scholarly journals Rapid Turnaround ADAMTS13 Testing Is Likely to Improve Diagnosis of Thrombotic Thrombocytopenic Purpura and Avoid Unnecessary Plasma Exchange

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Eric McGinnis ◽  
Spencer D. Martin ◽  
Tyler W. Smith
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Blood Product ◽  
Vancouver General Hospital ◽  
Adamts13 Activity ◽  
Clinical Tool ◽  
Thrombocytopenic Purpura ◽  
Hospital Patients ◽  
Life Threatening ◽  
Exposure Risks

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) resulting from severe ADAMTS13 deficiency, which is generally treated with therapeutic plasma exchange (PLEX). Although ADAMTS13 activity is often assayed to differentiate TTP from TMAs not requiring PLEX, technical and logistical constraints often limit rapid turnaround of results, with PLEX initiated based on clinical suspicion of TTP while awaiting ADAMTS13 activity results. We estimated the potential reduction in plasma product use if rapid turnaround ADAMTS13 activity testing were available in our centre. Methods: We reviewed medical records for all Vancouver General Hospital patients with ADAMTS13 activity testing since assay implementation. Patients receiving PLEX but ultimately diagnosed with a disease not requiring PLEX were identified as "potentially avoidable PLEX" (paPLEX), and their plasma product exposures and related blood product costs were estimated. Laboratory results, ADAMTS13 activity, and PLASMIC scores (a validated clinical tool for TTP diagnosis) of this group were compared to those of newly diagnosed TTP patients (N=35). Results: We identified 16 paPLEX patients, including TMAs secondary to malignant hypertension, infection, hemolytic uremic syndrome, illicit drug use, autoimmune renal disease, and malignancy (Table 1). These patients underwent 104 total PLEX cycles (3-12 per patient, median 6), involving 1,428 plasma units (28-199 per patient, median 71.5) and estimated product-associated costs of $187,759 CAD ($140,889 USD). Median platelet counts were significantly lower in TTP than the paPLEX group (7x109/L versus 38x109/L), as was serum creatinine (98µmol/L versus 224µmol/L). PLASMIC scores indicating low or intermediate likelihood of TTP were observed in 63% of patients receiving paPLEX and 17% of patients with TTP. All patients with TTP had ADAMTS13 activity < 10%, while all patients receiving paPLEX had ADAMTS13 activity ≥ 30%. Conclusions: Unnecessary PLEX carries significant patient blood product exposure risks and system costs that may be circumvented if TTP can be reliably distinguished from other TMAs at the time of initial presentation. In our cohort, ADAMTS13 activity results provided clear separation of these groups and improved upon TTP diagnosis by clinical judgement and PLASMIC scores. Rapid turnaround of ADAMTS13 activity testing results has the potential to reduce the unnecessary costs and blood product exposures resulting from PLEX administration to patients with non-TTP TMAs. Figure 1 Disclosures Smith: Alexion: Other: Participated in an advisory board without receiving financial compensation.

Pembrolizumab-induced thrombotic thrombocytopenic purpura

2019 ◽  
Vol 26 (5) ◽  
pp. 1237-1240 ◽  
Author(s):  
Marcus SR Dickey ◽  
Anant J Raina ◽  
Peter J Gilbar ◽  
Brendan L Wisniowski ◽  
Joel T Collins ◽  
...  
Keyword(s):  
Adverse Events ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Oral Prednisolone ◽  
Autoimmune Disorder ◽  
Community Acquired Pneumonia ◽  
Thrombocytopenic Purpura ◽  
Life Threatening

