Thrombotic thrombocytopenic purpura (TTP) is a multi-systemic microvascular disorder caused by imbalance between the formation of unusually large von Willebrand factor (vWF) multimer and cleaving proteinase ADAMTS13^1,2) TTP is used to present a constellation of symptoms of microangiopathic hemolytic anemia (MAHA), characteristic peripheral blood smear findings, fever, renal failure and neurologic abnormalities³⁾. It is sometimes characterized by combination of atypical clinical features, make it difficult to differentiate from other diseases such as idiopathic thrombocytopenic purpura (ITP), disseminated intravascular coagulation (DIC) and sepsis. Specifically, the diagnosis is challenging when TTP is maninfestated with multifocal cerebral infarction because many clinical conditions could result in. With the development of recent molecular diagnostics based on the ADAMTS 13 assay, the diagnosis rate of TTP has been refined compared to the past. However, the point that needs to be careful in the diagnosis of TTP is to consider the low sensitivity of ADAMTS 13 assay although it showed high specificity^3,4). Therefore, in the case of clinical presumptive TTP, the ADAMTS 13 assay is often demonstrated negative results. Although it is certain that the ADAMTS 13 assay is an important molecular method for diagnosing TTP, the availability of assay is limited to special lab and it takes a lot of time for diagnosis. Hence, it is not reasonable to depend on ADAMT 13 assay in the diagnosis of TTP, but the diagnosis based on clinical circumferences is more judicious not to delay the treatment^3,4). A recent targeted therapy with rituximab has been tried to alleviate the excessive immunologic responses in TTP, the results is currently anecdotal. Thus, therapeutic plasmapheresis (TPE) has been played a pivotal role in the treatment of TTP^5,6). In fact, prior to plasmapheresis was applied to treatment, the mortality rate of TTP had been reached 90%, but it decreased to less than 20% after introduction of plasmapheresis⁷⁾. In this report, clinical vignette of postoperative CNS-involved TTP treated by plasmapheresis and related literature would be reviewed.

A 78-year-old woman with the history of cerebral infarction three years ago, visited hospital because of right hip pain after slip down episode. In physical and radiologic examination, right hip fracture was diagnosed. There were no noticeable abnormalities in blood chemistry, cardiopulmonary and neurologic examination. Consequently, she underwent bipolar hemiarthroplasty (BPHA).

After 5-day recovery, she presented slightly decreased consciousness and disorientation without prominent neurologic deficits. In diffusion-weighted MR images, no diffusion–restricted lesion revealed, however, cerebral blood flow delay was noted in time-to-peak (TTP) images (Fig. 1A). Unfortunately, global aphasia and hypobulic compliance were immediately followed by period of consistent deterioration of consciousness. Multifocal cerebral infarction was noted over frontal, temporal lobe and cerebellar hemisphere in diffusion-weighted image and ADC map (Fig. 1B). However, there were no evidence of thromboembolic source. Cerebral vasculature including carotid artery was patent without luminal irregularities in contrast-enhanced MR angiography. Additionally, cardiac arrhythmia had not been reported during hospital course in continuous EKG monitoring. At presentation, her platelet count was 13 × 109/L with mild normochromic normocytic anemia (hemoglobin was 10.3 g/dL). Initial blood smear showed occasional schistocytes with true thrombocytopenia (Fig. 2). On the following day, unexplained fever was developed and thrombocytopenia steadily worsened to 2.5 x 109/L. At same time, oliguria and blood pressure drop was sustained and revealed due to non-territorial cardiac dysfunction in echocardiography (Fig. 3). Cumulatively, the diagnosis of thrombotic thrombocytopenic purpura (TTP) was considered. She continued to deteriorate further with severe respiratory distress and did not improve despite intensive respiratory and circulatory supports including inotropic agents. The schistocyte count (based on classical triangular hyperchromatic RBCs) was slightly increased after a serial investigation. Direct antiglobulin test (DAT) was negative. Serial blood investigations noted worsening of anemia (8.4 g/dL) and thrombocytopenia (11 × 109/L) with reticulocytosis (7.5%). Lactate dehydrogenase (LDH) was 929 U/L (high) and liver function test (LFT) was abnormal. AST, ALT, and total bilirubin were 95 U/L, 99 U/L, and 32 umol/L, respectively. Results of coagulation screening tests (PT, APTT, and fibrinogen) were normal. D-dimer was elevated (3.68 ug/mL). Autoimmune profiles were negative for antinuclear antibody (ANA) and double stranded DNA (dsDNA). Under impression of TTP, therapeutic plasmapheresis was performed daily for 10 days with goal of normalization of platelet count and LDH.

Serial peripheral blood smear showed a reduced number of schistocytes in the blood film with increasing platelet count after plasmapheresis. Her condition was steadily improved, and she was transferred to general ward after 20 days of ICU admission following sustained normalization of platelet count, hemoglobin, and LDH levels (Fig. 4).