Investigation of Side Effects of Plasmaexchange In the Treatment of Thrombotic Thrombocytopenic Purpura

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4661-4661
Author(s):  
Sarah Steinemann ◽  
Tanja Falter ◽  
Mirjeta Qorraj ◽  
Thomas Vigh ◽  
Inge Scharrer
Keyword(s):  
Side Effects ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Side Effect ◽  
Conflicts Of Interest ◽  
Allergic Reactions ◽  
Adamts13 Activity ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Wide Range ◽  
Von Willebrand

Abstract Abstract 4661 Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia, hemolytic anemia and microthrombi. A deficiency of the metalloprotease ADAMTS 13, which cleaves a Tys1605-Met1606 bond in the A2 subunit of von Willebrand factor (VWF), leads to formation of ultra large von Willebrand multimers (UL-VWF) and can cause platelet aggregation and mircovascular thrombosis. Treatment of choice is the substitution of plasma with plasmaexchange. There are two different plasma types available: Fresh Frozen Plasma (FFP) and solvent/detergent (s/d) treated plasma. This treatment may carry significant risks and side effects for the patients. Therefore we investigated the side effects of the therapy and furthermore the ADAMTS13 activity of the two plasma types. Methods: A questionnaire was send to 66 TTP patients of the Department of Hematology to evaluate different side effects of the therapy. 20 batches of FFP and 4 batches of s/d plasma of all blood groups were investigated on ADAMTS13 activity. The ADAMTS13 activity was detected with BCS-Method according to Böhm and two commercial FRET assays. Results: So far 34 patients were inquired about age, weight and suspected trigger situations that might have caused their TTP manifestation. The mean age of the patients was 34 years with a mean weight of 70kg. A previous infection caused TTP manifestation in 42% of the patients; drug therapy (22%) and pregnancy (17%) were other mentioned triggers. 94% of the patients suffered from an acquired TTP and only 6% had a hereditary TTP. The patients had 2.88 relapses and were treated with 16.27 plasmaexchanges. 56% had an additional therapy with Rituximab to achieve a faster remission of the disease. These patients needed less plasmaexchanges for recovery, which proofed to be significant at 2% level in a one sided t-test. Tingling (64.7%) and shivering (51%) were the most often mentioned side effects and simultaneously described as the strongest. Shivering was significantly correlated to tachycardia (p<0.01). Headaches were significantly correlated to hot flushes, tingling and collapse (p< 0.05). Side effects and allergic reactions occurred in the therapy with FFP as well as with s/d plasma. Another side effect was the complication that came along with infection of the venous access. Most patients had a central venous catheter (72%) and described infections and pruritus (60%), 50% of them mentioned this complication more than once. We found in usual FFP slightly higher ADAMTS13 activity levels (696.97 ng/ml) than in s/d virus inactivated plasma (643.86 ng/ml). The ADAMTS13 activity varied between the different assays (normal range: 666 ± 135ng/ml). Conclusion: Our investigation demonstrated that plasmaexchange therapy is still associated with a wide range of side effects. Side effects of plasmaexchange that were most frequently described by patients were tingling and shivering. Headaches also occurred in various cases. Patients suffered generally from more than one side effect at the same time during the treatment. Allergic reactions to the plasma therapy were mentioned by 65% of the patients. Disclosures: No relevant conflicts of interest to declare.

FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in acquired thrombotic thrombocytopenic purpura patients

2014 ◽  
Vol 112 (08) ◽  
pp. 297-303 ◽  
Author(s):  
Ilaria Mancini ◽  
Carla Valsecchi ◽  
Luca Lotta ◽  
Louis Deforche ◽  
Silvia Pontiggia ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Proteolytic Activity ◽  
Binding Activity ◽  
Adamts13 Activity ◽  
Flow Conditions ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryCollagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura (TTP). However, non-concordant results between the two assays have been reported in a small but relevant percentage of TTP cases. We investigated whether CBA or FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients with non-concordant measurements. Twenty plasma samples with non-concordant ADAMTS13 activity results, <10% using FRETS-VWF73 and ≥20% using CBA, and 11 samples with concordant results, <10% using either FRETS-VWF73 and CBA assays, were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13 activities were also measured under flow conditions and the VWF multimer pattern was defined in order to verify the presence of ultra-large VWF due to ADAMTS13 deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly increased in roughly 50% of the samples with non-concordant results, whereas it remained undetectable in all samples with concordant measurements. Under flow conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples with non-concordant results showed a ratio of high molecular weight VWF multimers higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of the observed differences.

