Table C.1 Chronological Summary of Critical Events, NHF Communications,
Critical Event |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
July 16, 1982: CDC MMWR reports immunesuppressive disorder identified in three hemophiliac patients |
July 14, 1982: Patient Alert #1 sent to NHF chapters and treatment centers |
Speculation that it may be transmitted similarly to hepatitis virus by blood and blood products |
Risk is minimal |
No change in treatment |
Dr. Aledort, NHF medical co-director to serve on PHS task force |
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Surveillance and reporting system being planned by CDC with NHF cooperation |
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''Dear Colleague" letter sent (July 19, 1982) to physicians by Dr. Aledort asking them to report any cases to state health departments and the NHF |
July 16, 1982: FDA Office of Biologics holds information exchange meeting on the three cases with NHF and CDC representatives |
July 19, 1982: Chapter Advisory #2 issued |
Cause of disease unknown |
No indication blood products are involved |
No change in treatment (refers to this as a CDC recommendation) |
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Epidemic known by CDC in some homosexuals and recent Haitian immigrants |
Risk is minimal |
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CDC investigating: (1) linkage between hemophiliacs and other populations; (2) whether the disease may be a virus transmitted similarly to hepatitis by blood products |
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July 27, 1982: PHS meeting on opportunistic infections in hemophiliacs |
July 30, 1982: NHF issues Medical Bulletin #2 and Chapter Advisory #3 (no mass mailings to chapter members required) |
The cause of the dysfunction found in three hemophiliacs is unknown, now defined as AIDS |
No information provided |
No information provided |
NHF agrees to work with CDC, FDA, and NIH to establish surveillance system of hemophiliacs with symptoms of opportunistic infections |
Critical Event |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
December 10, 1982: CDC MMWR reports four additional cases in hemophiliacs and one suspect case in an infant who had received a blood transfusion |
December 9, 1982: NHF issues Chapter Advisory #4 |
Two cases are children with hemophilia |
Illness may pose a significant risk for hemophiliacs |
Advisable not to introduce concentrates to patients who have never used them before (e.g., newborns, children under age 4, newly diagnosed cases, and mild hemophiliac cases) |
NHF sends out December 10 CDC MMWR to chapter members and emphasizes that patients and parents should be aware of potential risks |
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December 10, 1982: Medical Bulletin #3 issued |
Not acquired from contact with each other or other high-risk groups |
Increased concern that AIDS may be transmitted through blood products |
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December 21, 1982: NHF issues Medical Bulletin #4 and Chapter Advisory #5 |
All cases exposed to Factor VIII, no common lots found |
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No change in treatment for those who have received factor concentrates, and one should not withhold the use of clotting factor therapy when needed |
NHF provides treatment alternatives to chapter members for individuals not previously exposed to concentrate |
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No conclusive evidence that cryoprecipitate or fresh frozen plasma will reduce the risk of AIDS |
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January 4, 1983: CDC meeting in Atlanta to review data |
January 17, 1983: NHF issues Medical Bulletin #5 and Chapter Advisory #6 |
Growing incidence and increasing concern among hemophiliac patients that AIDS may be transmitted through blood products |
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Cryoprecipitate should be used for newborns and children under age 4 |
MASAC meeting on January 14, 1983, issues 12 recommendations to prevent AIDS in hemophiliac patients; the clinical options (at left) were recommendations made to physicians |
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Benefits of using cryoprecipitate therapy vs. factor concentrate for severe hemophilia A are under review |
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Critical Event |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
March 4, 1983: PHS issues recommendations to reduce the risk of AIDS |
March 9, 1983: NHF issues Medical Bulletin #6 and Chapter Advisory #7 |
Sexual contact should be avoided with persons known or suspected to have AIDS; multiple sex partners increase the probability of developing AIDS |
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Physicians should adhere strictly to medical indications for transfusions, and autologous blood transfusions are encouraged |
NHF urges Congress to provide additional funding to support AIDS research |
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NHF issues mental health report to orient those who treat hemophiliacs to the potential impact of AIDS and asks for medical observations, such as: the impact of the AIDS threat (e.g., number of calls from patients); behavioral or emotional problems; evidence of withholding or refusing factor replacement for acute bleeds; and the treatment center's response |
May 1983: Hyland Therapeutics recalls lot—a donor was identified who developed AIDS |
