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Fibrinogeno

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Il fibrinogeno, o fattore I della coagulazione, è un polipeptide plasmatico sintetizzato dal fegato con lo scopo di favorire l’emostasi secondaria (1,2).

STRUTTURA – Il fibrinogeno è formata da tre coppie di catene polipeptidiche (α, ß, γ) unite da ponti disolfuro  (3-5).

I geni preposti alla sintesi del fibrinogeno sono localizzati al terzo distale del braccio lungo del cromosoma 4, bande q23-q32.

 

FUNZIONE – Il fibrinogeno costituisce il substrato su cui agisce la trombina, un enzima proteolitico che determina la  scissione del fibrinogeno in fibrina e fibrinopeptidi di tipo A e B.

 Questa reazione rappresenta la tappa finale della cascata coagulativa grazie alla quale si viene a formare un intreccio proteico  formata da catene intrecciate di fibrina che inglobano piastrine e globuli rossi; si ha così la formazione di un coagulo che arresta l’emorragia. Terminata la sua funzione tampone, il coagulo si retrae e la fibrina viene degradata (fibrinolisi).

 in genere è associato ad altri esami del sangue quali:

  • PT (tempo di protrombina)
  • APTT, tempo di tromboplastina parziale attivata
  • Conta piastrinica
  • D-dimero.

CONCENTRAZIONI PLASMATICHE La concentrazione plasmatica di fibrinogeno aumenta, in parallelo alla sua velocità di sintesi, nella fase acuta di vari stimoli flogistici. I livelli di fibrinogeno nel plasma possono subire variazioni a causa di alterazioni genetiche (varianti eterozigotiche) o per variazioni di peso che determinano un più elevato rischio di trombosi venose profonde, infarto del miocardio, microangiopatie occlusive, ictus cerebrale e resistenza alla fibrinolisi (6-20).

I livelli normali di fibrinogeno si attestano tra 150 e 400 mg/dl con un valore medio che oscilla intorno ai 225 mg/dl.

IPERFIBRINOGENEMIA

Valori cronicamente elevati di fibrinogeno sono associati a un maggior rischio cardiovascolare (trombosi, ictus, malattie coronariche, angina pectoris e infarto).

I suoi livelli, insieme alle cosiddette proteine di fase acuta (proteina C reattiva, fattori del complemento, protrombina ecc.), aumentano durante processi infiammatori di qualsiasi origine, nella ripresa da un intervento chirurgico e durante la gravidanza.  La sintesi delle molecole di fibrinogeno è sovraregolata durante l’infiammazione dall’azione delle citochine ed in particolare dall’interleuchina-6 (IL-6) e dai glucocorticoidi. In gravidanza una lieve iperfibrinogenemia è fisiologica ed è funzionale a limitare le perdite ematiche del parto e post-partum ma un eccessivo aumento del fibrinogeno può far aumentare il rischio di aborto spontaneo, ARS, insufficienza placentare, IUGR e distacco di placenta.
Le altre possibili cause di una concentrazione di fibrinogeno elevata rispetto alla norma comprendono:

IPOFIBRINOGENEMIA – eziologia

Una riduzione dei valori di fibrinogeno si può osservare in caso di:

  • Gravi epatopatie (per ridotta capacità di sintesi epatica); in tal senso il fibrinogeno può essere utilizzato come marker della funzionalità epatica.
  • Coagulazione intravascolare disseminata -CID– (per l’eccessivo consumo dovuto alla presenza di numerosi trombi);
  • Afibrinogemia, disfibrinogemia o ipofibrinogemia (deficit ereditari che provocano diminuita produzione di fibrinogeno);
  • Malnutrizione grave;
  • Anemia;
  • Embolia
  • Emofilia;
  • Fibrinolisi;
  • Infezioni molto gravi;
  • Eclampsia e gestosi ipertensiva
  • Alcune forme tumorali (come leucemia e carcinoma della prostata);
  • Trasfusioni rapide, di grosse quantità di sangue
  • Disfibrinogenemia
  • farmaci steroidi anabolizzanti, androgeni, streptokinasi, urokinasi e alcuni farmaci antiepilettici usati per contrastare crisi epilettiche o in alcune malattie mentali come la schizofrenia o il bipolarismo.
  • Presenza elevata di antigeni del fibrinogeno i cui valori plasmatici sono 150-350 mg/dl.

Possono essere presenti anche deficit ereditari più o meno severi – sia nella quantità di fibrinogeno in circolo, sia nella sua funzionalità – con predisposizione a gravi emorragie.

DISFIBRINOGENEMIA –   si intende la presenza di molecole di di fibrinogeno non correttamente funzionanti. La disfibrinogenemia provoca almeno uno dei seguenti fenomeni: (1) rilascio anomalo di fibrinopeptidi, (2) difetti nella polimerizzazione della fibrina, (3) stabilizzazione anormale della fibrina e (4) resistenza alla fibrinolisi. Le disfibrinogenemie più comuni sono quelle che causano difetti di polimerizzazione.

Nella maggior parte dei casi, la disfibrinogenemia congenita è ereditata come carattere autosomico dominante con alti livelli di penetranza, ma alcuni pazienti mostrano un modello di ereditarietà autosomica recessiva. I pazienti possono essere omozigoti o eterozigoti per il difetto. La maggior parte degli individui affetti è eterozigote, con circa il 50% di fibrinogeno normale, che è adeguato per un’emostasi normale a meno che la molecola disfunzionale non interrompa la funzione del componente fibrinogeno normale. Alcuni individui con disfibrinogenemia hanno livelli di fibrinogeno ben al di sotto del normale.

References

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