Distinction of Inherited from Acquired Thrombotic Thrombocytopenic Purpura Applying the Cone and Plate(Let) Analyzer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 853-853 ◽  
Author(s):  
Boris Shenkman ◽  
Ulrich Budde ◽  
Dorothea Angerhaus ◽  
Reinhard Schneppenheim ◽  
Aharon Lubetsky ◽  
...  
Keyword(s):  
Shear Rate ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Whole Blood ◽  
Substantial Reduction ◽  
Blood Type ◽  
Normal Blood ◽  
Simple Method ◽  
Thrombocytopenic Purpura ◽  
Normal Plasma ◽  
Platelet Deposition

Abstract Measurement of von Willebrand factor-cleaving protease (VWF-CP) activity is useful for diagnosis of thrombotic thrombocytopenic purpura (TTP), but the current methods are cumbersome. We recently introduced a simple method of TTP detection using the Cone and Plate(let) Analyzer (CPA), that was based on the observation that mixing of acute TTP plasma (50 μL) with normal whole blood (150 μL) induces a significant increase in platelet deposition (surface coverage, %SC) on polystyrene surface under flow condition (1800 s−1) (Brit J Haematol, 120: 597, 2003). The test was specific for TTP, since plasma from patients with HUS, APLS, ITP or HIT did not affect normal platelet deposition. In this study, we further explored the potential use of the CPA method in differential diagnosis of inherited and acquired TTP by increasing the shear rate and by inducing the VWF-CP activity with BaCl2. TTP or normal plasma was mixed with normal blood (type O+) and the surface covered by platelets was tested under shear rates ranging between 1800 s−1 to 2500 s−1. Maximal difference in SC between TTP and normal plasma was observed at a shear rate of 2050 s−1. Under these conditions, plasmas of 5 patients with inherited TTP (ITTP), and 11 patients with acquired TTP (ATTP) yielded comparable increase in SC of normal platelets in whole blood, i.e. 77±19% and 78±17%, respectively. However, experiments in which BaCl2 was added to allow activation of VWF-CP resulted in a substantial distinction between inherited and acquired TTP plasma. While addition of BaCl2 to normal or inherited TTP plasma, both mixed with normal blood, yielded similar reductions of SC by 41±12% and 51±19%, only 11±4% reduction of SC was observed when acquired TTP plasma was used. These results suggest that when normal or inherited TTP plasma is mixed with normal blood, activation of VWF-CP cleaves large VWF multimers giving rise to substantial reduction in SC, whereas in the case of acquired TTP plasma the inhibitor of VWF-CP abolishes BaCl2-induced activation of VWF-CP and the ensuing reduction in SC. We conclude that introduction of BaCl2 in the CPA at high shear conditions may be useful for differentiation between inherited and acquired TTP.

Thrombotic Thrombocytopenic Purpura: Experience with Whole Blood Exchange Transfusion

1981 ◽  
Vol 7 (01) ◽  
pp. 25-32 ◽  
Author(s):  
Jerome Gottschall ◽  
Anthony Pisciotta ◽  
Joseph Darin ◽  
Clara Hussey ◽  
Richard Aster
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Whole Blood ◽  
Exchange Transfusion ◽  
Thrombocytopenic Purpura ◽  
Blood Exchange ◽  
Blood Exchange Transfusion

An enzyme immunoassay of ADAMTS13 distinguishes patients with thrombotic thrombocytopenic purpura from normal individuals and carriers of ADAMTS13 mutations

2004 ◽  
Vol 91 (04) ◽  
pp. 806-811 ◽  
Author(s):  
Wenhua Zhou ◽  
Han-Mou Tsai
Keyword(s):  
Fusion Protein ◽  
Enzyme Immunoassay ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Activity Level ◽  
Dependent Manner ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Normal Plasma ◽  
Normal Individuals

