WHY TO DO AUTOMATED CELL COUNTER ANALYSIS

This topic has been written because, I have felt through these years of working in hematology, the major reason for delay or difficulty in diagnosis in almost all the hematological disorders is due to the fact that more than 95% of hospitals do not have 24 hour access to expert advice on blood smears.

Most of the problems seen in the hematology unit can be easily diagnosed and many of them could be easily treated in the local clinics or nursing homes itself, if they had access to a good blood smear review.

However, even in the absence of smear review, most of the cases can still be diagnosed or at least suspected if an automated cell counter analyis is available along with basic clinical and biochemical details.

For basic use of MCV to classify hematological disorders, please see the flow chart for automated cell counter analysis for diagnosis, in this website.

Please see some of the examples :

(Most of the cases are summarized because the main intention is to present the utility of automated cell counter in rapid diagnosis. The idea of this presentation is to encourage all the doctors to make use of the automated cell counter and to depict how easily a diagnosis could be made. Any queries or any counter-arguments, comments etc. are welcome. Almost all the cases are examples from the author’s own experience. Most of the cases, you would agree the diagnosis is straight forward, but missed just for the absence of a good smear report or an automated cell counter analysis. Please note there is no intention to find fault with any one, but the main purpose, is to simplify diagnostic approach)

(Please note that values in automated cell counter are depicted as values per Litre and can be interpreted as follows:

Hb 100g/L which is equal to 10g/dl

WBC 5.5 X 109/L which is equal to 5,500 per cumm

Platelets 55 x 109/L which is equal to 55,000 per cumm)

Case 1:

A fourteen year old boy was referred from a village with fever of 10 days duration, jaundice and severe anemia. He was also semi-conscious. Hepatic encephalopathy was thought of. Preliminary investigations revealed that he had indirect hyperbilirubinemia.

Hb 50g/l

WBC 3.5

Platelets 20

MCV 81 (Normal 78-92)

Creatinine 2.1

Before looking at the smear, we know that this patient is having massive hemolyis as he has indirect hyperbilirubinemia. His anemia is not iron deficient as he has normal MCV. He has low platlelets which can be due to sepsis, DIC or massive hemolysis itself.

Only two major diagnostic possibilities are TTP (thrombotic thrombocytopenic purpura) or malaria. Smear confirmed massive falciparum infection and this patient had cerebral malaria.

Case 2:

50 year old male, a husband of a doctor had recurrent anemia. He had no clinical signs or symptoms. Because he had recurrent anemia, he was investigated for all possible hemolytic disorders (out of which one came positive. Remember in any blood test which are cumbersome and labour intensive, false positives and false negatives are very common). His anemia persisted.

Hb 66

MCV 68

RBC count 3.5

WBC 7.8

Platlets 506

RDW 24 (Normal upto 16)

A severe microcytic anemia with raised RDW, normal white cell but increased platlelet count. These features are sine qua non of IRON DEFICIENCY ANEMIA. He had endoscopy and was having a bleeding ulcer.

A high platelet count can occur in many but not in all cases of iron deficiency. Microcytic anemia with MCV less than 70 is highly suggestive of iron deficiency.

• What is RDW?

RDW (Red cell Distribution Width) is an indirect measure of anisocytosis. High RDW indicates severe anisocytosis.

Severe anisocytosis (HIGH RDW) can occur in following conditions:

• Iron deficiency anemia (as there is always a mixture of microcytic and normocytic cells)

• Megaloblastic anemia (there is a mixture of macrocytic, fragmented and normocytic cells)

• Acute hemolyis (due to the presence of normal RBC which are normocytic and many reticulocytes which are macrocytic)

• Acute microangiopathies such as TTP, HUS (due to the presence of normal RBCs and fragmented RBCs)

• Other causes being, sideroblastic anemia, recent transfusion etc (as transfused cells are spherocytic and smaller than normal RBC)

Case 3:

50 year old male, vegetarian, who had CABG 3 years back, has been found to be anemic for the past 2 years. He was diagnosed to have iron deficiency anemia, had iron therapy and had recurrent transfusions 4 times in the last 2 years.

Hb 65 g/L

MCV 106

RDW 22

WBC 2.3

Platelets 104

Biochemical parameters:

LDH 1300

S Bilirubin 3.2 (Indirect 2.2)

This patient has mild pancytopenia. Note macrocytic anemia, with gross anisocytosis (as evidenced by high RDW).

This is a case of Megaloblastic anemia.

