10 CASI CLINICI
10.2 Caso clinico 2
Il secondo caso clinico in esame è M.S., una femmina di anni 26.
Il 12/12/2017 M.S. si reca in PS per cefalea. La paziente è sottoposta a TAC encefalo che evidenzia una lesione ipodensa dx non interpretata come ischemica né emorragica ma dubbia per MAV (Malformazione Artero-Venosa).
Ad un successivo controllo la RMC encefalo evidenzia sofferenza multifocale della sostanza bianca periventricolare con aree malaciche compatibile con sofferenza encefalica perinatale.
La paziente presenta lieve deficit stenico dell’arto superiore sx successivamente evoluto in plegia. Contemporaneamente la paziente presenta un deterioramento dello stato di vigilanza con passaggio da rallentamento ideomotorio a franco sopore.
Figura 18. Esami di laboratorio eseguiti in pronto soccorso M.S.
Parametri Valori paziente Valori di
riferimento
Globuli bianchi 12,9 x1000/mcl 4.00-11.00
Globuli rossi 2,86 xmil/mcl 4.50-5.90
Emoglobina 8,6 g/dL 13.5-17.5 Ematocrito 25,3 % 40.0-50.0 MCV 88,5 fL 80.0-97.0 MCH 30,1 pg 26.0-34.0 MCHC 34 g/dL 31.0-37.0 RDW 19 % 12.0-15.0 Piastrine 24 x1000/mcl 130-450 Granulociti neutrofili 85 % 40.0-75.0 11 x1000/mcl 1.60-8.50 Granulociti eosinofili 0.4 % 0.50-7.00
59 0,05 x1000/mcl 0.05-0.50 Granulociti basofili 0,2 % 0.0-2.0 0,02 x1000/mcl 0.01-0.12 Linfociti 8,4 % 20.0-45.0 1,08 x1000/mcl 0.8-3.5 Monociti 6 % 2.0-10.0 0,8 x1000/mcl 0.10-1.00 Reticolociti (conta assoluta) 257,7 x1000/mcl 40-80 APTT 24 sec 27-37 PCR 0,43 mg/dL 0.0-0.5 Creatinina 0,92 mg/dL 0.50-1.20 Fosfatasi alcalina 66 U/L 40-130 Gamma GT 19 U/L 4-60
GOT-AST 32 U/L Fino a 40
GPT-ALT 17 U/L Fino a 45
Amilasi pancreatica 38 U/L 13-53 Bilirubina totale 2,21 mg/dL <=1.2 LDH 763 U/L 120-250
Vengono richiesti anche i virologici che risultano tutti negativi. L’aumento di LDH e reticolociti indica un’anemia emolitica.
Nei due giorni successivi le piastrine scendono a 17.000/uL e il laboratorio segnala la presenza di schistociti allo striscio ematico (3-4%).
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Il 14/12/2017 la paziente viene trasferita a Pisa dove le vengono somministrati steroidi e.v. e FFP 1000ml ed effettua in urgenza la prima PEx.
I parametri vitali rilevati sono: Pressione arteriosa: 100/70 mmHg Frequenza cardiaca: 110 bpm Saturazione O2: 99%
Viene sottoposto alla procedura di PEx:
• ogni giorno dal 14/12/2017 al 23/12/2017; • due volte a settimana dal 24/12/2017 all’ 8/01/2018; • una volta a settimana dal 15/01/2018 al 29/01/2018;
Il volume plasmatico stimato è 3500 ml e si scambiano 1,5 x volume plasmatico. Prima dell’inizio dello scambio plasmatico viene sempre valutato l’emocromo ed il suo andamento. Durante la procedura è infuso calcio gluconato per la profilassi delle reazioni da citrato. La paziente viene premedicata prima di ogni PEx con antistaminico per la profilassi di una sospetta anafilassi verso le proteine plasmatiche. Risulta in terapia anche con Deltacortene.
Nelle tabelle sottostanti si evidenziano gli andamenti di emoglobina e piastrine nel tempo.
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Figura 19. Valori di emoglobina e piastrine di M.S.
Emoglobina (g/dL) Piastrine X1000/uL 12/12/2017 8,6 24 13/12/2017 9,3 18 14/12/2017 9,6 17 22/12/2017 8,8 208 23/12/2017 11,3 185 24/12/2017 9,5 217 25/12/2017 9,4 228 27/12/2017 10,5 247 28/12/2017 10,1 244 28/12/2017 10,4 275 29/12/2017 10 240 30/12/2017 9,5 212 03/01/2018 10,3 152 08/01/2018 10,3 122 15/01/2018 9,8 151 16/01/2018 11 199 22/01/2018 10,6 225 29/01/2018 9,8 153
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Figura 20. Andamento temporale Hgb M.S.