SummaryRecent studies demonstrate that assay of ADAMTS13, a circulating zinc metalloprotease that cleaves von Willebrand factor (VWF) at the Y1605-M1606 bond, is an important tool in the diagnosis of thrombotic thrombocytopenic purpura (TTP). In order to develop a method that could be adapted for general use, we describe an enzyme immunoassay (EIA)-based method for measuring the activity of ADAMTS13 in patient plasma samples. A monomeric peptide consisting of the amino acid residues D1596-R1668 of VWF was produced that spanned the ADAMTS13 cleavage site and was franked by glutathione s-transferase (GST) and a 6His sequences at the amino and carboxyl termini respectively. When probed with either anti-GST or anti-6His, the VWF fragment appeared as a 38.1-kDa band. After incubation with normal plasma, the VWF fragment was replaced by a 30.4-kDa band, which was recognized by antiGST but not by anti-6His, consistent with the expected cleavage at the Y1605-M1606 bond. EDTA or plasma samples from patients with TTP inhibited this cleavage. After incubation with normal plasma, the VWF fusion protein immobilized onto antiGST coated microtiter plate wells lost its anti-6His binding activity in a timeand plasma concentration-dependent manner. By using this EIA, the ADAMTS13 activity level was less than 0.12 U/mL in patients with acquired or hereditary TTP, distinguishing these patients from normal individuals or carriers of one copy of mutant ADAMTS13 allele. These results suggest the EIA method based on the VWF fusion protein is a simple but promising alternative for measuring ADAMTS13 activity.

scholarly journals Studies on Thrombopoiesis. I. A Factor in Normal Human Plasma Required for Platelet Production; Chronic Thrombocytopenia Due to its Deficiency

Blood ◽  
1960 ◽  
Vol 16 (1) ◽  
pp. 943-957 ◽  
Author(s):  
IRVING SCHULMAN ◽  
MILA PIERCE ◽  
ABBY LUKENS ◽  
ZINET CURRIMBHOY
Keyword(s):  
Human Plasma ◽  
Normal Blood ◽  
Normal Human Plasma ◽  
Thrombocytopenic Purpura ◽  
Blood Banking ◽  
Platelet Production ◽  
Congenital Deficiency ◽  
Normal Plasma ◽  
Normal Human ◽  
Stimulating Factor

Abstract 1. A case of chronic thrombocytopenic purpura has been presented in which the pathogenesis appears to be due to congenital deficiency of a platelet-stimulating factor. 2. The factor exists in normal plasma and is stable on storage under normal blood banking conditions and on freezing. 3. The factor appears to act by stimulating megakaryocyte maturation and platelet production in an orderly and sequential manner.

scholarly journals Elevated plasma levels of syndecan-1 and soluble thrombomodulin predict adverse outcomes in thrombotic thrombocytopenic purpura

2020 ◽  
Vol 4 (21) ◽  
pp. 5378-5388
Author(s):  
Ruinan Lu ◽  
Jingrui Sui ◽  
X. Long Zheng
Keyword(s):  
Hospital Mortality ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Plasma Levels ◽  
Substantial Reduction ◽  
Simultaneous Increase ◽  
Serum Lactate Dehydrogenase ◽  
Thrombocytopenic Purpura ◽  
Lactate Dehydrogenase Activity ◽  
Soluble Thrombomodulin ◽  
Blood Disorder

Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal blood disorder resulting from acquired deficiency of plasma ADAMTS13 activity. Despite recent advances in early diagnosis and novel therapeutics, the mortality rate of acute iTTP remains as high as 10% to 20%. Moreover, a reliable clinical and laboratory parameter that predicts disease severity and outcomes is lacking. We show in the present study that plasma levels of syndecan-1 (Sdc-1) and soluble thrombomodulin (sTM) on admission were dramatically increased in patients with acute iTTP and remained substantially elevated in a subset of patients compared with healthy controls. The elevated admission plasma levels of Sdc-1 and sTM were associated with abnormal Glasgow coma scale scores, low estimated glomerular filtration rates, the need for intensive care, and in-hospital mortality rates. Moreover, a further simultaneous increase in plasma Sdc-1 and sTM levels at the time of clinical response/remission (eg, when normalization of platelet counts and substantial reduction of serum lactate dehydrogenase activity were achieved) was highly predictive of iTTP recurrence. These results demonstrate that endothelial injury, resulting from disseminated microvascular thromboses, is severe and persistent in patients with acute iTTP. Plasma levels of Sdc-1 and sTM on admission and in remission are predictive of in-hospital mortality and recurrence of acute iTTP, respectively. Thus, an incorporation of such novel plasma biomarkers into the risk assessment in acute iTTP may help implement a more vigorous and intensive therapeutic strategy for these patients.

