Low-Dose-Heparin versus niedermolekulares Heparin zur Thromboseprophylaxe in der operativen gynäkologischen Onkologie

Abstract

Zusammenfassung: In eine r prospekt iven dop pelb lind randomisierte n Studie wurden Wirksa m ke it und Vert räg lichke it e ine s niederm oleku lar en Heparins (M on o-Embol ex NM, Sandoz AG, Nürn berg) mi t unfraktio niertem Kalzium Hepari n in der Proph ylaxe post op erative r Venenthro m bosen be i gynäko log ischen Ma ligno mpatienti nne n ver g liche n. 2 h präoperativ und da nn in S-h-Intervallen postoper at iv erhielten 164 Pat ientinn en 3 x 50 000 IE unfraktion iert es Heparin (UFH) und 160 Patienti nnen 300 IU niederm olekul ares Hepari n (NMH) in Kombinat ion m it 2 Plazeboinj ekt icn en. Um die Inzidenz tiefer Beinvenent hrombose n (lVT) festzu st elle n. wurde prä-und pos to perativ a lle 2 Tage ei ne Imp ed an zpl eth ysm ogr aph ie du rchgefü hrt. Bei pa t ho logische m Befund od er klinischem Ve rdac ht e rfo lgt e eine Phleb og raphie. Phleb o g raph isch be st äti gte DVT trat en bei 6.3 % in der NMH-und be i 6,1% in de r UFH-Gru ppe a uf. Gleichzeitig e ntwi kke lt en 2.4 % in der UFH-und 4,3 % in de r NMH-Gruppe (m it e inem t öd lichen Ausg an g), e ine l un gen embolie. Die Inzid en z wa r statist isch nich t sign ifika nt unte rschied lich. Oie Rat e der po st o pe rat iven Blutungskom plikat io ne n (Wun dh ämat o m e: p = 0,01, Anzah l der Blutk o nse rve n: p = 0.0005) wa r zuunq unsten vo n UFH e rhö ht. Die Drainag everlu st e wa re n im Mitte l (295 ml UFH VS. 264 ml NMH) ident isch bei allerdings erhöhtem Ve rlust a m 3. po st op er ati ven Tag in de r UFH-Grup pe (p = 0,02). Oie vorliege nde St ud ie bei gy nä ko log ische n Malign ompat ientinn en ze igt eine hoh e abe r nicht unt e rschied liche pos tope rative Thro mb ose inziden z, wobe i l un gen embol ien nicht sig nifikan t häufige r während der NMH-Prophylaxe a uft rate n. Die lnziden z e rhe bliche r Blutu ngskomp likat ion en lag in der UFH-Gru ppe höh er. Oie e inmal ige Gabe de s niedermoleku la ren He parin s ist ebenso siche r wie unfra kt ioniertes He pari n zur Ve rhü tu ng ei ner OVTbe i wes e ntlich geringere n Blut ungs komplikat ione n. Prevention of Postoperative Venous Thrombosis. A Randomised Trial Comparing Lew-Dose Heparin and Low Molecular Weight Heparin in Gynaecological Oncology: In a prosp e ctive d oubl e-blind ra nd omi se d st udy t he efficacy en d sa fety of a lo w m o le cu lar weight hepa rin (lMWH) and un fract ion at ed he pa rin (UFH) were com pared in t he use of per to pe rative prophy laxis for t hrombosis in gy naecologi ca l pat ients underg o ing m ajor gyn aecolo gica l ca nce r surge ry. Th ree hundred and thirty pat ients were ra nd o m ly alloca te d t o the two prophylacti c g ro ups; 6 of t hese were dropo uts of t he st udy. Of th e remai ning 324 pa t ients 160 received 3000 IU of lo w molecul ar weig ht hep ar in a nd 164 re ceived subc uta neously 5000 IU un

State-of-the-Art Review : Chemotherapy and Thrombosis in Gynecologic Malignancy

“…However, neither TAT, Ddimer nor prothrombin fragment Fl + 2 significantly changed and the authors concluded that CMF therapy did not initiate disseminated intravascular coagulation (DIC). This view is supported by a study in which serial coagulation assays performed before each of six cycles , 4. Studies on changes in blood coagulation and blood rheology during hormonal cytoreductive therapy in breast cancer and miscellaneous cancer patients DVT, deep vein thrombosis; FPA, fibrinopeptid A; MPCA, monocyte procoagulant activity; TPA, tissue plasminogen activator; uPA, urokinasetype plasminogen activator; PAI-1, -2, plasminogen activator inhibitor type I or type 2; aPTT, activated partial thromboplastin time, PT, prothrombin time; TT, thrombin time; AC, adriamycin/cyclophosphamid; MPA, medroxyprogesterone acetate; PIP, plasmin inhibitor plasminogen; FDP, fibrinogen degradation products; CT, chemotherapy; JABCS, Japan Advanced Breast Cancer Study Group; ag, antigen; act, activity.…”

“…4.8% (range of means: 3.1-9.3%) was recorded. This is more than twice as high as compared to the average mean rate of 1.7% (range of means: 0-5.6%) found in eight studies during tamoxifen mono therapy based on a total of 3,184 patients without metastasis (7,54,63,64,(67)(68)(69)(70).…”

“…In four studies during concurrent tamoxifen and chemotherapy for nonmetastatic breast cancer in 1,102 patients (6,54,63,64) an average mean DVT incidence of EC, 5 fluorouracil/epirubicin/cyclophosphamide; CMF, cyclophosphamid/methotrexat/fluorouacil; AC, adriamycin/cyclophosphamid; EC, epirubicin cyclophosphamid; FPA, fibrinopeptide A; aPTT, activated partial thromboplastin time; PT, prothrombin time; TAT, thrombin-antithrombin complex; PIP, plasmin-inhibitor plasminogen; PAI-1, plasminogen activator inhibitor type 1; TPA, tissue plasminogen activator; TT, thrombin time; RBC, red blood cell; INR, International Normalized Ratio; ag, antigen; act, activity; VP, vincristine/prednisone. 4.8% (range of means: 3.1-9.3%) was recorded. This is more than twice as high as compared to the average mean rate of 1.7% (range of means: 0-5.6%) found in eight studies during tamoxifen mono therapy based on a total of 3,184 patients without metastasis (7,54,63,64,(67)(68)(69)(70).…”

Low molecular weight heparins: are they interchangeable? No

“…However, meta‐analyses on a drug class may fail to document a clinical effect in terms of efficacy/safety ratio when the different drugs behave differently in the various studies. In effect, when compared to UFH, some LMWHs showed better efficacy but equal safety [4,5], others better safety but equal efficacy [6–8], and still others equal efficacy but lower safety [9]. Halving the dose of the latter LMWH proved safer but less effective [10,11]; incidentally, this half‐dosage had been shown to be equally efficacious but safer than UFH [12]· Such conflicting results may annihilate one another when pooled in a meta‐analysis.…”