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The following is the complete blood count (CBC) when you first see the patient:

WBC (109/L)Hb (g/dL)MCV (fL)MCHC (g/dL)RDW-SD (fL)PLT (109/L)
7.08.09834.573.6155

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 109/L, RBC 4-6 x 1012/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45 fL, platelets (PLT) 150-450 x 109/L

The patient’s white cell count was normal. Does that mean the white cell differential must be normal?

a
Yes
b
No
There can be many permutations of abnormal numbers of white cell subtypes (neutrophils, monocytes, lymphocytes, eosinophils and basophils) with a normal total white cell count.

The following is a white cell differential from the patient:

Is this differential from the complete blood count shown on the first slide?

a
Yes
b
No

It is from the next day. You can tell that it is done at a different time because the absolute counts of the various white cell subtypes adds up to more than 7 x 109/L, which is the total white cell count on the first slide

The following is a white cell differential from the patient:

This differential is from the next day. Note that despite the normal total white cell count, there is a left shift (this is indicated by the increase in the number of immature granulocytes) and he has lymphocytopenia.

The learning point here is that you should NOT assume a normal differential when the white cell count is normal.

Are you surprised the mean cell volume (MCV) was not increased?

a
Yes
b
No
While it is true that chronic liver disease may be associated with macrocytosis, that is not always the case.

If you were told that the patient’s baseline mean cell volume (MCV) – before his admission to hospital – is high, what would be your explanation for the normal MCV when you see him?

We will get to the anemia in a moment (that is why you were asked to see the patient), but let’s consider the low platelet count.

Thrombocytopenia is the most common cytopenia in patients with cirrhosis and hypersplenism. Consider the following results in a cohort of 213 subjects with compensated cirrhosis without esophageal varices:

Occurrence of thrombocytopenia, anemia, or leukopenia at baseline in the cohort; HI, hematologic indices.
Different abnormal HI combinations; HI, hematologic indices.

Note: other studies report that up to 70% of cirrhotic patients have anemia.

The patient has been in hospital for almost a full month, so it is certainly possible that there are other factors contributing to his thrombocytopenia, for example infection or medication. But there were no signs of active infection and he was not taking any new medications. Moreover, A review of his old records reveals a chronically low platelet account of 80-100 x 109/L. Thus, his thrombocytopenia is likely secondary to his cirrhosis and portal hypertension.

Here is the time course of the patient’s hemoglobin for the 2 weeks prior to you seeing him (day 0) and the transfusions he received.

DayHb (g/dL)RBC transfusion
08.0
-17.7
-28.2
-37.21 unit
-47.9
-57.4
-67.3
-77.5
-87.5
-96.62 units
-107.7
-117.1
-127.8
-136.92 units
-147.6
Hemoglobin (Hb) concentration; RBC, red cell transfusion; u, unit.

As seen in the table, the patient has required multiple red cell transfusions to maintain Hb > 7 g/dL. A similar pattern was observed in the first 2 weeks of his admission. He has had a total of 12 units packed red cells over the past month.

His reticulocyte counts are as follows:

The absolute reticulocyte count is right at the cusp for what we would consider an appropriate bone marrow response (>120 x 109/L).

There is no evidence of blood loss:

  1. The patient does not have hematemesis or melena.
  2. Upper endoscopy early in his admission showed non-bleeding varices, and these were banded.
  3. His vital signs are stable – there is no hypotension or postural changes in blood pressure.

The following was the patient’s prothrombin time (PT) and activated partial thromboplastin time (aPTT) the day you saw him:

Do these results make it more likely that the patient is bleeding?

a
Yes
b
No
The PT and/or aPTT are often elevated in patients with cirrhosis, but they do not provide a reliable assessment of the hemostatic balance because the liver makes not only procoagulants but also anticoagulants, and the latter are not assayed using conventional clotting times.

So now you are wondering about hemolysis. Which of the following hemolytic markers are also seen in patients who have cirrhosis without hemolysis?

a
Elevated serum LDH
b
Elevated serum bilirubin
c
Elevated serum AST
The AST:ALT ratio is increased in alcoholic liver disease.
d
Decreased serum haptoglobin

Here are the test results for markers of hemolysis and cirrhosis:

Because of the overlap in hemolytic markers between hemolysis and cirrhosis, they cannot be reliably used to diagnose hemolysis in a patient with cirrhosis. But there is another test that will help. And it is one that should really come before biochemistry in the workflow – especially for hematologists.

Before looking at the peripheral smear, what are you now considering in the differential diagnosis?

a
Autoimmune hemolytic anemia (AIHA)
We can’t rule it out at this point, but it is likely the team and blood bank have done so given the frequency of his transfusions.
b
Copper excess
Wilsons disease is an interesting thought, but would be higher on the list of etiologies in a younger patient presenting with acute liver failure.
c
Spur cell anemia
Yes, this is a classic presentation for spur cell anemia, namely a patient with decompensated cirrhosis with increasing transfusion requirements.
d
Paroxysmal nocturnal hemoglobinuria
Can’t rule it out, but it is not associated with chronic liver disease and would be an incidental occurrence.

The following is the peripheral smear from this patient: