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Article ; Online: Epidural Catheter Use and Further Issues in Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant.

Tomassini, Loredana / Della Valle, Patrizia / D'Angelo, Armando

2020 Volume 180, Issue 2, Page(s) 332–333

MeSH term(s)	Anticoagulants ; Atrial Fibrillation ; Humans ; Warfarin
Chemical Substances	Anticoagulants ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2020-02-17
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2699338-7
ISSN	2168-6114 ; 2168-6106
ISSN (online)	2168-6114
ISSN	2168-6106
DOI	10.1001/jamainternmed.2019.5864
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Article ; Online: May restricted specificity of commercially available plasmin inhibitor activity assays affect correct diagnosis of antiplasmin deficiency?

Pozzi, Loris / Della Valle, Patrizia / D'Angelo, Armando

Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

2019 Volume 30, Issue 1, Page(s) 52–53

MeSH term(s)	Antifibrinolytic Agents/pharmacology ; Antifibrinolytic Agents/therapeutic use ; Hemorrhagic Disorders/diagnosis ; Hemorrhagic Disorders/drug therapy ; Hemorrhagic Disorders/pathology ; Humans ; alpha-2-Antiplasmin/deficiency
Chemical Substances	Antifibrinolytic Agents ; alpha-2-Antiplasmin
Language	English
Publishing date	2019-01-23
Publishing country	England
Document type	Letter
ZDB-ID	1033551-1
ISSN	1473-5733 ; 0957-5235
ISSN (online)	1473-5733
ISSN	0957-5235
DOI	10.1097/MBC.0000000000000788
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Zs.A 2920: Show issues

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Article ; Online: The development of various forms of lung injury with increasing tidal volume in normal rats.

D'Angelo, Edgardo / Koutsoukou, Antonia / Della Valle, Patrizia / Gentile, Guendalina / Pecchiari, Matteo

Respiratory physiology & neurobiology

2020 Volume 274, Page(s) 103369

Abstract: Sixty-three, open-chest normal rats were subjected to mechanical ventilation (MV) with tidal volumes ( ... ...

Abstract	Sixty-three, open-chest normal rats were subjected to mechanical ventilation (MV) with tidal volumes (V
MeSH term(s)	Animals ; Bronchoalveolar Lavage Fluid ; Cytokines/blood ; Disease Models, Animal ; Lung Injury/blood ; Lung Injury/etiology ; Lung Injury/pathology ; Lung Injury/physiopathology ; Male ; Pulmonary Edema/blood ; Pulmonary Edema/etiology ; Pulmonary Edema/pathology ; Pulmonary Edema/physiopathology ; Rats ; Rats, Sprague-Dawley ; Respiration, Artificial/adverse effects ; Respiratory Mechanics/physiology ; Tidal Volume/physiology ; von Willebrand Factor
Chemical Substances	Cytokines ; von Willebrand Factor
Language	English
Publishing date	2020-01-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2020.103369
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Zs.A 519: Show issues

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Article ; Online: Whole-Exome Sequencing in a Family with an Unexplained Tendency for Venous Thromboembolism: Multicomponent Prediction of Low-Frequency Variant Deleteriousness and of Individual Protein Interaction.

Lunghi, Barbara / Ziliotto, Nicole / Balestra, Dario / Rossi, Lucrezia / Della Valle, Patrizia / Pignatelli, Pasquale / Pinotti, Mirko / D'Angelo, Armando / Marchetti, Giovanna / Bernardi, Francesco

International journal of molecular sciences

2023 Volume 24, Issue 18

Abstract: Whole-exome sequencing (WES) in families with an unexplained tendency for venous thromboembolism (VTE) may favor detection of low-frequency variants in genes with known contribution to hemostasis or associated with VTE-related phenotypes. WES analysis in ...

Abstract	Whole-exome sequencing (WES) in families with an unexplained tendency for venous thromboembolism (VTE) may favor detection of low-frequency variants in genes with known contribution to hemostasis or associated with VTE-related phenotypes. WES analysis in six family members, three of whom affected by documented VTE, filtered for MAF < 0.04 in 192 candidate genes, revealed 22 heterozygous (16 missense and six synonymous) variants in patients. Functional prediction by multi-component bioinformatics tools, implemented by a database/literature search, including ClinVar annotation and QTL analysis, prioritized 12 missense variants, three of which (
MeSH term(s)	Humans ; Venous Thromboembolism/genetics ; Exome Sequencing ; von Willebrand Factor/genetics ; Genes, Regulator ; Computational Biology
Chemical Substances	von Willebrand Factor
Language	English
Publishing date	2023-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241813809
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Article ; Online: Platelet activation state in early stages of COVID-19.

Consolo, Filippo / Della Valle, Patrizia / Saracino, Marco / Bonora, Marta / Donadoni, Giovanni / Ciceri, Fabio / Tresoldi, Moreno / D'Angelo, Armando / Landoni, Giovanni / Zangrillo, Alberto

Minerva anestesiologica

2022 Volume 88, Issue 6, Page(s) 472–478

Abstract: Background: Platelet activation at the early stage of COVID-19 is poorly described. The need for antiplatelet therapy in patients with COVID-19 remains controversial. We characterized the platelet activation profile in hospitalized patients at the early ...

Abstract	Background: Platelet activation at the early stage of COVID-19 is poorly described. The need for antiplatelet therapy in patients with COVID-19 remains controversial. We characterized the platelet activation profile in hospitalized patients at the early stage of COVID-19 using the modified prothrombinase Platelet Activation State (PAS) Assay. Methods: Sixteen patients admitted to the emergency department of the IRCCS San Raffaele Hospital (Milan, Italy) between February 8 and April 2021 were enrolled. All patients presented with respiratory symptoms and tested positive for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Platelet activation was measured via the PAS Assay within 24 hours from patients' hospital admission. Data were compared with those measured in N.=24 healthy subjects (controls). Results: Platelet activation was significantly higher in COVID-19 patients with respect to controls (PAS=0.63 [0.58-0.98%] vs. 0.46 [0.40-0.65%], respectively; P=0.03). Of note, highest PAS values were measured in the two patients with the worst clinical outcome, i.e., death because of respiratory failure (PAS=2.09% and 1.20%, respectively). No differences in standard coagulation parameters were noted between these two patients and those who were later discharged home. Conclusions: This study provides evidence of significant platelet activation state at the early stage of COVID-19 and suggests that the patient-specific platelet activation profile is a reliable clinical marker to stratify COVID-19 patients at high risk of poor clinical outcome who might potentially benefit from antiplatelet therapy.
MeSH term(s)	COVID-19 ; Hospitalization ; Humans ; Platelet Activation ; Platelet Aggregation Inhibitors/therapeutic use ; SARS-CoV-2
Chemical Substances	Platelet Aggregation Inhibitors
Language	English
Publishing date	2022-03-22
Publishing country	Italy
Document type	Journal Article
ZDB-ID	123584-9
ISSN	1827-1596 ; 0026-4717 ; 0375-9393
ISSN (online)	1827-1596
ISSN	0026-4717 ; 0375-9393
DOI	10.23736/S0375-9393.22.16054-2
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Zs.A 516: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Bleeding in patients with continuous-flow left ventricular assist devices: acquired von Willebrand disease or antithrombotics?

Consolo, Filippo / Marasi, Alessandra / Della Valle, Patrizia / Bonora, Marta / Pieri, Marina / Scandroglio, Anna Mara / Redaelli, Alberto / Zangrillo, Alberto / D'Angelo, Armando / Pappalardo, Federico

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2021 Volume 62, Issue 1

Abstract: Objectives: To evaluate the competing pro-haemorrhagic contribution of acquired von Willebrand (vW) disease and antithrombotic therapy in patients implanted with continuous-flow left ventricular assist devices (LVADs).: Methods: We compared the ... ...

Abstract	Objectives: To evaluate the competing pro-haemorrhagic contribution of acquired von Willebrand (vW) disease and antithrombotic therapy in patients implanted with continuous-flow left ventricular assist devices (LVADs). Methods: We compared the extent of vW factor (vWf) degradation [vWf antigen (vWf:Ag)] and a decrease of functional activity of large vWf multimers [vWf collagen binding (vWf:CB)] in LVAD patients who did and did not suffer from bleeding. Data were measured pre-implant, at short-term (t1: <3 months) and long-term (t2: >12 months) follow-up. The occurrence of primary bleeding events, as well as bleeding recurrence, was correlated with patient-specific vWf profile and antithrombotic regimen. Indeed, patients were discharged on warfarin (international normalized ratio: 2-2.5) and aspirin, with the latter withhold after a first bleeding episode. Results: Fifty-three patients were enrolled. The median follow-up was 324 (226-468) days. We recorded 25 primary bleeding events (47% of patients). All primary events occurred in patients on warfarin and aspirin. Both vWf:Ag and vWf:CB decreased significantly post-implant (P = 0.0003 and P < 0.0001), and patients showing pathological vWf:CB/vWf:Ag ratio (<0.7) increased progressively over the time of support (pre-implant = 26%, t1 = 58%, t2 = 74%; P < 0.0001). Of note, activity of large vWf multimers of bleeders was significantly lower at t2 with respect to non-bleeders (vWf:CB: 61 (36-115) vs 100 (68-121), P = 0.04; vWf:CB/vWf:Ag ratio: 0.36 (0.26-0.61) vs 0.58 (0.33-0.96), P = 0.04). Despite these marked differences in the vWf profile, following aspirin discontinuation only 3 patients had bleeding recurrence. Conclusions: Aspirin contributes significantly to haemorrhagic events in the background of acquired vW disease; its discontinuation significantly reduces bleeding recurrence. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03255928; ClinicalTrials.gov Identifier: NCT03255928.
MeSH term(s)	Aspirin/adverse effects ; Fibrinolytic Agents/adverse effects ; Heart-Assist Devices/adverse effects ; Hemorrhage/chemically induced ; Hemorrhage/epidemiology ; Hemorrhage/prevention & control ; Humans ; Warfarin/adverse effects ; von Willebrand Diseases/etiology ; von Willebrand Factor/metabolism
Chemical Substances	Fibrinolytic Agents ; von Willebrand Factor ; Warfarin (5Q7ZVV76EI) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2021-11-18
Publishing country	Germany
Document type	Clinical Study ; Journal Article
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezab474
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Zs.A 2303: Show issues

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Article ; Online: Influence of Different Antithrombotic Regimens on Platelet-Mediated Thrombin Generation in Patients with Left Ventricular Assist Devices.

Consolo, Filippo / Pozzi, Loris / Pieri, Marina / Della Valle, Patrizia / Redaelli, Alberto / D'Angelo, Armando / Pappalardo, Federico

ASAIO journal (American Society for Artificial Internal Organs : 1992)

2019 Volume 66, Issue 4, Page(s) 415–422

Abstract: We characterized the biologic background of prothrombotic platelet function in the setting of durable left ventricular assist devices (LVADs) evaluating the role of different antithrombotic regimens. Platelet-mediated thrombin generation was quantified ... ...

