Thrombotic Thrombocytopenic Purpura (TTP)
The most likely diagnosis is C. Thrombotic thrombocytopenic purpura (TTP), based on the classic presentation of fever, neurological symptoms (headache), thrombocytopenia, microangiopathic hemolytic anemia with elevated reticulocytes, markedly elevated LDH, elevated indirect bilirubin, and critically—normal coagulation studies. 1
Diagnostic Reasoning
This patient presents with the hallmark features of TTP:
Microangiopathic hemolytic anemia (MAHA): Anemia (Hb 11.2 g/L) with elevated reticulocytes (4.9%), markedly elevated LDH (690 IU/L), and elevated indirect bilirubin (43 μmol/L) indicate hemolysis. 1, 2
Thrombocytopenia: Platelet count of 32 × 10⁹/L with petechiae demonstrates platelet consumption from microthrombi formation throughout the microcirculation. 1, 2
Neurological involvement: Headache is present in 39-80% of TTP cases and represents one of the most common presenting symptoms. 2
Fever: Present in this case (38.6°C), which occurs in TTP as part of the classic pentad, though not all five features need be present. 1
Normal coagulation studies: APTT, INR, and PT are all normal, which is critical for excluding DIC. 1
Why Not the Other Diagnoses?
Disseminated Intravascular Coagulopathy (DIC) - Excluded
DIC is definitively ruled out by the normal coagulation studies. 3 DIC would show prolonged PT/APTT and elevated INR due to consumption of clotting factors. The normal coagulation parameters in this patient make DIC incompatible with the presentation. 3
Immune Thrombocytopenia (ITP) - Excluded
The presence of hemolysis with elevated LDH, elevated indirect bilirubin, and reticulocytosis immediately excludes isolated ITP. 1, 4 ITP presents with isolated thrombocytopenia and a normal complete blood count otherwise. 3, 4 The presence of MAHA mandates consideration of thrombotic microangiopathy, not ITP. 1
Hemolytic Uremic Syndrome (HUS) - Less Likely
HUS typically presents with more severe renal dysfunction than TTP. 1 This patient has normal creatinine (66 μmol/L), which argues against HUS. 3 HUS usually follows acute gastrointestinal illness with bloody diarrhea appearing 4-5 days before HUS onset, which is not described here. 3 While neurological involvement occurs in 10-20% of HUS cases, it is more prominent in TTP. 3, 1
Confirmatory Testing Required
ADAMTS13 activity must be measured urgently when TMA is suspected. 3 Severely deficient ADAMTS13 activity (<10%) confirms TTP diagnosis. 2, 5 However, treatment should not be delayed while awaiting ADAMTS13 results if clinical suspicion is high. 2, 6
Peripheral blood smear examination for schistocytes should be performed, though absence of schistocytes does not exclude TMA due to low test sensitivity. 3, 1
Critical Clinical Pitfall
Do not wait for the complete pentad (fever, neurological symptoms, renal dysfunction, thrombocytopenia, MAHA) to diagnose TTP. 1 The presence of thrombocytopenia and MAHA alone, particularly with neurological symptoms and normal coagulation studies, is sufficient to initiate empiric treatment. 2, 6 Delayed diagnosis significantly increases mortality, which can approach 90% without treatment but improves to approximately 93% survival with prompt therapy. 2
Immediate Management Priority
Therapeutic plasma exchange, corticosteroids, and rituximab should be initiated immediately without waiting for ADAMTS13 results, as this combination improves 30-day survival to >90%. 2, 6 The clinical prediction score using platelet count <30 × 10⁹/L and creatinine <2.0 mg/dL supports empirical treatment initiation for TTP. 2