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Article ; Online: Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis.

Dimopoulos, Meletios A / Niesvizky, Ruben / Weisel, Katja / Siegel, David S / Hajek, Roman / Mateos, María-Victoria / Cavo, Michele / Huang, Mei / Zahlten-Kumeli, Anita / Moreau, Philippe

Blood cancer journal

2020 Volume 10, Issue 3, Page(s) 35

Abstract: The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m ...

Abstract	The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m
MeSH term(s)	Aged ; Aged, 80 and over ; Disease Progression ; Female ; Humans ; Male ; Multiple Myeloma/drug therapy ; Multiple Myeloma/mortality ; Oligopeptides/pharmacology ; Oligopeptides/therapeutic use ; Progression-Free Survival
Chemical Substances	Oligopeptides ; carfilzomib (72X6E3J5AR)
Language	English
Publishing date	2020-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-020-0300-y
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Article ; Online: Improving clots in trauma.

Weisel, John W

Blood

2023 Volume 142, Issue 8, Page(s) 684–686

MeSH term(s)	Fibrinogen ; Hemostatics
Chemical Substances	Fibrinogen (9001-32-5) ; Hemostatics
Language	English
Publishing date	2023-03-23
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.2023021282
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Zs.MO 364: Show issues

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Article ; Online: Chorography of blood proteins.

Weisel, John W

Journal of thrombosis and haemostasis : JTH

2023 Volume 21, Issue 6, Page(s) 1423–1425

MeSH term(s)	Humans ; Blood Proteins
Chemical Substances	Blood Proteins
Language	English
Publishing date	2023-05-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.02.009
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Zs.A 5805: 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: Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.

Moreau, Philippe / Mateos, Maria-Victoria / Berenson, James R / Weisel, Katja / Lazzaro, Antonio / Song, Kevin / Dimopoulos, Meletios A / Huang, Mei / Zahlten-Kumeli, Anita / Stewart, A Keith

The Lancet. Oncology

2018 Volume 19, Issue 7, Page(s) 953–964

Abstract: ... of the randomised, open-label, phase 3 A.R.R.O.W. trial, we recruited patients (aged 18 years and older ...

Abstract	Background: Twice a week carfilzomib at 27 mg/m Methods: In this prespecified interim analysis of the randomised, open-label, phase 3 A.R.R.O.W. trial, we recruited patients (aged 18 years and older) with relapsed and refractory multiple myeloma previously treated with two or three treatments, including a proteasome inhibitor and immunomodulatory agent, from hospital, clinic, oncology or medical centres. Key eligibility criteria were refractory to most recent therapy (including bortezomib or ixazomib) with measurable disease, and Eastern Cooperative Oncology Group Performance Status of 0 or 1. Patients were randomly assigned (1:1) to receive carfilzomib once a week (70 mg/m Findings: Between September, 2015, and August, 2016, 578 patients were recruited from 118 sites. 478 patients were randomly assigned and included in the efficacy analyses (240 to receive once weekly carfilzomib; 238 to receive twice weekly carfilzomib). Median progression-free survival was higher in the once weekly group than the twice weekly group (11·2 months [95% CI 8·6-13·0] vs 7·6 months [5·8-9·2]; hazard ratio [HR] 0·69, 95% CI 0·54-0·83; p=0·0029). The incidence of grade 3 or worse adverse events was higher in the once weekly group than the twice weekly group (68% [n=161] vs 62% [n=145]); the most common events were anaemia, pneumonia, and thrombocytopenia (42 [18%] vs 42 [18%], 24 [10%] vs 16 [7%], and 17 [7%] vs 16 [7%], respectively for once weekly carfilzomib vs twice weekly carfilzomib). A lower proportion of patients had grade 3 or worse cardiac failure in the once weekly group (7 [3%]) than in the twice weekly group (10 [4%]). Treatment-related deaths occurred in five (2%) of 238 patients in the once weekly group (sepsis [n=1], death [n=1], acute lung injury [n=1], acute respiratory distress syndrome [n=1], and tumour lysis syndrome [n=1]) and in two (1%) of 235 patients in the twice weekly group (plasma cell myeloma [n=1] and congestive heart failure [n=1]). There were 58 deaths in the once weekly group and 68 deaths in the twice weekly group at the time of data cutoff. Interpretation: Once weekly carfilzomib at 70 mg/m Funding: Amgen, Inc.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Dexamethasone/therapeutic use ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Humans ; Infusions, Intravenous ; Lenalidomide/therapeutic use ; Male ; Multiple Myeloma/drug therapy ; Multiple Myeloma/mortality ; Multiple Myeloma/pathology ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Oligopeptides/therapeutic use ; Prognosis ; Proteasome Inhibitors/therapeutic use ; Recurrence ; Risk Assessment ; Survival Analysis ; Treatment Outcome
Chemical Substances	Oligopeptides ; Proteasome Inhibitors ; carfilzomib (72X6E3J5AR) ; Dexamethasone (7S5I7G3JQL) ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2018-06-01
Publishing country	England
Document type	Clinical Trial, Phase III ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(18)30354-1
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Zs.A 5696: 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)
Zs.MO 460: Show issues

