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Article ; Online: iTTP: more long-term consequences.

Metjian, Ara

2023 Volume 141, Issue 3, Page(s) 216–217

MeSH term(s)	Humans ; Purpura, Thrombotic Thrombocytopenic/therapy ; Rituximab ; Recurrence
Chemical Substances	Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022018789
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Article: Caplacizumab in adult patients with acquired thrombotic thrombocytopenic purpura.

Hanlon, Ashley / Metjian, Ara

Therapeutic advances in hematology

2020 Volume 11, Page(s) 2040620720902904

Abstract: Thrombotic thrombocytopenic purpura (TTP) is usually a fatal disease caused by a deficiency of the metalloproteinase, ADAMTS13, often due to autoimmunity. This leads to the development of pathogenic multimers of von Willebrand factor (vWF), causing an ... ...

Abstract	Thrombotic thrombocytopenic purpura (TTP) is usually a fatal disease caused by a deficiency of the metalloproteinase, ADAMTS13, often due to autoimmunity. This leads to the development of pathogenic multimers of von Willebrand factor (vWF), causing an inappropriate interaction of platelets and vWF. This results in a thrombotic microangiopathy, which is treated with therapeutic plasma exchange and immune suppression. Although this treatment has reduced the mortality of TTP to only about 20%, there have been no recent significant advances in the treatment of TTP. Recently, a novel agent has been approved for use in TTP. Caplacizumab, which binds to the A1 domain of vWF, prevents the adhesion of platelets to vWF. It is a first in-class 'nanobody', that in clinical trials has shown marked efficacy in treating TTP and its complications. This review will discuss the development and implications of caplacizumab in the treatment of TTP.
Language	English
Publishing date	2020-02-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2585183-4
ISSN	2040-6215 ; 2040-6207
ISSN (online)	2040-6215
ISSN	2040-6207
DOI	10.1177/2040620720902904
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Article ; Online: rVWF: treatment finally reaches the modern age.

Metjian, Ara D

Blood

2015 Volume 126, Issue 17, Page(s) 1975–1976

Abstract: In this issue of Blood, Gill et al describe the results of the first phase 3 clinical trial evaluating recombinant von Willebrand factor (rVWF) for the treatment of hemorrhagic events in all patients with von Willebrand disease (VWD). ...

Abstract	In this issue of Blood, Gill et al describe the results of the first phase 3 clinical trial evaluating recombinant von Willebrand factor (rVWF) for the treatment of hemorrhagic events in all patients with von Willebrand disease (VWD).
MeSH term(s)	Female ; Hemostatics ; Humans ; Male ; Recombinant Proteins/pharmacokinetics ; von Willebrand Diseases/drug therapy ; von Willebrand Factor/pharmacokinetics
Chemical Substances	Hemostatics ; Recombinant Proteins ; von Willebrand Factor
Language	English
Publishing date	2015-10-22
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2015-08-664052
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Article ; Online: A rare CALR variant mutation and a review of CALR in essential thrombocythemia.

Diep, Robert / Metjian, Ara

Journal of thrombosis and thrombolysis

2018 Volume 45, Issue 3, Page(s) 457–462

Abstract: Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm characterized by megakaryocyte hyperplasia, thrombocytosis, thrombotic and hemorrhagic complications, and potential transformation into myelofibrosis and acute myeloid leukemia. ... ...

Abstract	Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm characterized by megakaryocyte hyperplasia, thrombocytosis, thrombotic and hemorrhagic complications, and potential transformation into myelofibrosis and acute myeloid leukemia. The vast majority of cases are driven by a somatic mutation in JAK2, CALR, or MPL. CALR, a gene that codes for the calcium-binding chaperone calreticulin, is the predominant mutation in patients with non-mutated JAK2 essential thrombocythemia, accounting for 20-25% of the overall somatic mutation frequency in ET. In this brief review of ET, we introduce a rare CALR mutation through a case presentation of a 58-year-old man with diffuse pulmonary emboli in the setting of thrombocytosis. We subsequently characterize the main types of CALR mutations and their value in diagnosis and prognosis of disease course, and lastly discuss the current clinical approach to ET.
MeSH term(s)	Calreticulin/genetics ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Pulmonary Embolism ; Thrombocythemia, Essential/diagnosis ; Thrombocythemia, Essential/genetics
Chemical Substances	CALR protein, human ; Calreticulin
Language	English
Publishing date	2018-01-13
Publishing country	Netherlands
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-018-1619-0
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Zs.A 4352: Show issues

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Article ; Online: C5 inhibition allows continued antineoplastic therapy in cancer- and chemotherapy-associated thrombotic microangiopathy.

Shah, Hridaya / Chen, Hang / Pan, Xiang-Zuo / Metjian, Ara / Brodsky, Robert A / Braunstein, Evan M / Chaturvedi, Shruti

Blood advances

2022 Volume 6, Issue 23, Page(s) 6071–6074

MeSH term(s)	Humans ; Thrombotic Microangiopathies/chemically induced ; Antineoplastic Agents/adverse effects ; Neoplasms/complications ; Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-05-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008395
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Zs.A 7153: Show issues

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Article ; Online: Real-world safety and effectiveness of recombinant porcine sequence factor VIII in acquired haemophilia A: A non-interventional, post-authorization safety study.

Tarantino, Michael D / Hardesty, Brandon / Metjian, Ara / Ortel, Thomas L / Chen, Jie / Badejo, Kayode / Ma, Alice / Cuker, Adam / Rajasekhar, Anita / Friedman, Kenneth D / Janbain, Maissaa

Haemophilia : the official journal of the World Federation of Hemophilia

2023 Volume 29, Issue 5, Page(s) 1259–1268

Abstract: Introduction: Recombinant porcine factor VIII (rpFVIII, susoctocog alfa) is indicated for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA).: Aim: To provide long-term real-world safety and effectiveness data for rpFVIII ... ...

Abstract	Introduction: Recombinant porcine factor VIII (rpFVIII, susoctocog alfa) is indicated for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). Aim: To provide long-term real-world safety and effectiveness data for rpFVIII in the management of AHA bleeding episodes. Methods: US PASS (NCT02610127) was a multicentre, uncontrolled, open-label, post-marketing safety surveillance study conducted in adults with AHA. Data were collected retrospectively or prospectively for 180 days after rpFVIII treatment. The primary outcome was the incidence of treatment-related serious adverse events (SAEs). Secondary outcomes included haemostatic effectiveness of rpFVIII and rpFVIII utilization. Results: Fifty-three patients were enrolled from December 2015 to June 2019 (prospective, n = 30; retrospective, n = 23). Six patients experienced seven treatment-related SAEs (incidence 12.0%). The most common treatment-related SAE was FVIII inhibition (inhibiting antibodies to rpFVIII; incidence 8.0%, 95% CI: 2.2-19.2). Five patients reported seven thromboembolic events; one was an SAE and possibly related to rpFVIII. Of bleeding events treated with rpFVIII, 80.3% (57/71) of bleeds resolved with rpFVIII. The median (range) dose of rpFVIII per infusion was 50 (10-300) units/kg, with a median (range) of 6.0 (1-140) infusions and a median (range) time from bleed onset to bleed resolution of 14.0 (2.0-132.7) days. Conclusion: In this real-world study of rpFVIII for AHA, no new safety signals were identified compared with previous clinical trial findings. Eighty percent of bleeds resolved with rpFVIII treatment.
MeSH term(s)	Swine ; Animals ; Factor VIII/adverse effects ; Hemophilia A/complications ; Retrospective Studies ; Prospective Studies ; Hemorrhage/drug therapy ; Hemorrhage/etiology ; Recombinant Proteins/adverse effects ; Treatment Outcome
Chemical Substances	Factor VIII (9001-27-8) ; Recombinant Proteins
Language	English
Publishing date	2023-08-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14832
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Zs.A 4249: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Novel therapeutic approaches for thrombotic thrombocytopenic purpura.

Tanhehco, Yvette C / Arepally, Gowthami / Metjian, Ara

Current opinion in hematology

2017 Volume 24, Issue 6, Page(s) 521–528

Abstract: Purpose of review: Acquired thrombotic thrombocytopenic purpura is an immune-mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13). Standard treatment ... ...

Abstract	Purpose of review: Acquired thrombotic thrombocytopenic purpura is an immune-mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13). Standard treatment with therapeutic plasma exchange and immunosuppression with steroids results in high remission and low mortality rates. However, a number of patients remain refractory to frontline therapy and/or experience multiple relapses. This study reviews emerging therapies for thrombotic thrombocytopenic purpura. Recent findings: Studies indicate that reducing anti-ADAMTS13 antibody levels through B-cell depletion or proteasome inhibition is effective for the management of refractory disease. Preliminary reports examining anti-CD20 therapy for the treatment of initial disease or as maintenance therapy for seropositive patients suggest the addition of immunosuppression in other disease phases may delay relapse. Exciting developments in targeted therapies to von Willebrand Factor and recombinant ADAMTS13 hold promise for transforming disease management. Summary: Approximately half of patients diagnosed with acquired thrombotic thrombocytopenic purpura experience refractory and/or relapsing disease. For these patients, a hematologic remission may be an insufficient therapeutic goal. With recent developments, it is now possible to envision a multifaceted approach targeting disease mechanisms that may dramatically improve outcomes for this otherwise debilitating disease.
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000375
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Zs.A 3703: Show issues

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Article ; Online: Safety and tolerability of solvent/detergent-treated plasma for pediatric patients requiring therapeutic plasma exchange: An open-label, multicenter, postmarketing study.

Josephson, Cassandra D / Goldstein, Stuart / Askenazi, David / Cohn, Claudia S / Spinella, Philip C / Metjian, Ara / Fasano, Ross M / Music-Aplenc, Lejla

Transfusion

2021 Volume 62, Issue 2, Page(s) 396–405

Abstract: Background: This study investigated the real-world safety and tolerability of solvent/detergent-treated (S/D) plasma for pediatric patients requiring therapeutic plasma exchange (TPE).: Study design and methods: LAS-213 was a multicenter, open-label, ...

Abstract	Background: This study investigated the real-world safety and tolerability of solvent/detergent-treated (S/D) plasma for pediatric patients requiring therapeutic plasma exchange (TPE). Study design and methods: LAS-213 was a multicenter, open-label, interventional, phase 4 study. Patients (≥2 to ≤20 years) receiving TPE therapy were eligible. A total plasma volume of 40-60 ml/kg was recommended, with an infusion rate not exceeding 0.020-0.025 citrate/kg body weight/min (<1 ml/kg body weight/min). The primary endpoint was assessment of safety, monitoring the following: serious adverse events (SAEs), adverse drug reactions (ADRs), thrombotic events (TEs), thromboembolic events (TEEs), and specific laboratory tests. Results: In total, 41 children (2 to <12 years [n = 15]; 12 to <17 years [n = 13]; ≥17 years [n = 13]) underwent 102 TPEs with a total of 135,137 ml of S/D plasma exchanged. Each patient group received between 1 and 6 TPEs (mean: 2.5 TPEs). Actual dose administered per TPE was 4-72 ml/kg (mean: 28.6 ml/kg), with a mean total volume of 1324.9 ml (range: 113-4000 ml). Overall safety was excellent for 96/102 (94.0%) TPEs. Six TPEs had a "moderate" safety profile for four patients experiencing eight ADRs. Of these, seven were mild in intensity and one (pyrexia) was moderate, all resolving by study end. Mild citrate toxicity (n = 2) was the most common ADR. One SAE was reported but was unrelated to the study drug. No TEs, TEEs, or changes in laboratory safety parameters were reported. Conclusion: S/D plasma was well tolerated and demonstrated favorable safety, supporting the use of S/D plasma for TPE in pediatrics.
MeSH term(s)	Body Weight ; Child ; Citric Acid ; Detergents ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Pediatrics ; Plasma Exchange/adverse effects ; Solvents
Chemical Substances	Detergents ; Solvents ; Citric Acid (2968PHW8QP)
Language	English
Publishing date	2021-12-20
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16775
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Article ; Online: A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura.

Abou-Ismail, Mouhamed Yazan / Zhang, Chong / Presson, Angela P / Chaturvedi, Shruti / Antun, Ana G / Farland, Andrew M / Woods, Ryan / Metjian, Ara / Park, Yara A / de Ridder, Gustaaf / Gibson, Briana / Kasthuri, Raj S / Liles, Darla K / Akwaa, Frank / Clover, Todd / Kreuziger, Lisa Baumann / Sridharan, Meera / Go, Ronald S / McCrae, Keith R /

Upreti, Harsh Vardhan / Gangaraju, Radhika / Kocher, Nicole K / Zheng, X Long / Raval, Jay S / Masias, Camila / Cataland, Spero R / Johnson, Andrew D / Davis, Elizabeth / Evans, Michael D / Mazepa, Marshall / Lim, Ming Y

Research and practice in thrombosis and haemostasis

2024 Volume 8, Issue 3, Page(s) 102388

Abstract: Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been ...

Abstract	Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort ( Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1016/j.rpth.2024.102388
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Article: Waldenström macroglobulinemia in hepatitis C: case report and review of the current literature.

Nipp, Ryan / Mitchell, Aaron / Pishko, Allyson / Metjian, Ara

Case reports in oncological medicine

2014 Volume 2014, Page(s) 165670

Abstract: Background. Recent literature has associated hepatitis C virus with the development of non-Hodgkin lymphoma. Hepatitis C virus infection appears to promote lymphoproliferation, providing a plausible mechanism for a causative association; however, despite ...

Abstract	Background. Recent literature has associated hepatitis C virus with the development of non-Hodgkin lymphoma. Hepatitis C virus infection appears to promote lymphoproliferation, providing a plausible mechanism for a causative association; however, despite prior reports of patients with comorbid hepatitis C infection and Waldenström macroglobulinemia, the literature is in disagreement regarding whether there exists an association between these two conditions. Case Presentation. This case report describes a 57-year-old African-American male with chronic hepatitis C infection and cryoglobulinemia who presented with several episodes of transient confusion and paralysis and was found to have symptomatic hyperviscosity. The recognition of his condition was facilitated by characteristic findings on ophthalmologic examination. He was subsequently diagnosed with Waldenström macroglobulinemia on bone marrow biopsy. Conclusions. An up to date, comprehensive review of the literature suggests an association between hepatitis C and Waldenström macroglobulinemia. Data on optimal treatment of patients with comorbid hepatitis C infection and Waldenström macroglobulinemia is limited. We have provided a comprehensive review of previously explored treatment options to guide management of other similar patients. Our patient has since been treated with repeated plasmapheresis with a plan to pursue antiviral therapy.
Language	English
Publishing date	2014-08-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2629911-2
ISSN	2090-6714 ; 2090-6706
ISSN (online)	2090-6714
ISSN	2090-6706
DOI	10.1155/2014/165670
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