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BACKGROUND Platelet (PLT) transfusions are probably harmful in patients with acquired idiopathic thrombotic thrombocytopenic purpura (aTTP). Introduction of a rapid assay for ADAMTS13 activity should reduce the time to definite diagnosis of aTTP, reduce the amount of inappropriately transfused PLT concentrates, and improve mortality and morbidity. STUDY DESIGN AND METHODS We selected 265 aTTP patients with severe ADAMTS13 deficiency. Of these, 91 patients were diagnosed by March 2005 (Period 1), when ADAMTS13 activity was measured by von Willebrand factor multimer assay, which took 4 to 7 days until the result was reported. An additional 174 patients were diagnosed after April 2005 (Period 2), when the activity was measured by a chromogenic enzyme-linked immunosorbent assay, which took 1 to 2 days. RESULTS We found no significant differences in 30-day survival rate between the two periods. Overall, 48 patients received PLT transfusions. Mortality was slightly greater between patients with (22.9%) versus without PLT transfusion (17.7%), but not significant. In Period 1, Cox proportional hazards regression analysis showed that older age (≥60 years) and PLT transfusion administration were independent factors associated with higher risks of 30-day mortality. In contrast, in Period 2, lower Rose-Eldor TTP severity score and use of plasma exchange and corticosteroid therapy were independent factors associated with higher survival rates while nonadministration of PLT transfusions was not. CONCLUSION Our results indicate that PLT transfusions are harmful for aTTP patients when the definite diagnosis of severe ADAMTS13 deficiency is delayed. If it can be done as soon as possible, PLT transfusions for severe bleeding or surgical interventions might be allowed with subsequent plasmapheresis.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) due to deficiency of the von Willebrand-cleaving protease ADAMTS13 is a hematologic emergency that requires prompt initiation of therapeutic plasma exchange (TPE). Long turnaround times (TATs) have precluded the use of pre-TPE measurement of ADAMTS13 activity for the initial diagnosis in most institutions. STUDY DESIGN AND METHODS An in-house rapid TAT (r-TAT) assay for ADAMTS13 activity was implemented after 18 months of validation. In a quasi-experimental design using interrupted time series analysis, patterns of plasma utilization in patients with suspected TTP were assessed after implementation of this assay for ADAMTS13 activity and compared to utilization patterns for patients who received plasma exchange before r-TAT assay implementation designated the standard TAT period. RESULTS In the 18 months after implementation of the r-TAT ADAMTS13 assay, there was a significant reduction in plasma utilization per patient suspected of having TTP (mean, 144.5 units vs. 63.3 units of plasma per patients suspected of having TTP; p = 0.002). The mean number of exchanges per patient and mean number of exchanges after achieving a platelet count of at least 150 × 10(9) /L were lower in the r-TAT cohort (p

Background Thrombotic thrombocytopenic purpura (TTP) is a life-threatening diagnosis requiring prompt initiation of therapeutic plasma exchange (TPE). Measurement of immature platelet (PLT) fraction (%-IPF) differentiates PLT consumption or destruction from hypoproduction. Study Design and Method Our study evaluated %-IPF changes over the course of TTP treated with TPE and as a measure of treatment efficacy. Eleven idiopathic TTP patients, two human immunodeficiency virus (HIV)-associated TTP patients, and five non-TTP patients with thrombocytopenia were enrolled into our study. All patients were treated with TPE and had ADAMTS13 activity measured. Results All idiopathic TTP patients had a significantly increased %-IPF and decreased absolute immature PLT count (A-IPC) and PLT count at presentation. An A-IPC value of less than 5 × 109/L at presentation has 84.6% sensitivity, 80% specificity, and 91.7% positive predictive value for diagnosing TTP. A concurrent steady decline in %-IPF and increased PLT counts toward normal was observed in TTP patients undergoing TPE. The A-IPC, however, showed an increase and decrease curve that was not seen in the two HIV-associated TTP patients with no response to TPE and the five non-TTP patients. More importantly, reaching an A-IPC ratio of 3 compared to baseline value during TPE can readily differentiate idiopathic TTP from the other two groups and is correlated with good clinical responses to TPE. An abrupt increase of A-IPC during TPE was also noted in a TTP patient who relapsed 3 days before PLT count decrease. A-IPC is positively correlated with ADAMTS13 activity at presentation but negatively correlated with ADAMTS13 activity during recovery. Conclusion A-IPC should be routinely analyzed for diagnosing and monitoring TTP patients.

