Fisiopatologia dell'Emostasi e della Coagulazione

La continuità vasale è controllata da un complesso di eventi denominato processo emostatico-coagulativo, responsabile della formazione del coagulo. Questo è costituito da una maglia di fibrina ed elementi figurati del sangue intrappolati al suo interno

FISIOPATOLOGIA DELL'EMOSTASI E DELLA COAGULAZIONE

La capacità di controllare e mantenere all’interno dei vasi il flusso del sangue dopo un danno vasale è deputata a un complesso di eventi fisiologici denominati nel loro insieme processo emostatico-emocoagulatorio, mediante la formazione del trombo emostatico o coagulo. Il coagulo è una massa fibro-spugnosa di consistenza gelatinosa costituito da fibrina entro cui vengono trattenuti gli elementi figurati del sangue. Esso si forma attraverso una serie di complesse reazioni enzimatiche a cascata quando il sangue fuoriesce dal vaso, all’interno o all’esterno del corpo, in seguito a lesioni dell’endotelio. In tale processo si possono distinguere due fasi, una cronologicamente precoce, l’emostasi primaria, che porta alla formazione del cosiddetto ‘trombo bianco’, costituito principalmente da piastrine e scarsa fibrina, e una più tardiva, emostasi secondaria o coagulazione del sangue, con formazione del ‘trombo rosso’ principalmente composto da un reticolo di fibrina con piastrine e globuli rossi imbrigliati al suo interno

A modified functional Global test to measure protein C, protein S activities and the activated protein C-resistance phenotype.

Identifying a defect affecting the protein C/protein S (PC/PS) anticoagulant system, using a single global test, has recently become possible thanks to a new methodological approach based on the activation of endogenous plasma PC by Protac, derived from Agkistrodon Contortix snake venom (ACV). The introduction of a commercial test (ProC Global), ACV-based, provides a useful tool for the screening of thrombotic patients since the most frequent causes of inherited thrombophilia are found in the PC/PS system. The test provides information only on the global activity of the anticoagulant pathway but not on PC and PS activity or on the factor V related conditions (e.g., FV Leiden). The present study shows that by carrying out the test alternating the presence of PC-, PS-, or FV-deficient plasma and using appropriate amounts of ACV, it is possible to increase the specificity of the test to correctly evaluate respectively the PC or PS activities or the activated protein C resistance condition (APC-R). These simple modifications applied to the original commercial test allow to detect exactly, using a single, basic methodology, the principal defects affecting the PC/PS anticoagulant pathway. Furthermore, carrying out the tests on an automated coagulometer, in combination or not with the classic ProC Global assay, it is possible to use a unique reagent profile to simultaneously investigate in the same or different samples, the PC, PS, and APC-R defect

Fisiopatologia della Coagulazione.

La capacità di controllare e mantenere all’interno del vaso il flusso di sangue dopo un danno vasale è deputata a un complesso di eventi fisiologici denominati nel loro insieme processo emostatico-coagulatorio, mediante la formazione del trombo emostatico. In tale processo si possono distinguere due fasi,una precoce, l’emostasi primaria, che porta alla formazione del cosiddetto “trombo bianco“, costituito principalmente da piastrine e scarsa presenza di fibrina, e una più tardiva, emostasi secondaria o coagulazione del sangue, con formazione del trombo rosso principalmente composto da un reticolo di fibrina con piastrine e globuli rossi imbrigliati al suo interno

C677T Substitution in the Methylenetetrahydrofolate Reductase Gene as a Risk Factor for Venous Thrombosis and Arterial Disease in Selected Patients.

BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia, due to a combination of genetic and environmental factors, is considered to be a risk factor for vascular disease. Individuals with the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR), due to homozygous C677T MTHFR gene mutation, have significantly raised plasma levels of homocysteine and may be at increased risk of vascular disease. However, it is still controversial a direct association between C677T homozygosity and the occurrence of vascular disease is still controversial. DESIGN AND METHODS: To clarify the contribution of C677T MTHFR mutation in arterial occlusive disease (AOD) or venous thromboembolism (VTE), we performed a case-controlled study including 160 cases with AOD and 180 cases with VTE attending our referral center and compared them with 200 matched healthy controls. MTHFR gene mutation was evaluated by PCR and odds ratios (OR) and the 95% confidence intervals (CI) were used to estimate the risk for venous or arterial thrombosis. RESULTS: There was a high prevalence of homozygotes for the mutated MTHFR allele among the whole group of cases with arterial disease (OR = 2.35, p = 0.001). Considering the AOD cases with and those without associated risk factors for arterial disease separately the difference remained significant only in the latter group (p = 0.168 and P<0.001 respectively). In contrast, the prevalence of mutated homozygotes among the whole group of cases with VTE was not significantly different from that in the control group (OR = 1.67; p = 0.070). Excluding VTE cases with inherited thrombophilia or with circumstantial risk situations the value increased in both subgroups (OR = 2.26; p = 0.006 and OR = 2.03; p = 0.033 respectively). Considering only VTE cases with neither inherited thrombophilia nor circumstantial risk situations the risk increased further (OR = 2.57; p = 0.017). INTERPRETATION AND CONCLUSIONS: These data suggest that in selected patients homozygosity for the MTHFR mutation increases the risk of both arterial and venous thromboses and that differences in selection criteria for the patient group may be responsible in part for the controversial association of the MTHFR mutation and vascular disease

Recurrent episodes of spontaneous subconjunctival hemorrhage in patients with factor XIII Val34Leu mutation.

PURPOSE: To report on the occurrence of frequent episodes of spontaneous subconjunctival hemorrhage (SCH) in patients with the Leu 34 allele of the coagulation factor XIII (FXIII), known to be associated with high hemorrhagic risk. DESIGN: Observational case series. METHODS: Five young adults who had suffered from recurrent idiopathic SCH not associated with any recognized ocular and systemic hemorrhagic risk factor were investigated. Accurate anamnestic, ophthalmologic, hematologic, and serologic examinations were performed, together with blood pressure measurements, electrocardiogram (ECG), and 24-hour Holter ECG recordings. FXIII Val34Leu polymorphism was studied by DNA chain polymerase reaction. RESULTS: DNA analyses showed that the hemorrhagic mutated Leu34 allele was present in four of our selected patients: two mutated homozygotes (Leu/Leu) and two heterozygotes (Val/Leu). In the last subject this polymorphism was not detected. All the other clinical evaluations did not disclose any significant abnormality. CONCLUSIONS: The FXIII Val34Leu mutation may be associated with an increased risk for spontaneous episodes of SCH