von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 778-785 ◽  
Author(s):  
Giuseppe Remuzzi ◽  
Miriam Galbusera ◽  
Marina Noris ◽  
Maria Teresa Canciani ◽  
Erica Daina ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Acute Phase ◽  
Von Willebrand Factor ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Uremic Syndrome ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Whether measurement of ADAMTS13 activity may enable physicians to distinguish thrombotic thrombocytopenic purpura (TTP) from hemolytic uremic syndrome (HUS) is still a controversial issue. Our aim was to clarify whether patients with normal or deficient ADAMTS13 activity could be distinguished in terms of disease manifestations and multimeric patterns of plasma von Willebrand factor (VWF). ADAMTS13 activity, VWF antigen, and multimeric pattern were evaluated in patients with recurrent and familial TTP (n = 20) and HUS (n = 29). Results of the collagen-binding assay of ADAMTS13 activity were confirmed in selected samples by testing the capacity of plasma to cleave recombinant VWF A1-A2-A3. Most patients with TTP had complete or partial deficiency of ADAMTS13 activity during the acute phase, and in some the defect persisted at remission. However, complete ADAMTS13 deficiency was also found in 5 of 9 patients with HUS during the acute phase and in 5 patients during remission. HUS patients with ADAMTS13 deficiency could not be distinguished clinically from those with normal ADAMTS13. In a subgroup of patients with TTP or HUS, the ADAMTS13 defect was inherited, as documented by half-normal levels of ADAMTS13 in their asymptomatic parents, consistent with the heterozygous carrier state. In patients with TTP and HUS there was indirect evidence of increased VWF fragmentation, and this occurred also in patients with ADAMTS13 deficiency. In conclusion, deficient ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and it is not the only determinant of VWF abnormalities in these conditions.

scholarly journals Active and Ultra-Large Von Willebrand Factor Is Significantly Elevated in Patients with Immune Thrombotic Thrombocytopenic Purpura

