 26.8) 0 29 (64.4; 47.8, 78.1) 9 (81.8; 48.2, 97.7) 9 (20; 9.5, 34.6) 2 (18.2; 2.3, 57.8) 1 (2.2; 0.1, 11.8) 0 13 (28.9; 16.4, 44.3) 1 (9.1; 0.2, 41.3) 45 11
Bypassing Concentrate N (%; 95% CI) 3 (37.5; 8.5, 75.5) 0 0 5 (62.5; 24.5, 91.5) 2 (25; 3.2, 65.1) 9
NUSS, HOFFMAN, AND HAMMOND ■ ED VISITS BY MALES WITH HEMOPHILIA
state. The tests were: 7 prothrombin times, 2 activated partial thromboplastin times, and 1 factor VIII activity. None were clinically indicated. Forty-three males had plain radiographs done in the ED. There were appropriate indications for all but one radiograph (2.3%, 95% CI⫽0.1, 12.3). Eighty-six percent of emergency discharge notes instructed follow-up with either the patients primary care provider or hematologist. Sixty-seven percent of discharge plans specifically mentioned follow-up care for hemophilia. DISCUSSION People with hemophilia frequently seek care in the ED; almost 20% of Coloradans with hemophilia visited the ED one or more times in 1998. The rate of ED visits by Coloradans with hemophilia was 45 per 100 hemophiliac people. This compares with the 1996 National Hospital Ambulatory Medical Care Survey (NHAMCS) estimated rate of 34.2 ED visits per 100 people in the general population.8 Twenty percent of males with hemophilia who visited the ED required hospitalization as compared with NHAMCS data showing that 11% of ED visits by the general population lead to hospitalization.8 Thus, although males with hemophilia visit the ED about as often, they are twice as likely to be admitted to the hospital from the ED than the general population. Although 18% of the hemophilia population studied were HIV-infected, only 9% of ED visits were for HIV-associated problems. As expected, the primary reason for ED visits, independent of age, was for hemorrhagic complications; hemorrhage was the impetus for 65% of ED visits. Despite a report of hemophilia, for reasons unknown, physicians chose to screen for a bleeding disorder on 11% of visits. The laboratory tests were not clinically indicated. Our study found serious problems with the care delivered to males with hemophilia in the ED and it’s documentation. Thirteen percent of hemorrhagic events warranted treatment, but were untreated. Seventy percent of males untreated had mild disease and thus generally have limited experience with hemorrhage and rely on medical advice. Negligence has previously been shown in reviews of general ED care in Colorado and Utah and in the Harvard Medical Practice study to be the cause of 70 % to 95% of ED adverse events.9,10,11,12 In our study 1 of 10 untreated males, returned to the ED with an elbow hemarthrosis which may have been prevented had treatment initially been given. We also found that on 12% of visits when males were treated for bleeding, either the wrong medication or wrong dose was prescribed. The Institute of Medicine has reported that medication errors kill 7,000 males per year.13 The leading error is incorrect drug calculations and ordering. We found the ordering documentation was critically inadequate. Most commonly recorded in the ED physicians records was the generic name, “antihemophilic factor” which is not sufficient or useful for surveillance of complications. Factor concentrates are produced in batches and each vial is labeled with a brand name and lot number so that when infectious and immunologic complications arise this information is used to identify males at risk. For example, the brand name and lot numbers recorded on hospital records
77
have been used to identify and test males who received contaminated factor concentrates in the 1980s and were exposed to hepatitis C and HIV. This information has also been used to identify particular batches of factor concentrate that were more immunogenic and induced a higher rate of inhibitor formation. Although our study was restricted to reviewing the records in one state for 1 year, the findings suggest there is room for improvement in the care delivered to males with hemophilia in the ED and its documentation. One major determinant of adverse events during hospitalization has been shown to be disease complexity.11 Given the rarity and complexity of hemophilia and the ever-changing array of treatment products, ED physician should not treat hemophilia patients in isolation. Hemophilia resources are available and should be accessed. As indicated earlier, many males with hemophilia have received extensive education about their disease and their knowledge should be sought and seen as helpful, rather than adversarial.5 There are published guidelines for emergency care for males with hemophilia which EDs should have on hand.14,15 The ED