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Article ; Online: Role of red blood cells in clinically relevant bleeding tendencies and complications.

Lassila, Riitta / Weisel, John W

Journal of thrombosis and haemostasis : JTH

2023 Volume 21, Issue 11, Page(s) 3024–3032

Abstract: The multiple roles of red blood cells (RBCs) are often neglected as contributors in hemostasis and thrombosis. Proactive opportunities to increase RBC numbers, either acutely or subacutely in the case of iron deficiency, are critical as RBCs are the ... ...

Abstract	The multiple roles of red blood cells (RBCs) are often neglected as contributors in hemostasis and thrombosis. Proactive opportunities to increase RBC numbers, either acutely or subacutely in the case of iron deficiency, are critical as RBCs are the cellular elements that initiate hemostasis together with platelets and stabilize fibrin and clot structure. RBCs also possess several functional properties to assist hemostasis: releasing platelet agonists, promoting shear force-induced von Willebrand factor unfolding, procoagulant capacity, and binding to fibrin. Additionally, blood clot contraction is important to compress RBCs to form a tightly packed array of polyhedrocytes, making an impermeable seal for hemostasis. All these functions are important for patients having intrinsically poor capacity to cease bleeds (ie, hemostatic disorders) but, conversely, can also play a role in thrombosis if these RBC-mediated reactions overshoot. One acquired example of bleeding with anemia is in patients treated with anticoagulants and/or antithrombotic medication because upon initiation of these drugs, baseline anemia doubles the risk of bleeding complications and mortality. Also, anemia is a risk factor for reoccurring gastrointestinal and urogenital bleeds, pregnancy, and delivery complications. This review summarizes the clinically relevant properties and profiles of RBCs at various steps of platelet adhesion, aggregation, thrombin generation, and fibrin formation, including both structural and functional elements. Regarding patient blood management guidelines, they support minimizing transfusions, but this approach does not deal with severe inherited and acquired bleeding disorders where a poor hemostatic propensity is exacerbated by limited RBC availability, for which future guidance will be needed.
MeSH term(s)	Humans ; Hemostasis ; Erythrocytes/metabolism ; Hemorrhage/complications ; Blood Platelets/metabolism ; Anemia ; Thrombosis ; Fibrin/metabolism
Chemical Substances	Fibrin (9001-31-4)
Language	English
Publishing date	2023-05-18
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.05.009
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Zs.A 5805: 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: Unresolved hemostasis issues in haemophilia.

Sidonio, Robert F / Weisel, John W / Stafford, Darrel

Haemophilia : the official journal of the World Federation of Hemophilia

2024 Volume 30 Suppl 3, Page(s) 70–77

Abstract: Despite rapid technological advancement in factor and nonfactor products in the prevention and treatment of bleeding in haemophilia patients, it is imperative that we acknowledge gaps in our understanding of how hemostasis is achieved. The authors will ... ...