scholarly journals Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 490-497 ◽  
Author(s):  
J Moake ◽  
M Chintagumpala ◽  
N Turner ◽  
P McPherson ◽  
L Nolasco ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Fluid Shear Stress ◽  
Platelet Rich Plasma ◽  
Shear Stresses ◽  
Thrombocytopenic Purpura ◽  
Plasma Infusion ◽  
Normal Plasma ◽  
Induced Aggregation

Abstract Two children with congenital chronic relapsing thrombotic thrombocytopenic purpura (TTP) have episodes every 3 weeks. These relapses can be prevented by the infusion of normal fresh-frozen plasma (FFP) without concurrent plasmapheresis. We conducted a study to determine whether the exposure of normal plasma to agents that inactivate human immunodeficiency virus and other viruses destroys the component necessary for the effective treatment of this type of TTP that requires only plasma infusion to prevent or reverse relapses. Clinical responsiveness and von Willebrand factor (vWF)-mediated fluid shear stress-induced platelet aggregation were evaluated before and after the infusion of 10 mL/kg FFP or solvent [tri(n- butyl)phosphate]/detergent (Triton X-100)-treated plasma (S/D plasma). Platelet aggregation at shear stresses of 90 to 180 dyne/cm2 (similar to those in the partially occluded microcirculation) imposed for 30 seconds was excessive using the citrated platelet-rich plasma of both patients, and was associated with the presence of unusually large vWF forms in patient platelet-poor plasma. Infusion with either FFP or S/D plasma at 3-week intervals caused the platelet count to increase to (or above) normal within 1 week (on 12 of 12 occasions); the disappearance or diminution of unusually large vWF forms within 1 hour (on 6 of 10 occasions studied); and the reversal within 1 to 4 hours of excessive shear-induced platelet aggregation (on 8 of 9 occasions studied). We conclude that a component in normal plasma resistant to S/D treatment is responsible for preventing thrombocytopenia and TTP episodes, and for controlling excessive shear-induced aggregation in these patients. Our results suggest that excessive in vivo platelet aggregation in chronic relapsing TTP and excessive in vitro vWF-mediated shear-induced aggregation may be similar phenomena.

scholarly journals Platelet-Delivered Recombinant ADAMTS13 Inhibits Platelet Adhesion and Aggregation on Collagen Surface Under Flow in the Presence of Autoantibodies from Acquired Thrombotic Thrombocytopenic Purpura

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1374-1374
Author(s):  
Mohammad S. Abdelgawwad ◽  
Jenny K. McDaniel ◽  
Wenjing Cao ◽  
Huy P. Pham ◽  
Lance A. Williams ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Whole Blood ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Effective Therapy ◽  
Confocal Imaging ◽  
Dependent Manner ◽  
Thrombocytopenic Purpura ◽  
Platelet Adhesion And Aggregation

