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ID naloge: 167 Letnik: 2003 Predmet: interna medicina
TESTI STRJEVANJA KRVI MED NOSECNOSTJO PRI ZDRAVIH IN PRI BOLNICAH Z VENSKO TROMBOZO
Avtor: Bor Antolic
Mentor: prof. dr. Polona Peternel
IZHODIŠCE: Venska tromboza (VT) je redek, a resen zaplet nosecnosti in poporodnega obdobja in je skupaj s svojim akutnim zapletom, pljucno embolijo (PE), glavni vzrok maternalne umrljivosti in obolevnosti. Zdravilo izbora za preprecevanje in zdravljenje venske tromboze je nizkomolekularni heparin (NMH), ki ga odmerjamo glede na telesno težo (TT). Vprašanja glede odmerjanja NMH za zdravljenje VT med nosecnostjo in potreba po zašciti pred VT v nosecnosti niso dokoncno rešena.
NAMEN: Spremljanje antikoagulacijskega ucinka NMH pri bolnicah z VT v sedanji ali pretekli nosecnosti in ocenjevanje aktivacije strjevanja krvi.
HIPOTEZA: Predpostavljamo, da odmerka NMH ni treba spreminjati glede na porast TT med nosecnostjo. Pricakujemo porast kazalcev aktivacije strjevanja krvi med nosecnostjo. Pri nosecnicah z VT pricakujemo vecji porast teh kazalcev kot pri zdravih.
METODE: V prospektivno raziskavo smo vkljucili 22 zaporednih nosecnic, starih od 20 do 42 (x? =32) let, ki so se zdravile v Klinicnem centru, v casu od aprila 2001 do maja 2003, zaradi VT v sedanji ali pretekli nosecnosti. Kontrolno skupino je sestavljalo 9 zdravih nosecnic, starih od 24 do 38 (x? =31) let. Bolnice smo razporedili v tri skupine. Skupino A je sestavljalo 11 nosecnic z VT v sedanji nosecnosti, ki so prejemale dalteparin v terapevtskem odmerku (200 i.e./kg izhodišcne TT v enem oziroma 100 i.e./kg v dveh odmerkih na dan) skozi vso nosecnost. V skupino B so bile vkljucene 4 nosecnice, ki so imele VT v pretekli nosecnosti. Prejemale so dalteparin v preventivnem odmerku (2500 ali 5000 i.e./dan). Odmerka dalteparina med nosecnostjo nismo spreminjali. V skupino C je bilo vkljucenih 7 nosecnic, ki so imele VT v pretekli nosecnosti, vedar so bile brez farmakološke zašcite med sedanjo nosecnostjo. Vsem preiskovankam, ki so prejemale dalteparin, smo dolocali aktivnost proti aktiviranemu faktorju X (aktivnost anti-Xa) v venski krvi enkrat mesecno s kromogeno metodo. Pri vseh preiskovankah smo enkrat mesecno merili kazalca aktivacije strjevanja krvi: protrombinski fragment 1+2 (F1+2) in kompleks trombin-antitrombin (TAT) z encimsko imunskimi metodami, D-dimer pa smo dolocali z imunoturbidimetricno metodo.
REZULTATI: Pri preiskovankah je TT med nosecnostjo narasla od 10,7 do 15,3 (x? =13,1) kg. Pri bolnicah iz skupine A, smo izmerili aktivnost anti-Xa v normalnem terapevtskem obmocju (0,66-1,03 i.e./mL) ves cas nosecnosti. Pri bolnicah iz skupine B smo izmerili aktivnost anti-Xa v obmocju od 0,34 do 0,65 i.e./mL. Pri skupini A smo med nosecnostjo izmerili porast F1+2 (0,9-1,6 nmol/L), TAT (1,7-4,4 mcg/L) in D-dimera (68-316 mcg/L), korelacija z meseci nosecnosti je bila povsod znacilna (p<0,05). Pri skupini B smo izmerili porast TAT (2,5-3,6 mcg/L) in D-dimera (130-375 mcg/L), korelacija povsod neznacilna (NS). Pri skupini C smo izmerili porast F1+2 (0,5-1,3 nmol/L), TAT (1,5-4,8 mcg/L) in D-dimera (131-760 mcg/L), korelacija povsod znacilna (p<0,05). Pri kontrolni skupini smo izmerili porast F1+2 (0,7-1,4 nmol/L), TAT (1,6-3,5 mcg/L) in D-dimera (67-406 mcg/L), korelacija povsod znacilna (p<0,05). Znacilnih razlik v porastu F1+2, TAT in D-dimeru med skupinami ni bilo.
