What is the most likely diagnosis for a female patient with fever, headache, scattered petechiae, thrombocytopenia (low platelet count), anemia (low hemoglobin), elevated lactate dehydrogenase (LDH), and indirect bilirubin, with impaired renal function (elevated creatinine) and normal coagulation studies?

Thrombotic Thrombocytopenic Purpura (TTP)

The most likely diagnosis is C. Thrombotic thrombocytopenic purpura (TTP). This patient presents with the classic triad of microangiopathic hemolytic anemia (elevated LDH, indirect bilirubin, reticulocytosis), thrombocytopenia, and fever with neurological symptoms (headache), which are hallmark features of TTP requiring immediate recognition and treatment. 1

Key Diagnostic Features Supporting TTP

The combination of hemolytic anemia with thrombocytopenia immediately excludes isolated ITP and mandates consideration of thrombotic microangiopathy. 1 This patient demonstrates:

• Microangiopathic hemolytic anemia with elevated LDH (690 IU/L, normal 60-160), elevated indirect bilirubin (43 μmol/L, normal 3.2-12.1), and reticulocytosis (4.9%, normal 0.2-1.2%), indicating red blood cell destruction 2, 1
• Severe thrombocytopenia (32 × 10⁹/L) from platelet consumption in microthrombi formation 1
• Neurological symptoms (headache) which are more prominent in TTP than other thrombotic microangiopathies 1
• Fever (38.6°C), part of the classic TTP pentad 2, 3
• Normal coagulation studies (PT, APTT, INR all normal), which definitively excludes DIC 1

Why Other Diagnoses Are Excluded

A. Immune Thrombocytopenia (ITP) - Excluded

The presence of hemolysis with schistocytes immediately excludes isolated ITP. 1 ITP patients have:

• Isolated thrombocytopenia without anemia (unless from bleeding) 2
• Normal LDH and bilirubin levels 1
• No reticulocytosis unless bleeding has occurred 2
• Fever is NOT typical of ITP and should prompt additional testing for alternative diagnoses 2

B. Hemolytic Uremic Syndrome (HUS) - Less Likely

HUS can be distinguished from TTP by:

• More severe renal dysfunction (this patient has normal creatinine of 66 μmol/L) 1
• Typically follows acute gastrointestinal illness with bloody diarrhea 1
• Less prominent neurological features compared to TTP 1

D. Disseminated Intravascular Coagulopathy (DIC) - Definitively Excluded

Normal coagulation studies are critical for excluding DIC. 1 DIC would show:

• Prolonged PT/APTT and elevated INR due to consumption of clotting factors 1
• Elevated D-dimers and decreased fibrinogen 2
• This patient has completely normal PT (11 sec), APTT (36 sec), and INR (1.1) 1

Critical Diagnostic Considerations

While the classic TTP pentad includes fever, thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, and renal dysfunction, not all five features need to be present. 2, 1, 4 This patient demonstrates four of five features, with only mild or absent renal dysfunction, which is characteristic of TTP rather than HUS. 1

The peripheral blood smear (referenced but not shown) would be expected to show schistocytes (fragmented red blood cells), which is pathognomonic for thrombotic microangiopathy. 2, 1 The absence of schistocytes on initial smear does not exclude TTP, as demonstrated in case reports where schistocytes appeared only on repeat smears. 5

Immediate Management Implications

TTP requires immediate recognition as delay in identification is associated with increased mortality and morbidity. 2 The first step is maintaining a high index of suspicion and immediately consulting hematology. 2

Empirical treatment with therapeutic plasma exchange, corticosteroids, and rituximab should be initiated immediately before ADAMTS13 results are available when clinical presentation strongly suggests TTP, as this improves survival from nearly zero to approximately 93%. 2, 3

ADAMTS13 activity must be measured urgently when thrombotic microangiopathy is suspected, with severely deficient activity (<10%) confirming TTP diagnosis. 1, 3