Identifying thrombotic thrombocytopenic purpura (TTP) among thrombotic microangiopathies (TMAs)


TMAs require urgent management, but variable presentation can make them difficult to distinguish1,2

TMA is a pathologic term used to describe occlusive microvascular or macrovascular disease, often with intraluminal thrombus formation.3 Presentation of TMAs varies widely, including but not limited to stroke, neurologic complications, severe renal failure, flu-like symptoms, and simple fatigue.4,5

This leads to the involvement of several physician specialists at the outset of patient care in clinic and hospital settings. Both—the variability of TMAs and the involvement of many specialties—pose a challenge to prompt recognition and diagnosis of TTP.4,5

Your role is crucial to the diagnosis and speed of appropriate treatment for TMAs6

In most cases, patients present at the emergency department for a nonspecific somatic complaint, and thrombocytopenia is subsequently discovered. More rarely, the results of a CBC can reveal thrombocytopenia during an appointment in a non-hospital setting.6

It is critical to suspect TMA when you see7,8:

severe thrombocytopenia

Thrombocytopenia

(defined as platelets <100 × 109/L)

Microangiopathic hemolytic anemia (MAHA)

Microangiopathic hemolytic anemia (MAHA)

characterized by the presence of
schistocytes in blood smear

Organ failure of varying severity

Organ failure

of varying severity

Thrombocytopenia associated with MAHA should suggest a TMA syndrome, even in the absence of organ failure.9

    Biological report sheet

    		    

    Blood count

     

     

    • Thrombocytopenia

     

    • Hemolytic anemia

     

    Reticulocyte count

    High (>120 g/L)*

     

    Hemoglobin

    Low

     

    Schistocytes on blood smear

    Present†

    A hallmark of TTP, but absence
    does not rule out a diagnosis

    Coombs test

    Negative‡

     

    Hemolysis evaluation

     

     

     

     

    • Hyperbilirubinemia

     

    • Haptoglobin low, even undetectable

     

    • High LDH rate§

    While not diagnostic, elevated LDH
    may predict organ damage

    Hemostasis assessment

     

     

    • Most often normal

     

    • D-dimer rate may be moderately elevated

     

    Biological report sheet

     


    Blood count
     

    • Thrombocytopenia

     

    • Hemolytic anemia

    Reticulocyte count

    High (>120 g/L)*

    Hemoglobin

    Low

    Schistocytes on blood smear

    Present†

    A hallmark of TTP, but absence does not rule out a diagnosis

    Coombs test

    Negative‡

    Hemolysis evaluation

    • Hyperbilirubinemia

     

    • Haptoglobin low, even undetectable

     

    • High LDH rate§

    While not diagnostic, elevated LDH may predict organ damage

    Hemostasis assessment

    • Most often normal

     

    • D-dimer rate may be moderately elevated

     

    See all important TTP lab markers

Understanding the types of TMAs can change how you treat the patient1,12

TMAs are classified into 2 types: primary and secondary. Primary TMAs have no clear underlying cause, while secondary TMAs may be caused by a number of clinical conditions. Recognizing the underlying cause, or lack thereof, can determine treatment course.1,12

    Primary TMAs

    Secondary TMAs

    • TTP (acquired/immune-mediated and hereditary)
    • Systemic lupus erythematosus

    • HUS (atypical/complement-mediated and Shiga toxin–producing E coli)
    • Pregnancy-associated (eg, hemolysis, elevated liver enzymes, low platelet count [HELLP] syndrome)

     

     
    • Hematopoietic progenitor cell transplantation
    • Drug-induced

     

The 2 primary TMAs—TTP and HUS—are often confused, but differentiating them is critical to determining appropriate treatment1,2

Historically, TTP and hemolytic uremic syndrome (HUS) were classified based on clinical findings: TTP for predominant neurologic involvement and HUS for the kidney-dominant diseases.1,13 With recent understanding of the molecular basis of TMAs, definitions have changed.1,7,8,11,13

TTP is now defined as ADAMTS13 deficiency

VS

HUS may be caused by Shiga toxin-producing E col (STEC-HUS) or genetic mutations in complement regulatory proteins (atypical or complement-mediated HUS)

Differentiation of TTP from HUS can be confounded by kidney involvement in TTP. 25% of patients with TTP had kidney injury in the Oklahoma TTP Registry.5,14,15

Variable presentation of TMAs, potential confusion with HUS, and lack of diagnostic protocols can result in a missed or delayed diagnosis of aTTP2,16

20% of patients with aTTP were misdiagnosed

This number may be underestimated due to the study being unable to exclude the possibility that some misdiagnosed patients may have died before their TTP diagnosis was made.16

The consequences of delayed diagnosis and treatment of TTP can be devastating, including organ failure or even death.7,11,15-17

Rapid recognition of aTTP is critical to
outcomes.

How to diagnose

Acute mortality and morbidity pose serious
risks in patients with aTTP.

Understand the burden

aTTP=acquired thrombotic thrombocytopenic purpura; CBC=complete blood count; E coli=Escherichia coli; LDH=lactate dehydrogenase.
 *Emphasizes the regenerative nature of anemia.
 †Nonsystematic presence of schistocytes, possibly late onset, hence the importance of repeating this test several times to increase the sensitivity of the examination.16
‡Test may turn out to be slightly positive in an autoimmune environment.16
§Related to hemolysis and organ tissue damage.6

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