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Background: Chamomile is consumed worldwide for enjoyment and its potentially desirable properties. Widespread patient resource websites, however, discourage preoperative chamomile intake, lest bleeding could worsen. This precaution, though, stems largely from indirect evidence in one case report. To evaluate if chamomile ingestion impacts coagulation assays via coumarin-like substances, we designed a randomized, placebo-controlled, crossover study., Materials and Methods: Healthy volunteers were randomized to three interventions in a cross-over-design spanning 5 weeks per subject. Interventions included 7-day consumption of chamomile tea (3 tea bags × 3 times daily = 9 tea bags daily), a chamomile extract capsule (3 times daily), or a placebo capsule (3 times daily). A 7-day washout period elapsed between intervention periods. The primary outcome was the change in prothrombin time (PT) before vs. after each intervention. Secondary outcomes included changes in the international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), reptilase time (RT), and fibrinogen (FG) surrounding each intervention., Results: All 12 enrolled subjects were randomized and completed the study. The primary outcome of PT change (mean ± SD) was similar across interventions (chamomile tea =  - 0.2 ± 0.4 s, extract capsule =  - 0.2 ± 0.4 s, and placebo capsule = 0.1 ± 0.5 s; p = 0.34). INR change was 0 s (p = 0.07) for each intervention. The aPTT, TT, RT, and FG, did not change significantly across interventions (p = 0.8, p = 0.08, p = 0.8, and p = 0.2 respectively)., Conclusions: Chamomile intake by tea or capsule does not prolong PT. These findings challenge the notion to avoid perioperative chamomile intake in patients not taking warfarin., Trial Registration: ClinicalTrials.gov, NCT05006378; Principal Investigator: Jonathon Schwartz, M.D.; Registered August 16, 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The inherited dysfibrinogenemias comprise rare congenital coagulation disorders which are clinically characterized by bleeding diathesis and, in occasional patients, by thrombotic tendency or combined bleeding-thrombotic events. In recent years, accumulating evidence suggested that fibrinogen has a critical role in the pathogenesis of neuroinflammatory disorders, including multiple sclerosis. We describe the presentation and long-term follow-up of a patient with inherited dysfibrinogenemia and concomitant clinical and laboratory evidence of demyelinating disease.   Case description:  A 16-year-old male patient presented in 2003 with bilateral sensory symptomatology preceded by an episode of epistaxis. His past medical history included episodes of spontaneous nosebleeds as well as Duane syndrome and mild atrophy of the right upper limb. Coagulation testing of the patient and his asymptomatic father revealed in both the presence of a clotting defect, consistent with inherited dysfibrinogenemia (named Fibrinogen Thessaloniki). Within seven months, the patient presented with a new episode of motor semiology whereas serial brain magnetic resonance imaging (MRI) scans revealed T2 lesions with bilateral distribution, some of which with gadolinium enhancement. The cerebrospinal fluid examination disclosed the presence of oligoclonal bands in the central nervous system compartment. The patient was started on azathioprine (2.5 mg/kg/24h) which led to clinical and radiological stabilization for nine years. In 2013, the dose of azathioprine was reduced, due to an elevation of his amylase levels, resulting in radiological deterioration with an increased T2 lesion load. The reinstitution of azathioprine at therapeutic doses led to radiological improvement and clinical stability as of today., Conclusion: The described case of inherited dysfibrinogenemia and concomitant multiple sclerosis provides speculative evidence for a causal link, rather than a chance association, between these two entities. Further studies are warranted to corroborate this hypothesis in experimental and clinical settings. HIPPOKRATIA 2017, 21(1): 49-51.

Integrin alphavbeta3 is specifically but transiently expressed on the tips of capillary sprouts as they invade the fibrin clot during angiogenesis of cutaneous wound repair. Specific blocking of alphavbeta3 function inhibits granulation tissue formation in cutaneous wounds. The mechanisms of regulation of alphavbeta3 expression on human dermal microvascular endothelial cells, however, have not been fully delineated. As alphavbeta3 was highly expressed on capillary sprouts in 5 d wounds rich in fibrin, but was almost undetectable on blood vessels in 7 d wounds rich in collagen, we hypothesized that the extracellular matrix environment could regulate human dermal micro- vascular endothelial cell alphavbeta3 expression. To address this, human dermal microvascular endothelial cells were cultured on surfaces coated with collagen, fibronectin, and gelatin, and mRNA levels of integrin alphav/beta3 were determined. Compared with human dermal microvascular endothelial cells on collagen, mRNA levels of alphav/beta3 were higher in human dermal microvascular endothelial cells on fibronectin and on gelatin. To simulate the in vivo environment better, human dermal microvascular endothelial cells cultured on collagen were overlaid by fibrin or collagen gels prior to assessment of alphav/beta3 mRNA levels. alphav/beta3 mRNA levels were higher in human dermal microvascular endothelial cells surrounded by a three-dimensional fibrin gel compared with a collagen gel, whether angiogenic factors were present or absent. As modulation of mRNA stability is a potential regulatory mechanism for integrin expression, integrin subunit mRNA stability was assessed. beta3 mRNA decayed much faster than alphav, alpha2, and beta1 mRNA. Three-dimensional fibrin gels enhanced alphav/beta3 mRNA stability compared with collagen gels. We propose that the provisional matrix molecules in the wound clot regulate angiogenesis associated with cutaneous wound repair through their modulation of integrin receptor expression.