ZAKLJUCKI: Aktivnost anti-Xa se pri bolnicah, ki so prejemale dalteparin, ni spreminjala in je ostajala kljub porastu TT venomer v terapevtskem odmocju, tako da menimo, da odmerjanje skladno s porastom TT v nosecnosti ni potrebno. Pri nosecnicah z VT v sedanji ali pretekli nosecnosti in pri zdravih preiskovankah so porasli kazalci aktivacije strjevanja krvi. Nismo zasledili znacilnih razlik v F1+2, TAT in D-dimerom med posameznimi skupinami, kar pripisujemo fiziološki prilagoditvi hemostatskega sistema med nosecnostjo in vplivu NMH na F1+2, TAT oziroma D-dimer.
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[Abstract / English version]
TESTI STRJEVANJA KRVI MED NOSECNOSTJO PRI ZDRAVIH IN PRI BOLNICAH Z VENSKO TROMBOZO
Author: Bor Antolic
Mentor: prof. dr. Polona Peternel
BACKGROUND: Venous thromboembolism (VT) is a rare but serious complication of pregnancy and puerperium and with its acute phase complication - pulmonary embolism (PE) - constitutes the major cause of maternal morbidity and mortality. Low-molecular-weight heparin (LMWH), administered in weight-adjusted doses, is the treatment of choice for VT. Dosing of LMWH for treatment of VT and the need for thromboprophylaxis during pregnancy is contentious.
AIM: To monitor the anticoagulant effect of LMWH in patients with an episode of VT in past or current pregnancy and to assess hemostatic system activation.
HYPOTHESIS: Dosing of LMWH during pregnancy needs not to be altered in proportion to the change in weight during pregnancy. The markers of hemostatic system activation increase during pregnancy. The increase of markers of hemostatic system activation is higher in pregnant women with VT than in healthy pregnant women.
METHODS: A prospective study was set in Ljubljana University Medical Centre. Twenty-two consecutive pregnant women, aged 20 to 42 (x? =32,0) yrs, with a past or present episode of VT, were included in the study between April 2001 and May 2003. The control group consisted of 9 healthy pregnant women, aged 24 to 38 (x? =31,2) yrs. We assigned our patients into three groups. Group A consisted of 11 pregnant women with VT in current pregnancy. They received LMWH dalteparin in initially weight-adjusted doses (100 IU/kg/bd or 200 IU/kg daily) during entire pregnancy. Group B consisted of 4 pregnant women with VT in their previous pregnancy. They received 2500 or 5000 IU of dalteparin daily. The dosing of dalteparin has not been altered during pregnancy. Group C consisted of 7 pregnant women with VT in their previous pregnancy, with no pharmacological prophylaxis during current pregnancy. We performed serial monthly anti-Xa assays in all patients on dalteparin using chromogenic method. We measured concentrations of markers of hemostatic system activation monthly in all groups. We used an enzyme-linked immunosorbent assay (prothrombin fragment 1+2 and thrombin-antithrombin complex) and immunoturbidimetric assay (D-dimer).
RESULTS: The average increase in body weight in the study group was 13,1 (10,7-15,3) kg. The anti-Xa activity of the patients receiving therapeutic doses of dalteparin stayed in target therapeutic range (0,66-1,03 IU/mL) during entire pregnancy. The measured anti-Xa activity of pregnant patients receiving prophylactic doses of dalteparin ranged from 0,34-0,65 IU/mL. In group A we found increase in F1+2 (0,9-1,6 nmol/L), TAT (1,7-4,4 mcg/L) and D-dimer (68-316 mcg/L) during pregnancy, correlation with months of pregnancy was significant (p<0,05). In group B we found increase in TAT (2,5-3,6 mcg/L) and D-dimer (130-375 mcg/L), correlation was always nonsignificant (NS). In group C we found increase in F1+2 (0,5-1,3 nmol/L), TAT (1,5-4,8 mcg/L) and D-dimer (131-760 mcg/L), correlation was always significant (p<0,05). In control group we found increase in F1+2 (0,7-1,4 nmol/L), TAT (1,6-3,5 mcg/L) and D-dimer (67-406 mcg/L), correlation was always significant (p<0,05). There were no differences in increments of F1+2, TAT or D-dimer activation among groups.
CONCLUSIONS: In all our patients receiving dalteparin the anti-Xa activity remained in the target range despite weight gain during pregnancy. We therefore think that adjusting the dose according to weight gain in pregnancy is not necessary. The markers of hemostatic system activation have increased in all four groups. There were no differences in concentrations of F1+2, TAT and D-dimer among groups, because, in our opinion, of the physiologic adaptation of coagulation system during pregnancy and the effect of LMWH on F1+2, TAT and D-dimer.
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