Abstract Background: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal syndrome. It is primarily caused by severe deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. ADAMTS13 is a plasma metalloprotease that cleaves von Willebrand factor (VWF), thereby reducing the platelet adhesion and aggregation under flow. Plasma exchange is the only effective initial therapy for acquired autoimmune TTP. However, in hospital mortality rate remains as high as 10-20% in addition to the concern about the complications associated with the placement of central catheter and the use of plasma products. Therefore, a better and more effective therapy is urgently needed. Objectives: To develop a more effective therapy, we determined the uptake and package of recombinant ADAMTS13 (rA13) in platelets and assessed the efficacy of platelets-delivered rA13 in inhibiting platelet adhesion and aggregation and thrombus formation under arterial shear. Methods: Human platelets were isolated from whole blood, washed, and incubated with various concentrations of rA13 (1-100 microgram/ml) at 25 and 37 degree Celsius for various times. The amount of rA13 uptake by platelets was determined in cell lysate by Western blotting and FRETS-VWF73 assays and in fixed cells by immunofluoresent microscopy and flow cytometry. The function of platelet delivered rA13 was also determined by shear-induced platelet adhesion and aggregation on collagen surface using a microfluidic system. Results: Freshly isolated and blood bank stored platelets were able to update rA13 in a temperature, concentration, and time-dependent manner. When rA13 (5 microgram/ml) was incubated with platelets, nearly all platelets were positive for rA13, assessed by immunofluoresent microscopy and flow cytometry. The rA13 inside platelets remained intact and was proteolytically active in cleaving FRETS-VWF73. Confocal imaging revealed that rA13 was partially co-localized with VWF in alpha granules of platelets. Microfluidic assay demonstrated that platelet-delivered rA13 was able to dramatically inhibit platelet adhesion and aggregation on collagen-coated surface under arterial shear (100 dyne/cm2) in the absence and presence of a human monoclonal antibody against ADAMTS13 (scFv4-20) that was isolated from a patient with acquired autoimmune TTP. These results were consistent with the inhibitory effects observed with mouse transgenic platelets expressing rA13 under the same conditions. When 1/3 of whole blood Adamts13-/- platelets were replaced with transgenic platelets (containing rA13), the coverage of all fluorescent platelets onto a VWF-collagen surface was dramatically reduced (data not shown). Conclusion: Our results demonstrate that platelets uptake and deliver rA13 to the site of thrombus formation under flow and the platelet-delivered rA13 may be efficacious for treating acquired TTP with inhibitors. Disclosures Zheng: Ablynx: Consultancy; Alexion: Research Funding.

Endothelial Microparticles (EMP) Inhibit ADAMTS13 Activity: Implications in Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3676-3676
Author(s):  
Joaquin J. Jimenez ◽  
Wenche Jy ◽  
Lucia M. Mauro ◽  
Ana C. Mauro ◽  
Laurence L. Horstman ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Adamts13 Activity ◽  
Immunomagnetic Beads ◽  
Endothelial Microparticles ◽  
Thrombocytopenic Purpura ◽  
Normal Plasma ◽  
Measured Activity ◽  
Platelet Aggregate

Abstract Deficiency of ADAMTS13 is implicated in the pathogenesis of congenital and some acquired idiopathic thrombotic thrombocytopenic purpura (TTP). However, injury to endothelial cells (EC) is also believed to play a major role. Endothelial microparticles (EMP), markers of EC injury, are elevated in acute TTP, and subsets of EMP have been shown to carry ULvWF. The aim of this study was to further characterize the role of EMP in TTP by assessing their effect on ADAMTS13 activity. METHODS. EMP derived from activated renal microvascular EC (RMVEC) and coronary artery EC (CAEC) were depleted of phenotypic subsets by negative panning with immunomagnetic beads against CD62E, CD31, or CD54. For clinical studies, platelet-poor plasmas (PPP) were selectively depleted of PMP and LMP by beads against CD41 and CD45, respectively. Antigenic phenotypes of EMP were measured by flow cytometry. vWF multimer size was analyzed by Western blotting after 0.8% argarose gel electrophoresis. Proaggregatory activity of vWF (free in plasma or on EMP) was assessed by incubation of washed platelets with EMP (some are vWF+) or soluble plasma vWF, and ristocetin for 10min, then measuring platelet aggregation by flow cytometry. To measure interaction of ADAMTS13 with EMP, PPP was incubated with EMP (1x105 – 1x108 EMP/mL) for 15min – 3hr, then centrifuged to remove EMP (15,000xg, 1hr), and ADAMTS13 activity remaining in the plasma was assayed by the method of Furlan et al [Blood, 1997, 89:3097]. RESULTS. (1) RMVEC released >2-fold more EMP than CAEC and the proportion of vWF+ EMP was 2-fold higher with RMVEC (65 ±17% of total) than with CAEC (30±12%), p<0.01. (2) We next selectively depleted total EMP of CD31+, CD62E+ or CD54+ subsets, then incubated with normal plasma (defined as 100% ADAMTS13 activity) and measured activity remaining after centrifugation. Maximal reduction of activity was seen with non-depleted (total) EMP, which was nearly the same as with the CD54-depleted preparations (all experiments at 1x108 EMP/mL for 3hr), resulting in a 71 ±23% reduction after centrifugation (p<0.01). However, depletion of EMP positive for CD31 or CD62E resulted in significantly less removal or inactivation of ADAMTS13 (55 ±17%, 35 ±8% inhibition, respectively. Similar results were observed with EMP from CAEC except that the effect was about 25% less. (3) To determine whether EMP from TTP patients can also negatively regulate ADAMTS13 activity, we isolated total MP by centrifugation from plasma of 3 acute TTP patients, and removed MP of platelet and leukocyte origin by immunomagnetic beads. The resulting EMP were incubated with normal plasma. As observed with in vitro-generated EMP, similar concentrations of patient EMP removed or inactivated ADAMTS13 activity in plasma, by 66 ±18% in these experiments (p<0.02). (4) To further test the ability of EMP to adsorb ADAMTS13, we found that preincubation of plasma with EMP, resulted in 57 ±10% increased platelet aggregate formation relative to absence of EMP preincubation, (p<0.01). CONCLUSION. EMP released from EC culture and EMP isolated from TTP plasma inactivated ADAMTS13 activity and enhanced formation of platelet aggregates. These findings further support the hypothesis that EMP play an important role in TTP by downregulating ADAMTS13 and promoting the formation of platelet rich microthrombi in microvasculature.