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 523-523
Author(s):  
Wenjing Cao ◽  
Alicia Veninga ◽  
Elizabeth M. Staley ◽  
Adam Miszta ◽  
Nicole Kocher ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Plasma Levels ◽  
Acute Episode ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background: Immune thrombotic thrombocytopenic purpura (iTTP), a potentially fatal hematological emergency, is primarily caused by acquired deficiency of ADAMTS13 activity due to autoantibodies. Immunoglobulin G (IgG)-type autoantibodies bind ADAMTS13 and inhibit its ability to cleave endothelium-derived ultra large von Willebrand factor (ULVWF). However, it remains poorly understood whether plasma VWF status can be used as a disease marker for diagnosis and monitoring therapy in patients with acute iTTP. Objective: To address this question, we determined plasma levels of VWF antigen (VWF:Ag), collagen-binding activity (VWF:CB), active forms of VWF (VWF:Ac), and VWF multimers in iTTP patients during acute episode and in early remission. Patients and Methods: From the Alabama registry, we identified 69 unique patients with a confirmed diagnosis of iTTP in whom plasma ADAMTS13 activity was <10 U/dL with positive inhibitors and elevated anti-ADAMTS13 IgGs. Of 69 patients, 21 had longitudinal plasma samples collected. Plasma samples from 56 healthy individuals, who did not have a hematological disease, cancer, and infection, were recruited as controls. Plasma levels of VWF:Ag, VWF:CB, and VWF:Ac were determined by an ELISA-based assay. Plasma VWF multimer distribution was assessed by an in-gel Western blotting assay following electrophoresis on a 1% SDS-agarose gel. Results: The mean age for our cohort iTTP patients was 43.9 ± 13.4 years. Twenty-six patients were male and 43 were female with male to female ratio of 1 to 1.7. Fifty-three patients were African American descents, 14 Caucasians, 1 Hispanic, and 1 unknown race. Plasma levels of VWF:Ag in acute iTTP patients were 289.4 ± 17.7%, significantly increased compared with those in the healthy controls (144.9 ± 7.6%) (p<0.0001); plasma levels of VWF:CB in these patients were 241 ± 17.9%, also significantly elevated compared with those in the healthy controls (149.9 ± 12.01%) (p=0.0001); additionally, plasma levels of VWF:Ac (304.6 ± 23.2%), assessed by its ability to bind anti-VWF-A1 nanobody, were more dramatically elevated compared with those in the controls (101.6 ± 5.9%) (p<0.0001). More interestingly, while the ratios of VWF:CB to VWF:Ag in patients with acute iTTP (0.8 ± 0.04) were lower than those in the healthy controls (1.0 ± 0.05) (p=0.0036), the ratios of VWF:Ac to VWF:Ag were significantly higher in patients with acute episode (1.2 ± 0.1) than those in the controls (0.8 ± 0.05) (p=0.0003). Furthermore, there was no statistically significant difference in the patient plasma levels of VWF:Ag (p=0.69) and VWF:CB (p=0.08) during acute episode and during early remission. However, the plasma levels of VWF:Ac in patients with acute disease were significantly higher than those in the early remission (p=0.002). Surprisingly, 90% (36/40) of out iTTP patients during acute episode showed the presence of ULVWF in their plasma using in-gel Western blotting, which allows the ULVWF to be detected without the transfer step to avoid any potential loss of larger VWF multimers during protein transfer. These ULVWF multimers disappeared in 3/4 iTTP patients in remission when ADAMTS13 activity recovered. In 28 healthy control samples, only one showed ULVWF. Conclusion: Our results demonstrate, for the first time in a large cohort, that active forms of VWF and ultra large VWF multimers are present in iTTP patient's plasma during the acute period, which is reduced or disappears during the early remission. Therefore, measuring active forms of VWF and ultra large VWF multimers may aid in diagnosis of iTTP and help monitoring of disease processes following therapy. Our ongoing study is to determine whether these biomarkers can be used to predict responses to treatment and long-term outcome. Disclosures Zheng: Alexion: Research Funding, Speakers Bureau.

Von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

1999 ◽  
Vol 82 (08) ◽  
pp. 592-600 ◽  
Author(s):  
Bernhard Lämmle ◽  
Miha Furlan
Keyword(s):  
Bone Marrow ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Complete Recovery ◽  
The United States ◽  
Severe Thrombocytopenia ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Platelet Aggregates ◽  
Patients Experience ◽  
Von Willebrand

IntroductionThrombotic thrombocytopenic purpura (TTP), a disseminated form of thrombotic microangiopathy, was initially described by Moschcowitz in 1924.1 TTP is defined by a pentad of findings, including severe thrombocytopenia, intravascular hemolysis with erythrocyte fragmentation, neurologic deficit, renal dysfunction, and fever.2–4 The thrombocytopenia occurs in the presence of normal or even increased numbers of megakaryocytes in the bone marrow, suggesting increased consumption. Platelet aggregates, found in the microcirculation, contain little if any fibrin polymers, indicating that activation of coagulation and fibrin formation may be secondary and limited in extent.About one-third of patients experience recurrent acute episodes at irregular and unpredictable intervals, whereas the majority of patients who recover from an acute TTP event experience no relapse and no persistent organ failure. TTP is usually classified as relapsing if complete remissions occurred between acute events and as chronic if complete recovery did not occur between bouts.Genetic predisposition to TTP has been shown in several siblings suffering from recurrent TTP.5 Thus, cases of TTP can be further divided according to whether the disease has a familial or genetic component or is not heritable. Acute episodes of TTP may be triggered by viral or bacterial infection, autoimmune disorders, bone marrow transplantation, drug therapy, cancer, chemotherapy, and pregnancy.3,4 The incidence of TTP is estimated to be two to eight cases per million people per year.3,6 Until four decades ago, the mortality rate was virtually 100% but has since decreased to less than 20% after introduction of plasma therapy. Still, there were more than 4,500 TTP-associated deaths recorded in the United States between 1968 and 1991.6