Abstract	We characterized the biologic background of prothrombotic platelet function in the setting of durable left ventricular assist devices (LVADs) evaluating the role of different antithrombotic regimens. Platelet-mediated thrombin generation was quantified using the Platelet Activity State (PAS) Assay and the Thrombin Generation Test (TGT) in 78 patients implanted with the HeartMate II (n = 10, 13%), the HeartMate 3 (HM3) (n = 30, 38%), or the HVAD (n = 38, 49%) and managed with oral anticoagulation plus aspirin (n = 46, 59%) or anticoagulation alone (n = 32, 41%). Coagulation parameters (platelet count, International Normalized Ratio (INR), activated Partial Thromboplastin Time, Fibrinogen and D-Dimer levels) and hemolysis (lactate dehydrogenase levels [LDH]) were also recorded to comprehensively characterize the hemostatic profile in the two groups. In patients without aspirin, the PAS assay revealed low-intensity increase in platelet prothrombinase activity (1.11-fold, p = 0.03). Similarly the TGT revealed moderate higher platelet reactivity when compared with patients receiving aspirin, consistent with reduction in lag time (0.87-fold, p < 0.001), increase in peak of thrombin generation (1.5-fold, p = 0.002) and thrombin generation rate (2-fold, p = 0.02), but comparable endogenous thrombin potential (p = 0.50). Coagulation parameters and LDH were comparable in the two groups (p > 0.05). Moreover, no differences were noted in platelet prothrombinase activity of patients implanted with the HM3 or HVAD. Our results suggest that, in the setting of durable LVADs, aspirin minimally modulates the biochemical pathway of platelet-mediated thrombin generation. Accordingly, re-evaluation of current antithrombotic management criteria in patients stratified according to bleeding/thromboembolic risk might be safe and beneficial to prevent adverse events.
MeSH term(s)	Aged ; Blood Coagulation/drug effects ; Blood Platelets/physiology ; Female ; Fibrin Fibrinogen Degradation Products ; Fibrinolytic Agents/therapeutic use ; Heart-Assist Devices/adverse effects ; Humans ; Male ; Middle Aged ; Thrombin/biosynthesis
Chemical Substances	Fibrin Fibrinogen Degradation Products ; Fibrinolytic Agents ; fibrin fragment D ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2019-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	759982-1
ISSN	1538-943X ; 0162-1432 ; 1058-2916
ISSN (online)	1538-943X
ISSN	0162-1432 ; 1058-2916
DOI	10.1097/MAT.0000000000001064
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Uk I Zs.199: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.B 2435: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology.

Gullotta, Giorgia Serena / De Feo, Donatella / Friebel, Ekaterina / Semerano, Aurora / Scotti, Giulia Maria / Bergamaschi, Andrea / Butti, Erica / Brambilla, Elena / Genchi, Angela / Capotondo, Alessia / Gallizioli, Mattia / Coviello, Simona / Piccoli, Marco / Vigo, Tiziana / Della Valle, Patrizia / Ronchi, Paola / Comi, Giancarlo / D'Angelo, Armando / Maugeri, Norma /

Roveri, Luisa / Uccelli, Antonio / Becher, Burkhard / Martino, Gianvito / Bacigaluppi, Marco

Nature immunology

2023 Volume 24, Issue 6, Page(s) 925–940

Abstract: Aging accounts for increased risk and dismal outcome of ischemic stroke. Here, we investigated the impact of age-related changes in the immune system on stroke. Upon experimental stroke, compared with young mice, aged mice had increased neutrophil ... ...

Abstract	Aging accounts for increased risk and dismal outcome of ischemic stroke. Here, we investigated the impact of age-related changes in the immune system on stroke. Upon experimental stroke, compared with young mice, aged mice had increased neutrophil clogging of the ischemic brain microcirculation, leading to worse no-reflow and outcomes. Aged mice showed an enhanced granulopoietic response to stroke that led to the accumulation of CD101
MeSH term(s)	Mice ; Animals ; Neutrophils ; Leukocytes ; Stroke/pathology ; Aging ; Ischemic Stroke/pathology
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01505-1
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Zs.A 5294: 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.MG 42: Show issues

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Article ; Online: Missense changes in the catalytic domain of coagulation factor X account for minimal function preventing a perinatal lethal condition.

Ferrarese, Mattia / Baroni, Marcello / Della Valle, Patrizia / Spiga, Ivana / Poloniato, Antonella / D'Angelo, Armando / Pinotti, Mirko / Bernardi, Francesco / Branchini, Alessio

Haemophilia : the official journal of the World Federation of Hemophilia

2019 Volume 25, Issue 4, Page(s) 685–692

Abstract: Introduction: Inherited deficiencies in the coagulation pathway provide diversified models to investigate the molecular bases of perinatal lethality associated with null-like variants. Differently from X-linked haemophilias, homozygous/doubly ... ...

