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Hematology
Like snow in summer
A 65-year-old man was referred to the Emergency Room by his GP, because he had developed acute abdominal pain and fever within the last two days. The man had experienced a brief spell of hematuria before that, but is not producing urine anymore. The man feels cold and clammy to the touch. Considering the acute pain, it was initially suspected that he had acute pancreatitis. A full blood count and general lab tests were requested, including ALAT, Creatinine, GGT, Lipase and CRP.
None of the chemical determinations (except CRP) could be performed due to interference caused by hemolysis and icterus.
ParameterEDAdditionalRef.Units
Hemoglobin
8.9
6.9
8-10.5mmol/L
Thrombocytes
125
-150-400⋅109/L
Leukocytes
70
-4-10⋅109/L
ASTn.d.-<35U/L
ALTn.d.
±450-550
<45U/L
LDHn.d.-<248U/L
GGTn.d.
>229
<55U/L
Bilirubin (total)n.d.-5-19µmol/L
Bilirubin (direct)n.d.-<5µmol/L
Creatininen.d.
±155-190
65-115µmol/L
Haptoglobin-
<0.1
0.4-2.1g/L
CRP
123
-<8mg/L
Lipasen.d.
±100-110
13-60U/L
DAT-
NEG
NEG-
Schistocytes-
NEG
NEG-
On appearance, the patient seems to have normal hemoglobin levels and mild thrombopenia. Following consultation between the ER and the Clinical Chemistry Laboratory, a haptoglobin, direct antiglobulin test and further investigation into schistocytes (additional lab) was performed. The ALAT, GGT, Creatinine and Lipase were also estimated by the Clinical Chemist. From the new results, it can be deduced that the patient is suffering from severe liver damage, decreased renal function, cholestasis, pancreatic disease and a non-immunological intravascular hemolysis.
The patient was sent for CT and emergency surgery to determine the cause of his symptoms. A blood sample was collected to determine his blood group before going to the OR. Once again, the hemolytic plasma produced unusable results.
Interference in the blood group determination due to hemolytic plasma. Additional centrifugation of the plasma did not yield much of an effect.
Doubts arise about the hemoglobin measurement. To confirm the results, the EDTA sample was centrifuged and the hemolytic plasma was replaced by physiological saline. After being mixed, the hemoglobin was determined once more: 6.9 mmol/L. The ER and the ICU are informed that the hemoglobin measurements need to be checked manually by the technician and that blood gas measurements are not reliable as a result of the hemolysis.
Most automatic blood cell counters and blood gas analyzers perform photospectrometric measurement of hemoglobin after lysis of the erythrocytes. In other words, they do not distinguish between intracellular and free hemoglobin. Analyzers by Sysmex include the HGB-O parameter, which can be reported if the sample is measured in the CBC-O mode. This parameter only includes the intracellular hemoglobin. Whether this method is used or not depends on the settings in the laboratory.
Intensive Care
The CT scan revealed gas-forming lesions. The surgery revealed a bloody liver. The patient was sent to ICU with several drains in position. New measurements were performed in ICU and (as predicted) a significant discrepancy was observed between the blood gas and hemoglobin measurement after plasma replacement. The patient immediately received a transfusion with 6 units of RBCs.
ParameterMethodED+5h+6.5h+7.5h+8.5hRef.Units
Hemoglobin
bloodgas
-
3.7
4.6
-
5.6
8-10.5mmol/L
Hemoglobin
hemocytometer
8.9
--
5.4
-8-10.5mmol/L
Hemoglobin
plasma exchange
6.8
0.9
2.7
3.9
3.4
8-10.5mmol/L
It is obvious that the hemolysis has continued. The erythrocyte impedance measurements reveal a double population of erythrocytes: one microcytic and one normocytic.
From left to right: erythrocyte impedance measurement in the ER, the ICU prior to transfusion and the ICU after transfusion. Two populations of erythrocytes are observed in ICU: the left peak reveals a microcytic population, the right peak reveals a normocytic population. Transfusion results in an increase of the normocytic population.
The microcytic population is explained by the presence of “ghost cells”. These are erythrocytes in which the membrane has been damaged. As a result, the contents of the erythrocyte start to leak and this eventually results in complete lysis. These cells are observed under the microscope as very light, spherocytic erythrocytes. As these cells are virtually empty, they are easily missed under a light microscope.
Ghost cells and echinocytes in a patient's blood smear. Both abnormalities result from membrane degradation.
Conclusion
The patient's blood culture revealed that he has an infection of Clostridium perfringens bacteria. The hemolysis continues despite antibiotic treatment. His hemoglobin disappears like snow in summer. A total of 32 units of RBCs are transfused. The patient died within 72 hours after developing symptoms, as a result of sepsis and organ failure.
Clostridium Perfringens is an anaerobic, gram-negative rod-shaped bacterium that occurs naturally in the intestines. In the case of an infection, the bacterium releases an alpha toxin (phospholipase C), which breaks down cell membranes into free fatty acids. These fatty acids are converted into - among others - prostaglandins and thromboxane, which results in severe vasoconstriction. Inhibition of the supply of oxygen-rich blood creates an anaerobic environment for the bacterium.
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