May 11, 1983: NHF issues Medical Bulletin #7 and Chapter Advisory #8 |
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Risk is low (12 hemophiliacs out of 20,000 developed AIDS) |
NHF and NHF AIDS Task Force recommends hemophiliacs maintain use of clotting-factor treatment |
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August 25–26, 1983: Hyland Therapeutics and ARC announce recall of lots (two each) from identified donors who were confirmed to have died of AIDS |
September 7, 1983: NHF issues Chapter Advisory #9 |
Not scientifically established that AIDS is transmitted through blood products |
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NHF reaffirms its recommendation that patients maintain use of concentrate or cryoprecipitate as prescribed by their physicians |
October 31, 1983: Cutter Laboratories announces withdrawal of 13 lots of Factor VIII and 1 lot of Factor IX, all from a donor who recently died of AIDS |
November 2, 1983: NHF issues Chapter Advisory #11 |
Not scientifically established that AIDS is transmitted through blood products |
Only a fraction of 1% of all hemophiliacs have contracted AIDS |
Despite the concern that may be raised by the recall of plasma products, the NHF reaffirms its recommendation that patients maintain the use of concentrate or cryorecipitate as prescribed by their physicians |
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No common lots have been identified, thus suggesting the great majority of hemohiliacs are not susceptible to AIDS |
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Critical Event |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
December 2, 1983: CDC MMWR update on AIDS in hemophiliac patients; results of treatment center survey show no cases occurred before September 1981; 21 hemophiliacs have been diagnosed with AIDS, additional patients have been reported with AIDS-related symptoms that do not fit the CDC criteria for an AIDS diagnosis |
December 2, 1983: NHF issues Medical Bulletin #8 with attached CDC MMWR (December 10); Medical Bulletin #9 and Chapter Advisory #12 issued on December 21, 1983 |
Etiology remains unknown, epidemiological evidence suggests an infectious disease |
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MASAC revises January 14, 1983, recommendations to prevent AIDS: adds modification of donor screening language; screen donors for symptoms; expedite the development of processing methods to inactivate viruses potentially present in factor concentrates |
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Possibility of transmission by blood and blood products is supported by increased incidence of AIDS in IV drug users and transfusion recipients |
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Cryoprecipitate and factor concentrates are associated with transmission of known viral agents (i.e., cytomegalovirus, hepatitis B, and non-A, non-B hepatitis) |
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January 16, 1984: Alpha Therapeutic recalls three lots contaminated with AIDS from a donor diagnosed with AIDS |
NHF issues Medical Bulletin #10 and Chapter Advisory #13 |
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NHF reaffirms its recommendation that patients maintain use of concentrate or cryoprecipitate as prescribed by their physicians |
MASAC recommends to blood product manufacturers that any lot of concentrate be recalled if it includes material from an individual who has been identified as having AIDS, or from an individual who, in the best judgment of the manufacturers, has characteristics strongly suggestive of AIDS |
January 1984: Annals of Internal Medicine publishes article on sexual transmission of AIDS |
January 30 and February 3, 1984: NHF issues Medical Advisory #11 and Chapter Advisory #14 |
First case of sexually transmitted AIDS from hemophiliac to spouse: a 70-year-old hemophiliac died of AIDS in May 1983; his wife had developed symptoms in January 1982 |
In the medical and scientific communities there are different points of view about whether sexual partners of hemophiliacs are at increased risk for AIDS; but all agree that if sexual partners are at increased risk for AIDS, the risk is "truly remote" |
Individual patients and their treaters need to consider whether or not they wish to use prophylactic methods if diagnosed with AIDS or strongly suspected of having AIDS; discuss with physician or treatment center team matters concerning sexual activity |
NHF recommends open discussion between sexual partners and advice from physicians |
Critical Event |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
April 2, 1984: core testing initiated |
April 16, 1984: NHF issues Chapter Advisory #15 |
January–March 1984:9 new cases of AIDS among hemophiliacs, total now is 33; fluctuations, such as an increase in the number of AIDS cases, are due to the small number base of hemophiliacs; antibody to hepatitis B core protein is found in many of the high-risk groups |
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DDAVP approved by FDA |
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April 1984: Lancet publishes Montagnier's isolation of LAV; Science publishes Gallo's isolation of HTLV-III (September 1985) |
May 9, 1984: NHF issues Chapter Advisory #16 |
HTLV-III may cause AIDS; both a test and a vaccine are several years away; genetic production of Factor VIII will reportedly also be available in several years |
