Increasing Incidence and Prevalence of Acquired Hemolytic Anemias in Denmark, 1980–2016

Figures & data

Table 1 Characteristics of Patients with Acquired Hemolytic Disorders in Denmark, 1980–2016

	AIHA, n = 2715	CAD, n = 112	Drug Induced, n = 397	PNH, n = 116	Acquired Hemolysis NOS, n = 2154	Other Defined Hemolysis, n = 374
% (95% CI)
Women	55.9 (54.0; 57.8)	51.8 (42.1; 61.3)	62.0 (57.0; 66.8)	50.0 (40.6; 59.4)	53.6 (51.5; 55.7)	46.0 (40.9; 51.2)
Deceased	63.8 (61.9; 65.6)	39.6 (30.5; 49.4)	79.6 (75.3; 83.5)	41.6 (32.4; 51.2)	66.9 (64.9; 68.9)	46.2 (41.0; 51.4)
Median (IQR)
Age at diagnosis, years	68.7 (53.8; 78.3)	71.9 (61.0; 78.6)	66.6 (53.1; 76.9)	48.4 (31.7; 67.0)	67.4 (48.5; 78.3)	57.1 (26.4; 73.1)
Age at death, years	78.6 (69.8; 85.1)	80.8 (74.5; 87.7)	77.2 (65.4; 84.4)	71.5 (56.5; 79.6)	77.3 (68.2; 84.9)	76.3 (64.3; 84.5)
Median survival, years	6.3 (1.3; 21.9)	8.8 (3.6; na)^a	4.5 (0.9; 16.2)	23.2 (6.8; na)^a	4.9 (0.9; 21.7)	13.5 (2.0; na)^a

Notes: ^aUpper bound in confidence intervals for median survival could not be calculated for CAD, drug-induced hemolysis, PNH, and the group of other defined hemolysis.

Abbreviations: AIHA, autoimmune hemolytic anemia; CAD, cold agglutinin disease; CI, confidence interval; na, not applicable; NOS, not otherwise specified; PNH, paroxysmal nocturnal hemoglobinuria.