Introduction Pembrolizumab is a humanised monoclonal antibody targeting the receptor programmed cell death protein-1 (PD-1), with anti-tumour activity demonstrated for many malignancies. Such immune checkpoint inhibitors are associated with many immune-related adverse events including rash, colitis, hepatitis, pneumonitis, endocrinopathy and, rarely, haematological adverse events, including immune-related thrombocytopenia. Case report We report a 60-year-old female with metastatic non-small cell lung cancer treated with pembrolizumab every three weeks. Following her fifth cycle, she presented to our hospital with community-acquired pneumonia. Thrombocytopenia developed the next day and, after detailed investigations, thrombotic thrombocytopenic purpura was diagnosed. Management and outcome Pembrolizumab was immediately ceased and plasma exchange commenced along with IV methylprednisolone 250 mg daily for three days followed by oral prednisolone. After five days of plasma exchange, platelet counts normalised and haemolytic anaemia resolved. Discussion Acquired thrombotic thrombocytopenic purpura is an autoimmune disorder caused by an inhibitory autoantibody against ADAMTS-13. While most cases of acquired thrombotic thrombocytopenic purpura are idiopathic, certain conditions (e.g. bacterial infection, autoimmune disorders, malignancies) and medications are associated with thrombotic thrombocytopenic purpura. Other potential causes were eliminated in our patient. As acquired thrombotic thrombocytopenic purpura is an autoimmune disorder, pembrolizumab, given its unique mechanism of action and association with immune-related adverse events, is believed to be implicated in the development of thrombotic thrombocytopenic purpura. This case is one of only two linking anti-PD-1 therapy to thrombotic thrombocytopenic purpura development (the other occurring in a patient on nivolumab plus ipilimumab). Thrombotic thrombocytopenic purpura is life-threatening and clinicians are advised to be aware of its possible occurrence in immune checkpoint inhibitor-treated patients.

Treatment of Thrombotic Thrombocytopenic Purpura with Heparin, Vincristine and Dexamethasone.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4113-4113
Author(s):  
Jinghua Wang ◽  
Na Liu ◽  
Fang Liu ◽  
Changgeng Ruan ◽  
Juan Liu ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
High Mortality ◽  
Binding Assay ◽  
Adamts13 Activity ◽  
Collagen Binding ◽  
Thrombocytopenic Purpura ◽  
Multiple Systems

Abstract Thrombotic thrombocytopenic purpura(TTP) is a serious, low morbidity and high mortality disease, which can simultaneously affect multiple systems in the patients’ body. In the event that the patients cannot be treated by plasma exchange(PE), mortality will be 95–100%(1). Between September, 2000 and May, 2003, thirteen patients with TTP were treated mainly by heparin, vincristine, dexamethasone, six of whom have acceptted one or two PE. The results were excellent. Twelve of the thirteen patients survived. One patient was dead. The ADAMTS13 activity was measured in 10 patients using a Residual-Collagen Binding Assay(R-CBA).

Correlation Of ADAMTS13 Activity With Baseline Characteristics and Management Patterns In Patients With Suspected Thrombotic Thrombocytopenic Purpura In The State Of Rhode Island

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3556-3556
Author(s):  
Nathan T. Connell ◽  
Joseph D. Sweeney
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Rhode Island ◽  
Turnaround Time ◽  
Activity Level ◽  
Activity Levels ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Baseline Characteristics ◽  
Pre Treatment

Abstract Introduction While the activity level of ADAMTS13 can be helpful in diagnosing patients with thrombotic thrombocytopenic purpura (TTP), the current long turnaround time of this test for most institutions limits its role in early clinical decision-making about the initiation of plasma exchange. Levels of ADAMTS13<10% are pathognomonic of TTP and levels in excess of 10% indicate an alternate cause of thrombotic microangiopathy. The aim of the study was to look at recent practice in the State of Rhode Island regarding the criteria for initiation of plasma exchange with a subsequent categorization of those patients based on ADAMTS13 activity levels. Methods Patients with a diagnosis of TTP were identified from hospital records of the major hospitals in Rhode Island which perform therapeutic apheresis in calendar years 2011 and 2012. From a chart review and blood bank records, baseline clinical parameters were collected, the number of therapeutic plasma exchanges (TPE) performed and the volume of plasma utilized. Pre-treatment ADAMTS13 activity was recorded if available in addition to the number of days from the initiation of TPE to test result availability. An analysis was performed to examine if patients who had a pre-treatment ADAMTS13 activity level ≤10% differed in baseline characteristics or response to TPE from those with activity levels >10%. Based on the normality of the distribution of the data, independent t-tests or Wilcoxon rank-sum tests were performed using SAS version 9.3. Results During this two year period, 24 patients received plasma exchange in Rhode Island for a presumptive diagnosis of TTP. The mean age was 47 years (range 20-89 years) and 38% were male. ADAMTS13 activity was available for 20 patients and 7 (30% of those exchanged) had documented pre-treatment activity levels ≤10% consistent with TTP. The median turnaround time for the ADAMTS13 assay was 10 days (range 2-52). Mean baseline parameters at the time of presentation are shown in the table. As expected, creatinine levels were lower in those patients with true TTP (p=0.0410). ADAMTS13 activity level was predictive of the number of days to a platelet count ≥150 x 109/L (Pearson correlation 0.56; p-value 0.0458). Overall, 4238 units of plasma were utilized for exchange. Of these 4238 units, 1886 were transfused to patients who were subsequently shown to have an ADAMTS13 activity >10%, and 813 of the 1886 units (20% of all plasma exchanged) were transfused after the results of enzyme activity were available in this population. Conclusions Based on an ADAMTS13 >10%, a significant volume of plasma was unnecessarily transfused. Reducing the turnaround time for the ADAMTS13 assay in tertiary care centers could help clinicians better determine which patients will benefit from plasma exchange, avoiding the morbidity and expense associated with large volume plasma exchange. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Critical Care COVID-19 Patient with a Picture of Thrombotic Thrombocytopenic Purpura

