Fibrinogen and Fibrin in Hemostasis and Thrombosis

Kattula, Sravya; Byrnes, James R.; Wolberg, Alisa S.

doi:10.1161/atvbaha.117.308564

Cited by 299 publications

(274 citation statements)

References 129 publications

(135 reference statements)

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“…Fibrinogen, a 340 kDa glycoprotein, plays a central role in hemostasis, specifically in clot formation and stabilization . Congenital fibrinogen disorders are rare, affecting approximately 1 to 2 in every million people in the general population .…”

Section: Introductionmentioning

confidence: 99%

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Lissitchkov

Madan

Khayat

et al. 2020

Journal of Thrombosis and Haemostasis

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Background Congenital fibrinogen deficiency is an ultra‐rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. Methods Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA®, Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four‐point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. Results Twenty‐five afibrinogenemia patients were treated with HFC: 24 for on‐demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92‐0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95‐0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09‐225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82‐1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. Conclusions Human fibrinogen concentrate was efficacious for on‐demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.

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Section: Introductionmentioning

confidence: 99%

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Lissitchkov

Madan

Khayat

et al. 2020

Journal of Thrombosis and Haemostasis

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“…On the other hand, it has been suggested that a procoagulant/anticoagulant axis can regulate tumor malignancy and progression with thrombin as a potent factor stimulating tumor growth, metastasis, and angiogenesis . Importantly, the prothrombotic clot phenotype remained a predictor of malignancy after adjustment for fibrinogen, a major determinant of clot characteristics . No such impact of plasma D‐dimer was observed.…”

Section: Discussionmentioning

confidence: 99%

“…The so‐called prothrombotic clot phenotype,that is, a combination of increased density of fibrin clot networks, reflected by low permeability coefficient (K s ) and reduced overall efficiency of fibrinolysis (CLT), has been demonstrated to predispose to VTE and its recurrences . Similar prothrombotic clot characteristics have been found in patients with gastrointestinal cancers and lung cancer…”

Section: Introductionmentioning

confidence: 91%

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

Mrozińska

Cieślik

Broniatowska

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Compact fibrin clots relatively resistant to lysis are observed in patients at increased risk of venous thromboembolism (VTE) including malignancy. The citrullinated histone H3 (H3Cit) predicts VTE in cancer patients. Objectives We performed a cohort study to investigate whether abnormal clot properties predict cancer diagnosis following unprovoked VTE. Methods In 369 consecutive patients aged <70 years without malignancy detected during routine screening, we determined plasma clot permeability (Ks) and clot lysis time (CLT), along with several prothrombotic markers and H3Cit after 2 to 8 months since VTE. Results During follow‐up (median, 37; interquartile range, 33‐39 months), malignancy was diagnosed in 22 patients (6%), who were older. This group had denser fibrin networks (−13% Ks), impaired fibrinolysis (+25.5% CLT), increased endogenous thrombin potential (ETP,+7%), soluble P‐selectin (+40.3%), and H3Cit (+169.2%) measured off anticoagulation after median 4 months since VTE. The Ks and CLT correlated with H3Cit (r = −.58 and r = .31, P < .05, respectively). The Kaplan–Meier survival analysis showed that reduced Ks (the first quartile, ≤6.2 × 10−9 cm2), prolonged CLT (the top quartile, >106 min), and higher ETP (the top quartile, >1657 nM × min) were predictors of cancer diagnosed during follow‐up. The multivariable Cox proportional hazards model showed that patients with the prothrombotic clot phenotype (low Ks and long CLT) had the highest risk of cancer diagnosis [hazard ratio(HR), 23.4; 95% confidence interval (CI), 6.67‐82.15]. Conclusions Prothrombotic clot properties following unprovoked VTE might help identify patients at risk of a diagnosis of cancer within the first 3 years of follow‐up.

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“…Fibrin is present at high concentrations in both venous and arterial thrombosis providing high sensitivity, but fibrin is not present in circulating blood resulting in potentially high specificity. 55 In addition, the fibrin concentration in thrombus is in the hundreds of micromolar, 56 making this a target compatible with most imaging modalities. Lastly, fibrin is present in fresh thrombi but when the thrombus becomes aged and organized, the fibrin is replaced by collagen and other fibrotic proteins.…”

Section: Fibrin As a Targetmentioning

confidence: 99%

Peptide-based fibrin-targeting probes for thrombus imaging

Oliveira

Caravan

2017

Dalton Trans.

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The development of new methods to image the onset and progression of thrombosis is an unmet need. Non-invasive molecular imaging techniques targeting specific key structures involved in the formation of thrombosis have demonstrated the ability to detect thrombus in different disease state models and in patients. Due to its high concentration in the thrombus and its essential role in thrombus formation, the detection of fibrin is an attractive strategy for identification of thrombosis. Herein we provide an overview of recent and selected fibrin-targeted probes for molecular imaging of thrombosis by magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical techniques. Emphasis is placed on work that our lab has explored over the last 15 years that has resulted in the progression of the fibrin-binding PET probe [64Cu]FBP8 from preclinical studies into human trials.

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Fibrinogen and Fibrin in Hemostasis and Thrombosis

Cited by 299 publications

References 129 publications

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

Peptide-based fibrin-targeting probes for thrombus imaging

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