{"id":1058,"date":"2017-01-30T22:28:56","date_gmt":"2017-01-30T21:28:56","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/30\/diagnostika-vrodenych-krvacavych-poruch-sekundarnej-hemostazy-jednoduchy-sprievodca-pre-bezne-klinicke-laboratoria\/"},"modified":"2017-10-03T10:37:55","modified_gmt":"2017-10-03T08:37:55","slug":"diagnosis-of-inherited-bleeding-disorders-of-secondary-hemostasis-a-simple-guide-for-routine-clinical-laboratories","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/diagnosis-of-inherited-bleeding-disorders-of-secondary-hemostasis-a-simple-guide-for-routine-clinical-laboratories\/","title":{"rendered":"Diagnosis of inherited bleeding disorders of secondary hemostasis: a simple guide for routine clinical laboratories"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0\r\nattachment at the end of the paper.\r\n\r\n<\/strong><\/span><\/pre>\n
Kli<\/strong>ni<\/strong>c<\/strong>k<\/strong>\u00e1 anamn\u00e9za<\/strong><\/p>\n
Hemost\u00e1za je pova\u017eovan\u00e1 za komplikovan\u00fd mechanizmus v organizme, ktor\u00e9ho cie\u013eom je zabr\u00e1ni\u0165 nadmern\u00e9mu krv\u00e1caniu v mieste poranenia cievy (1). Proces zastavania krv\u00e1cania za\u010d\u00edna v mieste po\u0161kodenia endotelu, \u010do ma za n\u00e1sledok spustenie procesu prim\u00e1rnej hemost\u00e1zy, ktor\u00fd v nasleduj\u00facom kroku vedie k spusteniu aktiv\u00e1cie sekund\u00e1rnej hemost\u00e1zy \u00a0(obr\u00e1zok 1).<\/p>\n
Aj ke\u010f v\u0161etky vroden\u00e9 poruchy zr\u00e1\u017eania krvi sa vyzna\u010duj\u00fa spolo\u010dn\u00fdm klinick\u00fdm sympt\u00f3mom \u2013 krv\u00e1can\u00edm, charakter, lokaliz\u00e1cia a intenzita krv\u00e1cania sa zvy\u010dajne pri jednotliv\u00fdch\u00a0 poruch\u00e1ch \u00a0hemost\u00e1zy \u00a0zna\u010dne l\u00ed\u0161i. V tabu\u013eke 1 s\u00fa uveden\u00e9 charakteristick\u00e9 klinick\u00e9 prejav y pri jednotliv\u00fdch vroden\u00fdch poruch\u00e1ch sekund\u00e1rnej hemost\u00e1zy. Deficity FVIII a FIX (hemof\u00edlia A a B) maj\u00fa tendenciu \u00a0vykazova\u0165 r\u00f4zne klinick\u00e9 prejavy\u00a0in\u00fdch deficitov faktorov, av\u0161ak ke\u010f\u017ee s\u00fa X-viazan\u00e9 reces\u00edvne ochorenia, maj\u00fa v\u00e4\u010d\u0161inov\u00fd podiel v mu\u017eskej popul\u00e1cii. Zriedka u symptomatick\u00fdch \u017eien m\u00f4\u017ee by\u0165 diagnostikovan\u00fd \u00a0deficit \u00a0FVIII alebo \u00a0FIX, ak v\u0161ak sa tieto deficity diagnostikuj\u00fa, zvy\u010dajne tieto pacientky definujeme ako \u201esymptomatick\u00e9 nosi\u010dky\u201c (2). \u010eal\u0161ie vz\u00e1cne \u00a0krv\u00e1cav\u00e9 ochorenia \u00a0sekund\u00e1rnej hemost\u00e1zy s\u00fa v\u00e4\u010d\u0161inou deden\u00e9 autozom\u00e1lne reces\u00edvne, a preto s\u00fa \u017eeny a mu\u017ei postihnut\u00ed s rovnakou \u00a0frekvenciou \u00a0(3). Najtypickej\u0161\u00edm \u00a0klinick\u00fdm pr\u00edznakom deficitu faktora b\u00fdva pr\u00edtomnos\u0165 \u00a0podko\u017en\u00fdch krv\u00e1can\u00ed, krv\u00e1can\u00ed z nosa, \u00fast a u \u017eien menor\u00e1gie. Najz\u00e1va\u017enej\u0161ie deficity FVIII a FIX m\u00f4\u017eu ma\u0165 pr\u00edtomn\u00e9 \u017eivot ohrozuj\u00face\u00a0 krv\u00e1canie po