No abstract

SummaryThe low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily.In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 ± 7,150 IU/day (mean ± SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distal-proximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean±SD) was 751 ± 339 ml (LMWH/DHE) and 736 ± 380 ml (UFH), whereas postoperative drain-loss volume (mean ± SD) was found to be 523 ± 333 ml (LMWH/DHE) and 581 ± 404 ml (UFH). Whole blood transfusion volumes (mean ± SD) were 570 ± 202 ml (LMWH/DHE) and 748 ± 455 ml (UFH). Additionally, red cell replacement volumes (mean ± SD) were 804 ± 435 ml (LMWH/DHE) and 720 ± 328 ml (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant.Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

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

BackgroundHyperkalemia is an infrequent but potentially serious complication of low molecular weight heparin (LMWH) use. While there are a number of trials comparing LMWH to unfractionated heparin (UFH) there is no comparison of the risk with LMWH versus placebo. Aim of the present post-hoc analysis of the PARAT trial was the description of serum potassium levels with certoparin compared to placebo.ResultsPARAT was a double-blind, placebo-controlled, randomized trial in patients with coronary artery disease receiving either 8,000 I.U. aXa per day or placebo. Serum potassium was monitored at baseline and at scheduled follow-up visits at 2 and 4–6 weeks and 3 and 4–6 months. Statistical evaluation included paired, two sided t-test for each of the treatment groups to compare baseline and follow-up values. A total of 117 patients (59 certoparin, 58 placebo) were included with a mean age of 59 years and 84.6% male gender. There was a statistically significant increase in serum potassium at two weeks after discharge compared to baseline (p < 0.001) in either group which remained elevated throughout the three months treatment phase. Differences between treatment groups were not statistically significant. After treatment discontinuation at the three months’ visit serum potassium returned to normal values (p = n.s. vs. baseline) in both groups. Overall 12 out of 59 patients receiving certoparin (20.3%) and 11 out of 58 patients receiving placebo (19.0%) experienced hyperkalemia based on threshold of >5.0 mmol/l at any time during the observation.ConclusionsWe conclude that there is no incremental risk of hyperkalemia with certoparin up to 8,000 I.U. aXa per day versus placebo in patients with coronary artery disease. The increase in serum potassium values in either group calls for clinical surveillance and the consideration of further risk factors predisposing to hyperkalemia.

BackgroundThe aim was to investigate, whether 5,000 IUaXa/day certoparin lowers the incidence of deep vein thrombosis (DVT) in patients undergoing elective hip replacement surgery vs. 3,000 IUaXa/day. Double-blind, multicenter, randomised trial in 500 patients. Primary endpoint: incidence of symptomatic or asymptomatic DVT (bilateral ascending venography).ResultsMean age was 71 ± 10 years with a higher prevalence of previous DVT (8vs.4%) and pulmonary embolism (PE) (4vs.1%) in the high dose group. Mean duration of surgery was 82 ± 32 and 85 ± 36 min. DVT was detected in 28 (11.1%) of the low dose and 35 (14.1%) of the high dose group (p = n.s.). Combined distal-proximal DVT was observed in 5 (2%) and 4 (1.6%) patients respectively. No difference in bleeding events was found.ConclusionThis trial confirms prior data showing that the conventional dosage of 3,000 IU aXa is effective and safe for the prevention of venous thromboembolic events after hip replacement surgery.