Macrocytic anemias can occur in MDS, aplastic anemia and megaloblastic anemia. But the characteristic of megaloblastic anemia is that this is a condition with acute dyserythropoiesis, which means most of the red cell precursors are destroyed in the marrow (intramedullar hemolysis). So these patients will have markedly high LDH (as a marker of massive red cell destruction) and may have indirect hyperbilirubinemia, if the process is hyperacute.

Remember that even a smear examination can sometimes misguide. This patient had many fragmented cells in the peripheral blood (due to the fragmentation of large macrocytes), which can be wrongly interpreted as microcytes. However, the automated cell counter classically picked up the predominant macrocytes. High RDW with macrocytosis and high LDH is a characteristic finding in megaloblastic anemia.

N.B: A word of caution here. As mentioned previously, the high reticulocyte content in acute hemolysis can present with macrocytic anemia esp. in autoimmune hemolytic anemia, which may also have elevated bilirubin and high LDH. However the smear examination in autoimmune hemolysis is characteristic with many spherocytes. A direct coomb’s test will also be helpful

Megaloblastic anemias very simple to diagnose and are the commonest anemias in our country next to iron deficiency.

Case 4:

62 year old lady was found to be very tired. She was found to be anemic and transfused and sent for further evaluation to the nearest corporate hospital. Her peripheral blood smear was reported as dimorphic anemia. (probably related to recent transfusion) She had endoscopy to rule out bleeding from GI tract and but was normal. However she required further transfusions and the anemia recurred.

Hb 72 g/L

MCV 102

RDW 17

WBC 2.2

Platelet 25

LDH 230 (Within normal limits)

This is a case of Aplastic anemia.

This patient has severe pancytopenia. Any bone marrow stress can produce mild macrocytosis. The normal LDH rules out megaloblastic anemia. The slightly high RDW is due to recent transfusion. And that is the reason for dimorphic blood picture.

If a complete cell counter analysis was available, diagnosis could have been made or suspected in a flash of a second.

Case 5:

An elderly lady found to have severe anemia, transfused repeatedly, but found to have more and more jaundiced and anemia persisted.

Hb 65

WBC 14.5

Platelet 430

MCV 110

MCH 53

MCHC 44

RDW 19

This is a case of auto-immune hemolytic anemia.

In auto immune hemolytic anemias, there is usually clumping of RBCs due to autoagglutination. This leads to falsely high MCH and MCHC values in many cases. The high MCV here is due to associated reticulocytosis. (Reticulocytes are larger than normal RBCs) These patients usually have elevated WBC counts and platelet counts due to marrow hyperactivity. In addition, they show biochemical evidence of hemolysis such as elevated indirect hyperbilirubinemia and LDH.

Case 6:

60 year old lady has severe back pain. She had mild anemia. She underwent many radiological investigations, including MRI which were normal.

Hb 78g/L

MCV 88

WBC 22.2

Platelets 25

Automated Diff: Neutrophil 10%, Lymphocyte 40%, Monocytes 50%

This is a case of acute Leukemia.

Note marked thrombocytopenia associated with anemia. The automated cell counter is not good in picking up the differentials correctly. The blasts in the peripheral blood are often counted as lymphocytes or monocytes.

Whenever, the automated cell counter shows increase in lymphocytes or monocytes, always suspect abnormal lymphoid population or blasts.

Case 7:

2 year old boy presented with acute respiratory distress. He was found to have a mediastinal mass. Patient had a non successful biopsy and was transferred to the tertiary centre in the city. His general condition worsened soon, requiring ventilation.

Hb 80g/L

MCV 85

WBC 18

Differential: 20% Neutrophil, 80%Lymphocytes

Platelets 140

Diagnosis: T Lymphoblastic Lymphoma with Leukemic spill over

This child had predominant lymphocytosis, more than expected for the age. The smear was looked at immediately which eventhough showed abnormal lymphoid population, they were not typical of blasts. Immediate flow cytometry confirmed that they were immature cells.

Based on the above finding, the child had T acute lymphoblastic lymphoma with early bone evidence of bone marrow infiltration. A thorocotomy was avoided and treatment initiated immediately to save the child from mediastinal syndrome.

N.B: In patients with lymphocytosis, if morphology is suspicious and hematological malignancy is strongly suspected, immediate markers (on flowcytometry) should clinch the diagnosis.

Case 8:

Elderly male presented with PUO. Extensive investigations revealed one small infiltrative lesion in the lung.

Hb 112

WBC 10.2

Differential: Neutrophil 35%, Lymphocytes 55%, Monocytes 10%.