poranen\u00ed, traume, menor\u00e1gie, krv\u00e1cania po rozsiahlych chirurgick\u00fdch z\u00e1krokoch alebo aj po men\u0161\u00edch invaz\u00edvnych z\u00e1krokoch, ako je extrakcia zuba. Okrem t\u00fdchto klinick\u00fdch prejavov sa u pacientov s \u0165a\u017ekou formou hemof\u00edlie \u00a0\u010dasto objavuj\u00fa opakovan\u00e9 \u00a0spont\u00e1nne \u00a0krv\u00e1cania do k\u013abov, ktor\u00e9 m\u00f4\u017eu vies\u0165 a\u017e k rozvoju hemofilickej \u00a0artropatie. Zn\u00ed\u017eenie t\u00fdchto spont\u00e1nnych krv\u00e1can\u00ed a rozvoja artropatie m\u00f4\u017eeme \u00a0docieli\u0165 adekv\u00e1tnou profylaktickou lie\u010dbou (1). Charakteristick\u00fdmi \u00a0klinick\u00fdm prejavmi \u00a0por\u00fach trombocytov a niektor\u00fdch foriem vWCH s\u00fa mukokut\u00e1nne krv\u00e1cania. Av\u0161ak, tieto prejavy s\u00fa zriedkav\u00e9 u pacientov s vrodenou poruchou sekund\u00e1rnej hemost\u00e1zy. D\u00f4le\u017eit\u00e1 \u00a0je podrobn\u00e1 \u00a0rodinn\u00e1 anamn\u00e9za \u00a0krv\u00e1cania, v tomto pr\u00edpade s\u00fa u pr\u00edbuzn\u00fdch pr\u00edtomn\u00e9 \u00a0\u010dast\u00e9 krv\u00e1cav\u00e9 \u00a0prejavy, av\u0161ak treba \u00a0myslie\u0165 aj nato, \u017ee nepr\u00edtomnos\u0165ou \u00a0krv\u00e1cav\u00fdch prejavov v rodinnej anamn\u00e9ze nem\u00f4\u017eeme jednozna\u010dne vyl\u00fa\u010di\u0165 vroden\u00fa poruchu hemost\u00e1zy, preto\u017ee d<\/em>e novo <\/em>mut\u00e1cie s\u00fa zodpovedn\u00e9 a\u017e za jednu tretinu v\u0161etk\u00fdch pr\u00edpadov (4). Okrem toho v diferenci\u00e1lnej diagnostike by sme mali myslie\u0165 aj na poruchy, \u00a0ktor\u00e9 s\u00fa charakterizovan\u00e9 \u00a0pr\u00edtomnos\u0165ou \u00a0protil\u00e1tok proti koagula\u010dn\u00fdm faktorom (napr\u00edklad z\u00edskan\u00e1 hemof\u00edlia) (5). D\u00f4le\u017eit\u00fd \u00a0je aj vek n\u00e1stupu klinick\u00fdch pr\u00edznakov, preto\u017ee vroden\u00e9 poruchy, najm\u00e4 tie najz\u00e1va\u017enej\u0161ie (hemof\u00edlia A a B, ktor\u00e1 sa vyzna\u010duje aktivitou koagula\u010dn\u00e9ho faktora < 5 %) sa zvy\u010dajne objavuj\u00fa u\u017e pri naroden\u00ed alebo po\u010das ran\u00e9ho detstva.<\/p>\n
P<\/strong>r<\/strong>v<\/strong>\u00e1 l\u00ednia hemokoagula\u010dn\u00fdch testov<\/strong><\/p>\n
P\u00f4vodn\u00fd model koagul\u00e1cie, ktor\u00fd pozost\u00e1va \u00a0z vonkaj\u0161ej, vn\u00fatornej a spolo\u010dnej cesty, u\u017e dlho reprezentuje spolo\u010dn\u00fd z\u00e1klad prvej l\u00ednie testov a bol vyvinut\u00fd na skr\u00edning pacientov s podozren\u00edm na krv\u00e1cav\u00e9 ochorenia. Tieto testy zah\u0155\u0148aj\u00fa protromb\u00ednov\u00fd \u00a0\u010das (PT), aktivovan\u00fd parci\u00e1lny tromboplast\u00ednov\u00fd \u010das (aPT T), tromb\u00ednov\u00fd \u00a0\u010das (T T) a vy\u0161etrenie fibrinog\u00e9nu (FBG) (1) PT, p\u00f4vodne \u00a0vyvinut\u00e9 Quickom \u00a0v roku 1935, ktor\u00e9 je z\u00e1kladn\u00fdm koagula\u010dn\u00fdm testom, zalo\u017een\u00fdm na citr\u00e1tovej plazme a aktiv\u00e1cii vonkaj\u0161ej dr\u00e1hy zr\u00e1\u017eania krvi (F VII) pomocou kalciov\u00e9ho tromboplast\u00ednu (6). Tento test je preto v\u00e4\u010d\u0161inou citliv\u00fd na poruchu \u00a0FVII a \u010fal\u0161\u00edch faktorov spolo\u010dnej