Approach to the Case

Describe the CBC on 8/1

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Normocytic anemia with anisocytosis and thrombocytopenia

The Hb dropped from 11.4 to 9.8 g/dL in just one day. Is this because the bone marrow shut down?

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No! A complete shutdown of erythropoiesis would result in a drop in Hb of only 0.1 g/dL/day (assuming normal RBC survival)

Name three possible mechanisms for the acute drop in Hb

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Bleed
Hemolysis
Dilutional (from lots of IV fluids)

Which of the following data support a diagnosis of hemolysis?

Elevated reticulocytes

Low haptoglobin

Thrombocytopenia

Elevated ALT

Elevated AST:ALT ratio

Assuming that the patient has hemolysis, is it likely to be congenital or acquired?

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Acquired since the Hb was previously normal

What test would you order next to sort our the cause of hemolysis?

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DAT (Coombs test; see next slide)

You will not be provided with the result of the DAT 🙂

The patient also has thrombocytopenia.

If the patient were an outpatient, what are some causes of thrombocytopenia to consider?

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Cirrhosis
Alcohol
APS
ITP
Congenital thrombocytopenia
Gestational thrombocytopenia (though this patient was male)

If the patient was presenting to urgent care, what are your top considerations?

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Cirrhosis
Alcohol
ITP with bleed
TMA
Infection

If the patient developed thrombocytopenia while in hospital, what are the top 2 considerations?

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Drugs
Infection

This patient presented with anemia and thrombocytopenia. Let’s place the differential diagnosis of these two findings side by side:

Assuming that there is one overarching diagnosis, which of the following are unlikely explanations:

Hyperproliferative anemia

By definition this patient has hyperproliferative anemia (the reticulocyte response is appropriate).

Hypoproliferative anemia

Intracorpuscular hemolysis

With two exceptions, all diseases in this category are congenital/hereditary and we know this patient’s Hb was previously normal. The two exceptions are acquired HbH disease and PNH, neither of which presents in this manner (e.g., with an acute drop in platelet count, preceding a major decline in Hb).

Warm autoimmune hemolytic anemia

We must consider combined AIHA and ITP (Evans syndrome).

Valve hemolysis

Leads to hemolysis but not thrombocytopenia.

The following schematic shows conditions that are more likely to be associated with concomitant anemia and thrombocytopenia (in red) vs. those that are less likely (light gray). Selected explanations are in blue.

We can reorganize the algorithms from the previous slides in table form. The conditions that may be associated with both anemia and thrombocytopenia are bolded. The abbreviations are found in a graphic on a previous slide:

Condition	Hemolytic anemia	Thrombocytopenia (TP)
Hypoproliferative	–	In B12 deficiency, primary BM process
Cold agglutinin disease	+	Not typically associated with TP
Alloimmune hemolysis	+	Not typically associated with TP
Evans syndrome	+	+
Wilson disease	+	Could present with TP, but not typically this acute
Babesiosis	+	+
C. perfringens	+	+ (most of these patients have TP from DIC)
DIC	+	+
TMA (TTP, HUS)	+	+
Valve hemolysis	+	Not typically associated with TP
Spur cell anemia	+	The anemia and TP would not typically develop this rapidly
Intracorpuscular causes	+	Maybe in PNH, but not with an acute drop in platelets
ITP with bleed	Positive hemolytic markers if resorbing internal hematoma	+
Alcohol	–	+
Primary BM process	–	+
TMA	+	+
ECMO	+ (though hemolytic anemia not common in this setting)	+
HLH	Positive hemolytic markers common owing to engulfment and destruction of red blood cells by activated macrophages; retics usually inappropriately low	+

Now let’s consider the fact that the ALT and AST are elevated. Red blood cells release AST when they are lysed, but very little if any ALT. Thus, although the elevated ratio of AST:ALT is increased, the elevated absolute level of ALT argues for the a hepatic origin. Refer back to the table on the previous slide and identify those conditions that are associated with hepatic injury.

Which diagnoses rise to the top of the list?

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Babesiosis
HLH (though retics not usually elevated as they were in this case)

Not knowing anything else about the patient, what test would you order next?

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Thin smear for parasites

The this smear shows the following:

The blue arrows point to red blood cells that have been infected with babesia (ring forms).

Is a thin smear diagnostic for babesiosis or do we need to order serology or PCR testing?

The smear is diagnostic

The smear is suggestive; we need serology or PCR testing

Would the following peripheral blood smear be a reassuring or concerning finding?

Reassuring

Concerning

The blue arrow is pointing to a Howell-Jolly body, indicative of asplenia which is a risk factor for more severe disease in a patient with babesiosis (the B indicates a burr cell, the P a platelet).

Treatment of babesiosis may consist of:

Antiviral agents

Atovaquone plus azithromycin

Clindamycin plus quinine

Plasmapheresis

Red cell exchange

More about the case

56 yo M previously well presented with fevers up to 103 degrees F at home with headaches. He went to urgent care where a CBC revealed a low platelet count. As a result, he was referred to the ED. Further questioning revealed nausea and fatigue. He lived a in wooded area, but had not noticed any tick bites. In the ED, his heart rate was 100, BP 100/60, T 100.9. Labs showed anemia, thrombocytopenia, positive hemolytic markers and transaminitis. A thin smear was ordered and showed the following:

He was admitted to hospital and treated with:

Quinine and clindamycin
6 rounds of exchange transfusion

Testing for anaplasmosis and Lyme was negative.

Babesiosis was confirmed with PCR:

His anemia and thrombocytopenia improved over the next several days, as did the degree of parasitemia. He was discharged on day 10 and followed up in ID clinic.

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