Approach to the Case

Which of the following data support a diagnosis of hemolysis?

Elevated reticulocytes
Low haptoglobin
Elevated ALT
Elevated AST:ALT ratio

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

The patient also has thrombocytopenia.

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:

ConditionHemolytic anemiaThrombocytopenia (TP)
HypoproliferativeIn 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
C. perfringens++ (most of these patients have TP from DIC)
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 bleedPositive hemolytic markers if resorbing internal hematoma+
Primary BM process+
ECMO+ (though hemolytic anemia not common in this setting)+
HLHPositive 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.

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?

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
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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