cesty koagul\u00e1cie (FX, protromb\u00ednu a FBG) (obr\u00e1zok 1). PT m\u00f4\u017ee \u00a0by\u0165 vyjadren\u00fd v sekund\u00e1ch alebo ako pomer medzi pacientovou a referen\u010dnou plazmou v medzin\u00e1rodnom normalizovanom pomere (INR), v ktorom je pomer upraven\u00fd indexom porovnania aktiva\u010dn\u00fdch vlastnost\u00ed trom- boplast\u00ednu s medzin\u00e1rodn\u00fdm referen\u010dn\u00fdm tromboplast\u00ednom (7). Hoci hodnoty vyjadrenia v INR sa be\u017ene pou\u017e\u00edvaj\u00fa na monitorovanie peror\u00e1lnej antikoagula\u010dnej terapie antagonistom \u00a0vitam\u00ednu K, v\u00fdsledky INR m\u00f4\u017eu by\u0165 spo\u013eahlivo pou\u017eit\u00e9 u vy\u0161etrovan\u00fdch pacientov \u00a0s vroden\u00fdmi alebo z\u00edskan\u00fdmi (ochorenia pe\u010dene) poruchami \u00a0koagula\u010dn\u00fdch faktorov (8). Pr\u00ed\u010dinami pred\u013a\u017een\u00e9ho PT m\u00f4\u017ee by\u0165 nespr\u00e1vny odber a preprava vzorky, malabsorpcia (\u010do vedie k nedostatku vitam\u00ednu \u00a0K), ochorenia \u00a0pe\u010dene, afibrinogen\u00e9mia, diseminovan\u00e1 intravaskul\u00e1rna koagul\u00e1cia (DIC), inhib\u00edcia koagula\u010dn\u00fdch \u00a0faktorov pri u\u017e\u00edvan\u00ed priamychantikoagulanci\u00ed, najm\u00e4 liekov inhibuj\u00facich FXa (apixaban a rivaroxaban) \u00a0(9, 10). aPT T bol p\u00f4vodne vyvinut\u00fd Langdellom et al. v roku 1953. Test je zalo\u017een\u00fd na rekalcifikovanej citr\u00e1tovej plazme, do ktorej je pridan\u00fd parci\u00e1lny tromboplast\u00edn \u00a0spolo\u010dne s jedn\u00fdm z aktiv\u00e1torov vn\u00fatornej cesty koagul\u00e1cie (kaol\u00edn, oxid kremi\u010dit\u00fd, kyselina el\u00e1gov\u00e1) \u00a0(1). Tento \u00a0test je citliv\u00fd na poruchy faktorov vn\u00fatornej cesty koagul\u00e1cie \u00a0(FVIII, FIX, FXI, FXII, prekalikre\u00edn) a taktie\u017e aj FX, protromb\u00ednu a FBG (obr\u00e1zok 1). Podobne \u00a0ako PT, m\u00f4\u017ee by\u0165 vyjadren\u00fd v sekund\u00e1ch alebo ako pomer \u00a0(7). Je zauj\u00edmav\u00e9, \u017ee deficit FXII je naj\u010dastej\u0161ou pr\u00ed\u010dinou\u00a0abnorm\u00e1lne pred\u013a\u017een\u00e9ho aPT T (30 a\u017e 50 % v\u0161etk\u00fdch pr\u00edpadov), \u010do je pova\u017eovan\u00e9 za ben\u00edgny stav. Pred\u013a\u017een\u00e9 aPT T b\u00fdva pri deficitoch faktorov FVIII, FIX, FXI, FXII, ale aj pri nespr\u00e1vnom odbere a preprave, pri \u0165a\u017ekej vWCH, inhib\u00edtoroch koagula\u010dn\u00fdch faktorov, DIC, lupus antikoagulans, pri lie\u010dbe hepar\u00ednom (najm\u00e4 s nefrakcionovan\u00fdm hepar\u00ednom), kumar\u00ednom, alebo aj pri u\u017e\u00edvan\u00ed priamych \u00a0peror\u00e1lnych antikoagulanci\u00ed \u00a0(9, 10). Vy\u0161etrenie FBG prebieha pomocou dvoch z\u00e1kladn\u00fdch met\u00f3d \u2013 funk\u010dn\u00e1 a imunologick\u00e1 (3). Funk\u010dn\u00e1 met\u00f3da \u00a0pod\u013ea Claussa bola p\u00f4vodne \u00a0op\u00edsan\u00e1 v roku 1957, je zalo\u017een\u00e1 na zriedenej citr\u00e1tovej plazme (1 : 10) \u00a0a premene FBG na fibr\u00edn pridan\u00edm vysokej koncentr\u00e1cie (100 U\/ml) tromb\u00ednu. Riedenie plazmy m\u00e1 za cie\u013e obmedzi\u0165 potenci\u00e1lny inhibi\u010dn\u00fd vplyv hepar\u00ednu alebo