celebrating 60 years of caring nhf nursing luncheon november 14, 2008 jim munn, rn, ms
TRANSCRIPT
Celebrating Celebrating 60 Years of 60 Years of
CaringCaringNHF Nursing LuncheonNHF Nursing Luncheon
November 14, 2008November 14, 2008
Jim Munn, RN, MSJim Munn, RN, MS
For it was taught: If she circumcised her first child and he died [as a result of bleeding from the operation] and a second one died [similarly], she must not circumcise her third child.
R. Judah, the Patriarch, redactor of the Mishnah
Rosner F. Medicine in the Bible and the Talmud, revised ed, New York: Yeshiva University Press, Ktav Publishing House, 1995.
Hemophilia: Early Hemophilia: Early ObservationsObservations
- Second Century- Second Century
Early ObservationsEarly Observations
Tenth Century Islamic Surgeon Abul Qasim Tenth Century Islamic Surgeon Abul Qasim Al-Zahravi (Albucasis) 936-1013 CE Al-Zahravi (Albucasis) 936-1013 CE – Considered greatest surgeon of Middle AgesConsidered greatest surgeon of Middle Ages– Referred to a condition interpreted by scholars Referred to a condition interpreted by scholars
as hemophilia in his encyclopedic work on as hemophilia in his encyclopedic work on medicine and surgery, medicine and surgery, al-Tasrifal-Tasrif
Al-Tasrif Uman ‘Ajiza An Al-Taalif.
Early Early ObservationsObservations
““If a woman had her first son If a woman had her first son circumcised and he died as circumcised and he died as a result of the circumcision, a result of the circumcision, which enfeebled his which enfeebled his strength, and she similarly strength, and she similarly had her second [son] had her second [son] circumcised and he died as circumcised and he died as a result of the circumcision a result of the circumcision - whether [the latter child] - whether [the latter child] was from her first husband was from her first husband or her second husband - the or her second husband - the third son may not be third son may not be circumcised at the proper circumcised at the proper time [on the eighth day of time [on the eighth day of life]…”life]…”22
1. Rosner F. “Moses Maimonides.” Ann Intern Med. 1965;372:1135-1204.2. Mishneh Torah, Hilkhot Milah. 1:18.
Twelfth Century Physician and Talmudist Maimonides states in the Mishneh Torah1
Early ObservationsEarly Observations
1803: John Conrad Otto1803: John Conrad Otto Provided first accurate Provided first accurate
account of hemophilia in account of hemophilia in the modern medical the modern medical literature literature
His investigation of His investigation of “bleeders” was published in “bleeders” was published in a New York journal under a New York journal under the title, “An Account of an the title, “An Account of an Hemorrhagic Disposition Hemorrhagic Disposition Existing in Certain Families”Existing in Certain Families”
Traced to woman who Traced to woman who settled in Plymouth, New settled in Plymouth, New Hampshire in 1720Hampshire in 1720
Otto JC. The Medical Repository. 1803;Vol VI (No 1):1-4.
Early ObservationsEarly Observations
1820:1820: Nasse of BonnNasse of Bonn– GermanGerman physician 1778-1851physician 1778-1851– Formulated observations on Formulated observations on
inheritance of hemophiliainheritance of hemophilia– ““Nasse’s Law” Nasse’s Law”
Transmitted by unaffected females to Transmitted by unaffected females to their sonstheir sons
Nasse CF. Arch Med Erfahr. 1(1820):385.
Early ObservationsEarly Observations 1828: 1828: The word “hemophilia” first appears The word “hemophilia” first appears
in a description of inherited bleeding in a description of inherited bleeding disorders by Physician Frederick Hopff at the disorders by Physician Frederick Hopff at the University of ZurichUniversity of Zurich
1840: 1840: First recorded case of hemophilia First recorded case of hemophilia treatment by transfusion written by Samuel treatment by transfusion written by Samuel Lane in Lane in The Lancet The Lancet 11
1893: 1893: First documentation of abnormal First documentation of abnormal prolongation of coagulation in capillary tube prolongation of coagulation in capillary tube in hemophilicsin hemophilics22
