J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website http://www.thejh.org

Original Article

Volume 6, Number 1, March 2017, pages 12-20

Warm Autoimmune Hemolytic Anemia: Clinical Profile and Management

**Table 1.** Prevalence and Type of Antibodies in Secondary AIHA in Adults
Underlying disorder	Prevalence of AIHA	wAIHA	cAIHA	References
NHL: non-Hodgkin lymphoma; SLE: systemic lupus erythematosus; CVID: common variable immune deficiency; ALPD: autoimmune lymphoproliferative disease; SCT: stem cell transplantation.
CLL	2.3-4.3%	87%	7%	[24, 25]
NHL (except CLL)	2.6%	More common	Less common	[26]
IgM gammopathy	1.1%	No	All	[27]
Hodgkin lymphoma	0.19-1.7%	Almost all	Rare	[28]
Solid tumors	Very rare	2/3	1/3	[29]
Ovarian dermoid cyst	Very rare	All	No	[30]
SLE	6.1%	Almost all	Rare	[31]
Ulcerative colitis	1.7%	All	No	[32]
CVID	5.5%	All	No	[33]
ALPD	50%	All	No	[34]
After allogeneic SCT	4.4%	Yes	Yes	[35]
After organ transplantation	5.6% (pancreas)	Yes	No	[36]
Drug-induced in CLL	2.9-10.5%	Almost all	Rare	[37]
Interferon α	Incidence: 11.5/100,000 patient-years	All	0	[38]

Table 1. Prevalence and Type of Antibodies in Secondary AIHA in Adults

Underlying disorder

Prevalence of AIHA

wAIHA

cAIHA

References

NHL: non-Hodgkin lymphoma; SLE: systemic lupus erythematosus; CVID: common variable immune deficiency; ALPD: autoimmune lymphoproliferative disease; SCT: stem cell transplantation.

CLL

2.3-4.3%

87%

[24, 25]

NHL (except CLL)

2.6%

More common

Less common

[26]

IgM gammopathy

1.1%

All

[27]

Hodgkin lymphoma

0.19-1.7%

Almost all

Rare

[28]

Solid tumors

Very rare

2/3

1/3

[29]

Ovarian dermoid cyst

Very rare

All

[30]

SLE

6.1%

Almost all

Rare

[31]

Ulcerative colitis

1.7%

All

[32]

CVID

5.5%

All

[33]

ALPD

50%

All

[34]

After allogeneic SCT

4.4%

Yes

[35]

After organ transplantation

5.6% (pancreas)

Yes

[36]

Drug-induced in CLL

2.9-10.5%

Almost all

Rare

[37]

Interferon α

Incidence: 11.5/100,000 patient-years

All

[38]

**Table 2.** Comparison of Characteristics of Patients With Primary and Secondary wAIHA
Characteristics	Primary wAIHA	Secondary wAIHA	P value
Females	12	26	> 0.05
Males	17	20	> 0.05
Mean age at wAIHA onset in years	51.7 ± 20.5	54.3 ± 25.7	> 0.05
Clinical features at the time of onset, n (%)	27 (93.10%)	31 (67.39%)	> 0.05
Anemia, n (%)	21 (72.41%)	29 (63.04%)
Jaundice/dark urine, n (%)	11 (37.93%)	15 (32.60%)
Chest pain/ACS, n (%)	3 (10.34%)	5 (10.86%)
Characteristics of patients at onset
Mean hemoglobin level at AIHA onset (g/dL)	7.1 ±1.7	6.3 ±1.2	0.029
Mean reticulocyte level at AIHA onset (× 10⁹/L)	323 ± 179	262 ± 156	> 0.05
Mean MCV level at AIHA onset (fL)	109 ± 16	104 ± 18	> 0.05
Decreased level of haptoglobin (%)	27 (93.10%)	43 (93.47%)	> 0.05
Increased LDH level (%)	29 (100%)	42 (91.30%)	> 0.05
Increased Bilirubin level (%)	25 (86.20%)	39 (84.78%)	> 0.05
DAT pattern
IgG	15 (51.72%)	15 (32.60%)	> 0.05
IgG + C3d	14 (48.27%)	30 (65.21%)	> 0.05
C3d	0%	1 (2.17%)
IgA	0%	2 (4.34%)
Treatment administered
Blood transfusion	20 (68.96%)	34 (73.91%)	> 0.05
Response to corticosteroid (%)	28 (96.55%)	40 (86.95%)	> 0.05
Dependence on corticosteroid (%)	17 (58.62%)	32 (69.56%)	> 0.05
Complete response to corticosteroid (%)	20 (68.96%)	30 (65.21%)	> 0.05
Second line treatment (%)	19 (65.51%)	32 (69.56%)	> 0.05
Rituximab usage	14 (48.27%)	23 (50%)	> 0.05
Splenectomy	1 (3.4%)	15 (32.60%)	< 0.05
Disease remission at last consultation	22 (75.86%)	33 (71.76%)	> 0.05
Complete remission of AIHA	14 (48.27%)	23 (50%)	> 0.05
Partial remission of AIHA	8 (27.58%)	12 (26.08%)	> 0.05
Active disease	8 (27.58%)	14 (30.43%)	> 0.05
Venous thrombosis	4 (13.79%)	11 (23.91%)	> 0.05
Deaths	3 (10.34%)	4 (8.69%)	> 0.05