Identification of ADAMTS13 Peptide Sequences Recognized by Autoantibodies in Patients with Acquired Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2286-2286
Author(s):  
Yusuke Yamaguchi ◽  
Takanori Moriki ◽  
Hideo Wada ◽  
Masanori Matsumoto ◽  
Yoshihiro Fujimura ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Peptide Sequence ◽  
Adamts13 Activity ◽  
Lambda Phage ◽  
Thrombocytopenic Purpura ◽  
C Terminus ◽  
Epitope Sequence ◽  
Von Willebrand ◽  
The Impact ◽  
Inhibitor Titer

Abstract Anti-ADAMTS13 autoantibodies are considered to play pivotal roles in the pathophysiology of acquired thrombotic thrombocytopenic purpura (TTP). They inhibit the ADAMTS13 function resulting in the appearance of ultra-large von Willebrand factor (VWF) multimers. Major binding sites of the autoantibodies were reported to be in the cysteine-rich/spacer domains. To clarify the precise peptide sequences recognized by anti-ADAMTS13 IgG autoantibodies, we constructed a random cDNA fragment library expressing various peptides of ADAMTS13 on the surface of lambda phage and screened the library using purified IgG from 13 TTP patients. Diverse peptide sequences were obtained from almost entire ADAMTS13 domains such as metalloprotease, disintegrin, TSP1-1, cysteine-rich, spacer, TSP1- 2, 3, 4, 5, 7, 8 and CUB1. In particular, we detected an identical 26 amino-acid epitope sequence in the C-terminus of spacer domain from Gly662 to Val687 (sp662–687) shared by 5 TTP patients. Moreover, the peptide sequence was exactly included in one of the VWF binding epitope sites that we previously determined (Blood110 (11), 795a, 2007). We then assessed the impact of specific autoantibody to ADAMTS13 activity measured by FRETS-VWF73 or EIA and ADAMTS13 inhibitor titer in each of TTP patient plasma. However, both of the ADAMTS13 activity and inhibitor titer seemed not correlated with the existence of specific sp662–687 IgG autoantibody. These observations suggest that the autoantibody to sp662–687 may be one specific feature of TTP, although other epitopes are also involved in the pathogenesis of the disorder.

Evaluation of Clotting Factor Concentrates for Treatment of Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3678-3678
Author(s):  
Tanja Falter ◽  
Mirjeta Qorraj ◽  
Sarah Steinemann ◽  
Thomas Vigh ◽  
Inge Scharrer
Keyword(s):  
Human Plasma ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Blood Group ◽  
Conflicts Of Interest ◽  
Blood Groups ◽  
Clotting Factor ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Clotting Factor Concentrates

Abstract Abstract 3678 Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by microthrombi, hemolytic anemia as well as thrombocytopenia. These symptoms are caused by a decreased activity of the protease ADAMTS13 which cleaves the von Willebrand Factor (VWF), due to mutation of the ADAMTS13-gene or autoantibodies. At the moment, the only available immediate therapy is plasmapheresis with Fresh Frozen Plasma (FFP) which may induce side effects. Therefore an alternative therapy might be the treatment with clotting factor concentrates. Methods: 40 plasma samples were tested, consisting of FFP and solvent/detergent treated plasma, four batches of each blood group; VWF/VIII concentrates (Wilate®; Wilfactin®; Haemate®P; Immunate®; Kogenate®, Beriate®). In all samples ADAMTS13 activity, antigen and autoantibodies against ADAMTS13 were investigated. Additionally, the samples were tested for the presence of ultralarge VWF multimers. The BCS method according to Böhm, two ELISAs (Technozym®ADAMTS13 and Actifluor™ADAMTS13) and the electrophoresis on a SDS gel were used. Results: ADAMTS13 activity was found in all VWF)VIII concentrates, which are produced from human plasma, but only with a very low activity (Wilate® 5.6%; Wilfactin® 2.8%; Haemate®P 13%; Immunate® 3.7%). ADAMTS13 activity was not detectable in the factor VIII concentrates (Kogenate® <2%; Beriate® <2%). Usual FFP and solvent/detergent treated plasma samples, contained much higher ADAMTS13 activity and antigen values than concentrates (FFP 78.6%, solvent/detergent treated plasma 77.6%). However a difference of activity between individual blood groups was evident in FFP samples (blood group A 69.4%; B 64.9%; AB 98.1%; 0 82.0%). Ultralarge VWF multimers could be demonstrated in VWF containing concentrates, less in VIII concentrate from human plasma and not in FFP and solvent/detergent treated plasma samples. As expected recombinant-produced VIII concentrate contained no traces of ultralarge VWF. In all analyzed samples antibodies were negative. Conclusion: For therapy of TTP clotting factor concentrates cannot be used as an alternative to the usual FFP and solvent/detergent treated plasma, because their ADAMTS13 activity values are too low. In addition, the VWF/VIII concentrates contain higher quantities of ultralarge VWF multimers, which are contraindicated for TTP patients. The differences of ADAMTS13 activity in FFP samples varies between the individual blood groups and batches. Solvent/detergent treated plasma shows less variation in ADAMTS13 activity due to the manufacturing process involving plasma pooling. Disclosures: No relevant conflicts of interest to declare.