1. Farr AD. J Royal Soc Med. April 1981;74(4):301-305.2. Wright AE. Br Med J. 1893;2:223-225.
Early Observations: Early Observations: Other Highlights of the Early Other Highlights of the Early 1900s1900s
1911: 1911: Publication of “monumental review of Publication of “monumental review of pedigrees of families with bleeding disorders”pedigrees of families with bleeding disorders”11
1920-1930: 1920-1930: Hemophilia treatments published; Hemophilia treatments published; plasma for transfusions introducedplasma for transfusions introduced
1926: 1926: Erik vonWillebrand describes bleeding Erik vonWillebrand describes bleeding disorder affecting both sexesdisorder affecting both sexes
1937: 1937: IV administration of redissolved plasma IV administration of redissolved plasma precipitate shown to shorten blood clotting timeprecipitate shown to shorten blood clotting time22
1937:1937: First permanent blood bank established in First permanent blood bank established in USUS
1. Ingram GIC. J Clin Pathol. 1976;6:3.2. Brinkhous KM. A Short History of Hemophilia. Handbook of Hemophilia. New York: American Elsevier, 1975.
1940s1940s
Early to Mid-1940s:Early to Mid-1940s: Medical progress accompanies Medical progress accompanies warwar– Charles Drew sets standard for collecting, storing Charles Drew sets standard for collecting, storing
and transporting plasma under “battlefield and transporting plasma under “battlefield conditions”conditions”
– Edwin Cohn, Harvard biochemist, first to use Edwin Cohn, Harvard biochemist, first to use fractionation process to produce albumin in 1944fractionation process to produce albumin in 194411
– Albumin usefulness spurs research in blood Albumin usefulness spurs research in blood component therapy by “clotters” component therapy by “clotters”
– 1946-1947: 1946-1947: Hemophilia defect in plasma Hemophilia defect in plasma componentcomponent22
1. Latham A Jr. Vox Sang. 1986;51(3):249-52.2. Brinkhous KM. Proc Soc Exper Biol and Med. Oct. 1947;66:117-120.
1940s1940s
1948: 1948: A golden decade A golden decade for coagulation for coagulation research beginsresearch begins
Hemophilia Hemophilia Foundation Foundation established 6/15/48established 6/15/48
Hemophilic dog Hemophilic dog colony established: colony established: Chapel Hill, North Chapel Hill, North CarolinaCarolina
Smith N. A History of the National Hemophilia Foundation. New York: National Hemophilia Foundation, 1984.
©UNC Center for Thrombosis and Hemostasis
1950s1950s
First First recommendation recommendation for home infusion for home infusion
1959: First 1959: First hemophilia hemophilia treatment center treatment center in Rochester, NYin Rochester, NY
Smith N. A History of the National Hemophilia Foundation. New York:National Hemophilia Foundation, 1984.
Photos of Mary Gooley (above) courtesy of theMary M. Gooley Hemophilia Center, Rochester, NY
1950s1950s
Biggs R, et al. Br Med J. Dec. 27, 1952;1378. With permission from BMJ Publishing Group.
1950s1950s
1952: 1952: Evolution of the definition of hemophilia:Evolution of the definition of hemophilia:– A A blood clotting disorder affecting males with blood clotting disorder affecting males with
two possible major protein deficiencies: two possible major protein deficiencies: • FVIII - Hemophilia A FVIII - Hemophilia A • FIX - Hemophilia BFIX - Hemophilia B
– Thromboplastin generation test for measuring Thromboplastin generation test for measuring FVIII developedFVIII developed
– Coagulation cascade discoveredCoagulation cascade discovered
Langdell RD, et al. J Lab Clin Med. 1953;41:637-647.
