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Hematology
Kissing Disease
A young woman, aged 16 years, presents to Accident & Emergency department (A&E) because she fainted during physical exertion. She explains that she has been feeling tired and short of breath for a number of days and has had a fever for one day. Her urine is darker than normal. History-taking reveals that she has suffered from periodic blood loss in her stool for almost a year, accompanied by lower abdominal pain. This has not been causing any significant weight loss.
The initial lab tests reveal normocytic anemia with undetectable haptoglobin, which is indicative of hemolysis. The patient has slightly elevated liver enzymes and an elevated CRP. Also worth noting are an elevated LDH and a severely elevated ferritin. The microscopic differentiation at this point reveals a mildly reactive presentation, with activated lymphocytes.
ParameterED+5d+1mRef.Units
Hemoglobin
5.7
5.2
6.5
7.2-9.5mmol/L
MCV
88
93
104
83-100fL
Thrombocytes
167
335
451
150-400⋅109/L
Leukocytes
6.6
12
6
4.5-13⋅109/L
Promyelocytes
0
0
-0⋅109/L
Myelocytes
0.1
0.1
-0⋅109/L
Metamyelocytes
0.1
0.1
-0⋅109/L
Bands
0.4
0
-0-0.1⋅109/L
Neutrophils
2.3
4.3
2.4
1.8-8⋅109/L
Lymphocytes
3.4
6.4
2.9
1.2-5.2⋅109/L
Plasma cells
0.1
0
-0⋅109/L
Monocytes
0.2
1
0.6
0.2-0.9⋅109/L
Eosinophils
0.1
0.1
0.1
0-0.4⋅109/L
Basophils
0
0
0.1
0-0.1⋅109/L
Ferritin
1813
--10-100µg/L
AST
82
118
24
<30U/L
ALT
72
132
38
<34U/L
LDH
578
647
265
<241U/L
GGT
50
79
44
<40U/L
Bilirubin (total)
26
34
8
5-19µmol/L
Bilirubin (direct)
8
12
3
<5µmol/L
Creatinine
56
--50-95µmol/L
Haptoglobin
<0.1
--0.4-2.1g/L
CRP
44
--<8mg/L
Because the girl does not look overly sick, does not have any active blood loss and the above-mentioned values could easily be consistent with a viral infection, she is sent home and given the advice to contact the out-of-hours GP service if the situation deteriorates. The anemia is attributed to chronic rectal blood loss, for which additional diagnostic tests will be required at a later stage.
Five days later she presents to A&E again with headache, dizziness and a fever. Her liver values have deteriorated. Her blood cell count is now indicative of lymphocytosis. Microscopic analysis reveals normal and (very) atypical lymphocytes, as well as many smudge cells.
Normal and activated lymphocytes. A normal, resting lymphocyte is small and round. Activated lymphocytes can differ greatly in morphology, but often have large(r) nuclei with fanned out cytoplasm that can take on strange shapes.
Smudge cells in a preparation are the result of the mechanical stress placed on the cell during smearing of the blood sample. Although a number of these cells will almost always be present, a high number could be indicative of abnormal proliferation of a cell line.
These abnormal lymphocytes, found in a young woman, combined with elevated liver values, could well be consistent with an acute infection of the Epstein-Barr virus (EBV). This does indeed appear to be the case; IgM antibodies against the virus are detected.
In general, the detection of only IgM antibodies points to an acute infection. IgG antibodies are formed at a later stage.
Course
As active treatment is generally not available for mononucleosis, she was sent home to recover. She returned for a check-up after one month. She was already feeling much better and her lab values have improved.
Background
The pathogen that causes mononucleosis is the Epstein-Barr virus (EBV). This virus can result in significantly abnormal lymphocytes in the blood count, particularly in adolescents. These activated lymphocytes are generally quite fragile, which results in smudge cells.
The EBV-IgM antibodies that have formed can cross-react with erythrocytes. This results in complement activation and intravascular hemolysis. The severity of the anemia in this patient is probably due to a combination of hemolysis caused by the virus and by the rectal blood loss.
A currently unknown mechanism also causes liver damage, characterized by elevated ALAT, ASAT and LDH. This damage is often mild and not clinically relevant. The patient can also suffer from cholestasis (elevated GGT and bilirubin), which in turn can cause jaundice. The elevated Ferritin can be explained on the one hand by the acute phase and on the other hand by the damage to the liver.
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