Platelets 254

This patient had high grade Non Hodgkin’s Lymphoma

The patient had extensive investigations incluing FNAC of the mass which unfortunately yielded no results. Empirical steroid therapy relieved the symptoms. But few months, later, he presented again with fever, this time with pancytopenia. And bone marrow examination confirmed infiltration with high grade lymphoma. Ultimately he died even before therapy was started. A mild lymphocytosis in the automated cell counter, if looked at by the clinician could have alerted early on.

Although in these cases, smear is more helpful, the illustration depicts, how even without a smear, a strong possibility of hematological malignancy (lymphoma) can be suspected.

Case 9:

62 year old male, was admitted with second episode of stroke. He had history of stroke 6 months back.

Hb 210g/L

WBC 15.5

Platelets 700

This is a case of Polycythemia Rubra Vera

This is a simple case. Just illustrated because the Hb done elsewhere at the time of first stroke was 18g/dl. Since he was a smoker, it was thought of due to smoking and asked to stop the same. However “PANmyelosis” (Increase in all 3 cell lines) is characteristic of polycythemia vera, which can be easily picked up in an automated cell counter report. Along with other diagnostic criteria, his diagnosis was confirmed. He was started on regular venesections.

Case 10:

• 40 year old male, an executive, had swelling of knee joint. Was found to have hemarthrosis. He had previous surgery in the same joint few years ago. MRI and arthroscopy of the joint did not reveal any diagnostic clue. He has to go through the ritual of repeated examinations for few weeks. Finally referred to a physcician to rule out any systemic disease.

Hb 150g/L

WBC 34

Platelets 800

A differential count was ordered by the physcician and the pathologist confirmed chronic myeloid leukemia. An automated counter revealed panmyelosis. However, the initial manual blood counts showed only elevated WBC count which was assumed to be due to inflammation.

All myeloproliferative and myelodysplastic syndromes can have abnormal functioning cells inspite of normal or increased counts. This patient inspite of having thrombocytosis, had platelet function defect, which led to bleeding at a vulnerable site (site of previous surgery).

This is also a simple case, just to depict that basic investigations such as automated cell counter gives an easy clue in myeloproliferative disorders. Even though smear is diagnostic in this case, in the absence of smear reporting by qualified personnel, there can be delays in diagnosis, even in simple disorders such as these. Especially in patients with splenomegaly, unnecessary investigations such as ultrasonagram or an endoscopy could be avoided, if the counts are looked into carefully.

(Please note that, this column is specially written to highlight the usefulness of automated cell counter which is still not available in many peripheral centres and in some urban centres as well.Again it is reiterated that THIS IS NOT TO BLAME ANYONE FOR THE LATE DIAGNOSIS)

Case 11:

30 year old male presented with acute renal failure. He was unwell with joint pains few weeks ago and took ayurvedic treatment. He was initially treated in a nearby nursing home and later referred to an advanced renal centre. He had a creatinine of 4.5mg/dl had high uric acid levels and mildly elevated LDH.

An automated cell counter value revealed

Hb 64

WBC 6.4

Platelets 120

This patient probably would have steroids along with the native treatment he received, which probably normalized the WBC count. However, acute cell turn over had produced tumour lysis with concomitant renal failure. The mild pancytopenia, immediately gave us a clue that this is a case of acute lymphoblastic leukemia, presenting with renal failure due to the above mentioned reason. A bone marrow confirmed the same, and his renal failure reverted to normal with simple hydration.

So the reasons for automated cell counter analysis when manual counts are available at 5-10 times cheaper cost are made clear, I believe. The reasons are many fold,

• You can come to a diagnosic clue, even without looking at the smear in many cases

• Manual counts eventhough are quite appropriate, is subjected to lot of errors, in our country due to various reasons (not depicted here for ethical reasons)

• Most of the advanced tests are not available in many centres. The automated cell counter by giving diagnostic clue will help the doctor to decide what further tests are needed and where it can be done, thereby minimizing time, money and most importantly saving the patient in many cases

• As you saw in some of the examples above, hematological diseases need not always present with anemia and can present with arthritis, stroke, renal failure, loss of consciousness etc..

• So, atleast for patients with any prolonged illness, those requiring many extensive investigations and those requiring in-patient care, an automated cell counter analysis should form the baseline. It is definitely cost-effective in these patients, who may have to spend many times more and even may have significant morbidity if a simple treatable hematological diagnosis is missed in time.

 
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