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Hematology
Gluttony
An 80-year-old man was referred to Accident & Emergency department (A&E) due to abnormal blood counts (see lab results). Upon arrival in A&E the patient was found to be jaundiced and with pain in the abdomen and lumbar region. The man is sweating more profusely than normally, but does not have a fever at that point (with use of paracetamol). His liver is palpable and his spleen is enlarged.
ParameterED24hRef.Units
Hemoglobin
7
5.8
8-10.5mmol/L
Thrombocytes
26
21
150-400⋅109/L
Leukocytes
70
35
4-10⋅109/L
Blasts
20
3
0⋅109/L
Neutrophils
29
21
1.5-6.5⋅109/L
Lymphocytes
4.2
5.5
1-3.5⋅109/L
Monocytes
0.7
2.5
0.2-0.9⋅109/L
ASTn.d.
408
<35U/L
ALT
158
107
<45U/L
LDHn.d.
9756
<248U/L
GGT
242
161
<55U/L
Bilirubin (total)
86
126
5-19µmol/L
Bilirubin (direct)n.d.
107
<5µmol/L
Creatinine
170
271
65-115µmol/L
ALP
899
858
40-120U/L
Ferritin
42869
47316
30-300µg/L
CRP
155
-<8mg/L
DAT
POS
-NEG-
When the paracetamol is stopped the patient develops a fever and becomes delirious. A striking feature of the lab results is the very severely elevated LDH and Ferritin. He also has elevated liver enzymes and his renal function is deteriorating. The blood cell count reveals leukocytosis with a lot of monocytes and monocytic, blast-like cells (referred below). In addition to these conspicuous cells, the monocytes also contain phagocytic cell debris.
Peripheral blood of the patient with activated monocytes with many vacuoles. A number of monocytes contain phagocytic cell debris.
Blastoid cells with nucleoli and a relatively dense or coarse nuclear chromatin pattern. Generous basophilic cytoplasm with projections, granules and vacuoles.
It is striking to note that the blasts were reduced 24 hours later, whereas a tripling in the number of monocytes was observed. The cells are indeed hard to define and flow cytometry was used to check whether blasts are present. This revealed that this is not the case, the cells have a young monocytic phenotype (CD34-, CD117-, CD14+/-,CD11b+/-, CD64+).
Course
Due in part to the extremely high ferritin and LDH, the patient was diagnosed with a hemophagocytic syndrome (Hemophagocytic lymphohistiocytosis, HLH), secondary to a malignancy; chronic monomyeloid leukemia. The patient is treated with, among others, dexamethasone to suppress the hyperinflammation caused by the hemophagocytic syndrome. The treatment of his CMML will be initiated after that. The dexamethasone starts having an effect and the ferritin and LDH decrease. The liver and kidney values improve and the patient is discharged.
The extremely high ferritin is a consequence of inflammation and production by macrophages, but does not play a pathological role by itself.
Background
Hemophagocytic syndrome is an immune disease resulting in uncontrolled activation of - among others - monocytes and macrophages, because the regulatory role of NK cells and T-lymphocytes is lost. Another name for this syndrome is hemophagocytic lymphohistiocytosis (HLH). This syndrome can occur as a result of a genetic mutation (primary HLH) or as a result of a provoking factor, such as a malignancy or an infection (secondary HLH).
Contrary to what the name of the syndrome suggests, the phagocytosis of erythrocytes is rarely observed in peripheral blood or the bone marrow.
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