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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (5): 921-927. doi: 10.19723/j.issn.1671-167X.2021.05.018

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Relationship between marked hyperferritinemia and hemophagocytic lymphohistiocytosis

GAO Wei-bo,SHI Mao-jing,ZHANG Hai-yan,WU Chun-bo(),ZHU Ji-hong   

  1. Department of Emergency, Peking University People’s Hospital, Beijing 100044, China
  • Received:2019-11-30 Online:2021-10-18 Published:2021-10-11
  • Contact: Chun-bo WU E-mail:wuchunbowcb@163.com

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Abstract:

Objective: To investigate the relationship between marked hyperferritinemia (MHF) and hemophagocytic lymphohistiocytosis(HLH). Methods: The clinical data of 123 patients with MHF admitted to Peking University People’s Hospital from January 2017 to September 2018 were collected, including demographics, baseline characteristics, signs and symptoms, blood routine, blood biochemistry, coagulation function parameters, such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), d-dimer (D-D), fibrin degradation product (FDP), blood ferritin, natural killer (NK) cell activity, soluble interleukin (IL)-2 receptor and bone marrow examination. According to the diagnosis of HLH, the patients were divided into HLH group and non HLH group. The patients were divided into death group and survival group according to the 3-month follow-up results. The groups were compared and statistically analyzed. Results: In the 123 patients with MHF, the average age was (44.2±17.4) years with a male/female ratio of 1.3 ∶1. The most common causes were hematolo-gic malignancies, rheumatologic and inflammatory disorders, iron overload, and HLH. HLH was enriched as the ferritin increased, and the HLH ratios were 28.8%, 40.0%, 54.5%, 50.0%, 50.0% in ferritin value of 10 000-19 999, 20 000-29 999, 30 000-39 999, 40 000-49 999 μg/L,more than 50 000 μg/L respectively. There were 46 cases of HLH, among which 15 cases were secondary to malignancies,14 cases secondary to rheumatologic disorders, 2 cases secondary to infection, and 15 cases with no clear precipitating cause. There were significant differences between the HLH group and non-HLH group in hepatomegaly, splenomegaly, lymphadenectasis, albumin (ALB), fibrinogen(Fib), P<0.05, and no significant differences in age, gender, fever, disturbance of consciousness, ferritin level on presentation, maximum ferritin level, cytopenia in 2 or more cell lines, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), triglyceride (TG), coagulation parameters (PT, APTT, D-D, FDP, exception of Fib), and mortality rate (P>0.05). There were significant differences between the death group and survival group in disturbance of consciousness, platelet count, PT, TBIL, and DBIL (P<0.05), but no significant differences in age, gender, fever, hepatomegaly, splenomegaly, lymphadenectasis, ferritin level on presentation, maximum ferritin level, neutrophils, hemoglobin, ALT, AST, ALB, TG, coagulation parameters (Fib, APTT, D-D, FDP, exception of PT) and the HLH ratio (P>0.05). Conclusion: HLH was enriched as the ferritin increased, but marked hyperferritinemia was not specific for HLH in adults.

Key words: Hyperferritinemia, Hemophagocytic lymphohistiocytosis, Prognosis

CLC Number: 

  • R557.4

Table 1

Clinical manifestations of 123 patients with marked hyperferritinemia"

Clinical symptoms and signs Proportion of total cases,n (%) HLH,n (%)
Fever 100 (81.3) 38(38.0)
Splenomegaly 51 (41.5) 29(56.9)
Hepatomegaly 22 (17.9) 15(68.2)
Lymphadenopathy 53 (43.1) 29(54.7)
Disturbance of consciousness 16 (13.0) 6(37.5)
Hemocytopenia (more than 2 lines) 40 (32.5) 14(35.0)
Neu(<1.0×109/L) 25 (20.3) 8(32.0)
Hb(<90 g/L) 49 (39.8) 19(38.8)
PLT(<100×109/L) 86 (69.9) 33(38.4)
Hypertriglyceridemia (≥3.0 mmol/L) 38 (30.9) 17(44.7)
Low fibrinogen (≤1.5 g/L) 25 (20.3) 16(64.0)

Table 2

HLH rate of 5 groups with marked hyperferritinemia"

Ferritin n HLH, n (%)
10 000-19 999/(μg/L) 66 19 (28.8)
20 000-29 999/(μg/L) 20 8 (40.0)
30 000-39 999/(μg/L) 11 6 (54.5)
40 000-49 999/(μg/L) 10 5 (50.0)
≥50 000/(μg/L) 16 8 (50.0)

Table 3

Comparison of clinical characteristics between HLH group and non-HLH group"