1950s1950s
1958: 1958: First use of prophylaxis in Hemophilia First use of prophylaxis in Hemophilia A conducted in Sweden by Prof. Inga A conducted in Sweden by Prof. Inga Marie NilssonMarie Nilsson
1960s1960s
1960s:1960s: NIH grants create research climateNIH grants create research climate 1961: 1961: Hyland Laboratories begins work on FVIII Hyland Laboratories begins work on FVIII
concentrateconcentrate 1966: 1966: Peanut flour touted as treatment for Peanut flour touted as treatment for
hemophilia – hemophilia – Nature Nature 11
1. Nature. February 13, 1969. Vol. 185, No. 4711, pp. 469-470.
1960s1960s
1965:1965:Discovery ofDiscovery ofCryoprecipitateCryoprecipitateJudith Graham Pool, Judith Graham Pool,
MDMD
File photo courtesy of HANDI, NHF.
Pool JG, Shannon AE. N Engl J Med. 1965:273:1443-1447.
1960s1960s
1966: 1966: Hyland Hyland announces announces commercial commercial availability of FVIII availability of FVIII concentratesconcentrates
1969:1969: FIX FIX concentrate concentrate licensedlicensed11
1. Hoag MS, et al. N Eng J Med.1969;280(11):581-6.
1960s1960s
Continuous infusionContinuous infusion Predictable and sustained level over timePredictable and sustained level over time Cost savings due to decreasedCost savings due to decreased
– Laboratory evaluationsLaboratory evaluations– Clearance over timeClearance over time
Ideal replacement for surgical interventions Ideal replacement for surgical interventions and specific bleeding episodes in hemophilia and specific bleeding episodes in hemophilia
McMillan CW, et al. Br J Haematol. 1970;18:659-667.Hathaway WE, et al. Am J Hematol.1984;17:85-88.Shulman NR, et al, Ann Intern Med. 1967;67:856.
1969: 1969: First hemophilia camp established First hemophilia camp established
1960s1960s
1970s1970s 1970s:1970s: Home infusion therapy: a commonHome infusion therapy: a common treatment practice treatment practice 1971:1971: von Willebrand’s factor identified¹ von Willebrand’s factor identified¹ 1974:1974: First successful immune tolerance² First successful immune tolerance² 1975: 1975: Federally funded comprehensive Federally funded comprehensive
hemophilia treatment centers initiatedhemophilia treatment centers initiated 1977: 1977: Mannucci discovers DDAVP increases Mannucci discovers DDAVP increases
FVIII and vWF levelsFVIII and vWF levels33
1. Zimmerman, TS, et al. J Clin Invest.1971;50:244-254.2. Brackmann HH, Lancet 1977; 2 (8044): 933.3. Mannucci PM. Lancet. 1977;1:869-872.
Regional Hemophilia Regional Hemophilia Treatment Center Treatment Center NetworkNetwork
1970s1970s
Revisiting use of Prophylaxis Revisiting use of Prophylaxis UK study – 9 boys with Hem A <1%UK study – 9 boys with Hem A <1%- Randomized, blinded, crossover studyRandomized, blinded, crossover study- Had target joints presentHad target joints present- Received 25% correction with FVIII or placebo once a Received 25% correction with FVIII or placebo once a
week, followed by week of restweek, followed by week of rest- Showed 15% reduction in bleeding episodes in 100 Showed 15% reduction in bleeding episodes in 100
day period (from 13.6 episodes to 11.6)day period (from 13.6 episodes to 11.6)- 66% decrease in bleeds in first three days of the 66% decrease in bleeds in first three days of the
weekweek Aronstam. 1976. Aronstam. 1976. Brit J Haematol. Brit J Haematol.
33:81.33:81..
1970s1970s
Transmission of blood-borne diseases:Transmission of blood-borne diseases:– Hepatitis B: HBVHepatitis B: HBV– Hepatitis non-A, non-B: Later called “C”Hepatitis non-A, non-B: Later called “C”– HIVHIV
Mannucci PM, et al. J Clin Pathol. 1975;28(8):620-624.Schramm W, et al. Blut. 1989;59(4):390-392.