staff should be aware that most males with hemophilia who attend treatment centers carry a card with them which indicates their diagnosis, treatment products, and hematology physician, with an on-call telephone number. The emergency staff should contact the primary hemophilia careprovider for advice. We believe a more comprehensive surveillance study of ED care of males with hemophilia is warranted. In the interim, based on our findings, we recommend greater collaboration between the ED physician and the primary hemophilia-care giver with the goal of improving hemophilia care. REFERENCES 1. Soucie JM, Evatt B, Jackson D, and the Hemophilia Surveillance System Project Investigators: Occurrence of hemophilia in the United States. Am J Hem 1998; 59: 288-294 2. DiMichele D, Neufeld EJ: Hemophilia: A new approach to an old disease. Hematol Oncol Clin North Am 1998; 12: 1315-1344 3. Nuss R, Hedegaard H, Riske B, et al: Medical care for haemophilia. Haemophilia 1998; 4: 806-811 4. Soucie JM, Nuss R, Evatt B, et al: Mortality among males with hemophilia: Relations with source of medical care. Blood 2000; 96: 437-442 5. Anonymous: Emergency room care for hemophilac patients. Understanding and overcoming difficulties. J Florida Med Assoc 1993; 80: 250-4 6. Hemophilia of Georgia, U.S.A.: Protocols for the treatment of haemophilia and von Willebrand disease. Haemophilia 2000; 6: 84-93 7. Pezzullo JC: Exact Binomial and Poisson Confidence Intervals. Available at http://davidmlane com/hyperstat/confidence_intervals html. Accessed June 19, 2001 8. McCaig LF, Stussman BJ: National Hospital Ambulatory medical care survey: 1996 ED summary. Advance data from vital and health statistics; no. 293. Hyattsville, MD, National Center for Health Statistics, 1997 9. Thomas EJ, Studdert DM, Burstin HR, et al: Incidence and types of adverse events and negligent care in Utah and Colorado. Med Care 2000; 38: 261-271 10. Brennan TA, Leape LL, Laird NM, et al: Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I. N Engl J Med 1991; 324: 370-6 11. Leape LL, Brennan TA, Laird N, et al : The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377-84
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12. Localiao AR, Lawthers AG, Brennan TA, et al : Relation between malpractice claims and adverse events due to negligence. Results of the Harvard Medical Practice Study N Engl J Med 1991; 325: 245-51 13. Kohn LT, Corrigan JM, Donaldson MS (eds): To err is human: Building a safer healthcare system. Institute of Medicine report. Washington, DC, National Acadamy Press, 1999
14. Wulff, K, Zappa S, Womack M (eds): The Nursing Group of Hemophilia Region VI.: Emergency care of patients with hemophilia. An instructional manual for medical professionals (ed 2). Oklahoma City, OK, Corporate Communications, 1999 15. Hathaway WE, Goodnight Jr. SH (eds): Disorders of Hemostasis and Thrombosis. A Clinical Guide (ed 2). Mc-Graw Hill, New York, 2001
Hemophilia is an X-linked genetically transmitted disorder which affects one in 5,000 males.1 The term hemophilia is used to describe people with a significantly reduced coagulation protein factor VIII or factor IX activity level. Because the disorder is X-linked most affected people are males. Males with hemophilia experience excessive hemorrhage into joints, skin, soft tissue, muscle, and solid organs.2 Given the rarity and complexity of hemophilia, there have been extensive efforts to localize care to specialized hemophilia treatment centers. Hemophilia patient satisfaction with hemophilia treatment centers has been shown to be high.3 Mortality is decreased in people with hemophilia who receive hemophilia comprehensive care.4 However, most centers are in urban areas, there are a limited number of centers, hours of operation are restricted, and one-third of males with hemophilia do not receive care at these centers.1 Thus, many males with hemophilia seek care in the ED (ED). However, we previously found that more than 50% of people with hemophilia who sought care in Colorado EDs were not or only somewhat satisfied with care received in that setting.3 A primary complaint was lack of hemophilia knowledge on the part of the ED staff.3 This is consistent with the emergency medicine literature which states, “Hemophiliac patients represent a challenge to ED physicians”
From the Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado Health Sciences Center and the Colorado Department of Public Health and Environment, Denver, CO. Supported by the Centers for Disease Control and Prevention, Contract grant no. U27/CCU809781. Manuscript received February 26, 2001, returned May 1, 2001, revision received June 26, 2001, accepted June 30, 2001. Address reprint requests to Rachelle Nuss, MD, P.O. Box 6507, Mail-Stop F416, Aurora, CO 80045-0507. E-mail: rachelle.nuss@ uchsc.edu Key Words: Hemophilia, ED, medical errors. Copyright 2002, Elsevier Science (USA). All rights reserved. 0735-6757/02/2002-0002$35.00/0 doi:10.1053/ajem.2002.30098 74