Items HLH (n=46) Non-HLH (n=77) P
Age/years, M (P25, P75) 48 (31, 61) 41 (27, 56) 0.178
Male/female, n 22/24 47/30 0.153
Fever, n (%) 38 (82.6) 62 (80.5) 0.774
Splenomegaly, n (%) 29 (63.0) 22 (28.6) 0.000
Hepatomegaly, n (%) 15 (32.6) 7 (9.1) 0.001
Lymphadenopathy, n (%) 29 (63.0) 24 (31.2) 0.001
Disturbance of consciousness, n (%) 6 (13.0) 10 (13.0) 0.993
Initial ferritin/(μg/L), M (P25, P75) 12 558 (6 249, 22 407) 13 901 (10 463, 24 059) 0.386
Ferritin MAX/(μg/L), M (P25, P75) 24 816 (13 528, 41 885) 16 774 (11 909, 29 421) 0.075
WBC/(×109/L), M (P25, P75) 4.6 (2.2, 8.9) 4.3 (2.6, 9.9) 0.824
Neu /(×109/L), M (P25, P75) 3.2 (1.4, 6.6) 2.9 (1.3, 7.7) 0.913
Hb/(g/L), x ?±s 95.8±23.0 96.2±26.8 0.924
PLT/(×109/L), M (P25, P75) 52 (24, 109) 38 (18, 140) 0.453
ALT/(U/L), M (P25, P75) 78 (33, 191) 58 (25, 251) 0.960
AST/(U/L), M (P25, P75) 94 (50, 216) 63 (33, 195) 0.099
LDH/(U/L), M (P25, P75) 779 (505, 1 432) 455 (296, 805) 0.003
ALB/(g/L), x ?±s 29.7±6.6 33.9±6.2 0.001
TG/(mmol/L), M (P25, P75) 2.6 (1.4, 4.1) 2.2 (1.4, 3.2) 0.216
TBIL/(mmol/L), M (P25, P75) 14.0 (10.3, 66.5) 13.3 (9.0, 25.2) 0.387
DBIL/(mmol/L), M (P25, P75) 6.8 (3.1, 47.2) 5.8 (3.1, 14.6) 0.347
Fib/(g/L), M (P25, P75) 2.01 (1.33, 3.65) 2.79 (1.91, 3.62) 0.011
D-D/(μg/L), M (P25, P75) 2247 (853, 5 761) 812 (257, 3 027) 0.002
FDP/(mg/L), M (P25, P75) 19.0 (7.9, 50.3) 7.7 (2.5, 24.0) 0.002
PT/s, M (P25, P75) 12.4 (10.8, 14.7) 12.2 (11.3, 14.0) 0.647
APTT/s, M (P25, P75) 33.2 (29.0, 40.8) 30.9 (28.0, 35.9) 0.044
Mortality, n (%) 7 (15.2) 10 (13.0) 0.729

Table 4

Comparison of clinical characteristics between death and survival group"

Items Death group (n=17) Survival group (n=106) P
Age/years, M (P25, P75) 57 (30, 75) 44 (29, 56) 0.101
Male/female, n 11/6 58/48 0.441
Fever, n (%) 15 (88.2) 85 (80.2) 0.649
Splenomegaly, n (%) 8 (47.1) 43 (40.6) 0.614
Hepatomegaly, n (%) 5 (29.4) 17 (16.0) 0.320
Lymphadenopathy, n (%) 8 (47.1) 45 (42.5) 0.722
Disturbance of consciousness, n (%) 8 (47.1) 8 (7.5) 0.000
Initial ferritin/(μg/L), M (P25, P75) 11 225 (2 648, 28 526) 13 801(10 209, 22 242) 0.638
Ferritin MAX/(μg/L), M (P25, P75) 22 349 (13 621, 39 473) 18 177 (12 601, 34 026) 0.501
WBC/(×109/L), M (P25, P75) 4.6 (1.1, 15.1) 4.6 (2.7, 8.6) 0.814
Neu /(×109/L), M (P25, P75) 3.3 (0.6, 6.9) 3.2 (1.6, 6.2) 0.981
Hb/(g/L), x ?±s 87.8±22.0 96.4±24.9 0.116
PLT/(×109/L), M (P25, P75) 26 (13, 38) 67 (23, 165) 0.013
ALT/(U/L), M (P25, P75) 68 (27, 252) 56 (26, 162) 0.648
AST/(U/L), M (P25, P75) 117 (39, 642) 65 (36, 151) 0.290
LDH/(U/L), M (P25, P75) 714 (244, 2 479) 492 (294, 761) 0.183
ALB/(g/L), x ?±s 30.6±5.8 32.8±6.7 0.230
TG/(mmol/L), M (P25, P75) 2.2 (1.1, 3.5) 2.4 (1.4, 4.4) 0.199
TBIL/(mmol/L), M (P25, P75) 27.8 (12.2, 111.8) 12.6 (8.4, 27.2) 0.045
DBIL/(mmol/L), M (P25, P75) 17.3 (6.7, 71.3) 5.2 (2.7, 14.8) 0.017
Fib/(g/L), M (P25, P75) 2.34 (1.49, 3.69) 2.57 (1.85, 3.48) 0.504
D-D/(μg/L), M (P25, P75) 1 615 (167, 4 067) 848 (308, 3 146) 0.889
FDP/(mg/L), M (P25, P75) 11.2 (3.8, 32.0) 7.7 (2.8, 23.1) 0.665
PT/s, x ?±s 14.6±3.6 12.6±2.5 0.046
APTT/s, x ?±s 39.2±14.5 32.0±6.2 0.069
HLH ratio, n (%) 7 (41.2) 39 (36.8) 0.729
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