Background Thrombotic thrombocytopenic purpura (TTP) requires immediate treatment with plasma exchange (PE) to prevent disease mortality and/or morbidity. Frequently, PE is initiated before blood sample is collected to confirm ADAMTS13 deficiency. However, the effect of PE treatments on the evaluation of ADAMTS13 is uncertain. Moreover, the pertinence of ADAMTS13 activity during PE therapy to prediction of treatment outcomes is unclear. Thus, clarification of the diagnostic and prognostic values of ADAMTS13 activity obtained during PE treatment is an unmet clinical need. Study Design and Methods A total of 212 sequential samples were obtained during the course of daily PE treatment from 19 patients with acquired TTP. ADAMTS13 activity levels were determined in these longitudinal samples for analysis. Results After the initial three daily PE procedures, the sensitivities of ADAMTS13 activity in diagnosis of TTP (

Background The von Willebrand factor (VWF)-cleaving protease, ADAMTS13, is often deficient in cases of thrombotic thrombocytopenic purpura (TTP). The primary treatment of TTP is therapeutic plasma exchange (TPE) utilizing a variety of plasma products that help restore ADAMTS13 activity. However, multiple replacement products are available to choose from. Thawed plasma products have a variable refrigerated shelf life depending on the product type; stability of ADAMTS13 in thawed products stored at 1 to 6 degrees C has not been determined. Study design and methods ADAMTS13 activity was measured in three types of plasma products and cryoprecipitate. Fresh-frozen plasma (FFP) aliquots and cryoprecipitate-poor plasma (CPP) products were produced from 10 whole-blood (WB) donations. Twenty-four-hour plasma products were manufactured from 10 additional WB donations. ADAMTS13 activity in these products at time of thaw and after 5 days of storage at 1 to 6 degrees C was measured with a modified version of the FRETS-VWF73 fluorogenic assay. ADAMTS13 activity at time of thaw was measured in 10 units of cryoprecipitate and five related CPP products. Results ADAMTS13 is present in similar amounts in FFP, CPP, and 24-hour plasma products. Storage at 1 to 6 degrees C for up to 5 days did not significantly diminish ADAMTS13 activity. The concentration of ADAMTS13 in cryoprecipitate was significantly higher than that observed in plasma products. Conclusion FFP, CPP, and 24-hour plasma products should be equally effective for ADAMTS13 restoration through TPE and should remain so for the duration of the shelf life of the thawed products.

BACKGROUND Plasma stored refrigerated for up to 5 days after thawing is common practice in many US hospitals. Therefore, clotting factor activities in fresh-frozen plasma (FFP), plasma frozen within 24 hours (PF24), and solvent/detergent-treated plasma (SDP), thawed and stored at 1 to 6°C for up to 5 days, were investigated. STUDY DESIGN AND METHODS Five A, B, O, and AB units of FFP, PF24, and SDP were thawed and maintained for 5 days at 1 to 6°C. The activity of factor (F)V, FVII, FVIII, protein S (PS), and ADAMTS13 was determined in each unit at baseline and every 24 hours thereafter for 5 days. RESULTS After thaw, mean values of the variables tested were within the normal range in all three plasma products although, in SDP, FVIII activity was significantly lower (p = 0.0039). After 5 days of storage all factors significantly declined except for ADAMTS13 activity, which was stable. Mean FVIII and ADAMTS13 activity was comparable in all three plasma products and within the normal range, mean FV activity was significantly lower in FFP and PF24 (p

During the past 17 years, thrombotic thrombocytopenic purpura (TTP) has become defined by a severe deficiency of ADAMTS13.1 However this definition is not equivalent to a diagnosis of TTP. ADAMTS13 measurements have become common in our evaluation and management of patients with suspected TTP, but there are still uncertainties about the interpretation of these measurements. To address these uncertainties, we need to consider three questions. Addressing these questions is something that clinicians do whenever seeing a patient for whom the question is, “Does she have TTP?”

Background Cryosupernatant plasma (CSP) is used in Canada for plasma exchange in thrombotic thrombocytopenic purpura. The refrigerated storage time for thawed CSP is limited in many areas to not more than 24 hours postthaw. Because large volumes of CSP are needed for plasma exchange, procedural postponement can lead to product wastage. To determine if CSP storage could be extended, we measured coagulation-related activities in CSP thawed and stored at 1 to 6°C for up to 5 days. Study Design and Methods Thirty-six CSP units were thawed, refrigerated, and sampled aseptically at 0, 24, 48, and 120 hours postthaw. Clotting factor activities (Factor [F]V, FVII, FVIII, and fibrinogen) and prothrombin time were measured using an automated coagulation analyzer, and von Willebrand factor (vWF) and ADAMTS13 activities using enzyme-linked immunosorbent assay. Results Fibrinogen, FVIII, and vWF activities were unchanged from thaw values after 120 hours of storage; ADAMTS13, FV, and FVII activities were significantly lower than at thaw, but mean reductions were only −2.6, −7.7, and −12%, respectively. Losses were proportionately greater in the first 24 hours of refrigerated storage. Conclusions Extending the refrigerated storage of CSP from 1 to 5 days had little impact on product quality. The retention of more than 97% of initial mean ADAMTS13 activity after 5 days of refrigerated storage suggests that the shelf life of thawed refrigerated CSP could be extended without meaningful losses of its likely most important ingredients. CSP postthaw storage could be aligned to that of refrigerated thawed frozen plasma, currently available for transfusion in some jurisdictions for up to 5 days postthaw.