fibr\u00edn\/FBG degrada\u010dn\u00fdch produktov vr\u00e1tane D-dim\u00e9rov. \u010cas potrebn\u00fd na vytvorenie zrazeniny sa potom prenesie na kalibra\u010dn\u00fa \u00a0krivku, z ktorej sa vypo\u010d\u00edta kone\u010dn\u00e1 \u00a0koncentr\u00e1cia \u00a0FBG (11). Met\u00f3da pod\u013ea Claussa je najviac pou\u017e\u00edvanou met\u00f3dou v klinick\u00fdch laborat\u00f3ri\u00e1ch, pri\u010dom imunologick\u00e9 testy FBG (elektroimunodif\u00fazia alebo met\u00f3da LIA \u2013 liquid immuno assay) sa pou\u017e\u00edvaj\u00fa ako sekund\u00e1rne \u00a0testy pri diagnostike dysfibrinogen\u00e9mie, pri ktorej je diskrepancia v\u00fdsledkov medzi koncentr\u00e1ciou \u00a0antig\u00e9nu \u00a0a funk\u010dnou aktivitou FBG (3, 4).<\/p>\n
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D<\/strong>r<\/strong>u<\/strong>h<\/strong>\u00e1 a tretia l\u00ednia hemokoagula\u010dn\u00fdch testov<\/strong><\/p>\n
Abnormalita \u00a0testov prvej l\u00ednie m\u00f4\u017ee by\u0165 pr\u00ed\u010dinou jednej alebo viacer\u00fdch vroden\u00fdch por\u00fach sekund\u00e1rnej hemost\u00e1zy, av\u0161ak neumo\u017e\u0148uje presne charakterizova\u0165 poruchu, preto ani jednozna\u010dne ur\u010di\u0165 sp\u00f4sob lie\u010dby. V\u0161etky rutinn\u00e9 klinick\u00e9 laborat\u00f3ria m\u00f4\u017eu \u013eahko vykon\u00e1va\u0165 testy PT, aPT T a testy FBG (12, 13). Av\u0161ak v\u00fdznamn\u00e9 technologick\u00e9 pokroky, ku ktor\u00fdm do\u0161lo v priebehu posledn\u00fdch desa\u0165ro\u010d\u00ed, umo\u017enili okrem rutinn\u00fdch testov hemost\u00e1zy vykon\u00e1vanie \u010fal\u0161\u00edch \u0161pecifick\u00fdch testov, ktor\u00e9 umo\u017e\u0148uj\u00fa zlep\u0161i\u0165 a identifikova\u0165 dan\u00fa poruchu, a t\u00fdm klasifikova\u0165 z\u00e1va\u017enos\u0165 ochorenia. Tieto testy s\u00fa v\u00e4\u010d\u0161inou zalo\u017een\u00e9 na vy\u0161etren\u00ed jednotliv\u00fdch koagula\u010dn\u00fdch faktorov. Medzin\u00e1rodn\u00e1 \u00a0spolo\u010dnos\u0165 \u00a0pre tromb\u00f3zu \u00a0a hemost\u00e1zu (ISTH) uv\u00e1dza klasifik\u00e1ciu vroden\u00fdch \u00a0por\u00fach sekund\u00e1rnej hemost\u00e1zy pod\u013ea funk\u010dnej \u00a0aktivity koagula\u010dn\u00e9ho \u00a0faktora na \u0165a\u017ek\u00fa, stredne \u00a0\u0165a\u017ek\u00fa a \u013eahk\u00fa formu. Z tohto d\u00f4vodu s\u00fa z\u00e1va\u017en\u00e9 deficity charakterizovan\u00e9 zvy\u0161kovou aktivitou \u00a0FII, FV, FVIII, FIX < 1 %; FVII, FX, FXI a FXII 5 \u2013 10 %, a FBG < 0,1 g.l-1 (14, 15, 16). Hoci t\u00e1to klasifik\u00e1cia m\u00f4\u017ee by\u0165 u\u017eito\u010dn\u00e1 pre mana\u017ement lie\u010dby, je pozoruhodn\u00e9, \u017ee klinick\u00fd fenotyp je tie\u017e z\u00e1visl\u00fd od \u010fal\u0161\u00edch faktorov, ako je vek, pr\u00ed\u010dina \u00a0krv\u00e1cania (di\u00e9ta, trauma, pe\u010de\u0148ov\u00e9 a obli\u010dkov\u00e9 funkcie), funkcia prim\u00e1rnej hemost\u00e1zy (funkcia a po\u010det krvn\u00fdch do\u0161ti\u010diek, \u00farove\u0148 aktivity a vWF), aktivita in\u00fdch koagula\u010dn\u00fdch faktorov a fibrinolytick\u00e9ho potenci\u00e1lu (15).<\/p>\n