Hepatitis B Virus: HBVHepatitis B Virus: HBV
Lipid-enveloped DNA virus Lipid-enveloped DNA virus Replicates within liver cellsReplicates within liver cells Transmitted by exchange of Transmitted by exchange of
bodily fluids bodily fluids 90% recover with immunity; 90% recover with immunity;
10% develop chronic HBV of 10% develop chronic HBV of which 20-30% progress to which 20-30% progress to cirrhosiscirrhosis
Virion sensitive to heat and Virion sensitive to heat and solvent/detergentsolvent/detergent
1981:1981: Hep B vaccine plasma Hep B vaccine plasma derivedderived
1987:1987: Hep B vaccine Hep B vaccine recombinant licensedrecombinant licensed Electron micrograph of Hepatitis B
Virions courtesy of the CDC
The Price of The Price of IndependenceIndependenceNon-A, non-B (Hepatitis C)Non-A, non-B (Hepatitis C) recognized recognized
as transmissible via plasma-derived as transmissible via plasma-derived productsproducts– 1986: Commercial screening for non-A, non-1986: Commercial screening for non-A, non-
B hepatitis surrogate markersB hepatitis surrogate markers– 1989: Hepatitis C isolated1989: Hepatitis C isolated– 1990: Hepatitis C Ab testing of donated 1990: Hepatitis C Ab testing of donated
blood beginsblood begins
Hepatitis C Virus: Hepatitis C Virus: HCVHCV
Lipid-enveloped RNA virus Lipid-enveloped RNA virus Replicates within infected liver cellsReplicates within infected liver cells Transmitted by the exchange of bodily fluids Transmitted by the exchange of bodily fluids 85% or more with acute HCV infection 85% or more with acute HCV infection
progress to chronic hepatitisprogress to chronic hepatitis**
Virion sensitive to heat and solvent/detergent Virion sensitive to heat and solvent/detergent No vaccine availableNo vaccine available
* Seeff LB. Am J Med. Dec. 1999;107[6B]:10S-15S.
1980s1980s
MMWR July 16, 1982/31(27):365-367.
The Price of The Price of IndependenceIndependence
1983: 1983: Suspicion that HIV threatened the worldwide blood Suspicion that HIV threatened the worldwide blood supplysupply
April 1, 1983:April 1, 1983: Hemofil-T, first heat-treated FVIII concentrate in Hemofil-T, first heat-treated FVIII concentrate in the U.S.the U.S.
1984:1984: MontagnierMontagnier11 and Gallo and Gallo22 discover HTLV-3 (HIV) discover HTLV-3 (HIV) 1984:1984: Efficacy of heat treatment for viral inactivation Efficacy of heat treatment for viral inactivation
demonstrateddemonstrated 1984:1984: Recall of blood products initiatedRecall of blood products initiated 1985: 1985: ELISA test used to detect HIV antibodies among blood ELISA test used to detect HIV antibodies among blood
donorsdonors
1985:1985: Safety net: Safety net:
1. Barre-Sinoussi F, et al. Science 1983; 220(4599):868-71.2. Gallo RC, et al. Science 1984; 4;224(4648):500-3.
1. Donor deferral2. Viral inactivation methods3. HIV antibody testing
The Heroes We Care ForThe Heroes We Care For
Photo courtesy of Mary Lou Cygan, R.N., P.N.P.
1980s1980s
1990s1990s 1991 – Karolinska University – Stockholm,
Sweden
Dr. Petrini and colleagues describe prevention of joint disease in boys with hemophilia under age two.
Lusher, J. 2008. HemAware. 13: 8.
1990s1990s
Soucie JM, et al. Blood. 2000;96(2):437-442.
CharacteristicsCharacteristics HTC (%)HTC (%) Non-HTC (%)Non-HTC (%) PP
SeveritySeverity
MildMild 21.821.8 52.852.8 <.001<.001
ModerateModerate 24.224.2 26.726.7
SevereSevere 54.054.0 20.520.5
InhibitorsInhibitors 6.06.0 2.32.3 <.001<.001
Liver diseaseLiver disease 2.32.3 0.70.7 .002.002
HIV infectionHIV infection 31.131.1 17.117.1 <.001<.001
AIDSAIDS 8.28.2 5.95.9 .02.02
1990s1990s
Soucie JM, et al. Blood. 2000;96(2):437-442.
