Vox Sang. 19: 406-409 (1970)

Hemophilia, Hepatitis and HAA

JESSICA H. LEWIS

Department of Medicine, University of Pittsburgh and Central Blood Bank, Pittsburgh, Pa.

I . HAA and Anti-HAA in Patients with Hepatitis

Hepatitis is a serious, although relatively infrequent, complication of therapy in hemophilia. The detection of HAA (hepatitis-associated or Australia antigen) and its antibody, anti-HAA, may be of im- portance in eliminating this type of v i r u s carrier from donor lists and, in predicting immunity to serum hepatitis (SH) but not to infectious hepatitis (I H). Counter-immuno-electrophoresis was used in these studies to detect and titer HAA and anti-HAA.

The widespread therapeutic u0e of fractions prepared from large pools of plasma has increased the risk of exposure t o SH and has produced an apparent sharp increase in the incidence of jaundice (table I) in a group of about 300 hemophiliacs seen in this clinic. Of the 12 recent cases (1969 and 1970), 10 had received commercially prepared fractions containing factor VIII or IX. Two patients re- ceived only cryoprecipate, 4 units each, 39 and 32 days before jaundice. It is interesting that these are the only 2 hepatitic patients, in whom a positive HAA was found. One donor to the second of these patient was found to be HAA-positive and developed hepatitis himself. Both of these hemophiliacs are now HAA- and anti-HAA- negative.

Three of the hemophiliacs (table I) had clearcut histories of previous jaundice occurring 4 to 8 weeks after plasma or whole blood trans- fusions. One, AK (table 11), had negative HAA and anti-HAA both before and after the second episode. The short incubation period in the second infection is suggestive of IH. The other patients who suf- fered two episodes of jaundice also showed negative tests for HAA

LEWIS 407

Table Z. Jaundice in hemophilia (15 years)

1955-65 1966 0 1967 0 1968 1 1969 6 (3 previous jaundice) 1970 (6 months) 6

10 + ? 6 by history in childhood

In the next three months of 1970, two additional cases of hepatitis have been seen. Samples before and during the jaundiced period were negative for HAA and anti-HAA. One of these patients died.

Table IZ. Jaundice twice in a hemophiliac (A.K.)

1965 whole blood + plasma 8 weeks Jaundice 8/10/69-8/20/69 47 G ~ o 2 H y

HAA Anti-HAA

8/13/69 0 0

10129169 0 0 2/ 5/70 0 0 2/10/70 0 0

8/22/69 Jaundice

and anti-HAA during or shortly after the second infection. These findings suggest that the previous hepatitis infection had produced no immunity or that each had two separate infections which did not confer cross-immunity.

In three of the hepatitis patients, anti-HAA was positive before jaundice developed and in two others it was found on the day of admission to the hospital. These findings suggest either that anti- HAA is not protective against SH or that the jaundice was due to IH.

If it is presumed that both SH and I H can be transmitted by blood products, 2 of these hemophiliacs clearly had SH, 3 probably had both, 5 possibly had IH. In the last two, appropriate samples were not available for testing.

Table 111. HAA and anti-HAA in hemophiliacs without jaundice

Patients Samples HAA Anti-HAA

Rarely treated 13 120 0 0 2 5 + 0 Frequently treated 23 141 0 0 15 139-79 0 0

-60 0 + a 46 0 +

I I . HAA and Anti-HAA in Patients without Hepatitis

HAA and anti-HAA may be found in these often transfusedpatients without any sign of current or previous disease. Four hundred and fifty one plasma samples from 123 hemophiliacs (A or B) were avail- able in our freezers. In table 111, the patients have been divided into two groups: rarely treated and frequently treated. In the rarely treated group 2 patients were found who showed a persistently positive test for the antigen. Both were small boys who had had no jaundice. In one, the last treatment consisted of 4 units of cryo- precipitate 9 months before the antigen was found. His HAA has

50 ANRC 33 HY I 1 -

SEPT. OCT. NOV. JULY JAN. 1968 1969 1970

Fig. 1. Rise and fall in anti-HAA titer during two operative procedures on a hemo- philiac (T.C.).

(211) Hemophilia, Hepatitis and HAA 409

persisted for 10 months. The other boy had received pooled fraction 3 months earlier. No rarely treated patient had a positive antibody test.

Of the 48 frequently treated patients, 141 samples on 23 were negative for HAA or anti-HAA. Fifteen patients showed positive antibody in about half of their samples and 8 in all samples.

Figure 1 shows the rise in anti-HAA titer on 2 occasions in a hemophiliac, T.C., who received 2 courses of prophylactic fraction therapy during operative procedures. This patient never developed jaundice or any illness which might be considered anicteric hepatitis. Five other patients have shown a similar rise and fall in antibody titer on more than one occasion suggesting that antigen must con- taminate many fractions and that, in low titer. it may lead to anti- body production. Many pooled plasma fractions have been tested and no HAA detected.

111. Conclusion

These findings suggest, but do not confirm, that pooled plasma products may contain agents which can produce two types of hepatitis (SH and IH). The antigen, HAA, is associated with SH but may also be found in patients without manifest hepatitis. That anti-HAA may develop in patients treated with pooled products suggests that these materials contain HAA, although in titer too low to be detected by the usual methods.

Author’s address: Dr. JESSICA H. LEWIS, Department of Medicine, University of Pittsburgh and Central Blood Bank, Piasburgh, Pa. (USA)