because they are “particularly well-educated and experienced in their disease and its treatment, whereas ED doctors may have little experience with management.”5 This conundrum prompted us to study the descriptive epidemiology of ED visits by males with hemophilia. The study findings are discussed. METHODS To design and evaluate appropriate prevention programs for the morbidities associated with hemophilia, the Centers for Disease Control and Prevention (CDC) funded a Hemophilia Surveillance Study (HSS). Data were collected for this study by medical chart review to determine the prevalence of hemophilia, assess the demographics and determine the primary morbidities of hemophilia. In 1992 six state health departments (Colorado, Georgia, Louisiana, Massachusetts, Oklahoma, and New York) were funded to participate in this study in conjunction with their local Hemophilia Diagnostic and Treatment centers. Details of the HSS have been reported extensively.1 A brief summary of study definitions and treatment follows. Hemophilia disease severity was determined by the factor VIII or IX activity level.2 Males with a factor VIII or IX activity ⬍1% were considered severely affected. Moderately affected males have a factor VIII or IX activity of 1% to 5%. Males with ⬎5% to 30% factor VIII or IX activity level have mild hemophilia. The frequency of hemorrhage is determined by disease severity. Treatment is generally administered for confirmed or suspected acute bleeding events. Males with moderate or severe factor VIII deficiency are treated with intravenous factor VIII concentrates, either recombinant or human pooled plasma-derived. Males with mild factor VIII deficiency receive a synthetic compound, DDAVP, if they are proven responsive to it. Males with factor IX deficiency require treatment with either recombinant or pooled plasma derived concentrates. After exposure to factor concentrate, 15-33 % of males with severe factor VIII deficiency and 1% to 3% of factor IX deficient develop an inhibitor or antibody to the factor for which they are deficient.2 In general, routine factor concentrates are no longer effective when an inhibitor develops. Males with an inhibitor require treatment with alternative factor concentrates often referred to as bypassing concentrates.2 For the HSS project, hemophilia was made a reportable condition in Colorado so that all males with hemophilia could be identified and relevant records reviewed. When the Colorado data abstractor was reviewing the medical record for every identified hemophiliac person in Colorado, in addition to the data to be collected for the HSS, we requested the abstractor review and record ED visit data for the substudy reported here. There were 185 males with hemophilia identified in Colorado in 1998. Data were abstracted from all 144 medical
NUSS, HOFFMAN, AND HAMMOND ■ ED VISITS BY MALES WITH HEMOPHILIA
records of Colorado males with hemophilia who visited an ED from January 1 to December 31, 1998. Of these, 7 visits to out of state hospitals and 10 nursing visits for factor concentrate infusion only were excluded. Two visits by a single individual were also excluded, as he did not inform the ED that he had severe hemophilia. The remaining 125 ED visits by 51 males who were evaluated by a physician are the basis of this report. Data were collected directly from the ED report and recorded onto a data collection sheet designed specifically for this study. Variables included demographics, type and severity of disorder, time of visit, referral to the ED, HIV status, and types of treatment received. Missing information was supplemented using the Colorado Hemophilia registry from the HSS project. The reason for the visit was reviewed and grouped into hemophilia and nonhemophilia-related categories. The need for any blood tests and radiographs performed was reviewed by one of the authors, a hematologist with 15 years experience in hemophilia care (R.N.). The administration of factor concentrate to treat bleeding episodes was reviewed for appropriate indication and correct dose according to published guidelines.2,6 Administration of intravenous DDAVP was also reviewed and assessed according to published guidelines.2,6 The ED records were studied to determine whether follow-up instructions relevant to hemophilia-associated complications were