Medzi \u00a0\u010fal\u0161ie testy druhej l\u00ednie, ktor\u00e9 sa m\u00f4\u017eu realizova\u0165 v rutinn\u00fdch klinick\u00fdch laborat\u00f3ri\u00e1ch, patria test na diferenci\u00e1lnu diagnostiku medzi vroden\u00fdm deficitom koagula\u010dn\u00e9ho faktora, pr\u00edtomnos\u0165ou inhib\u00edtorov alebo antikoagulanci\u00ed \u00a0(17), testy na diagnostiku vWCH (vWF antig\u00e9n a aktivita, napr\u00edklad ristocet\u00ednov\u00fd kofaktor, test v\u00e4zby kolag\u00e9nu \u2013 colagen binding assay \u2013 CBA (1) a tromb\u00ednov\u00fd \u010das (T T). T T je zalo\u017een\u00fd na rekalcifikovanej citr\u00e1tovej plazme a aktiv\u00e1cii tvorby fibr\u00ednu pridan\u00edm tromb\u00ednu do testo- vanej vzorky. Tento test sa pou\u017e\u00edva hlavne na detekciu por\u00fach FBG a na identifik\u00e1ciu kontaminovanej vzorky s inhib\u00edtorom tromb\u00ednu, najm\u00e4 liekmi inhibuj\u00facimi \u00a0FIIa, ako je napr\u00edklad dabigatran. Aj ke\u010f tento test bol pou\u017e\u00edvan\u00fd v minulosti ako test prvej l\u00ednie, jeho vyu\u017eitie na skr\u00edning pacientov s podozren\u00edm na vroden\u00e9 poruchy sekund\u00e1rnej hemost\u00e1zy je do zna\u010dnej miery irelevantn\u00e9, vzh\u013eadom \u00a0na to, \u017ee kombin\u00e1cia testov PT, aPT T a FBG, ktor\u00fa v\u00e4\u010d\u0161ina laborat\u00f3ri\u00ed vykon\u00e1va, je dostato\u010dn\u00e1 \u00a0(18). Samozrejmos\u0165ou je, \u017ee T T m\u00f4\u017ee by\u0165 u\u017eito\u010dn\u00fd ako s\u00fa\u010das\u0165 rutinnej diagnostiky na odl\u00ed\u0161enie lie\u010dby hepar\u00ednom a priamymi inhib\u00edtormi anti-Xa (10).<\/p>\n
Testy tretej l\u00ednie zah\u0155\u0148aj\u00fa imunologick\u00e9 met\u00f3dy na odl\u00ed\u0161enie kvantitat\u00edvnych por\u00fach od kvalitat\u00edvnych por\u00fach koagula\u010dn\u00fdch faktorov a taktie\u017e k nim \u00a0zara\u010fujeme \u00a0aj genetick\u00e9 \u00a0anal\u00fdzy, ktor\u00fdch \u00a0cie\u013eom \u00a0je identifik\u00e1cia \u0161pecifick\u00fdch mut\u00e1ci\u00ed v g\u00e9ne k\u00f3duj\u00facom \u00a0pr\u00edslu\u0161n\u00fd koagula\u010dn\u00fd faktor. T\u00fdmito testami dod\u00e1vame \u00a0jasn\u00fd obraz o tejto skupine ochoren\u00ed \u00a0(1). Za zmienku stoj\u00ed, \u017ee testy tretej l\u00ednie nie s\u00fa be\u017ene dostupn\u00e9\u00a0 a \u010dasto s\u00fa finan\u010dne n\u00e1ro\u010dnej\u0161ie a z\u00e1rove\u0148 vy\u017eaduj\u00fa \u0161pecializovan\u00e9 technick\u00e9 vybavenie a spr\u00e1vnu \u00a0interpret\u00e1ciu \u00a0v\u00fdsledkov. T\u00e1to diagnostika \u00a0je s\u00fastreden\u00e1 \u00a0do \u0161pecializovan\u00fdch centier (3).<\/p>\n
 <\/p>\n
Pr<\/strong>a<\/strong>gm<\/strong>a<\/strong>t<\/strong>i<\/strong>c<\/strong>k<\/strong>\u00fd diagnostick\u00fd pr\u00edstup u pacienta s neobjasnen\u00fdm krv\u00e1can\u00edm<\/strong><\/p>\n
Vzh\u013eadom na zlo\u017eitos\u0165 prim\u00e1rnej a sekund\u00e1rnej hemost\u00e1zy by mala presn\u00e1 diagnostika vroden\u00fdch krv\u00e1cav\u00fdch por\u00fach sekund\u00e1rne hemost\u00e1zy zah\u0155\u0148a\u0165 zhroma\u017e\u010fovanie \u00fadajov osobnej a rodinnej anamn\u00e9zy, v\u00fdsledky prvej l\u00ednie testov (skr\u00edningov\u00fdch testov), ktor\u00e9 s\u00fa doplnen\u00e9 vy\u0161etreniami druhej alebo \u00a0aj tretej l\u00ednie testov. Tieto vy\u0161etrenia definit\u00edvne stanovia