Abstract	Despite rapid technological advancement in factor and nonfactor products in the prevention and treatment of bleeding in haemophilia patients, it is imperative that we acknowledge gaps in our understanding of how hemostasis is achieved. The authors will briefly review three unresolved issues in persons with haemophilia (PwH) focusing on the forgotten function that red blood cells play in hemostasis, the critical role of extravascular (outside circulation) FIX in hemostasis in the context of unmodified and extended half-life FIX products and finally on the role that skeletal muscle myosin plays in prothrombinase assembly and subsequent thrombin generation that could mitigate breakthrough muscle hematomas.
MeSH term(s)	Humans ; Hemophilia A/therapy ; Hemostasis ; Thrombin ; Hemorrhage ; Thromboplastin ; Factor VIII
Chemical Substances	Thrombin (EC 3.4.21.5) ; Thromboplastin (9035-58-9) ; Factor VIII (9001-27-8)
Language	English
Publishing date	2024-04-04
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.14999
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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)
Zs.MO 450: Show issues

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Article ; Online: A novel technique to quantify the kinetics of blood clot contraction based on the expulsion of fluorescently labeled albumin into serum.

Peshkova, Alina D / Weisel, John W / Litvinov, Rustem I

Journal of thrombosis and haemostasis : JTH

2024

Abstract: Background: The platelet-driven contraction or retraction of blood clots has been utilized to obtain blood serum for laboratory studies, but now, in vitro clot contraction assays are used in research laboratories and clinics to assess platelet ... ...

Abstract	Background: The platelet-driven contraction or retraction of blood clots has been utilized to obtain blood serum for laboratory studies, but now, in vitro clot contraction assays are used in research laboratories and clinics to assess platelet functionality. The static final extent of clot contraction measured using a clot size or expelled serum volume can be supplemented substantially with a dynamic analysis. Objectives: To provide a step-by-step protocol for a relatively simple and affordable new automated methodology to follow the kinetics of blood clot contraction, which allows for simultaneous measurements of various samples at a time and requires only a fluorescence plate reader. Methods: The kinetics of clot contraction in whole blood was assessed by continuously detecting the fluorescence intensity of fluorescein isothiocyanate-albumin added to a blood sample before clotting and expelled into the serum during clot shrinkage. Results: The clots are formed and fluorescence is measured in the wells of a black multiwell plate using a standard plate fluorescent reader. The specificity of this technique for clot contraction has been demonstrated by the strong inhibitory effects of blebbistatin, latrunculin A, and abciximab. To validate the new technique, increased fluorescence intensity in the contracting clots was measured in parallel with a visual decrease in clot size performed with the same blood samples. Conclusion: The resulting clot contraction dynamics based on the expulsion of fluorescein isothiocyanate-albumin can be quantified using a number of kinetic parameters as well as a phase kinetics analysis. The advantages and drawbacks of the new technique are discussed.
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2024.02.012
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Article ; Online: Blood clot contraction: Mechanisms, pathophysiology, and disease.

Litvinov, Rustem I / Weisel, John W

Research and practice in thrombosis and haemostasis

2022 Volume 7, Issue 1, Page(s) 100023

Abstract: A State of the Art lecture titled "Blood Clot Contraction: Mechanisms, Pathophysiology, and Disease" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. This was a systematic description of blood clot ... ...

Abstract	A State of the Art lecture titled "Blood Clot Contraction: Mechanisms, Pathophysiology, and Disease" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. This was a systematic description of blood clot contraction or retraction, driven by activated platelets and causing compaction of the fibrin network along with compression of the embedded erythrocytes. The consequences of clot contraction include redistribution of the fibrin-platelet meshwork toward the periphery of the clot and condensation of erythrocytes in the core, followed by their deformation from the biconcave shape into polyhedral cells (polyhedrocytes). These structural signatures of contraction have been found in
Language	English
Publishing date	2022-12-23
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1016/j.rpth.2022.100023
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Article ; Online: Visualizing thrombosis to improve thrombus resolution.

