Table 2

FVIII inhibitory titers, mortality and specific rates of hydrolysis, and activation of coagulation factors by IgG purified from the plasma of 65 patients with acquired hemophilia

Patient no.Inhibitory titer, BU/mL*Mortality of patients†Hydrolysis of FVIII,‡ mmol/min per mole IgGHydrolysis of FIX,§ mmol/min per mole IgGActivation of FIX,‖ mmol/min per mole IgG
1 40 D 0.45 ± 0.2 0.03 ± 0.01 0.29 ± 0.05 
2 63 A 0.15 ± 0.0 0.29 ± 0.45 0.96 ± 0.10 
3 128 D 0.14 ± 0.1 0.44 ± 0.38 0.07 ± 0.00 
4 114 D 0.13 ± 0.1 0.37 ± 0.06 0.03 ± 0.02 
5 380 ND 0.17 ± 0.0 0.35 ± 0.19 0.03 ± 0.01 
6 32 A 0.12 ± 0.1 0.37 ± 0.18 0.23 ± 0.02 
7 49.4 ND 0.08 ± 0.0 0.49 ± 0.29 0.02 ± 0.01 
8 3.1 D 0.38 ± 0.2 0.42 ± 0.14 0.95 ± 0.32 
9 42 A 0.13 ± 0.0 0.33 ± 0.26 1.33 ± 0.34 
10 6 A 0.17 ± 0.0 0.64 ± 0.42 2.01 ± 0.56 
11 14 D 0.08 ± 0.0 0.01 ± 0.01 0.33 ± 0.12 
12 2 A 0.12 ± 0.1 0.17 ± 0.13 0.70 ± 0.15 
13 40 A 0.16 ± 0.1 0.21 ± 0.02 0.21 ± 0.05 
14 2 A 0.22 ± 0.0 0.73 ± 0.02 3.43 ± 0.48 
15 80 A 0.18 ± 0.0 0.32 ± 0.02 0.28 ± 0.06 
16 52 A 0.14 ± 0.0 1.04 ± 0.14 3.49 ± 0.59 
17 100 A 0.36 ± 0.1 0.17 ± 0.08 0.42 ± 0.04 
18 10 A 0.09 ± 0.0 0.36 ± 0.27 0.13 ± 0.03 
19 1.4 D 0.10 ± 0.0 0.38 ± 0.29 0.05 ± 0.02 
20 18 D 0.08 ± 0.0 0.54 ± 0.61 0.19 ± 0.06 
21 1050 ND 0.15 ± 0.1 0.35 ± 0.16 0.05 ± 0.03 
22 330 D 0.14 ± 0.1 0.28 ± 0.05 0.59 ± 0.07 
23 18 A 0.30 ± 0.1 0.97 ± 0.13 1.78 ± 0.17 
24 1.3 D 0.05 ± 0.0 0.50 ± 0.17 0.59 ± 0.00 
25 60 D 0.06 ± 0.0 0.16 ± 0.05 0.04 ± 0.00 
26 1 A 0.06 ± 0.0 0.18 ± 0.07 0.20 ± 0.04 
27 4 A 0.10 ± 0.1 0.27 ± 0.09 0.42 ± 0.04 
28 56 ND 0.07 ± 0.0 0.08 ± 0.05 1.98 ± 0.17 
29 4.5 A 0.13 ± 0.0 0.17 ± 0.07 0.14 ± 0.04 
30 1.5 A 0.08 ± 0.0 1.10 ± 0.04 0.89 ± 0.28 
31 3 A 0.11 ± 0.1 0.34 ± 0.08 0.07 ± 0.03 
32 7 A 0.19 ± 0.0 0.39 ± 0.23 2.13 ± 0.71 
33 362.7 A 0.08 ± 0.0 0.10 ± 0.10 0.04 ± 0.01 
34 249.2 ND 0.09 ± 0.1 0.19 ± 0.18 0.06 ± 0.03 
35 62 A 0.32 ± 0.0 0.41 ± 0.22 0.31 ± 0.03 
36 54 A 0.21 ± 0.1 0.13 ± 0.11 0.02 ± 0.01 
37 1 ND 0.13 ± 0.1 0.11 ± 0.07 0.07 ± 0.03 
38 105.4 ND 0.10 ± 0.0 0.05 ± 0.04 0.04 ± 0.01 
39 92.5 ND 0.09 ± 0.0 0.14 ± 0.11 0.03 ± 0.01 
40 26.6 D 0.10 ± 0.1 0.09 ± 0.08 0.03 ± 0.00 
41 10 D 0.17 ± 0.0 0.33 ± 0.02 0.85 ± 0.13 
42 29.9 ND 0.10 ± 0.0 0.15 ± 0.12 0.03 ± 0.01 
43 4.9 A 0.30 ± 0.2 0.24 ± 0.16 0.12 ± 0.03 
44 13 A 0.10 ± 0.0 0.34 ± 0.17 0.26 ± 0.09 
45 58.2 ND 0.17 ± 0.0 0.25 ± 0.14 0.03 ± 0.01 
46 25 A — 0.08 ± 0.03 0.08 ± 0.03 
47 35 D — 0.62 ± 0.08 0.38 ± 0.03 
48 190 D — 0.07 ± 0.01 0.07 ± 0.00 
49 6.2 A — 0.02 ± 0.01 0.05 ± 0.02 
50 50 A — 0.32 ± 0.12 0.22 ± 0.02 
51 5.5 A — 0.14 ± 0.06 0.09 ± 0.02 
52 13.6 A — 0.07 ± 0.02 0.10 ± 0.05 
53 8 A — 0.17 ± 0.03 0.16 ± 0.06 
54 3 A — 0.10 ± 0.02 0.12 ± 0.03 
55 1.5 ND — 0.02 ± 0.01 0.06 ± 0.02 
56 28 ND — 0.04 ± 0.03 0.08 ± 0.02 
57 27 A — 0.19 ± 0.07 0.04 ± 0.00 
58 1.7 D — 0.12 ± 0.05 0.11 ± 0.04 
59 4.4 D — 0.10 ± 0.02 0.07 ± 0.03 
60 98 A — 0.04 ± 0.01 0.05 ± 0.02 
61 45 A — 0.29 ± 0.06 0.29 ± 0.05 
62 2 A — 0.28 ± 0.05 0.20 ± 0.04 
63 1 ND — 0.25 ± 0.02 0.26 ± 0.07 
64 11.5 A — 0.39 ± 0.01 0.38 ± 0.09 