klinick\u00fd fenotyp \u00a0pacienta \u00a0(4). Pr\u00edstup k diagnostike pacienta \u00a0s vrodenou krv\u00e1cavou poruchou sekund\u00e1rnej hemost\u00e1zy mo\u017eno navrhn\u00fa\u0165 nieko\u013ek\u00fdmi praktick\u00fdmi odpor\u00fa\u010daniami, ktor\u00e9 s\u00fa uveden\u00e9 \u00a0na obr\u00e1zku 2. Pri poruch\u00e1ch sekund\u00e1rnej hemost\u00e1zy je pr\u00edtomn\u00fd \u010dastej\u0161\u00ed v\u00fdskyt hemat\u00f3mov do hlbok\u00fdch \u0161trukt\u00far (tabu\u013eka 1) ako mukokut\u00e1nnych \u00a0krv\u00e1can\u00ed, aj ke\u010f vytvorenie hranice medzi poruchami prim\u00e1rnej a sekund\u00e1rnej hemost\u00e1zy b\u00fdva \u010dasto \u0165a\u017eko stanovite\u013en\u00e9 (12). Pri podozren\u00ed \u00a0na poruchu prim\u00e1rnej hemost\u00e1zy (porucha funkcie alebo po\u010dtu trombocytov) je d\u00f4le\u017eit\u00e9 doplni\u0165 \u0161pecifick\u00e9 testy na vWCH (antig\u00e9n a aktivita vWF), aby sa vyl\u00fa\u010dila alebo potvrdila bu\u010f pr\u00edtomnos\u0165 vWCH, alebo in\u00fdch por\u00fach trombocytov (19, 20). Ako u\u017e bolo spomenut\u00e9, pozit\u00edvna rodinn\u00e1 anamn\u00e9za krv\u00e1cav\u00e9ho ochorenia je d\u00f4le\u017eit\u00e1 pre pr\u00edtomnos\u0165 vroden\u00e9ho \u00a0stavu. Av\u0161ak, nedostatok klinicky v\u00fdznamn\u00fdch sympt\u00f3mov u pr\u00edbuzn\u00fdch pacienta nie v\u017edy sved\u010d\u00ed o z\u00edskanej poruche (a\u017e 30 % deficitov koagula\u010dn\u00fdch \u00a0faktorov sa jav\u00ed ako de novo<\/em>). Ak bol n\u00e1stup prv\u00fdch klinick\u00fdch prejavov pri naroden\u00ed alebo v ranom detstve, zv\u00e4\u010d\u0161a ide o vroden\u00e9 poruchy oproti z\u00edskan\u00fdm poruch\u00e1m, ktor\u00e9 m\u00f4\u017eu vznikn\u00fa\u0165 po\u010das cel\u00e9ho \u017eivota (DIC, z\u00edskan\u00e1 hemof\u00edlia, inhib\u00edtory na in\u00e9 koagula\u010dn\u00e9 faktory, ochorenia \u00a0pe\u010dene, antikoagula\u010dn\u00e1 terapia) (1).<\/p>\n
 <\/p>\n
Z<\/strong>\u00e1<\/strong>ver<\/strong><\/p>\n
Pr\u00edtomnos\u0165 krv\u00e1can\u00ed do hlbok\u00fdch \u00a0\u0161trukt\u00far poukazuje \u00a0na poruchu sekund\u00e1rnej hemost\u00e1zy. U pacientov s vroden\u00fdmi poruchami \u00a0je \u010dast\u00e1 pozit\u00edvna rodinn\u00e1 anamn\u00e9za, nedostatok klinicky v\u00fdznamn\u00fdch \u00a0sympt\u00f3mov u pr\u00edbuzn\u00fdch pacientov m\u00f4\u017ee sved\u010di\u0165 o z\u00edskanej poruche hemost\u00e1zy. D\u00f4le\u017eit\u00e9 v r\u00e1mci diagnostiky krv\u00e1cav\u00fdch por\u00fach sekund\u00e1rnej hemost\u00e1zy je okrem vyhodnotenia \u00a0koagula\u010dn\u00fdch \u00a0testov prvej l\u00ednie aj vy\u0161etrenie testov druhej l\u00ednie, najm\u00e4 vy\u0161etren\u00ed jednotliv\u00fdch koagula\u010dn\u00fdch faktorov, ktor\u00e9 n\u00e1m poskytuj\u00fa z\u00e1klad pre predbe\u017en\u00fa diagn\u00f3zu. Na definit\u00edvne stanovenie diagn\u00f3zy je nutn\u00e9 doplni\u0165 aj testy tretej l\u00ednie (imunologick\u00e9 testy koagula\u010dn\u00fdch \u00a0faktorov a geneticko-molekulov\u00e1 anal\u00fdza), ktor\u00e9 n\u00e1m potvrdzuj\u00fa kone\u010dn\u00fa \u00a0diagn\u00f3zu, pr\u00edpadne konkr\u00e9tny deficit faktora (kvantitat\u00edvne alebo funk\u010dn\u00e9).<\/p>\n