8,6 9,3 9,6 8,8 11,3 9,5 9,4 10,5 10,1 10,4 10 9,5 10,3 10,3 9,8 11 10,6 9,8 12/12/2017 19/12/2017 26/12/2017 02/01/2018 09/01/2018 16/01/2018 23/01/2018 g/ d L emoglobina
63
Figura 21. Andamento temporale plt M.S.
Come si evidenzia dai grafici, la conta piastrinica si è normalizzata e contestualmente la paziente ha presentato risoluzione dei segni neurologici.
Il paziente ad oggi è in buona salute ed esegue emocromo e controlli periodici in ematologia, per scongiurare l’evenienza di una recidiva.
24 1817 208 185 217 228 247244 275 240 212 152 122 151 199 225 153 12/12/2017 19/12/2017 26/12/2017 02/01/2018 09/01/2018 16/01/2018 23/01/2018 x1000/ u L piastrine
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INDICE FIGURE E TABELLE
Figura 1. Fisiopatologia PTT. Nella PTT, a causa dell'assenza di ADAMTS-13 funzionale (assente per difetto congenito o inibito da specifici autoanticorpi), i
multimeri VWF ultralarge vengono rilasciati nel sangue e si legano spontaneamente alle piastrine per formare aggregati all'interno dei microvasi arteriosi e capillari. Gli
aggregati piastrinici VWF sono abbastanza grandi da formare microtrombi che
inducono ischemia tissutale, consumo di piastrine e anemia emolitica microangiopatica (schistociti su striscio di sangue). (2) ... 11 Figura 2. Giocatori noti e sconosciuti coinvolti in PTT. Tra le caratteristiche note coinvolte nell'evento PTT, il deficit grave di ADAMTS-13, acquisito tramite specifici autoanticorpi o ereditato tramite mutazioni del gene ADAMTS-13, è l'unico fattore di causa identificato finora. Altri fattori sono ben stabiliti come fattori predisponenti per la PTT acquisita (cioè sesso femminile, etnia nera, HLADRB1 * 11 e obesità). Inoltre, condizioni fisiopatologiche che aumentano i livelli di VWF plasmatici come
infiammazione, sepsi o gravidanza sono note per agire potenzialmente come fattori precipitanti di episodi acuti di PTT acquisita o congenita. Altri attori ancora sconosciuti sono sospettati di essere coinvolti nell'evento PTT: questi possono essere proteine del sistema ADAMTS-13 / VWF o candidati cellulari come piastrine o cellule endoteliali. (2) ... 13 Figura 3. Principali contesti clinici associati all'episodio acuto iniziale di PTT (2) 15 Figura 4. Indagini in caso di sospetta PTT (6) ... 16 Figura 5. Forme tipiche per l'identificazione specifica degli schistociti. (a)
cheratocita (freccia superiore) e cellula elmetto (freccia inferiore), vicino a un eritrocita policromatofilo nell'angolo ... 18 Figura 6. Striscio di sangue periferico da un caso di porpora trombotica
trombocitopenica. (a) le frecce indicano le cellule elmetto (in basso a sinistra), un microsferocita (in alto a sinistra), un cheratocita (parte centrale); (b) le anomalie morfologiche includono microsfere, cheratociti, cellule elmetto e diversi schistociti a mezzaluna e triangolari. (28) ... 20 Figura 7. Flow chart per la conta degli schistociti in accordo con le linee guida ICSH. (28) ... 21 Figura 8. Classificazione piastrinopenie. ... 25
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Figura 9. Diagnosi differenziale delle microangiopatie trombotiche (TMA) che si presentano con anemia emolitica microangiopatica (MAHA). IA-HUS, sindrome emolitico-uremica associata a infezione; MAHAT, MAHA e trombocitopenia; PTT,
porpora trombotica trombocitopenica. (1) ... 33
Figura 10. Marcatori clinici e di laboratorio in relazione alla data della diagnosi di TMA. La data della diagnosi TMA è contrassegnata come giorno 0 (linea verticale). Per ogni variabile, le linee verticali bianche rappresentano il giorno medio in cui il criterio è diventato positivo. (51) ... 34
Figura 11. Protocollo per il trattamento nella PTT acuta (6) ... 41
Figura 12. Separatore cellulare usato per il PEx (60) ... 42
Figura 13. Diagramma di flusso per la gestione terapeutica del PTT acquisito ad insorgenza nell'età adulta. (2) ... 50
Figura 14. Esami di laboratorio eseguiti in pronto soccorso M.F. ... 51
Figura 15. Valori di emoglobina e piastrine di M.F. ... 55
Figura 16. Andamento temporale emoglobina M.F. ... 56
Figura 17. Andamento temporale piastrine M.F. ... 57
Figura 18. Esami di laboratorio eseguiti in pronto soccorso M.S. ... 58
Figura 19. Valori di emoglobina e piastrine di M.S. ... 61
Figura 20. Andamento temporale Hgb M.S. ... 62
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