given. DATA ANALYSIS All data were entered into a Microsoft Access database and analyzed using SAS system for Windows, version 7 (Cary, NC). Descriptive demographics are reported as percentages or proportion of the total Coloradan hemophilia population and as percentages or proportion of the ED visits. Confidence intervals around these percentages and proportions were calculated using the exact method for binomial proportions.7 RESULTS There were 125 visits by 51 males to 25 hospitals in Colorado in 1998. The data are shown in Table 1. The distribution of race/ethnicity for emergency visits is heavily skewed because of one black individual with 22 ED visits in 1998. This individual was 47 years old, HIV and hepatitis C infected, had severe factor VIII deficiency, was severely mentally ill, and was living in a nursing home where caregivers were unable to administer factor concentrate. The demographics of all males identified with hemophilia in Colorado in 1998 (n⫽185) are shown in Table 2 for comparison with the demographics of the subset of males with hemophilia who visited the ED any time that year (n⫽51). The median age, race/ethnicity, hemophilia type, hemophilia severity, percent inhibitor positive and HIVinfected is comparable between the groups. The 4 inhibitorpositive males who visited the ED had a total of 16 visits giving them a rate of 3.75 per person versus 2.3 visits per person in the remaining 47 inhibitor-negative males. Medical records revealed that males contacted their physician before 56% (95% CI⫽46.8, 64.9) of ED visits (n⫽70). This included 48.8% (95% CI⫽33.3, 64.5) of visits by boys younger than 21 years of age (n⫽21) and 59.8%
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TABLE 1. Demographics of ED Visits by Coloradans With Hemophilia During 1998
Variable Age ⬍21 years ⱖ21 years Race/ethnicity White Black Hispanic Hemophilia type VIII deficient IX deficient Hemophilia severity Mild Moderate Severe Inhibitor Positive Negative HIV-infected Yes No
No. Visits (n ⫽ 125)
Percentage of Visits (95% CI)
43 82
34.4 (26.1, 43.4) 65.6 (56.6, 73.9)
84 28 13
67.2 (58.2, 75.3) 22.4 (15.4, 30.7) 10.4 (5.7, 17.1)
103 22
82.4 (74.6, 88.6) 17.6 (11.4, 25.4)
36 33 56
28.8 (21.1, 37.6) 26.4 (18.9, 35.0) 44.8 (35.9, 54.0)
16 109
12.8 (7.5, 20.0) 87.2 (80.1, 92.5)
53 72
42.4 (33.6, 51.6) 57.6 (48.4, 66.4)
(95% CI⫽48.3, 70.4) of visits by men 21 years or more (n⫽49). The majority of ED visits were between 5:00 PM and 8:00 AM (n⫽81, 64.8%, 95% CI⫽55.8, 73.1). This finding remained consistent when stratified by age (⬍21 years n⫽25, 58.1%, 95% CI⫽42.1, 73.0; 21 years or older, n⫽56, 68.3%, 95% CI⫽57.1, 78.1) although visits after midnight up to 8AM were more frequently by males 21 years old or more (22.0%, 95% CI⫽13.6, 32.4 and 7.0%, 95% CI⫽1.5, 19.1 respectively). Diagnoses made during the ED visits relative to hemophilia severity are shown in Table 3. When stratified by age, the most common reason for an ED visit in those younger than 21 years of age, was traumatic hemorrhage in males with mild hemophilia (n⫽11, 25.6%, 95% CI⫽13.5, 41.2). In males 21 years of age or older, the most common reason was hemorrhage without a recognized precipitating event in those with severe hemophilia (n⫽20, 24.4%, 95% CI⫽15.6, 35.1). Eighty-one (64.8%, 95% CI⫽55.8, 73.1) of the 125 ED visits were for hemorrhage as shown in Table 3. Factor concentrate or DDAVP was indicated for 77 of these visits and administered on 65 visits (84.4%, 95% CI⫽74.4,91.7). After evaluation, it was recognized on 2 of the 12 visits where treatment was omitted but not prescribed, and individuals were immediately referred to an alternative hospital that stocked factor concentrate. Information about the remaining 10 visits where treatment was omitted but not prescribed is shown in Table 4. The decision not to treat was discussed with the primary hemophilia-care provider on 2 of these 10 visits. The untreated 2-year-old child returned to the ED the next day with an elbow hemarthrosis and was then treated with factor concentrate. Of the 65 factor concentrate infusions, there were errors in administration for 5 (7.7%, 95% CI⫽2.6, 17.1); Two individuals received a concentrate other than that ordered and three individuals received one-half the appropriate dose
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TABLE 2. Demographics of Coloradans With Hemophilia who Visited the ED Compared With all Coloradans With Hemophilia
Variable Age ⬍21 years ⱖ21 years Race/ethnicity White Black Hispanic Unknown Hemophilia type VIII deficient IX deficient Hemophilia severity Mild Moderate Severe Inhibitor Positive Negative HIV-infected Yes No Unknown
TABLE 3.