Weisel, John W / Litvinov, Rustem I

Research and practice in thrombosis and haemostasis

2021 Volume 5, Issue 1, Page(s) 38–50

Abstract: The severity, course, and outcomes of thrombosis are determined mainly by the size and location of the thrombus, but studying thrombus structure and composition has been an important but challenging task. The substantial progress in determination of ... ...

Abstract	The severity, course, and outcomes of thrombosis are determined mainly by the size and location of the thrombus, but studying thrombus structure and composition has been an important but challenging task. The substantial progress in determination of thrombus morphology has become possible due to new intravital imaging methodologies in combination with mechanical thrombectomy, which allows extraction of a fresh thrombus from a patient followed by microscopy. Thrombi have been found to contain various structural forms of fibrin along with platelet aggregates, leukocytes, and red blood cells, many of which acquire a polyhedral shape (polyhedrocytes) as a result of intravital platelet-driven contraction. The relative volume fractions of thrombus components and their structural forms vary substantially, depending on the clinical and pathogenic characteristics. This review summarizes recent research that describes quantitative and qualitative morphologic characteristics of arterial and venous thrombi that are relevant for the pathogenesis, prophylaxis, diagnosis, and treatment of thrombosis.
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1002/rth2.12469
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Article ; Online: The Story of the Fibrin(ogen) αC-Domains: Evolution of Our View on Their Structure and Interactions.

Medved, Leonid / Weisel, John W

Thrombosis and haemostasis

2021 Volume 122, Issue 8, Page(s) 1265–1278

Abstract: Although much has been established concerning the overall structure and function of fibrinogen, much less has been known about its two αC regions, each consisting of an αC-connector and an αC-domain, but new information has been accumulating. This review ...

Abstract	Although much has been established concerning the overall structure and function of fibrinogen, much less has been known about its two αC regions, each consisting of an αC-connector and an αC-domain, but new information has been accumulating. This review summarizes the state of our current knowledge of the structure and interactions of fibrinogen's αC regions. A series of studies with isolated αC regions and their fragments demonstrated that the αC-domain forms compact ordered structures consisting of N- and C-terminal subdomains including β sheets and suggested that the αC-connector has a poly(L-proline) type II structure. Functionally, the αC-domains interact intramolecularly with each other and with the central region of the molecule, first demonstrated by electron microscopy and then quantified by optical trap force spectroscopy. Upon conversion of fibrinogen into fibrin, the αC-domains switch from intra- to intermolecular interactions to form ordered αC polymers. The formation of αC polymers occurs mainly through the homophilic interaction between the N-terminal subdomains; interaction between the C-terminal subdomains and the αC-connectors also contributes to this process. Considerable evidence supports the idea that the αC-regions accelerate fibrin polymerization and affect the final structure of fibrin clots. The interactions between αC-regions are important for the mechanical properties of clots, increasing their stiffness and extensibility. Conversion of fibrinogen into fibrin results in exposure of multiple binding sites in its αC regions, providing interaction of fibrin with different proteins and cell types during hemostasis and wound healing. This heretofore mysterious part of the fibrinogen molecule is finally giving up its secrets.
MeSH term(s)	Estrone/analogs & derivatives ; Fibrin/metabolism ; Fibrinogen/metabolism ; Humans ; Peptide Fragments/metabolism ; Polymers ; Protein Structure, Tertiary ; Thrombosis
Chemical Substances	Peptide Fragments ; Polymers ; Estrone (2DI9HA706A) ; Fibrin (9001-31-4) ; Fibrinogen (9001-32-5) ; estropipate (SVI38UY019)
Language	English
Publishing date	2021-12-13
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/a-1719-5584
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Zs.MO 433: Show issues

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