Table 2. Comparison of Characteristics of Patients With Primary and Secondary wAIHA

Characteristics

Primary wAIHA

Secondary wAIHA

P value

Females

> 0.05

Males

> 0.05

Mean age at wAIHA onset in years

51.7 ± 20.5

54.3 ± 25.7

> 0.05

Clinical features at the time of onset, n (%)

27 (93.10%)

31 (67.39%)

> 0.05

Anemia, n (%)

21 (72.41%)

29 (63.04%)

Jaundice/dark urine, n (%)

11 (37.93%)

15 (32.60%)

Chest pain/ACS, n (%)

3 (10.34%)

5 (10.86%)

Characteristics of patients at onset

Mean hemoglobin level at AIHA onset (g/dL)

7.1 ±1.7

6.3 ±1.2

0.029

Mean reticulocyte level at AIHA onset (× 10⁹/L)

323 ± 179

262 ± 156

> 0.05

Mean MCV level at AIHA onset (fL)

109 ± 16

104 ± 18

> 0.05

Decreased level of haptoglobin (%)

27 (93.10%)

43 (93.47%)

> 0.05

Increased LDH level (%)

29 (100%)

42 (91.30%)

> 0.05

Increased Bilirubin level (%)

25 (86.20%)

39 (84.78%)

> 0.05

DAT pattern

IgG

15 (51.72%)

15 (32.60%)

> 0.05

IgG + C3d

14 (48.27%)

30 (65.21%)

> 0.05

C3d

1 (2.17%)

IgA

2 (4.34%)

Treatment administered

Blood transfusion

20 (68.96%)

34 (73.91%)

> 0.05

Response to corticosteroid (%)

28 (96.55%)

40 (86.95%)

> 0.05

Dependence on corticosteroid (%)

17 (58.62%)

32 (69.56%)

> 0.05

Complete response to corticosteroid (%)

20 (68.96%)

30 (65.21%)

> 0.05

Second line treatment (%)

19 (65.51%)

32 (69.56%)

> 0.05

Rituximab usage

14 (48.27%)

23 (50%)

> 0.05

Splenectomy

1 (3.4%)

15 (32.60%)

< 0.05

Disease remission at last consultation

22 (75.86%)

33 (71.76%)

> 0.05

Complete remission of AIHA

14 (48.27%)

23 (50%)

> 0.05

Partial remission of AIHA

8 (27.58%)

12 (26.08%)

> 0.05

Active disease

8 (27.58%)

14 (30.43%)

> 0.05

Venous thrombosis

4 (13.79%)

11 (23.91%)

> 0.05

Deaths

3 (10.34%)

4 (8.69%)

