2025 – PAGE 292 – HEMATOLOGY & ONCOLOGY

(DOUBLE TAKE) HEMOLYTIC UREMIC SYNDROME (HUS) AND THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are two distinct disorders, but they are very similar disorders that can suddenly cause small thrombi throughout the body.

• Hemolytic Uremic Syndrome(HUS): There are 3 types of HUS that affect children. Shiga toxin-producing Escherichia coli (STEC) accounts for > 90% of cases and is the most commonly tested form of HUS. The STEC results in abdominal pain, vomiting and bloody diarrhea. Other forms of HUS include Pneumococcal-associated HUS in young children with pneumonia, and lastly complement-mediated HUS due to mutations in genes for complement proteins. These two are not likely to be tested. HUS symptoms may include fever, hemolytic anemia, thrombocytopenia, renal failure, and neurologic changes. Thrombi within the kidneys often cause renal dysfunction, so look for uremia, hematuria, oliguria, or an elevated creatinine. Thrombi in the skin may result in purpura or ecchymoses. Altered mentation, seizures, coma and hypertension may also occur. Hemolysis is caused by verotoxin and is Coombs negative. The complement levels are normal in STEC HUS. The bug may have been contracted from bad meat or milk ingestion.
• Thrombotic Thrombocytopenic Purpura (TTP): TTP may be associated with certain medications, pregnancy, or certain infections. In its most common form, antibodies develop which destroy the ADAMTS13 enzyme responsible for cleaving von Willebrand factor. An excess of VWF leads to an excess of clotting. A similar symptom profile to that of HUS may be present, including fever, hemolytic anemia, thrombocytopenia, renal failure, and neurologic changes. ADAMTS13 testing will show decreased activity.

PEARL: Although thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are often indistinguishable, some key differences may help. As the name suggests, hemolytic uremic syndrome is more likely to include renal failure. The classic triad of HUS includes Hemolytic anemia with schistocytes, Acute renal failure and Thrombocytopenia, so these findings will definitely be presented for any HUS case on the boards, but other findings of fever and neurologic changes may not. For TTP patients, thrombi are more likely to form in the brain (rather than the kidneys), so the neurologic symptoms are often much more severe in TTP patients (seizures, stroke, etc.) than HUS patients. TTP is also a disorder that tends to affect teens, whereas HUS tends to affect children under the age of five.

MNEMONIC: Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS) can be recalled by using the mnemonic FAT RN. Fever, Anemia, Thrombocytopenia, Renal Failure, and Neurologic Symptoms.

MNEMONIC: The mnemonic which encompasses the classic triad for HUS is simply HAT (Hemolytic anemia, Acute renal failure, and Thrombocytopenia).

MNEMONIC: TTP occurs in adolescents and more commonly results in severe neurological symptoms than those of HUS. TTP = Teen = Top of head.

(DOUBLE TAKE) WISKOTT-ALDRICH SYNDROME

For Wiskott-Aldrich syndrome, look for a patient with a history consistent with the triad of SMALL Thrombocytes, frequent Infections, and Eczema. Platelets can be small in size and/or number. This is an X-linked disorder, so it will only be found in MALES. Patients develop both T and B cell problems as they age. IgM is usually LOW, while IgA may be HIGH. A history may include findings such as petechiae, bloody diarrhea, bloody circumcision, eczema, and/or otitis media. There is an increased risk of lymphoma in the third decade of life. A BMT is curative.

• MNEMONIC: Wiskott Aldrich = wiXotT ostrich = Imagine a WISe OSTRICH wearing some nerdy black glasses, a tux, and a TIE with the word “T-I-E” spelled down the front.
• MNEMONIC: (image)

• • KEY: X-linked, small T = Represents small platelets (low MPV) and Thrombocytopenia, I = Infections, E = Eczema, Mirrored W = M and arrows show that IgM is low, Duplicate A refers to IgA, and arrows show that IgA levels are increased.
• PEARL: In Idiopathic Thrombocytopenic Purpura (ITP), platelets are BIGGER.