Retrospective Analysis of Patients Afflicted with Thrombotic Thrombocytopenic Purpura: A Single Institutional Experience.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2200-2200
Author(s):  
Manali K. Kamdar ◽  
Phillip Chae ◽  
Maria Javaid ◽  
Negin Mesaghian ◽  
Kevin O'Brien ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Blood Group ◽  
Conflicts Of Interest ◽  
Severe Thrombocytopenia ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Congenital Deficiency ◽  
Predominant Symptom ◽  
Threatening Condition

Abstract Abstract 2200 Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is an acute life threatening condition characterized by thrombocytopenia, microangiopathic hemolytic anemia, with or without renal failure or neurologic abnormalities, and without another cause for thrombotic microangiopathy. The majority of cases of TTP are associated with a low ADAMTS13 activity which results from antibody to this enzyme. A minority of patients have TTP secondary to congenital deficiency of this enzyme. The mainstay of therapy for TTP is plasmapheresis (PEX) which has increased survival in affected patients from 10% to more than 75%. While TTP is considered as an uncommon disorder, at our institution we suspected that the diagnosis was made more commonly. Therefore we set out to perform a retrospective analysis of cases of TTP to evaluate cases diagnosed over the past 10 years. Methods: We performed a retrospective analysis of all cases of microangiopathy undergoing pheresis at our institution for presumed TTP from May 2007 to April 2012. A total of 112 patients had PEX initiated for presumed TTP however 11 of these were later determined to have some other etiology causing the constellation of symptoms and PEX was discontinued. The remaining 101 patients were entered into a database and further analyzed. Demographically, we captured patients from 30 of the 100 North Carolina counties because 3 other institutions in our state perform plasma exchange for TTP. ADAMTS13 activity and inhibitor levels were measured in 69 out of 101 patients. In our registry there were 80 patients with Idiopathic TTP and 21 patients with secondary TTP. Patients with idiopathic TTP were further divided based on the ADAMTS13 activity. Results: Discussion: Our analysis demonstrated that TTP was more common in females, African American population with a median age group in the mid forties with neurological symptoms being the predominant symptom of presentation. While hematocrit was higher in patients with idiopathic TTP these patients were noted to have increased incidence of ADAMTS13 levels less than 10% with inhibitors as compared to those with secondary TTP. Idiopathic TTP patients had more incidence of multiple relapses and required more Rituximab in addition to PEX. We compared our results with the results published from the Oklahoma registry. Similar to the Oklahoma registry results patients with ADAMTS13 levels less than 10% had more severe thrombocytopenia, renal dysfunction, required more sessions of PEX, had higher relapses and percentage of death compared to patients with idiopathic TTP with ADAMTS13 levels more than 10%. Patients with ADAMTS13 less than 10% required more Rituximab during first diagnosis of idiopathic TTP. In this group blood group A+ was seen more often whereas blood group O+ was prevalent in the group with ADAMTS more than 10%. Comparison amidst these groups brought out similarities between two distinct registries in the US. Our registry is another large registry of patients similar to the Oklahoma TTP registry. While many similarities are seen with the Oklahoma group there were a few differences as cited above. Disclosures: No relevant conflicts of interest to declare.

