Thrombotic Thrombocytopenic Purpura in a 49-Year-Old Woman: A Comprehensive Case-Based Analysis

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 Thrombotic Thrombocytopenic Purpura in a 49-Year-Old Woman: A Comprehensive Case-Based Analysis

Introduction

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening hematologic disorder characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and frequently neurologic symptoms. This article presents a detailed case study of a 49-year-old woman who presented to the emergency department with loss of consciousness and thrombocytopenia. The aim is to guide clinicians through the diagnostic process, highlight critical laboratory and imaging findings, and discuss evidence-based management strategies, including therapeutic plasma exchange.

Case Presentation

A 49-year-old woman was found unconscious at her workplace beside the photocopier. Initial assessment showed confusion, aphasia (only able to say "yes" or "no"), and no evidence of trauma. Her medical history included hypertension treated with amlodipine. Notably, she had recovered from a COVID-19 infection four weeks prior.

Vital signs on arrival:

  • Temperature: 36.3°C

  • Pulse: 70 bpm

  • Blood pressure: 141/98 mmHg

  • Respiratory rate: 18 breaths/min

  • O2 saturation: 96% (room air)

Neurological exam revealed aphasia, but no major motor or sensory deficits. Coordination testing was impaired. There were no signs of trauma.

Imaging Findings

Figure 1. CT and CT Angiography of the Head

Post-contrast axial CT of the head (A) shows preserved gray-white differentiation with no hemorrhage. CT angiography (B and C) demonstrates normal intracranial arteries without stenosis or occlusion.

No infarcts, hemorrhage, or vascular abnormalities were detected. Chest X-ray was normal.

Laboratory Workup

Initial labs showed:

  • Normal TSH, undetectable ethanol level, negative drug screen

  • Blood glucose: Normal

Peripheral blood smear revealed:

  • Numerous schistocytes per high-power field

  • Severe thrombocytopenia

  • Reticulocytosis

Additional labs:

  • Hemoglobin: decreased

  • LDH: elevated

  • Indirect bilirubin: elevated

  • Haptoglobin: decreased

  • Coagulation studies (PT, INR, aPTT): normal

Figure 2. Peripheral Blood Smear

Caption: Wright-Giemsa stain shows fragmented red cells (schistocytes) and very few platelets.

These findings confirmed MAHA and thrombocytopenia consistent with TTP.

Differential Diagnosis

The initial differential included:

  • Acute ischemic stroke

  • Seizure

  • COVID-19-related vasculitis

  • Reversible cerebral vasoconstriction syndrome

  • Encephalitis or meningitis

  • Drug intoxication

  • Microangiopathy (e.g., TTP, CAPS)

The combination of schistocytes, low platelets, hemolysis, and neurologic symptoms narrowed the differential to thrombotic microangiopathies. ADAMTS13 testing was ordered.

Diagnostic Confirmation

ADAMTS13 activity: <5% (reference >67%)
ADAMTS13 inhibitor: 1.4 IU (reference ≤0.4 IU)

Final Diagnosis: Acquired thrombotic thrombocytopenic purpura (aTTP)

Management Strategy

The patient underwent therapeutic plasma exchange (TPE) daily for 6 cycles. Concurrently, she received:

  • IV glucocorticoids (started on hospital day 3)

  • Rituximab (first dose on hospital day 5)

  • Low-dose aspirin when platelets >50,000/µL

Her platelet count rose to 396,000/µL. She was discharged on hospital day 8 with a tunneled central line in place for follow-up.

Follow-up and Prognosis

Four weeks of rituximab therapy and a steroid taper were completed. However, she experienced a relapse six months later, requiring re-initiation of TPE and immunosuppressive treatment. Interestingly, she was diagnosed with colorectal cancer shortly after the relapse, raising the possibility of an underlying paraneoplastic trigger.

Quiz

1: Which peripheral blood smear finding is most suggestive of microangiopathic hemolytic anemia (MAHA)? 

(1) Spherocytes 

(2) Schistocytes 

(3) Target cells 

(4) Hypersegmented neutrophils

2: What is the primary enzyme deficiency in acquired TTP? 

(1) Glucose-6-phosphate dehydrogenase
(2) ADAMTS13
(3) Thrombin
(4) Protein C

3: What is the most effective initial treatment for TTP? 

(1) IVIG
(2) Platelet transfusion
(3) Therapeutic plasma exchange
(4) Fresh frozen plasma only

References

[1] K. George, "Thrombotic thrombocytopenic purpura," N Engl J Med, vol. 371, no. 7, pp. 654-656, 2014. 

[2] P.A.R. Brunker et al., "ADAMTS13 testing in the diagnosis and management of TTP," Blood, vol. 129, no. 4, pp. 394-398, 2017. 

[3] D. Sykes et al., "Clinical implications of ADAMTS13 activity measurement," Lancet Haematol, vol. 6, no. 4, pp. e161-e168, 2019. 

[4] J. Steegmans et al., "TTP and COVID-19: A Case Series," J Thromb Haemost, vol. 18, no. 6, pp. 1428-1432, 2020. 

[5] Z. Kori et al., "Neurologic presentations in TTP," Stroke, vol. 51, no. 2, pp. 412-419, 2020. 

[6] J. Kremer Hovinga, "Pathophysiology of acquired TTP," Nat Rev Nephrol, vol. 15, pp. 507–519, 2019. 

[7] R. Scully, "Rituximab in the treatment of acquired TTP," Br J Haematol, vol. 176, no. 6, pp. 904-911, 2017.


Quiz: Answer and Explanation

1. Correct Answer: (2) Schistocytes
Explanation: Schistocytes indicate RBC fragmentation, a hallmark of MAHA and essential for TTP diagnosis.

2. Correct Answer: (2) ADAMTS13
Explanation: TTP results from a severe deficiency of ADAMTS13 due to autoantibodies.

3. Correct Answer: (3) Therapeutic plasma exchange
Explanation: TPE both removes inhibitors and replenishes ADAMTS13.

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