Fib420 is a recently identified subclass of normal human fibrinogen in which two extended alpha chain isoforms (alphaE) replace the common alpha chains, yielding a molecule (ca. 420 kD) which is larger than the more abundant 340-kD form. Evidence for preservation of this subclass throughout vertebrate evolution suggests it performs some as yet unidentified vital function. A survey was undertaken to establish the range of plasma Fib420 levels in normal, healthy adults and in placental cord (fetal) blood. For measuring Fib420, a quantitative Western blot assay was developed using monoclonal antibody against the exon-VI encoded C-terminus of the molecule's unique alphaE chain. This alphaE chain signal was normalized to that of the beta chain, common to both fibrinogen forms. Analysis of plasma samples from the adult and newborn cohorts (n = 25 each; total fibrinogen ca. 2.6 mg/mL in both) revealed a statistically significant difference, with a mean level of 100 +/- 28 microg/mL in the neonate compared to 34 +/- 7 microg/mL in the adult. On average, 1 out of every 100 fibrinogen molecules in adult plasma belongs to the Fib420 subclass. Unlike in the newborn, adult Fib420 levels remained the same over a wide range of total plasma fibrinogen. The striking difference observed between these two cohorts suggests a changing developmental expression of the Fib420 subclass and a homeostatic control operating in later stages of life.

Gas-phase, water-soluble components of cigarette smoke cause delayed fibrin self-assembly and prevent fibrin cross-linking by inactivation of factor XIIIa (plasma transglutaminase). These anticoagulant properties of smoke are demonstrable in plasma, suggesting they play a role in the pathophysiology of smoking.

These studies have been directed at evaluating the role played by proteolysis (fibrinogenolysis) in vivo in prolonging the thrombin time of human umbilical cord ("fetal") fibrinogen. The aggregation rate of cord fibrin compared with that from adult plasma is always delayed when the reaction is carried out under conditions of relatively high ionic strength (e.g., 0.29); this difference is not apparent at relatively low ionic strength (e.g., 0.09). In addition, as assessed by turbidimetric techniques, the maximum absorbance attained by cord fibrin is considerably less than that attained by adult fibrin. Coagulable fibrinogen catabolites (i.e., fraction I-5) are present in cord plasma and, like their counterparts from adult plasma, lack various portions of the COOH-terminal region of the A alpha chain. However, their presence in plasma does not explain the behavioral differences between cord and adult fibrin. Moreover, differences revealed by turbidimetric comparison of cord and adult fibrin from plasma fraction I-2 persist in fibrin from fraction I-5; it therefore appears that the COOH-terminal region of the A alpha chain does not contain the structure(s) accounting for the unique behavior of "fetal" fibrinogen.

The alpha chain 572-574 Arg-Gly-Asp sequence of fibrinogen appears to play only a minor role in platelet aggregation based on the ability of fibrinogen preparations lacking alpha chain carboxyterminal segments to support platelet aggregation, but synthetic Arg-Gly-Asp-Ser (RGDS) peptides are capable of inhibiting platelet aggregation and fibrinogen binding. The present study thus examined the ability of RGDS peptides to inhibit platelet interactions with a plasmic degradation product of fibrinogen (8D-50) that resembles an intermediate fragment X. Gel-filtered, human blood platelets suspended in 0.01 mol/L HEPES-buffered modified Tyrode's solution, pH 7.5, were stimulated with 20 mumol/L adenosine diphosphate and the binding of 125I-labeled 8D-50 or intact fibrinogen (0.01 to 0.6 mg/mL) assessed in the presence of 0 to 117 mumol/L RGDS. The data revealed that RGDS decreased the apparent affinity of 8D-50 and intact fibrinogen for platelets but did not affect the maximum number of binding sites. RGDS thus appears to be a competitive inhibitor not only of intact fibrinogen (Ki = 12 +/- 2 mumol/L) but also of 8D-50 (Ki = 15 +/- 3 mumol/L) (mean +/- SD, n = 3).