Original Papers 0 1990 S.Karger AG, Basel 0042-9007/90/0583-0177 $2.75/0

Vox Sang 1990;58:177-181

Transmission of Human Parvovirus Bl9 by Coagulation Factor Concentrates M . D . Williams", B. J . Cohenb, A . C. Beddall", K . J. Pasia, l? P. Mortimerb, E G . H. Hill" "HaematologyDepartment, The Children's Hospital, Birmingham, UK; bPHLS Virus Reference Laboratory, Central Public Health Laboratory, Colindale, London; UK

Abstract. The prevalence of antibody to human parvovirus B19 was determined in 86 children with congenital bleeding disorders. Forty-seven of 53 boys (89%) receiving non-heat-treated factor VIII or prothrombin complex concentrates were anti-B19 IgG positive compared with 38% of their age-matched controls and 48% of children treated with cryoprecipitate. Acute B19 virus infection occurred in 2 boys 3-4 weeks after they had received the same batch of commercial factor VIII concentrate. Of 11susceptible children who had only received heat-treated National Health Service factor VIII concentrate (8Y), 1acquired anti-B19 IgG. This suggests that 8Y heat-treated concentrate has a much reduced risk of transmitting B19 virus and, by implication, other less heat-stable viruses such as human immunodeficiency virus.

Introduction Infection with human parvovoirus B19 (B19 virus) usually causes a minor, febrile illness or is asymptomatic [1,2]. In children there may be a characteristic rash, erythema infectiosum [3] and in adults, arthropathy [4]. Aplastic crisis as a result of acute interruption of haemopoiesis may occur in patients with congenital haemolytic anaemias [ 5 ] . Reports that this virus might be spread by inoculation [l, 61 were followed by sero-epidemiological evidence of transmission by coagulation concentrates and less frequently by transfused blood or cryoprecipitate [7]. Lyophilised coagulation factor concentrates used in the treatment of haemophilia A and B are prepared from large donor plasma pools and often contain over 5,000 plasma donations [8]. Because of pool size and because manufacturing processes until recently have not included a heating step in the preparation of concentrate, the final product has often been contaminated with viruses: recipients of factor concentrates have been exposed to Epstein-Barr and cytomegalovirus [9], hepatitis B and hepatitis non-A non-B viruses [lo] and to the human immunodeficiency virus (HIV) [ll].The risk to recipients from factor concentrates containing these and other viruses is of great concern, par-

ticularly with the advent of the acquired immune deficiency syndrome (AIDS), and has resulted in the introduction of heat treatment at some stage in the preparation of all factor concentrates. As B19 virus is relatively heat stable, the pattern of its transmission in unheated and heat-treated concentrates is of special interest. We have investigated 86 children with haemostatic disorders for evidence of B19 virus exposure and examined its relationship to the type and quantity of coagulation factor replacement received. Included in the study were 12 boys who have been treated solely with a British National Health Service (NHS) heat-treated factor VIII concentrate, 8Y this concentrate is prepared from HIV-antibody screened blood donors and dry-heated at 80°C for 72 h. Patients and Methods Patients All patients were children attending the Regional Paediatric Haemophilia Unit, The Children's Hospital, Birmingham (BCH) and complete treatment records were available for each child. The patients were grouped according to the type of treatment received from January 1980 up to the time of testing. Group 1.45 children (aged 1-19 years) with haemophilia A who had received either commercial (Armour Intermediate Purity Factorate) or

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NHS non-heat-treated factor VIII concentrates, or both these products. Stored samples of sera from June 1983were available for testing in this group of patients. Group 2. 21 children (aged 1-16 years) who had only received cryoprecipitate. This group included 6 children with haemophilia A , 9 with von Willebrand’s disease, 5 with combined factorV and VIII deficiency and 1 child with an isolated factor V deficiency. Group 3. 8 children (aged 3-15 years) treated with unheated NHS prothrombin complex concentrates. 7 children had haemophilia B and 1child factor X deficiency. Group 4. 12 boys with haemophilia A (aged 4 weeks to 16 years) who had been treated only with NHS, heat-treated factor VIII concentrate, 8Y. Controls. Specimens from 283 children (aged 1month to 19 years) who had been bled for other investigations whilst patients of the BCH were used to establish the prevalence of B19 infection in normal children. None of the control group had received blood or blood products and none had a bleeding disorder. Informed consent was obtained from the parents of all children entered into this study. Three age-matched controls were randomly selected for each bleeding disorder patient and tested for anti-B19 IgM and IgG antibodies.

Williams/Cohen/Beddall/Pasi/Mortimer/Hill

Table 1. Prevalence of anti-B19 IgG in children receiving factor replacement therapy and in age-matched controls Anti-B19 IgG level

n

%

mean

SEM

45

40

89’

26.60

4.65

135

53

39

26.01

3.93

2a Cryoprecipitate

21

10

48*

15.01

5.17

2b Controls

63

26

41

23.37

5.07

8

7

88’

41.37

15.64

3b Controls

24

7

29

26.37

13.22

4a 8Y FVIII concentrate

12

23

17’

4b Controls

36

11

l a Unheated FVIII concentrate Ib Controls

3a Unheated prothrombin complex concentrate



Methods Each child in groups 1-4 was tested for B19 antigen and anti-B19 IgM and IgG by radioimmunoassay (RIA), the levels of antibody being measured in arbitrary units derived from a standard curve based o n dilutions of strongly positive control sera [12]. The group 4 children were tested both before and up to 25 months after the introduction of 8Y concentrate (range 3-25 months, mean 11.3 months). Three age-matched controls were randomly selected for each bleeding disorder patient prior to testing for anti-B19 IgM and IgG antibody. Antibody levels of

Transmission of human parvovirus B19 by coagulation factor concentrates.

The prevalence of antibody to human parvovirus B19 was determined in 86 children with congenital bleeding disorders. Forty-seven of 53 boys (89%) rece...
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