Abstract	Introduction: Inherited deficiencies in the coagulation pathway provide diversified models to investigate the molecular bases of perinatal lethality associated with null-like variants. Differently from X-linked haemophilias, homozygous/doubly heterozygous null variants in the rare autosomally inherited deficiency of factor X (FX) might be incompatible with perinatal survival. Aim: To provide experimental evidence about the null/close-to-null FX function. Methods: The residual secreted (ELISA) and functional (thrombin generation assays) protein levels associated with the novel nonsense (c.1382G>A; p.Trp461Ter) and missense (c.752T>C; p.Leu251Pro) variants, found in the proposita with life-threatening symptoms at birth, were characterized through recombinant (r)FX expression. Results: The rFX-461Ter showed very low secretion and undetectable function. Expression and function of the predicted readthrough-deriving missense variants (rFX-461Tyr, rFX-461Gln) were also severely impaired. These unfavourable features, due to nucleotide and protein sequence constraints, precluded functional readthrough over the 461 stop codon. Differently, the poorly secreted rFX-251Pro variant displayed residual function that was characterized by anti-TFPI aptamer-based amplification or selective inhibition of activated FX function by fondaparinux in plasma and found to be reduced by approximately three orders of magnitude. Similarly to the rFX-251Pro, a group of catalytic domain missense variants cause poorly secreted molecules with modest function in FX-deficient patients with life-threatening symptoms. Conclusions: Our data, contributing to the knowledge of the very severe FX deficiency forms, support life-saving requirement of trace FX function, clearly exemplified by the dysfunctional but not completely inactive rFX-251Pro variant that, albeit with severely reduced function, is compatible with a residual activity ensuring minimal haemostasis and permitting perinatal survival.
MeSH term(s)	Amino Acid Sequence ; Catalytic Domain/genetics ; Factor X/chemistry ; Factor X/genetics ; Factor X/metabolism ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Infant, Newborn ; Intracranial Hemorrhages/genetics ; Intracranial Hemorrhages/metabolism ; Intracranial Hemorrhages/prevention & control ; Mutation, Missense ; Phenotype
Chemical Substances	Factor X (9001-29-0)
Language	English
Publishing date	2019-04-17
Publishing country	England
Document type	Case Reports ; 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.13761
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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: The protein C pathway and sepsis.

Della Valle, Patrizia / Pavani, Giulia / D'Angelo, Armando

Thrombosis research

2012 Volume 129, Issue 3, Page(s) 296–300

Abstract: After the discovery of the key components of the protein C (PC) pathway a beneficial effect on survival of the infusion of activated protein C (APC) in animal models of sepsis was demonstrated, leading to the development of recombinant human activated ... ...

Abstract	After the discovery of the key components of the protein C (PC) pathway a beneficial effect on survival of the infusion of activated protein C (APC) in animal models of sepsis was demonstrated, leading to the development of recombinant human activated protein C (rh-APC) as a therapeutic agent. It soon became clear that rather than the anticoagulant and profibrinolytic activities of APC, its anti-inflammatory and cytoprotective properties played a major role in the treatment of patients with severe sepsis. Such properties affect the response to inflammation of endothelial cells and leukocytes and are exerted through binding of APC to at least five receptors with intracellular signaling. The main APC protective mechanism involves binding of the Gla-domain to the endothelial protein C receptor (EPCR) and cleavage of protease activated receptor 1 (PAR-1), eliciting suppression of proinflammatory cytokines synthesis and of intracellular proapoptotic pathways and activation of endothelial barrier properties. However, thrombin cleaves PAR-1 with much higher catalytic efficiency, followed by pro-inflammatory, pro-apoptotic and barrier disruptive intracellular signaling, and it is unclear how APC can exert a protective activity through the cleavage of PAR-1 when thrombin is also present in the same environment. Interestingly, in endothelial cell cultures, PAR-1 cleavage by thrombin results in anti-inflammatory and barrier protective signaling provided occupation of EPCR by the PC gla-domain, raising the possibility that the beneficial effects of rh-APC might be recapitulated in vivo by administration of h-PC zymogen to patients with severe sepsis. Recent reports of h-PC infusion in animal models of sepsis support this hypothesis.
MeSH term(s)	Animals ; Antigens, CD/blood ; Blood Coagulation/drug effects ; Endothelial Cells/metabolism ; Humans ; Protein C/metabolism ; Protein C/therapeutic use ; Receptors, Cell Surface/metabolism ; Recombinant Proteins/therapeutic use ; Sepsis/blood ; Sepsis/drug therapy ; Signal Transduction
Chemical Substances	Antigens, CD ; Protein C ; Receptors, Cell Surface ; Recombinant Proteins
Language	English
Publishing date	2012-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2011.11.013
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