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July 13, 1984: CDC MMWR reported 72% of severe asymptomatic hemophiliac had antibody to LAV antigens using the Western blot test |
July 31, 1984: NHF issues Chapter Advisory #17 and Medical Bulletin #12 |
HTLV-III/LAV implicated as the causative agent for AIDS; too early for scientific information about the relationship between testing positive and having AIDS |
Testing positive for HTLV-III/LAV does not suggest a diagnosis of AIDS |
No information from NHF; CDC MMWR states that prevention measures should stress that transmission has been only from sexual contact, sharing of contaminated needles, and, less often, from transfusion of blood or blood products |
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August 31, 1984: Alpha Therapeutic recalls four lots of Factor VIII and four lots of Factor IX from an identified donor who was confirmed to have AIDS |
September 6, 1984: NHF issues Medical Bulletin #13 and Chapter Advisory #18 |
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NHF reaffirms its recommendation that patients maintain use of concentrate or cryoprecipitate as recommended by their physicians |
MASAC reaffirms October 23, 1983, policy on recall |
Critical Even |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
October 5, 1984: ARC recalls AHF found to have been from a single donor who developed AIDS |
October 13, 1984: NHF issues Medical Bulletin #15 and Chapter Advisory #20 containing MASAC recommendations concerning AIDS and the treatment of hemophilia |
Heat-treated products appear to have no negative impact in terms of inhibitor development from heat treatment |
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On October 13, 1984, MASAC revises its recommendations: treaters using coagulation factor concentrates should strongly consider changing to heat-treated products |
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Insufficient data to know with certainty whether heat-treated products should be universally adopted; preliminary evidence suggests that HTLV-III/LAV is heat labile |
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Reevaluate all elective surgical procedures |
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Use DDAVP for mild or moderate hemophiliacs |
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Cryoprecipitate should be used for newborns, children under age 4, and newly diagnosed patients; continue treating bleeding episodes with clotting factor as prescribed by their physicians |
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Provide patient education and psychosocial support |
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October 26, 1984: CDC MMWR reports information on the viral inactivation success of heat treatment |
November 5, 1984: NHF issues Medical Bulletin #16 and Chapter Advisory #21 |
MMWR provides scientific evidence on the efficacy of heat treatment |
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NHF reiterates MASAC recommendation that treaters should strongly consider changing to heat-treated products |
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November 4, 1984: the media reports that 70%–90% of hemophiliacs are infected with AIDS |
November 5, 1983: NHF issues Medical Bulletin #17 and Chapter Advisory #22 in response to misleading information |
58 Cases of AIDS in hemophiliacs; 32 have died |
The presence of antibodies for HTLV-III/LAV does not suggest a diagnosis of AIDS |
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FDA licenses three manufacturers for heat-treated Factor IX (1984) |
December 11, 1984: NHF issues ''sensitive" Medical Bulletin (#19) that includes a list of AIDS cases among hemophiliacs; 58 cases are listed. |
Not known whether heat changes effectiveness for patients with inhibitors |
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Treaters should strongly consider changing to heat-treated products; studies are under way to determine efficacy for hepatitis |
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December 12, 1984: NHF issues Medical Bulletin #18 and Chapter Advisory #23 |
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Critical Event |
NHF Communication |
Knowledge Base |
Risk Assessment |
Clinical Option |
NHF Action |
October 1984: CDC determines that heat treatment is effective against HIV |
December 4, 1985: NHF issues Medical Bulletin #32 and Chapter Advisory #37 |
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MASAC recommends (and the NHF Executive Committee approves) that physicians prescribe only heat-treated products for patients who do not have inhibitors |
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Heat-treated products should be used for newborns, children under age 4, and newly diagnosed hemophiliacs |
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Hepatitis B vaccine should be administered shortly after birth because of the problem of non-A, non-B hepatitis (not eliminated with heat treatment) risks and benefits should be weighed for each individual |
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DDAVP should be used for mild or moderate hemophilia A patients; when it does not work, these patients should be treated with cryoprecipitate; for newborns, children under age 4, and newly identified patients with mild or moderate factor IX deficiency, fresh frozen plasma can be used, but in many circumstances, heat-treated product Factor VIII or IX may be the more appropriate therapy |
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