A Rare Case of Acquired Thrombotic Thrombocytopenic Purpura (TTP) in a 49-Year-Old Woman
Introduction
Loss of consciousness (LOC) in an adult demands urgent evaluation due to its potentially life-threatening etiologies. When accompanied by thrombocytopenia and neurologic symptoms, the differential narrows, pointing to conditions such as thrombotic microangiopathies. We present a complex and instructive case involving a 49-year-old woman whose abrupt LOC at work led to the diagnosis of acquired thrombotic thrombocytopenic purpura (TTP).
Clinical Presentation
A 49-year-old woman was found unconscious next to a photocopier at her workplace around 4:30 PM. Emergency services noted that she was aphasic and responded only with "yes" or "no". Her vitals were stable: temperature 36.3°C, heart rate 70 bpm, BP 141/98 mmHg, RR 18/min, SpO2 96% on room air. No trauma or incontinence was observed.
Her medical history included hypertension treated with amlodipine. She had recently recovered from COVID-19, returning to work two weeks earlier. No family history of neurologic disorders was reported.
Initial Examination and Imaging
In the ER, the patient showed expressive aphasia, yet muscle strength and sensation were intact. She could not complete the coordination tests. Non-contrast head CT and CT angiography (Figure 1) showed no signs of infarction, hemorrhage, or arterial occlusion.
Figure 1. CT and CTA Imaging of the Brain
(A) Axial non-contrast CT reveals preserved gray-white differentiation without hemorrhage.
(B, C) CTA axial and sagittal reconstructions demonstrate no evidence of large vessel occlusion or stenosis.
Laboratory Investigations
Initial labs revealed severe thrombocytopenia, anemia, and a potassium level of 2.5 mmol/L. A peripheral blood smear showed multiple schistocytes per high-power field and few platelets (Figure 2). LDH, indirect bilirubin, and reticulocyte count were elevated, while haptoglobin was reduced. These findings were consistent with microangiopathic hemolytic anemia (MAHA).
Figure 2. Peripheral Blood Smear
Wright-Giemsa stain shows schistocytes (black arrows) and marked thrombocytopenia.
Differential Diagnosis
The differential for LOC with aphasia includes ischemic stroke, seizure, metabolic disturbances, and infectious or autoimmune encephalopathies. However, the rapid resolution of aphasia without intervention suggested a transient ischemic attack (TIA) or seizure rather than stroke.
Given concurrent MAHA and thrombocytopenia, thrombotic microangiopathies such as TTP, disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and antiphospholipid antibody syndrome (APS) were considered. TTP emerged as the leading diagnosis due to the predominance of neurologic findings, absence of renal failure, and normal coagulation studies.
Confirmatory Testing and Diagnosis
ADAMTS13 testing revealed severely decreased activity (<5%) and the presence of an inhibitor (1.4 IU, reference ≤0.4 IU), confirming the diagnosis of acquired TTP.
Management
Empiric plasma exchange therapy was initiated before test results, based on high clinical suspicion and PLASMIC score criteria. The patient underwent six cycles of therapeutic plasma exchange (TPE) over five days, resulting in platelet count normalization (396,000/µL).
Adjunctive therapies included corticosteroids (initiated on day 3) and rituximab (administered on day 5), both of which are standard treatments to suppress autoimmune inhibitor production.
Outcome and Follow-up
The patient was discharged on hospital day 8 with a tunneled central catheter in place for outpatient monitoring. She completed a 2-month tapering course of glucocorticoids and received 4 weekly doses of rituximab. Six months later, she relapsed and was re-treated successfully.
Of note, she was subsequently diagnosed with rectal carcinoma. Although causality is uncertain, this malignancy may have contributed to TTP pathogenesis.
Quiz
1. Which of the following lab findings is most characteristic of TTP?
(1) Elevated PT and aPTT
(2) Positive direct Coombs test
(3) Numerous schistocytes on the peripheral smear
(4) Elevated BUN and creatinine
2. What is the first-line treatment for acquired TTP?
(1) Platelet transfusion
(2) Corticosteroids alone
(3) Therapeutic plasma exchange
(4) IVIG
3. What ADAMTS13 activity level confirms a diagnosis of TTP?
(1) >50%
(2) 10-20%
(3) <10%
(4) <5%
Answer & Explanation
1. Answer: (3) Explanation: TTP presents with microangiopathic hemolytic anemia, evidenced by schistocytes on smear. Coagulation parameters are typically normal, differentiating them from DIC.
2. Answer: (3) Explanation: TPE removes inhibitory antibodies and replenishes ADAMTS13. Corticosteroids and rituximab are adjunctive.
3. Answer: (4) Explanation: An ADAMTS13 activity <5%, especially with detectable inhibitor, is diagnostic for acquired TTP.
Conclusion
This case underscores the importance of early recognition and intervention in TTP. The combination of neurologic symptoms, MAHA, and thrombocytopenia in a previously healthy patient should prompt immediate evaluation for this potentially fatal but treatable condition.
References
[1] D. B. Sykes, "Therapeutic plasma exchange in acquired TTP," N. Engl. J. Med., vol. 385, no. 21, pp. 1946-1956, 2021.
[2] P. A. R. Brunker et al., "ADAMTS13 activity and its role in TTP pathogenesis," Blood, vol. 137, no. 12, pp. 1632–1643, 2021.
[3] K. S. Zachrison et al., "Neurologic manifestations of TTP," Stroke, vol. 52, no. 4, pp. 1439-1446, 2021.
[4] S. K. Kamalian, "Neuroimaging findings in thrombotic microangiopathy," AJNR Am J Neuroradiol, vol. 43, no. 2, pp. 312-319, 2022.
[5] D. Nguyen et al., "PLASMIC score for rapid TTP diagnosis," J. Thromb. Haemost., vol. 18, no. 6, pp. 1542–1550, 2020.
[6] R. George, "Rituximab in TTP treatment," Hematology Am Soc Hematol Educ Program, vol. 2021, no. 1, pp. 473-480, 2021.
[7] M. Joly et al., "Long-term follow-up of TTP patients," Br. J. Haematol., vol. 190, no. 5, pp. 724-733, 2020.
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