65 9 A — 0.17 ± 0.02 0.16 ± 0.06 
IVIg 0 — 0.06 ± 0.03 0.06 ± 0.06 0.01 ± 0.00 
Patient no.Inhibitory titer, BU/mL*Mortality of patients†Hydrolysis of FVIII,‡ mmol/min per mole IgGHydrolysis of FIX,§ mmol/min per mole IgGActivation of FIX,‖ mmol/min per mole IgG
1 40 D 0.45 ± 0.2 0.03 ± 0.01 0.29 ± 0.05 
2 63 A 0.15 ± 0.0 0.29 ± 0.45 0.96 ± 0.10 
3 128 D 0.14 ± 0.1 0.44 ± 0.38 0.07 ± 0.00 
4 114 D 0.13 ± 0.1 0.37 ± 0.06 0.03 ± 0.02 
5 380 ND 0.17 ± 0.0 0.35 ± 0.19 0.03 ± 0.01 
6 32 A 0.12 ± 0.1 0.37 ± 0.18 0.23 ± 0.02 
7 49.4 ND 0.08 ± 0.0 0.49 ± 0.29 0.02 ± 0.01 
8 3.1 D 0.38 ± 0.2 0.42 ± 0.14 0.95 ± 0.32 
9 42 A 0.13 ± 0.0 0.33 ± 0.26 1.33 ± 0.34 
10 6 A 0.17 ± 0.0 0.64 ± 0.42 2.01 ± 0.56 
11 14 D 0.08 ± 0.0 0.01 ± 0.01 0.33 ± 0.12 
12 2 A 0.12 ± 0.1 0.17 ± 0.13 0.70 ± 0.15 
13 40 A 0.16 ± 0.1 0.21 ± 0.02 0.21 ± 0.05 
14 2 A 0.22 ± 0.0 0.73 ± 0.02 3.43 ± 0.48 
15 80 A 0.18 ± 0.0 0.32 ± 0.02 0.28 ± 0.06 
16 52 A 0.14 ± 0.0 1.04 ± 0.14 3.49 ± 0.59 
17 100 A 0.36 ± 0.1 0.17 ± 0.08 0.42 ± 0.04 
18 10 A 0.09 ± 0.0 0.36 ± 0.27 0.13 ± 0.03 
19 1.4 D 0.10 ± 0.0 0.38 ± 0.29 0.05 ± 0.02 
20 18 D 0.08 ± 0.0 0.54 ± 0.61 0.19 ± 0.06 
21 1050 ND 0.15 ± 0.1 0.35 ± 0.16 0.05 ± 0.03 
22 330 D 0.14 ± 0.1 0.28 ± 0.05 0.59 ± 0.07 
23 18 A 0.30 ± 0.1 0.97 ± 0.13 1.78 ± 0.17 
24 1.3 D 0.05 ± 0.0 0.50 ± 0.17 0.59 ± 0.00 
25 60 D 0.06 ± 0.0 0.16 ± 0.05 0.04 ± 0.00 
26 1 A 0.06 ± 0.0 0.18 ± 0.07 0.20 ± 0.04 
27 4 A 0.10 ± 0.1 0.27 ± 0.09 0.42 ± 0.04 
28 56 ND 0.07 ± 0.0 0.08 ± 0.05 1.98 ± 0.17 
29 4.5 A 0.13 ± 0.0 0.17 ± 0.07 0.14 ± 0.04 
30 1.5 A 0.08 ± 0.0 1.10 ± 0.04 0.89 ± 0.28 
31 3 A 0.11 ± 0.1 0.34 ± 0.08 0.07 ± 0.03 
32 7 A 0.19 ± 0.0 0.39 ± 0.23 2.13 ± 0.71 
33 362.7 A 0.08 ± 0.0 0.10 ± 0.10 0.04 ± 0.01 
34 249.2 ND 0.09 ± 0.1 0.19 ± 0.18 0.06 ± 0.03 
35 62 A 0.32 ± 0.0 0.41 ± 0.22 0.31 ± 0.03 
36 54 A 0.21 ± 0.1 0.13 ± 0.11 0.02 ± 0.01 
37 1 ND 0.13 ± 0.1 0.11 ± 0.07 0.07 ± 0.03 
38 105.4 ND 0.10 ± 0.0 0.05 ± 0.04 0.04 ± 0.01 
39 92.5 ND 0.09 ± 0.0 0.14 ± 0.11 0.03 ± 0.01 
40 26.6 D 0.10 ± 0.1 0.09 ± 0.08 0.03 ± 0.00 
41 10 D 0.17 ± 0.0 0.33 ± 0.02 0.85 ± 0.13 
42 29.9 ND 0.10 ± 0.0 0.15 ± 0.12 0.03 ± 0.01 
43 4.9 A 0.30 ± 0.2 0.24 ± 0.16 0.12 ± 0.03 
44 13 A 0.10 ± 0.0 0.34 ± 0.17 0.26 ± 0.09 
45 58.2 ND 0.17 ± 0.0 0.25 ± 0.14 0.03 ± 0.01 
46 25 A — 0.08 ± 0.03 0.08 ± 0.03 
47 35 D — 0.62 ± 0.08 0.38 ± 0.03 
48 190 D — 0.07 ± 0.01 0.07 ± 0.00 
49 6.2 A — 0.02 ± 0.01 0.05 ± 0.02 
50 50 A — 0.32 ± 0.12 0.22 ± 0.02 
51 5.5 A — 0.14 ± 0.06 0.09 ± 0.02 
52 13.6 A — 0.07 ± 0.02 0.10 ± 0.05 
53 8 A — 0.17 ± 0.03 0.16 ± 0.06 
54 3 A — 0.10 ± 0.02 0.12 ± 0.03 
55 1.5 ND — 0.02 ± 0.01 0.06 ± 0.02 
56 28 ND — 0.04 ± 0.03 0.08 ± 0.02 
57 27 A — 0.19 ± 0.07 0.04 ± 0.00 
58 1.7 D — 0.12 ± 0.05 0.11 ± 0.04 
59 4.4 D — 0.10 ± 0.02 0.07 ± 0.03 
60 98 A — 0.04 ± 0.01 0.05 ± 0.02 
61 45 A — 0.29 ± 0.06 0.29 ± 0.05 
62 2 A — 0.28 ± 0.05 0.20 ± 0.04 
63 1 ND — 0.25 ± 0.02 0.26 ± 0.07 
64 11.5 A — 0.39 ± 0.01 0.38 ± 0.09 
65 9 A — 0.17 ± 0.02 0.16 ± 0.06 
IVIg 0 — 0.06 ± 0.03 0.06 ± 0.06 0.01 ± 0.00 