2020 ◽  
Author(s):  
Rehab AL-Ansari ◽  
Mohanad Bakkar ◽  
Leena Abdalla ◽  
Khaled Sewify
Keyword(s):  
Mechanical Ventilation ◽  
Critical Care ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
Therapeutic Plasma Exchange ◽  
Thrombocytopenic Purpura ◽  
Threatening Condition ◽  
Life Threatening

Background: Thrombotic thrombocytopenic purpura (TTP) is an uncommon haematological disease which can occur at any age and may present with COVID-19. This case describes a COVID-19 complication associated with a presentation resembling TTP. Case description: A 51-year-old man who had received a kidney transplant and was on immunosuppressant medication, was admitted to a critical care unit with severe COVID-19 pneumonia/acute respiratory distress syndrome (ARDS) which required intubation, mechanical ventilation and inotropic support. The course was complicated by the classic pentad of thrombocytopenia, intravascular haemolysis, acute kidney injury, neurological symptoms and fever, which prompted the diagnosis of probable TTP. After five sessions of therapeutic plasma exchange, the patient’s general status improved, he was weaned off mechanical ventilation and his renal panel and haemolytic markers normalized. Conclusion: TTP is a life-threatening condition which requires urgent management with therapeutic plasma exchange. This case highlights some possible complications of COVID-19 generally and in immunocompromised patients specifically. The potential role of plasma exchange in COVID-19 patients without a positive diagnosis of TTP (the so-called ‘TTP resembling presentation’) is an area of further research.

scholarly journals Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4043-4049 ◽  
Author(s):  
X. Long Zheng ◽  
Richard M. Kaufman ◽  
Lawrence T. Goodnough ◽  
J. Evan Sadler
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
High Titer ◽  
Patient Treatment ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Hematopoietic Stem ◽  
Complete Clinical Remission ◽  
Inhibitor Level

Abstract Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of adisintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P &lt; .00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% (≈ 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (&gt; 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P &lt; .02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.

Survival and relapse in patients with thrombotic thrombocytopenic purpura

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1500-1511 ◽  
Author(s):  
Johanna A. Kremer Hovinga ◽  
Sara K. Vesely ◽  
Deirdra R. Terrell ◽  
Bernhard Lämmle ◽  
James N. George
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Signs And Symptoms ◽  
Population Based ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Estimated Risk ◽  
Subsequent Relapse ◽  
Organ Dysfunctions