Po\u010fakovanie: <\/em>P<\/em>r<\/em>\u00e1<\/em>c<\/em>a bola podporen\u00e1 projektmi: APVV 0222-11, Vega\u00a0<\/em>1<\/em>\/<\/em>0<\/em>1<\/em>68<\/em>\/<\/em>1<\/em>6<\/em>, Grant Univerzity Komensk\u00e9ho (<\/em>U<\/em>K<\/em> \/334\/2015) <\/em>a Martinsk\u00e9 centrum pre biomedic\u00ednu \u00a0(BioMed Martin, ITMS 26220220187), ktor\u00e9 s\u00fa spolufinanco- van\u00e9 zo zdrojov E\u00da.<\/em><\/p>\n
 <\/p>\n
L<\/strong>it<\/strong>e<\/strong>ra<\/strong>t<\/strong>\u00fa<\/strong>ra<\/strong><\/p>\n
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        1. de Moerloose P, Casini A, Neerman-Arbez M. Congenital fibrinogen disorders: an upd\u00a0Semi<\/em>n<\/em>T<\/em>h<\/em>r<\/em>om<\/em>b Hemost. <\/em>2013;39:585\u2013595.<\/li>\n<\/ol>\n
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                            2. \u0160kor\u0148ov\u00e1 I, Sta\u0161ko J, Holl\u00fd \u00a0P, et al. Anal\u00fdza \u00a0multim\u00e9rov \u00a0von Willebrandovho \u00a0faktora pri von Willebrandovej chorobe. V<\/em>ask <\/em>me<\/em>d<\/em>. <\/em>2014;6:32\u201334.<\/li>\n
                            3. Sta\u0161ko J, Stan\u010diakov\u00e1 \u00a0L, Sokol J, et al. Krv\u00e1cav\u00e9 trombocytopatie. Vask med. <\/em>2013;5:74\u201380.<\/li>\n<\/ol>\n
                               <\/p>\n
                               <\/p>\n
                               <\/p>\n","protected":false},"excerpt":{"rendered":"
                              *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper. Klinick\u00e1 anamn\u00e9za Hemost\u00e1za je pova\u017eovan\u00e1 za komplikovan\u00fd mechanizmus v organizme, ktor\u00e9ho cie\u013eom je zabr\u00e1ni\u0165 nadmern\u00e9mu krv\u00e1caniu v mieste poranenia cievy (1). Proces zastavania krv\u00e1cania za\u010d\u00edna v mieste po\u0161kodenia endotelu, \u010do<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[294],"tags":[653,654,652,651,655,656],"class_list":["post-1058","post","type-post","status-publish","format-standard","hentry","category-hematology","tag-bleeding-disorders","tag-coagulation","tag-diagnosis","tag-factor-deficiencies","tag-laboratory-testing","tag-secondary-hemostasis","typ_clanku-review-article"],"acf":{"abstrakt":"
                              Diagnosis of inherited bleeding disorders of secondary hemostasis remains a great challenge for most clinical laboratories. Bleeding can be essentially caused by a variety of acquired or congenital conditions which impair either primary or secondary hemostasis. Since a universally agreed approach for the diagnostics of hemorrhagic disorders is still unavailable, this article aims to provide an easy guidance for routine clinical laboratories.\u00a0 This pragmatic approach to identifying and diagnosing inherited bleeding disorders of secondary hemostasis entails a multifaceted strategy based on a collection of personal and family history data, the results of first-line tests which can then be followed by second-or third-line analyses to definitely establish the specific nature and the severity of the bleeding phenotype. Briefly, the presence of profound hemorrhages rather than mucocutaneous bleeding is suggestive of a disorder of secondary hemostasis. Although a positive