Mortality decreased Mortality decreased 40%40% in patients using a in patients using a comprehensive hemophilia treatment center comprehensive hemophilia treatment center (HTC(HTC))
““The finding that HTCs have a significant effect onThe finding that HTCs have a significant effect on
reducing mortality in patients with hemophilia supportsreducing mortality in patients with hemophilia supports
the effectiveness of such centers in providing the effectiveness of such centers in providing specializedspecialized
preventative care.”preventative care.”
1990s1990s
Prophylaxis recommendationProphylaxis recommendation PrimaryPrimary
– Early institution ~ 1-2 years with the aim of Early institution ~ 1-2 years with the aim of maintaining trough > 1%maintaining trough > 1%
– Longitudinal assessment of joint status essentialLongitudinal assessment of joint status essential SecondarySecondary
– Appropriate for intervention to prevent joint and Appropriate for intervention to prevent joint and other disease associated morbiditiesother disease associated morbidities
MASAC Recommendation #35. March 11, 1994.
2000s2000s
Gene therapy trials begunGene therapy trials begun Joint Outcome Study publishedJoint Outcome Study published11
National Pain SurveyNational Pain Survey Willetabs and Wilbrintin advertised as Willetabs and Wilbrintin advertised as
treatment for vWDtreatment for vWD
Manco-Johnson, et al. NEJM. 2007. Vol. 357:(6) 535-544.
Hemophilia A: Evolution of Hemophilia A: Evolution of TherapyTherapy
YearYear TherapyTherapy
19501950 Plasma (1-FVIII U/ml)Plasma (1-FVIII U/ml)
19661966 Cryoprecipitate (5-FVIII U/ml)Cryoprecipitate (5-FVIII U/ml)
19751975 Lyophilized concentrates (30-FVIII U/ml)Lyophilized concentrates (30-FVIII U/ml)
19831983 Heat treatment of lyophilized concentrates for viral Heat treatment of lyophilized concentrates for viral attenuationattenuation
19851985 Introduction of a solvent detergent for viral inactivationIntroduction of a solvent detergent for viral inactivation
19881988 Monoclonal antibody-purified FVIII concentrates with Monoclonal antibody-purified FVIII concentrates with heat or solvent detergent treatmentheat or solvent detergent treatment
19921992 Recombinant DNA products: 1Recombinant DNA products: 1stst generation generation
2000s2000s 22ndnd & 3 & 3rd rd generation recombinant productsgeneration recombinant products
Hemophilia B: Evolution of Hemophilia B: Evolution of TherapyTherapy
YearYear TherapyTherapy
19501950 Plasma (1-FIX U/ml)Plasma (1-FIX U/ml)
19751975 Lyophilized prothrombin complex concentrates or PCC Lyophilized prothrombin complex concentrates or PCC (30-FIX U/ml)(30-FIX U/ml)
19851985 Heat treatment of lyophilized concentrates for viral Heat treatment of lyophilized concentrates for viral attenuationattenuation
Development of a solvent detergent for viral Development of a solvent detergent for viral inactivationinactivation
19921992 Chromatographic/monoclonal antibody-purified FIX Chromatographic/monoclonal antibody-purified FIX concentrate with ultrafiltration and thiocyanate concentrate with ultrafiltration and thiocyanate treatmenttreatment
19971997 Recombinant DNA productRecombinant DNA product
The The FutureFuture Longer acting concentratesLonger acting concentrates Recombinant therapy for vWDRecombinant therapy for vWD Alternate route therapiesAlternate route therapies Gene transplantationGene transplantation Elimination of transfusion-associated infectionsElimination of transfusion-associated infections Understand and overcome inhibitor Understand and overcome inhibitor
developmentdevelopment Quality of life issuesQuality of life issues
– Elimination of joint morbidityElimination of joint morbidity– Optimizing the individual’s social and academic Optimizing the individual’s social and academic
performanceperformance
…the promise of achieving your potential
The Future…The Future…