Coloradans With Hemophilia who Visited the ED N ⫽ 51 N, (%; 95% CI)
All Coloradans With Hemophilia N ⫽ 185 N, (%; 95% CI)
24 (47.1; 32.9, 61.5) 27 (52.9; 38.5, 67.1)
75 (40.9; 33.4, 48.0) 110 (59.1; 52.0, 66.6)
42 (82.4; 69.1, 91.6) 3 (5.9; 1.2, 16.2) 6 (11.8; 4.4, 23.9) 0
149 (80.5; 74.1, 86.0) 7 (3.7; 1.5, 7.6) 21 (11.4; 7.2, 16.8) 8 (4.4; 1.9, 8.3)
39 (76.5; 62.5, 87.2) 12 (23.5; 12.8, 37.5)
142 (76.6; 70.0, 82.6) 43 (23.4; 17.4, 30.0)
23 (45.1; 31.1, 59.7) 13 (25.5; 14.3, 39.6) 15 (29.4; 17.5, 43.8)
78 (42.2; 35.0, 49.6) 49 (26.5; 20.3, 33.5) 58 (31.3; 24.7, 38.6)
4 (8.0; 2.2, 18.9) 46 (92.0; 78.6, 96.7)
5 (2.7; 0.8, 6.2) 180 (97.3; 93.8, 99.1)
12 (23.5; 12.8, 37.5) 39 (76.5; 62.5, 87.2) 0
32 (17.3; 12.1, 23.5) 143 (77.3; 70.6, 83.1) 10 (5.4; 2.6, 9.7)
Diagnoses Made at ED Visits
Reason by Severity:
N (N ⫽ 125)
Percentage of Total (95% CI)
Traumatic hemorrhage Severe hemophilia Moderate hemophilia Mild hemophilia Hemorrhage (no known trauma) Severe hemophilia Moderate hemophilia Mild hemophilia HIV-associated problem* Severe hemophilia Moderate hemophilia Mild hemophilia Trauma (not bleeding) Severe hemophilia Moderate hemophilia Mild hemophilia Other† Severe hemophilia Moderate hemophilia Mild hemophilia Unknown
47 17 11 19 34 23 8 3 11 6 5 0 11 2 0 9 22 7 9 5 1
37.6 (48.4, 66.4) 13.6 (8.1, 20.9) 8.8 (4.5, 15.2) 15.2 (9.4, 22.7) 27.2 (19.6, 35.9) 18.4 (12.0, 26.3) 6.4 (2.8, 12.2) 2.4 (0.5, 6.9) 8.8 (4.5, 15.2) 4.8 (1.8, 10.2) 4.0 (1.3, 9.1) 0 8.8 (4.5, 15.2) 1.6 (0.2, 5.7) 0 7.2 (3.3, 13.2) 16.8 (11.4, 25.4) 5.6 (2.3, 11.2) 7.2 (3.3, 13.2) 4.0 (1.3, 9.1) 0.8 (0.0, 4.4)
*All males with HIV-associated problems were ⬎18 years old. †The “Other” category is comprised of the following complaints: Pulmonary/Cardiac/Upper Respiratory Infections (n ⫽ 8), Nonhemophilia related pain (n ⫽ 6), Abdominal complaint/pain (n ⫽ 5), Hemophilia related infusion only (n ⫽ 1), Hemophilia related pain (n ⫽ 1).