AbstractSurvival of patients with thrombotic thrombocytopenic purpura (TTP) improved dramatically with plasma exchange treatment, revealing risk for relapse. The Oklahoma TTP Registry is a population-based inception cohort of all 376 consecutive patients with an initial episode of clinically diagnosed TTP (defined as microangiopathic hemolytic anemia and thrombocytopenia with or without signs and symptoms of ischemic organ dysfunctions) for whom plasma exchange was requested, 1989 to 2008. Survival was not different between the first and second 10-year periods for all patients (68% and 69%, P = .83) and for patients with idiopathic TTP (83% and 77%, P = .33). ADAMTS13 activity was measured in 261 (93%) of 282 patients since 1995. Survival was not different between patients with ADAMTS13 activity < 10% (47 of 60, 78%) and patients with 10% or more (136 of 201, 68%, P = .11). Among patients with ADAMTS13 activity < 10%, an inhibitor titer of 2 or more Bethesda units/mL was associated with lower survival (P = .05). Relapse rate was greater among survivors with ADAMTS13 activity < 10% (16 of 47, 34%; estimated risk for relapse at 7.5 years, 41%) than among survivors with ADAMTS13 activity of 10% or more (5 of 136, 4%; P < .001). In 41 (93%) of 44 survivors, ADAMTS13 deficiency during remission was not clearly related to subsequent relapse.

scholarly journals Sepsis Mimicking TTP-Case Report and Review of Literature

2020 ◽  
pp. 1-2
Author(s):  
Vijay Raju Krupesh ◽  
◽  
Biswabikash Mohanty ◽  
Srinivas B J ◽  
Sachin Jadhav ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disease Stage ◽  
Total Leucocyte Count ◽  
Adamts13 Activity ◽  
Total Plasma ◽  
Thrombocytopenic Purpura ◽  
Clinical Dilemma ◽  
Total Plasma Exchange ◽  
Multifocal Disease

Here we report a case of Sepsis mimicking as thrombotic thrombocytopenic purpura in a cancer patient with Urothelioma. A 61-year-old man with High grade Urothelial Carcinoma of left renal pelvis (Multifocal disease) Stage-4 presented with Fever on and off since 1 week and shortness of breath at rest since 2 days and hematuria since 1 day.Later in the course, he developed thrombocytopenia followed by MAHA (Micro Angiopathic haemolytic Anaemia), and other lab abnormalities .Thrombotic thrombocytopenic purpura (TTP) was suspected, and total plasma exchange was considered. Since serum procalcitonin,Total leucocyte count was very high and also had elevated prothrombin time, ADAMTS13(a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) was sent for confirmation showed that ADAMTS13 activity of more than 10% for which plasmapheresis was delayed , later patient was treated for sepsis , but patient did not respond and succumbed . This case shows that Sepsis can mimic TTP making diagnosis and treatment extremely difficult. In this type of clinical dilemma to do total plasma exchange (TPE) which is the main modality of treatment for TTP ADAMTS13 activity helps us to prioritise treatment

scholarly journals Case Report: Two Cases of Pediatric Thrombotic Thrombocytopenic Purpura Treated With Combined Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Costanza Tripiciano ◽  
Paola Zangari ◽  
Mauro Montanari ◽  
Giovanna Leone ◽  
Laura Massella ◽  
...  
Keyword(s):  
Platelet Count ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Combined Therapy ◽  
Laboratory Data ◽  
Adamts13 Activity ◽  
Laboratory Findings ◽  
Thrombocytopenic Purpura ◽  
Life Threatening ◽  
Successful Clinical Outcome ◽  
Von Willebrand

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. Over 95% of TTPs are acquired, due to autoantibody inhibitors. In children, acquired TTP is a very rare, life-threatening disease. To date, no consensus exists on the treatment strategy of pediatric TTP. We report the cases of two pediatric patients with a diagnosis of TTP, successfully treated with a combination of various therapeutic approaches. Although the patients complained of different sets of symptoms, laboratory data showed Coombs negative hemolytic anemia, renal impairment, and low platelet count in both cases. The diagnosis of acquired TTP was supported by the PLASMIC score and confirmed by the reduction of the ADAMTS13 activity and the presence of anti-ADAMTS13 antibodies. Intravenous immunoglobulin, corticosteroids, and plasma exchange (PEX) were performed without delay. As soon as available, caplacizumab was added to the therapy, with a prompt normalization of platelet count. Nevertheless, ADAMTS13 activity was persistently low, and anti-ADAMTS13 antibodies level was high; thus, a course of rituximab was administered, with persistent normalization of laboratory findings. No adverse events were observed during the treatment. In our experience, the combined use of PEX, caplacizumab, and immunosuppressive therapy during the acute phase of the disease is safe and may have a significant impact on the prognosis with successful clinical outcome and decrease in life-threatening events.

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