— indicates not documented.

*

Inhibitory titers were measured in plasma using the modified Bethesda assay.

†

Mortality was documented in the case of 52 of the 65 patients over a period of 365 days. A indicates alive; D, deceased; and ND, not documented.

‡

The results are mean ± SD of 4 independent experiments. Rates of FVIII hydrolysis were calculated by densitometric analysis of Western blots. Spontaneous hydrolysis that occurred on incubation of FVIII in the presence of buffer alone was subtracted from each analysis. The mean coefficient of variation was 0.53 ± 0.22 (range, 0.09-1.15).

§

The results are mean ± SD of 3 or 4 independent experiments. Rates of FIX hydrolysis were calculated by densitometric analysis of Western blots. Spontaneous hydrolysis that occurred on incubation of FIX in the presence of buffer alone was subtracted from each analysis. The mean coefficient of variation was 0.47 ± 0.32 (range, 0.01-1.58). The detection limit in our assay was 0.6 nM of hydrolyzed protein, equivalent to a rate of hydrolysis of 6 μmol/min per mole IgG.

‖

The results are mean ± SD of 3 independent experiments. Rates of FIX activation were calculated in a functional assay as described (“Activation of FIX”). The mean coefficient of variation was 0.26 ± 0.15 (range, 0.00-0.55).

P < .05 for the comparison with intravenous immunoglobulins, using 1-way analysis of variance post-hoc test (2-tailed test).

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