family history is frequently reported in patients with congenital conditions, the lack of clinically meaningful symptoms in patient\u2019s relatives may be indicative of an acquired disorder. The next step encompasses the assessment of first-line coagulation tests (i.e., prothrombin time, activated partial thromboplastin tim and fibrinogen test), what makes sense particularly if family history is not suggestive of a specific factor deficiency. The emergence of abnormal data of these assays and the variable combination of their results is then helpful to guide the performance of second-line tests, in particular, specific coagulation factor assays which will then provide a reasonable basis for a preliminary diagnosis. Third-line tests (immunoassays of coagulation factors and genetic and molecular analysis) which is concentrated in the specialized centres is necessary for the final confirmation of the diagnosis.<\/p>\n
                              Key words:<\/strong> factor deficiencies, diagnosis, bleeding disorders, coagulation, laboratory testing, secondary hemostasis<\/p>\n","casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"
                                \r\n \t
                              • Pulmonary aspergillosis<\/li>\r\n \t
                              • Infections caused by cytomegalovirus \u2013 diagnosis and therapy<\/li>\r\n \t
                              • Long-term molecular remission as a precondition for successful pregnancy in patients with chronic myelocyte leukemia<\/li>\r\n \t
                              • Chromosome 11 aberrations in a patient with acute myeloid leukemia \u2013 a case study<\/li>\r\n \t
                              • New biomarkers in diagnosing IgA nephropathy<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2016-02","to_ping":"","pinged":"","post_modified":"2017-08-16 21:36:48","post_modified_gmt":"2017-08-16 19:36:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2016-02\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"98","upload_clanok":{"ID":1059,"id":1059,"title":"Newslab_2_2016_Diagnostika vroden\u00fdch krv\u00e1cav\u00fdch por\u00fach","filename":"Newslab_2_2016_Diagnostika-vroden\u00fdch-krv\u00e1cav\u00fdch-por\u00fach.pdf","filesize":269405,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/01\/Newslab_2_2016_Diagnostika-vroden\u00fdch-krv\u00e1cav\u00fdch-por\u00fach.pdf","link":"https:\/\/www.newslab.sk\/en\/diagnosis-of-inherited-bleeding-disorders-of-secondary-hemostasis-a-simple-guide-for-routine-clinical-laboratories\/newslab_2_2016_diagnostika-vrodenych-krvacavych-poruch\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2_2016_diagnostika-vrodenych-krvacavych-poruch","status":"inherit","uploaded_to":1058,"date":"2017-02-01 19:39:47","modified":"2017-02-01 19:39:47","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1058","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1058"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1058\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1058"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1058"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1058"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}