TABLE 4. ED Visits Resulting in Discharge Without Appropriate Treatment
Age (years)
Diagnosis (deficiency)
2 11 13
Mild IX Severe IX Mild IX
22
Mild VIII
22 31
Mild VIII Mild VIII
34 43
Mild VIII Mild IX
49
Moderate IX
78
Moderate VIII
Problem Elbow trauma Abdominal pain Traumatic elbow hemarthrosis Thigh trauma Forearm hemorrhage Hematemesis/infiltrate on chest x-ray film Hematemesis Abdominal pain/blood in stool Shoulder/epigastric pain Bleeding foot
Reason for no Treatment With DDAVP or Factor Concentrate None None None No factor concentrate at hospital No DDAVP in hospital None None None None None
of factor concentrate. The primary hemophilia-care provider was contacted for one of these visits. On 5 visits (7.7%, 95% CI⫽2.6, 17.1) when factor concentrate was administered, the dose given was not recorded; 4 of the 5 visits were by one child to the same ED. The primary hemophilia-care provider was contacted just once. The frequency of factor concentrate infusions for which the brand name and lot number were recorded is shown in Table 5. Overall, the brand name of concentrate was recorded on 13.9% (95% CI⫽6.5, 24.7) of the records. Whether recombinant or pooled human plasma-derived concentrate had been administered could be discerned for 40% (95% CI⫽28.0, 52.9) of the infusions. The lot number administered was indicated on 24.6% (95% CI⫽14.8, 36.9) of records. DDAVP was prescribed on 8 visits. This includes one visit by an individual who was not a candidate for DDAVP. The DDAVP dose was recorded as milligrams per kilogram on 2 records although the correct dose is on a microgram per kilogram basis. One record had no dose for DDAVP recorded. The primary hemophilia care provider was contacted for just one of the visits. Narcotics were prescribed to 6 males (11.8%, 95% CI⫽4.4, 23.9) who visited the ED. They received narcotics on 19 of their 21 ED visits (15.2%, 95% CI⫽9.4, 22.7 of all ED visits). Five of the 6 males were 21 years of age or older. Three of the 6 males had an inhibitor. The primary need for narcotics was to treat hemophilia-associated bleeding pain. Ten coagulation blood tests were obtained on 6 males presenting to the ED with known hemophilia in their steady TABLE 5. Infused
Frequency of Documentation for Factor Concentrates VIII Concentrate N (%; 95% CI)
Brand name Generic Recombinant Intermediate Lot number Total
IX Concentrate N (%; 95% CI)
6 (13.3; 5.1, 26.8) 0 29 (64.4; 47.8, 78.1) 9 (81.8; 48.2, 97.7) 9 (20; 9.5, 34.6) 2 (18.2; 2.3, 57.8) 1 (2.2; 0.1, 11.8) 0 13 (28.9; 16.4, 44.3) 1 (9.1; 0.2, 41.3) 45 11
Bypassing Concentrate N (%; 95% CI) 3 (37.5; 8.5, 75.5) 0 0 5 (62.5; 24.5, 91.5) 2 (25; 3.2, 65.1) 9
NUSS, HOFFMAN, AND HAMMOND ■ ED VISITS BY MALES WITH HEMOPHILIA
state. The tests were: 7 prothrombin times, 2 activated partial thromboplastin times, and 1 factor VIII activity. None were clinically indicated. Forty-three males had plain radiographs done in the ED. There were appropriate indications for all but one radiograph (2.3%, 95% CI⫽0.1, 12.3). Eighty-six percent of emergency discharge notes instructed follow-up with either the patients primary care provider or hematologist. Sixty-seven percent of discharge plans specifically mentioned follow-up care for hemophilia. DISCUSSION People with hemophilia frequently seek care in the ED; almost 20% of Coloradans with hemophilia visited the ED one or more times in 1998. The rate of ED visits by Coloradans with hemophilia was 45 per 100 hemophiliac people. This compares with the 1996 National Hospital Ambulatory Medical Care Survey (NHAMCS) estimated rate of 34.2 ED visits per 100 people in the general population.8 Twenty percent of males with hemophilia who visited the ED required hospitalization as compared with NHAMCS data showing that 11% of ED visits by the general population lead to hospitalization.8 Thus, although males with hemophilia visit the ED about as often, they are twice as likely to be admitted to the hospital from the ED than the general population. Although 18% of the hemophilia population studied were HIV-infected, only 9% of ED visits were for HIV-associated problems. As expected, the primary reason for ED visits, independent of age, was for hemorrhagic complications; hemorrhage was the impetus for 65% of ED visits. Despite a report of hemophilia, for reasons unknown, physicians chose to screen for a bleeding disorder on 11% of visits. The laboratory tests were not clinically indicated. Our study found serious problems with the care delivered to males with hemophilia in the ED and it’s documentation. Thirteen percent of hemorrhagic events warranted treatment, but were untreated. Seventy percent of males untreated had mild disease and thus generally have limited experience with hemorrhage and rely on medical advice. Negligence has previously been shown in reviews of general ED care in Colorado and Utah and in the Harvard Medical Practice study to be the cause of 70 % to 95% of ED adverse events.9,10,11,12 In our study 1 of 10 untreated males, returned to the ED with