Low‐dose surgical prophylaxis: Optimization of use of World Federation of Hemophilia Humanitarian Aid donated clotting factor concentrates to developing countries

Abstract The current mainstay of therapy for hemophilia is to replace the deficient clotting factor with the intravenous administration of exogenous clotting factor concentrates. Prophylaxis factor replacement therapy is now considered the standard of care in both pediatric and adult patients with hemophilia with a severe phenotype to protect musculoskeletal health and improve quality of life. Heterogeneity in bleeding presentation among patients with hemophilia due to genetic, environmental, and treatment-related factors has been well described. Accordingly, the World Federation of Hemophilia recommends an individualized prophylaxis regimen that considers the factors mentioned above to meet the clinical needs of the patient, which can vary over time. This review focuses on the practical points of choosing the type of factor concentrate, dose, and interval while evaluating appropriate target trough factor levels and bleeding triggers such as level of physical activity and joint status. We also discuss the use of a pharmacokinetics assessment and its incorporation in the clinic for a tailored approach toward individualized management. Overall, adopting an individualized prophylaxis regimen leads to an optimal utilization of factor concentrates with maximum efficacy and minimum waste.

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Antibody to Hepatitis G Mrus after a Vapour-Heated Factor Vlll Goncentrate

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647291 ◽

1990 ◽

Vol 64 (02) ◽

pp. 232-234 ◽

Cited By ~ 21

Author(s):

P M Mannucci ◽

A R Zanetti ◽

M Colombo ◽

A Chistolini ◽

R De Biasi ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B ◽

Factor Viii ◽

Alanine Aminotransferase ◽

Household Contact ◽

Clotting Factor ◽

Double Infection ◽

Marked Elevation ◽

Clotting Factor Concentrates

SummaryTo evaluate whether or not clotting factor concentrates exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984–1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti- HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.

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Azidothymidine (AZT) in the Treatment of Symptomatic HIV-1-Infected Hemophiliacs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647263 ◽

1990 ◽

Vol 64 (01) ◽

pp. 108-112 ◽

Cited By ~ 5

Author(s):

S Eichinger ◽

I Pabinger ◽

H Hartl ◽

C Stain ◽

S Mayerhofer ◽

...

Keyword(s):

Risk Groups ◽

Clotting Factor ◽

Bleeding Tendency ◽

Probability Of Survival ◽

Immunodeficiency Virus ◽

Progression Of Disease ◽

Bleeding Episodes ◽

Clotting Factor Concentrates ◽

Dose Dependent ◽

Hiv 1

SummaryTwenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months.At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with intermption of treatment. Three patients developed severe leukopenia and 3 patients severe anemii during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was intermpted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of noncompliance.No signiticant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted.We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patientr ur. comparable to those seen in other risk groups . AzT does not increase the bleeding tendency in this patient group.

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Revision of the Protocol Recommended for Studies of Safety from Hepatitis of Clotting Factor Concentrates

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646630 ◽

1989 ◽

Vol 61 (03) ◽

pp. 532-534 ◽

Cited By ~ 17

Author(s):

Pier Mannuccio Mannucci ◽

Massimo Colombo

Keyword(s):

Clotting Factor ◽

Clotting Factor Concentrates

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Acute Hepatitis C in Haemophiliacs Due to “Virus-Inactivated” Clotting Factor Concentrates

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646358 ◽

1992 ◽

Vol 68 (06) ◽

pp. 781-781 ◽

Cited By ~ 16

Author(s):

A Gerritzen ◽

B Scholt ◽

R Kaiser ◽

K E Schneweis ◽

H-H Brackmann ◽

...

Keyword(s):

Hepatitis C ◽

Acute Hepatitis ◽

Clotting Factor ◽

Acute Hepatitis C ◽

Clotting Factor Concentrates

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Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648807 ◽

1994 ◽

Vol 72 (01) ◽

pp. 033-038 ◽

Cited By ~ 7

Author(s):

N Schinaia ◽

A M G Ghirardini ◽

M G Mazzucconi ◽

G Tagariello ◽

M Morfini ◽

...

Keyword(s):

Cumulative Incidence ◽

National Registry ◽

Factor Ix ◽

Clotting Factor ◽

Coagulation Disorders ◽

Factors Associated ◽

Kaplan Meier ◽

Significant Difference ◽

Congenital Coagulation Disorders ◽

Clotting Factor Concentrates

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

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Hepatitis-Free Interval After Clotting Factor Therapy in First Infused Haemophiliacs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661664 ◽

1986 ◽

Vol 56 (03) ◽

pp. 268-270 ◽

Cited By ~ 10

Author(s):

M Morfini ◽

D Rafanelli ◽

G Longo ◽

A Messori ◽

P Rossi Ferrini

Keyword(s):

Life Table ◽

Lower Risk ◽

Clotting Factor ◽

Rank Test ◽

Life Table Method ◽

Table Method ◽

Log Rank Test ◽

Free Interval ◽

Post Infusion ◽

Clotting Factor Concentrates

SummaryPost-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis.To evaluate this hypothesis, we retrospectively reviewed the medical records of 25 first infused haemophiliacs (from 1981 to 1984) treated with unheated commercial clotting factor concentrates (n = 19) or cryoprecipitate (n = 6).The hepatitis-free interval after the beginning of therapy was expressed as exposure days. The end point of each patient, i.e. the hepatitis occurrence, was defined as an increase of aminotransferases (ALT and AST) and/or the seroconversion of HBV-markers, which were checked every three months.The life-table method and log-rank test showed that cryo-precipitates had a significantly longer hepatitis-free interval (p = 0.0131, log-rank test) and a lower risk of transmitting hepatitis (p = 0.01-0.05, life-table method) than the commercial concentrates. However, the safety of cryoprecipitate therapy was shown to cover only a few exposure days, and so the real advantage of this product depends on the bleeding frequency of the patient concerned.We believe that these methods and our findings may be useful to assess and compare the safety of the new “heat-treated” clotting factor concentrates.

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