SummaryIn two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The first study comparing 1 x 7′500 anti-factor Xa IU LMW heparin daily with 2 x 5′000 IU UF heparin was interrupted because of excessive bleeding complications (LMW heparin: 11/23 pts, UF heparin: 2/20 pts, p <0.01). In the second study (146 pts) the dose of LMW heparin was reduced to 1 x 2′500 anti-factor Xa IU. Bleeding complications (LMW heparin: 14.9%, UF heparin: 15.3%) and thromboembolic events (LMW heparin: 2.86%, UF heparin: 2.94%) were equal among the two groups.2′500 anti-factor Xa IU/day of this LMW heparin fragment, corresponding to 15 mg/day, is the lowest dose of a LMW heparin used in a randomized clinical trial and was found to be a safe and efficient regimen in perioperative thrombosis prophylaxis. An advantage of LMW heparin over UF heparin is its once daily administration.

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AT III deficiency is associated with a high risk of venous thromboembolism, particularly in pregnancy. As prophylactic treatment it has been recommended to normalize plasma levels of AT in by use of AT III concentrates, besides giving heparin.We report on the prophylactic treatment of three sisters (age 21, 25, 32 years) with congenital AT in deficiency (38-53%, normal: 80-120%) as well as a reduced inducible fibrinolytic activity (1.2, 5.8, 7.9%, normal: >8.5%), who already had suffered from severe thromboembolism. During pregnancy prophylactic measures were taken individually, depending on the plasma level of 3-throm-boglobulin (BTG) determined every 2-3 weeks. At the time of the first increase of BTG (around 10th week of gestation) prophylaxis with s. c.heparin 2x7'500IU/d was started, leading to normalization of BTG. When BTG was again elevated, the dose of heparin was successively increased up to 2x15'000IU/d; thereby, functional AT IH levels remained in the range of 28-50%. Two patients received only heparin throughout the pregnancy. However, in one patient BTG levels could not be normalized by heparin alone (60-130ng/ml, normal: <43ng/ml). Injections of AT in concentrate, 11000IU, led to reduction of BTG within 2 hrs (60 → 42, 220 → 61 ng/ml). Therefore, AT m was given from the 25th week of gestation in increasing amounts up to 5'000IU/week (funct. AT m in plasma: 51 -72%) in addition to heparin (2x12'500IU/d), resulting in BTG levels of 33-51 ng/ml. From the onset of labour, all patients received AT IU concentrates (two patients l'OOOIU every second day, one patient 1'0001U daily) together with i. v. heparin 20'000-27'500IU/d, until the oral anticoagulant treatment started after delivery had reached therapeutic levels. The amount of AT m concentrate totally administered was 5'000IU in two patients and 66'000IU in one patient. None of the patients showed ever signs of venous thrombosis.Our observations demonstrate that instead of an AT in substitution with the aim to normalize its plasma level, an effective thrombosis prophylaxis - monitored by plasma levels of BTG - may be achieved with heparin alone or combined with low amounts of AT in concentrate.