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CASE REPORTS
Anti-C5 antibody treatment for delayed hemolytic
transfusion reactions in sickle cell disease
Delayed hemolytic transfusion reaction (DHTR) is an unpredictable severe complication of transfusion in patients with sickle cell disease (SCD). It presents clini- cally as a vaso-occlusive crisis (VOC), often associated with the failure of one or more organs, after the transfu- sion of packed red blood cells (pRBC).1,2 Hyperhemolysis is encountered in the most severe forms. Both transfused and autologous red blood cells (RBC) are lysed.
The mechanisms underlying DHTR remain unclear.
Alloantibodies against RBC antigens were initially thought to underlie the pathophysiology, but no such antibodies are detected in about a third of the cases.3
RBC degradation products, such as hemoglobin and heme, are released into the bloodstream during intravas- cular hemolysis. These elements and heme-loaded mem- brane microvesicles have recently been implicated in inflammation and organ injury in DHTR.4 Complement is activated via the classical pathway, by alloantibodies, and/or via the alternative pathway, by free heme.5 Heme- dependent complement deposits on the endothelium contribute to organ damage.6 Due to these vascular lesions, hyperhemolysis often progresses to multiple
Table 1. Clinical and biological findings at diagnosis and during follow-up. This series
Habibi et al. 69; 99
65 (94.2%) 48/21 30 ± 9
2 ± 3
51 (51.5%) 48 (48.5%)
10 [8-14] (MD=19)
78 [69-93] (MD=5)† 758 [554-958] (MD=16)
45% 3%
4% 2% 2% 35%
55 [45-63] (MD=5)† 1335 [798-2086] (MD=7) 180 [121-240] (MD=14) 46 [31-53] (MD=26)†
41 (40%) 6.2±4 15.9 ± 10 10±2 6%
Patient characteristics
Number of patients; DHTR episodes Hb βSβS
Sex F/M
Age, years
Number of pRBC units in transfusion episode Transfusion indications
Preventive measure Vaso-occlusive complications Other
Timeline
Days from transfusion to DHTR diagnosis
Days from transfusion to anti-C5 infusion Biological findings in the emergency room
Total Hb level, g/dL
LDH level, IU/L
Treatment**
EPO
Corticosteroids
Plasma or albumin exchange IV immunoglobulins Anti-CD20 antibody
Anti-C5 antibody
Secondary pRBC transfusion
Extreme biological findings Lowest total Hb level, g/dL Highest LDH level, IU/L
Lowest reticulocyte count, 109/L Delta Hb‡, g/dL
Outcome
ICU admission
ICU-stay duration, days Hospital-stay duration, days Transfusion-to-death interval, days Death
18; 18 18 (100%) 11/7 24.6 ± 12.6 2 ± 1.9
5 (27.8%) 11 (61.1%) 2 (11.1%)
8 [7-12.8]
10.5 [9-15.5]
63.5 [53.3-77.8] (NA=6*) 1612 [ 825-2702] (NA=6*)
17 (94.4%) 1 (5.6%) 4 (22.2%) 9 (50%) 7 (38.9%) 16 (100%) 14 (77.8%)
30.5 [25.5-42.8] 3337 [2573-7986] 46.1 [35.8-84.8] (MD=2) 57.5 [45.8-67.5] (MD=4)
17 (94.4%) 17.7 ± 10.2 35.6 ± 25.3 51.7 ± 47.9 3 (16.7%)
P=0.03 P<0.01
P<0.01 P<0.01 P<0.01 P=0.06
P<0.01 P<0.01
2694
Continuous variables are expressed as means ± one standard deviation (SD) or medians (MD,[interquartile range]),depending on whether they are normally or asymmet- rically distributed. Categorical variables are expressed as numbers (%). For comparison with the largest published delayed hemolytic transfusion reaction (DHTR) series, the data in column 2 are reprinted from Habibi et al.1 with permission.The patients of our series,who received anti-C5 antibody, had very severe DHTR with hyperhemolysis (P-values in column 3 compare our patients with those of the historical series).*Six patients had not even been discharged,due to the severity of their DHTR,**All patients in both series also received supportive vaso-occlusive crisis (VOC) treatment, hydration, oxygenation, and analgesia. †Values were converted to g/L (from g/dL in Habibi et al.). ‡Delta hemoglobin ( Hb) is the difference between the highest and lowest values available post-transfusion. F: female; M: male; pRBC: packed red blood cells, LDH: lac- tate dehydrogenase, EPO: erythropoietin.
haematologica | 2020; 105(11)