Table 2 Incidence of Acquired Hemolytic Diseases in Denmark, 1980–2016

		Incidence per 100 000 Person-Years (95% CI)
		1980–1993	1994–2007	2008–2016
AIHA
	All	0.81 (0.74; 0.87)	1.43 (1.35; 1.52)	1.77 (1.66; 1.89)
	Age <20	0.25 (0.19; 0.32)	0.26 (0.19; 0.33)	0.35 (0.27; 0.46)
	Age 20–50	0.25 (0.20; 0.30)	0.43 (0.36; 0.50)	0.51 (0.42; 0.61)
	Age >50	1.76 (1.60; 1.93)	3.12 (2.91; 3.33)	3.34 (3.10; 3.59)
	Female	0.86 (0.77; 0.96)	1.50 (1.38; 1.62)	1.71 (1.56; 1.87)
	Male	0.64 (0.56; 0.73)	1.18 (1.07; 1.29)	1.48 (1.34; 1.63)
CAD
	All	na	0.03 (0.02; 0.04)	0.18 (0.15; 0.22)
	Age <20	na	0.00 (0.00; 0.02)	0.00 (0.00; 0.02)
	Age 20–50	na	0.01 (0.00; 0.02)	0.03 (0.01; 0.06)
	Age >50	na	0.07 (0.04; 0.10)	0.39 (0.31; 0.49)
	Female	na	0.03 (0.02; 0.06)	0.16 (0.12; 0.21)
	Male	na	0.02 (0.01; 0.04)	0.17 (0.12; 0.22)
Drug Induced
	All	0.31 (0.27; 0.36)	0.08 (0.06; 0.11)	0.12 (0.09; 0.15)
	Age <20	0.02 (0.00; 0.05)	0.04 (0.02; 0.08)	0.02 (0.00; 0.05)
	Age 20–50	0.10 (0.07; 0.14)	0.03 (0.02; 0.06)	0.05 (0.02; 0.08)
	Age >50	0.74 (0.64; 0.86)	0.15 (0.11; 0.20)	0.21 (0.15; 0.28)
	Female	0.35 (0.29; 0.41)	0.09 (0.06; 0.12)	0.11 (0.07; 0.15)
	Male	0.23 (0.19; 0.29)	0.07 (0.05; 0.10)	0.10 (0.07; 0.15)
PNH
	All	0.04 (0.03; 0.06)	0.05 (0.03; 0.06)	0.08 (0.06; 0.11)
	Age <20	0.01 (0.00; 0.04)	0.01 (0.00; 0.03)	0.01 (0.00; 0.03)
	Age 20–50	0.04 (0.02; 0.06)	0.04 (0.03; 0.07)	0.08 (0.05; 0.12)
	Age >50	0.06 (0.03; 0.10)	0.06 (0.03; 0.09)	0.09 (0.06; 0.14)
	Female	0.04 (0.02; 0.07)	0.04 (0.02; 0.06)	0.07 (0.04; 0.11)
	Male	0.04 (0.02; 0.07)	0.05 (0.03; 0.07)	0.07 (0.04; 0.11)
Acquired Hemolysis NOS
	All	0.81 (0.74; 0.87)	0.99 (0.92; 1.07)	1.28 (1.18; 1.38)
	Age <20	0.34 (0.27; 0.43)	0.30 (0.23; 0.38)	0.34 (0.26; 0.44)
	Age 20–50	0.25 (0.20; 0.31)	0.34 (0.28; 0.41)	0.46 (0.38; 0.55)
	Age >50	1.67 (1.51; 1.84)	2.01 (1.85; 2.19)	2.24 (2.05; 2.45)
	Female	0.81 (0.72; 0.90)	1.01 (0.91; 1.11)	1.16 (1.04; 1.29)
	Male	0.69 (0.61; 0.78)	0.85 (0.76; 0.94)	1.15 (1.03; 1.28)
Other Defined Hemolysis
	All	0.02 (0.01; 0.03)	0.26 (0.22; 0.29)	0.33 (0.28; 0.38)
	Age <20	0.02 (0.01; 0.05)	0.21 (0.15; 0.28)	0.17 (0.11; 0.24)
	Age 20–50	0.02 (0.01; 0.04)	0.12 (0.08; 0.16)	0.14 (0.10; 0.20)
	Age >50	0.01 (0.00; 0.04)	0.38 (0.31; 0.46)	0.49 (0.40; 0.59)
	Female	0.02 (0.01; 0.03)	0.23 (0.18; 0.28)	0.26 (0.21; 0.33)
	Male	0.02 (0.01; 0.04)	0.25 (0.21; 0.31)	0.32 (0.26; 0.40)

Notes: Incidences of acquired hemolytic diseases estimated as cumulative new diagnosed patients in each period, using cumulative stratified census data as the denominator. CAD diagnosis was not defined in the ICD before 1994.

Abbreviations: AIHA, autoimmune hemolytic anemia; CAD, cold agglutinin disease; CI, confidence interval; na, not applicable; NOS, not otherwise specified; PNH, paroxysmal nocturnal hemoglobinuria.

Figure 1 Prevalence of acquired hemolysis in Denmark, 1980–2016.

Notes: The overall prevalence proportion with 95% confidence intervals for all acquired hemolytic diseases, calculated on 1st of January each year, using census data as the denominator. The 95% confidence intervals were calculated using the Clopper–Pearson method. CAD diagnosis was not defined in the ICD before 1994. Data were based on a national cohort of patients from Denmark diagnosed in 1980–2016.
Abbreviations: AIHA, autoimmune hemolytic anemia; CAD, cold agglutinin disease; CI, confidence interval; NOS, not otherwise specified; PNH, paroxysmal nocturnal hemoglobinuria.