The Frequency and the Significance of ADAMTS-13 Neutralising Inhibitors in 62 Patients with Non-Familial Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3945-3945
Author(s):  
Martina Böhm ◽  
Manuela Krause ◽  
Charis Von Auer ◽  
Wolfgang Miesbach ◽  
Inge Scharrer
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Inhibitory Activity ◽  
Thrombocytopenic Purpura ◽  
Plasma Exchange Therapy ◽  
Normal Plasma ◽  
Initiation Of Therapy ◽  
Inhibitor Titer ◽  
Ristocetin Cofactor

Abstract Neutralising inhibitors against ADAMTS-13 are detected in 51–67% of patients with Thrombotic Thrombocytopenic Purpura (TTP). These ADAMTS-13 inhibitors have not been very well characterised and the diagnostic or the prognostic value of these inhibitors is not established. In the present study, we measured ADAMTS-13 activity and the corresponding inhibitor titer in 96 samples from 62 patients with TTP at various stages of their disease. All patients presented with non-familial TTP. For patients with severe ADAMTS-13 activity without detectable inhibitor heritable ADAMTS-13 deficiency was excluded by either normalisation of ADAMTS-13 activity in remission or by detecting normal ADAMTS-13 activity in first degree family members. ADAMTS-13 activity was quantified by measuring the residual ristocetin cofactor activity of the substrate. The inhibitor against ADAMTS-13 was detected by mixing patient plasma, either neat or diluted, with normal plasma. The inhibitor concentration neutralising 50% of ADAMTS-13 activity in a 1:1 dilution of patient plasma with normal plasma was defined as 1 U/ml. Inhibitors were considered non-detectable (<0.4 U/ml), if residual ADAMTS-13 activity in the mixture was higher than 75%. Samples with ADAMTS-13 activity >6.25% were heat-inactivated (30 min at 56°C) before testing for inhibitory activity. We found severe ADAMTS-13 deficiency in 89% (24/27) of the samples from patients with acute untreated TTP. 87% (21/24) of these samples were positive for inhibitory activity. The inhibitor titer ranged from 0.4 to 62 U/ml with a median of 1 U/ml. One patient with acute TTP demonstrated ADAMTS-13 activity of 34% despite an inhibitor titer of 0.6 U/ml. The sensitivity of a positive inhibitor test for the diagnosis of TTP was thus 82%. The inhibitor titer before initiation of therapy could not be correlated with the platelet count, the CRP-level or the response to PE-therapy, if patients with an index episode and patients with a relapse were analysed separately. Severe ADAMTS-13 activity was detected in 15/31 samples collected from patients during plasma exchange therapy. 93% (14/15) of these samples were positive for an inhibitor with a titer ranging between 0.6 and 47 U/ml (median: 3 U/ml). 12 of 37 patients tested in remission presented with severe ADAMTS-13 deficiency, 6 of them were positive for inhibitory activity (range: 1–52 U/ml; median: 5 U/ml). The inhibitor titer for patients, which were analysed during acute untreated TTP as well as in remission (n=5), was notable not related to the stage of disease. Five patients with positive inhibitory activity at admission demonstrated mild ADAMTS-13 deficiency in remission without detectable inhibitor. In contrast, we detected inhibitory activity of 0,6–0,8 U/ml in 3 samples from two patients with measurable ADAMTS-13 activity. These low titer inhibitors were only detectable, if samples were heat inactivated before performing the inhibitor assay. Our data demonstrate, that inhibitors against ADAMTS-13 are very heterogeneous. It is highly suspected, that some of these inhibitors can either completely or partly neutralise ADAMTS-13 function in vivo without being detectable in vitro. Inhibitors against ADAMTS-13 might, on the other side, not always completely inhibit ADAMTS-13 function, since they can occur in patients with high residual ADAMTS-13 activity. Inhibitor titers show a wide variation and the clinical significance of the inhibitor titer before, during and after therapy needs to be further investigated.