an elbow hemarthrosis which may have been prevented had treatment initially been given. We also found that on 12% of visits when males were treated for bleeding, either the wrong medication or wrong dose was prescribed. The Institute of Medicine has reported that medication errors kill 7,000 males per year.13 The leading error is incorrect drug calculations and ordering. We found the ordering documentation was critically inadequate. Most commonly recorded in the ED physicians records was the generic name, “antihemophilic factor” which is not sufficient or useful for surveillance of complications. Factor concentrates are produced in batches and each vial is labeled with a brand name and lot number so that when infectious and immunologic complications arise this information is used to identify males at risk. For example, the brand name and lot numbers recorded on hospital records
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have been used to identify and test males who received contaminated factor concentrates in the 1980s and were exposed to hepatitis C and HIV. This information has also been used to identify particular batches of factor concentrate that were more immunogenic and induced a higher rate of inhibitor formation. Although our study was restricted to reviewing the records in one state for 1 year, the findings suggest there is room for improvement in the care delivered to males with hemophilia in the ED and its documentation. One major determinant of adverse events during hospitalization has been shown to be disease complexity.11 Given the rarity and complexity of hemophilia and the ever-changing array of treatment products, ED physician should not treat hemophilia patients in isolation. Hemophilia resources are available and should be accessed. As indicated earlier, many males with hemophilia have received extensive education about their disease and their knowledge should be sought and seen as helpful, rather than adversarial.5 There are published guidelines for emergency care for males with hemophilia which EDs should have on hand.14,15 The ED staff should be aware that most males with hemophilia who attend treatment centers carry a card with them which indicates their diagnosis, treatment products, and hematology physician, with an on-call telephone number. The emergency staff should contact the primary hemophilia careprovider for advice. We believe a more comprehensive surveillance study of ED care of males with hemophilia is warranted. In the interim, based on our findings, we recommend greater collaboration between the ED physician and the primary hemophilia-care giver with the goal of improving hemophilia care. REFERENCES 1. Soucie JM, Evatt B, Jackson D, and the Hemophilia Surveillance System Project Investigators: Occurrence of hemophilia in the United States. Am J Hem 1998; 59: 288-294 2. DiMichele D, Neufeld EJ: Hemophilia: A new approach to an old disease. Hematol Oncol Clin North Am 1998; 12: 1315-1344 3. Nuss R, Hedegaard H, Riske B, et al: Medical care for haemophilia. Haemophilia 1998; 4: 806-811 4. Soucie JM, Nuss R, Evatt B, et al: Mortality among males with hemophilia: Relations with source of medical care. Blood 2000; 96: 437-442 5. Anonymous: Emergency room care for hemophilac patients. Understanding and overcoming difficulties. J Florida Med Assoc 1993; 80: 250-4 6. Hemophilia of Georgia, U.S.A.: Protocols for the treatment of haemophilia and von Willebrand disease. Haemophilia 2000; 6: 84-93 7. Pezzullo JC: Exact Binomial and Poisson Confidence Intervals. Available at http://davidmlane com/hyperstat/confidence_intervals html. Accessed June 19, 2001 8. McCaig LF, Stussman BJ: National Hospital Ambulatory medical care survey: 1996 ED summary. Advance data from vital and health statistics; no. 293. Hyattsville, MD, National Center for Health Statistics, 1997 9. Thomas EJ, Studdert DM, Burstin HR, et al: Incidence and types of adverse events and negligent care in Utah and Colorado. Med Care 2000; 38: 261-271 10. Brennan TA, Leape LL, Laird NM, et al: Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I. N Engl J Med 1991; 324: 370-6 11. Leape LL, Brennan TA, Laird N, et al : The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377-84
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12. Localiao AR, Lawthers AG, Brennan TA, et al : Relation between malpractice claims and adverse events due to negligence. Results of the Harvard Medical Practice Study N Engl J Med 1991; 325: 245-51 13. Kohn LT, Corrigan JM, Donaldson MS (eds): To err is human: Building a safer healthcare system. Institute of Medicine report. Washington, DC, National Acadamy Press, 1999
14. Wulff, K, Zappa S, Womack M (eds): The Nursing Group of Hemophilia Region VI.: Emergency care of patients with hemophilia. An instructional manual for medical professionals (ed 2). Oklahoma City, OK, Corporate Communications, 1999 15. Hathaway WE, Goodnight Jr. SH (eds): Disorders of Hemostasis and Thrombosis. A Clinical Guide (ed 2). Mc-Graw Hill, New York, 2001