Table 3 Prevalence of Acquired Hemolytic Diseases in Denmark, 1980–2015

		Prevalence per 100 000 (95% CI)
		1980	2000	2015
AIHA
	All	2.52 (2.10; 2.99)	9.46 (8.65; 10.32)	17.01 (15.96; 18.12)
	Age <20	1.77 (1.15; 2.59)	7.92 (6.44; 9.63)	12.39 (10.56; 14.44)
	Age 20–50	0.88 (0.53; 1.38)	5.39 (4.50; 6.42)	11.27 (9.93; 12.73)
	Age >50	5.59 (4.46; 6.92)	16.17 (14.32; 18.19)	26.38 (24.21; 28.70)
	Female	2.78 (2.17; 3.50)	10.57 (9.38; 11.87)	19.06 (17.49; 20.73)
	Male	2.25 (1.71; 2.92)	8.31 (7.25; 9.49)	14.94 (13.55; 16.44)
CAD
	All	na	0.02 (0.00; 0.10)	1.04 (0.79; 1.34)
	Age <20	na	0.00 (0.00; 0.29)	0.00 (0.00; 0.28)
	Age 20–50	na	0.04 (0.00; 0.24)	0.39 (0.18; 0.75)
	Age >50	na	0.00 (0.00; 0.22)	2.43 (1.81; 3.21)
	Female	na	0.04 (0.00; 0.21)	1.12 (0.77; 1.59)
	Male	na	0.00 (0.00; 0.14)	0.96 (0.63; 1.40)
Drug Induced
	All	0.80 (0.57; 1.09)	1.48 (1.17; 1.85)	1.50 (1.20; 1.86)
	Age <20	0.07 (0.00; 0.38)	0.71 (0.33; 1.35)	1.06 (0.58; 1.79)
	Age 20–50	0.37 (0.16; 0.73)	0.85 (0.52; 1.31)	1.48 (1.03; 2.07)
	Age >50	2.13 (1.46; 3.01)	2.92 (2.17; 3.85)	1.80 (1.27; 2.48)
	Female	1.31 (0.91; 1.83)	2.08 (1.57; 2.70)	1.97 (1.48; 2.55)
	Male	0.28 (0.11; 0.57)	0.87 (0.55; 1.31)	1.03 (0.69; 1.48)
PNH
	All	0.18 (0.08; 0.33)	0.69 (0.49; 0.96)	1.04 (0.79; 1.34)
	Age <20	0.00 (0.00; 0.25)	0.16 (0.02; 0.57)	0.38 (0.12; 0.89)
	Age 20–50	0.23 (0.08; 0.54)	0.93 (0.59; 1.41)	1.70 (1.21; 2.33)
	Age >50	0.27 (0.07; 0.68)	0.76 (0.40; 1.30)	0.73 (0.41; 1.20)
	Female	0.15 (0.04; 0.39)	0.70 (0.42; 1.10)	1.09 (0.74; 1.54)
	Male	0.20 (0.06; 0.46)	0.68 (0.40; 1.08)	1.00 (0.66; 1.44)
Acquired Hemolysis NOS
	All	2.52 (2.10; 2.99)	7.26 (6.56; 8.02)	12.51 (11.60; 13.47)
	Age <20	1.15 (0.67; 1.85)	9.11 (7.52; 10.93)	14.21 (12.25; 16.40)
	Age 20–50	1.44 (0.98; 2.05)	4.88 (4.03; 5.86)	10.09 (8.83; 11.48)
	Age >50	5.39 (4.28; 6.70)	9.17 (7.79; 10.72)	14.12 (12.54; 15.84)
	Female	2.74 (2.14; 3.45)	7.75 (6.74; 8.88)	13.13 (11.83; 14.53)
	Male	2.29 (1.74; 2.96)	6.76 (5.80; 7.83)	11.88 (10.64; 13.23)
Other Defined Hemolysis
	All	0.08 (0.02; 0.20)	1.48 (1.17; 1.85)	3.30 (2.85; 3.81)
	Age <20	0.07 (0.00; 0.38)	2.14 (1.41; 3.11)	5.32 (4.15; 6.72)
	Age 20–50	0.09 (0.01; 0.34)	1.15 (0.76; 1.67)	2.45 (1.85; 3.18)
	Age >50	0.07 (0.00; 0.37)	1.46 (0.94; 2.15)	2.97 (2.27; 3.81)
	Female	0.04 (0.00; 0.21)	1.11 (0.75; 1.59)	2.91 (2.32; 3.61)
	Male	0.12 (0.02; 0.35)	1.86 (1.38; 2.46)	3.70 (3.02; 4.48)

Notes: Prevalence proportions were estimated as the number of living persons assigned the diagnosis at the latest on the 1st of January in each of the years 1980, 2000, and 2015, with stratification by age and sex, with population denominators derived from census data. CAD diagnosis was not defined in the ICD before 1994.

Abbreviations: AIHA, autoimmune hemolytic anemia; CAD, cold agglutinin disease; CI, confidence interval; na, not applicable; NOS, not otherwise specified; PNH, paroxysmal nocturnal hemoglobinuria.