scholarly journals Presence of a platelet aggregating factor in the plasma of patients with thrombotic thrombocytopenic purpura (TTP) and its inhibition by normal plasma

Blood ◽  
1979 ◽  
Vol 53 (2) ◽  
pp. 333-338 ◽  
Author(s):  
EC Lian ◽  
DR Harkness ◽  
JJ Byrnes ◽  
H Wallach ◽  
R Nunez
Keyword(s):  
Platelet Aggregation ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Normal Plasma

Three patients with thrombotic thrombocytopenic purpura (TTP) were treated by infusion of normal plasma with dramatic responses. The plasmas collected from these patients during relapse induced in vitro aggregation of washed platelets from both normal donors and the patients during remission. The platelet aggregating factor was not dialyzable or adsorbable by Al(OH)3 and was not inactivated by diisopropylfluorophosphate, hirudin, or heparin in the presence of normal amounts of antithrombin. In contrast to the platelet aggregation induced by platelet isoantibody, the platelet aggregating activity of TTP plasma diminished as a function of time when it was incubated with normal plasma at 37 degrees C. These observations suggest that at least some instances of TTP appear to be due to deficiency of a plasma inhibitor to counteract a platelet aggregating factor demonstrated to be present in the plasma of these patients.

scholarly journals Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 490-497 ◽  
Author(s):  
J Moake ◽  
M Chintagumpala ◽  
N Turner ◽  
P McPherson ◽  
L Nolasco ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Fluid Shear Stress ◽  
Platelet Rich Plasma ◽  
Shear Stresses ◽  
Thrombocytopenic Purpura ◽  
Plasma Infusion ◽  
Normal Plasma ◽  
Induced Aggregation

Two children with congenital chronic relapsing thrombotic thrombocytopenic purpura (TTP) have episodes every 3 weeks. These relapses can be prevented by the infusion of normal fresh-frozen plasma (FFP) without concurrent plasmapheresis. We conducted a study to determine whether the exposure of normal plasma to agents that inactivate human immunodeficiency virus and other viruses destroys the component necessary for the effective treatment of this type of TTP that requires only plasma infusion to prevent or reverse relapses. Clinical responsiveness and von Willebrand factor (vWF)-mediated fluid shear stress-induced platelet aggregation were evaluated before and after the infusion of 10 mL/kg FFP or solvent [tri(n- butyl)phosphate]/detergent (Triton X-100)-treated plasma (S/D plasma). Platelet aggregation at shear stresses of 90 to 180 dyne/cm2 (similar to those in the partially occluded microcirculation) imposed for 30 seconds was excessive using the citrated platelet-rich plasma of both patients, and was associated with the presence of unusually large vWF forms in patient platelet-poor plasma. Infusion with either FFP or S/D plasma at 3-week intervals caused the platelet count to increase to (or above) normal within 1 week (on 12 of 12 occasions); the disappearance or diminution of unusually large vWF forms within 1 hour (on 6 of 10 occasions studied); and the reversal within 1 to 4 hours of excessive shear-induced platelet aggregation (on 8 of 9 occasions studied). We conclude that a component in normal plasma resistant to S/D treatment is responsible for preventing thrombocytopenia and TTP episodes, and for controlling excessive shear-induced aggregation in these patients. Our results suggest that excessive in vivo platelet aggregation in chronic relapsing TTP and excessive in vitro vWF-mediated shear-induced aggregation may be similar phenomena.

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