Recovery and Half-Life of von Willebrand Factor-Cleaving Protease after Plasma Therapy in Patients with Thrombotic Thrombocytopenic Purpura

1999 ◽  
Vol 81 (01) ◽  
pp. 8-13 ◽  
Author(s):  
Rodolfo Robles ◽  
Beat Morselli ◽  
Pierre Sandoz ◽  
Bernhard Lämmle ◽  
Miha Furlan
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Half Life ◽  
Protease Activity ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Plasma Infusion ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryPlasma exchange using fresh-frozen plasma (FFP) for replacement was given to two brothers during a relapse of thrombotic thrombocytopenic purpura (TTP). A constitutional deficiency of von Willebrand factor(vWF)-cleaving protease had been previously established in both patients. No inhibitor of vWF-cleaving protease was present in patients’ plasmas. They received plasma exchange for four and three consecutive days, respectively. In both patients, the activity of vWF-cleaving protease after the first plasmapheresis session was evaluated and was found to be virtually identical to anticipated activity calculated from predicted patient plasma volume and volume of exchanged plasma. Pathologic platelet counts and lactate dehydrogenase levels were normalized in both patients within 4-6 days. The biologic half-life of vWF-cleaving protease was determined in these patients following the last plasma exchange. The respective half-lives of 3.3 and 2.1 days represent the lowest known clearance rates of proteases in circulating human plasma.Another patient with relapsing TTP was treated with plasma exchange and/or plasma infusion for 10 consecutive days during the first relapse, 221-231 days after the initial TTP event. Pharmacokinetic studies of vWF-cleaving protease were performed after plasma exchange on day 221 and after plasma infusion on day 231. High level of an IgG in patient plasma, capable of completely inhibiting protease activity in an equal volume of normal plasma, had been established prior to first plasmapheresis. There was no measurable protease activity at any time during plasma therapy. Following plasma exchange, the level of the inhibitor was transiently slightly depressed. After 10 days of plasma therapy, the concentration of the inhibitor in patient plasma was increased about 5-fold. We suggest that, in contrast to protease deficient patients without circulating inhibitor, complementary therapy including immunosuppressive treatment, vincristine and/or splenectomy is indicated in patients with acquired inhibitors of vWF-cleaving protease. Testing for vWF-cleaving protease inhibitor may be useful in predicting the response to plasma exchange in patients with TTP.

scholarly journals Characterization of Two Cases of Congenital Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5005-5005
Author(s):  
Xia Bai ◽  
JIan Su ◽  
Lijuan Cao ◽  
Changgeng Ruan
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Binding Assay ◽  
Conflicts Of Interest ◽  
Hek293 Cells ◽  
Novel Mutations ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Introduction: Congenital thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombus due to the mutations of ADAMTS13, which cleaves its substrate von Willebrand factor(VWF) in shear-induced unfolding condition. Most of the congenital TTP we found is woman with pregnancy. Here, we characterize two children suspected with congenital TTP. Methods:ADAMTS13 activities were analyzed by residual collagen binding assay (R-CBA) plus FRET-VWF substrate. And the inhibitors of ADAMTS13 were analyzed by 9:1 mixture of patient and pooled normal plasma followed by R-CBA. The secretion of recombinant ADAMTS13 mutants was studied. Results: Two children, one aged four months and the other aged three years old, were diagnosed with congenital TTP because their ADAMTS13 activities were less than 5% (both FRET-VWF and R-CBA), and there are short of ADAMTS13 inhibitors. The following mutations were found: Q1385P, Y177C, C522R. In addition to the previously reported mutation of Y177C, the two novel mutations (Q1385P and C522R) failed to secrete from the HEK293 cells. Conclusion: Two children with congenital TTP were determined thanks to screening of ADAMTS13 activity and its corresponding inhibitor assays, and it seems that congenital TTP could occur in different ages although most of congenital TTP we found were women with pregnancy. Disclosures No relevant conflicts of interest to declare.

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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