> 0.05

**Table 3.** WAIHA Characteristics Secondary to Lymphoma
Characteristics	Secondary to lymphoma (N = 18)	Other forms (N = 58)	P
Female patients	11	27	> 0.05
Male patients	7	30	> 0.05
Mean age of onset (years)	69.7 ± 21.5	44.7 ± 23.2	0.012
Clinical symptoms at the time of onset	14 (77.77%)	45 (77.58%)	> 0.05
Investigations
Mean hemoglobin at onset (g/dL)	6.4 ± 1.5	6.6 ± 1.8	> 0.05
Hypogammaglobulinemia, n (%)	10 (55.55%)	6 (10.34%)	0.01
Monoclonal gammaglobulin, n (%)	13 (72.22%)	10 (17.24%)	0.0019
Direct antiglobulin test (DAT)
IgG	2 (11.11%)	30 (51.72%)	0.029
IgG + C3d	14 (77.77%)	28 (48.27%)	> 0.05
C3d	9%	0%
IgA	0%	4%
Treatment
Blood transfusion	95%	49%	0.02
Response to corticosteroids (%)	94%	90%	> 0.05
Dependence on corticosteroids	94%	58%	0.006
Second line of treatment (%)	96%	51%	0.005
Rituximab	64%	41%	> 0.05
Splenectomy	5 (36%)	5 (11%)	0.04
Disease remission at last visit	57%	76%	> 0.055
Complete remission of AIHA	5 (36%)	23 (50%)
Partial remission of AIHA	3 (21%)	12 (26%)
Active disease	6 (43%)	11 (24%)
Thrombosis	2 (14%)	7 (15%)	> 0.05
Deaths	3 (21%)	2 (4%)	> 0.05

Table 3. WAIHA Characteristics Secondary to Lymphoma

Characteristics

Secondary to lymphoma (N = 18)

Other forms (N = 58)

Female patients

> 0.05

Male patients

> 0.05

Mean age of onset (years)

69.7 ± 21.5

44.7 ± 23.2

0.012

Clinical symptoms at the time of onset

14 (77.77%)

45 (77.58%)

> 0.05

Investigations

Mean hemoglobin at onset (g/dL)

6.4 ± 1.5

6.6 ± 1.8

> 0.05

Hypogammaglobulinemia, n (%)

10 (55.55%)

6 (10.34%)

0.01

Monoclonal gammaglobulin, n (%)

13 (72.22%)

10 (17.24%)

0.0019

Direct antiglobulin test (DAT)

IgG

2 (11.11%)

30 (51.72%)

0.029

IgG + C3d

14 (77.77%)

28 (48.27%)

> 0.05

C3d

IgA

Treatment

Blood transfusion

95%

49%

0.02

Response to corticosteroids (%)

94%

90%

> 0.05

Dependence on corticosteroids

94%

58%

0.006

Second line of treatment (%)

96%

51%

0.005

Rituximab

64%

41%

> 0.05

Splenectomy

5 (36%)

5 (11%)

0.04

Disease remission at last visit

57%

76%

> 0.055

Complete remission of AIHA

5 (36%)

23 (50%)

Partial remission of AIHA

3 (21%)

12 (26%)

Active disease

6 (43%)

11 (24%)

Thrombosis

2 (14%)

7 (15%)

> 0.05

Deaths

3 (21%)

2 (4%)

> 0.05

**Table 4.** Most Common Causes of Secondary wAIHA
B-cell lymphoma	18 (39.13%)
Systemic lupus erythematosus	9 (19.56%)
Rheumatoid arthritis	8 (17.39%)
Chronic lymphocytic leukemia	3 (6.52%)
Common variable immune deficiency	2 (4.34%)
Renal cell carcinoma	2 (4.34%)
Secondary to drug usage
Alpha methyldopa	2 (4.34%)
Carbamazepine	2 (4.34%)

Table 4. Most Common Causes of Secondary wAIHA

B-cell lymphoma

18 (39.13%)

Systemic lupus erythematosus

9 (19.56%)

Rheumatoid arthritis

8 (17.39%)

Chronic lymphocytic leukemia

3 (6.52%)

Common variable immune deficiency

2 (4.34%)

Renal cell carcinoma

2 (4.34%)

Secondary to drug usage

Alpha methyldopa

2 (4.34%)

Carbamazepine

2 (4.34%)