The economy class syndrome--a survey of 19 cases.

BACKGROUND: Thromboembolic events during or immediately after long-distance flights (economy class syndrome--ECS) are gaining more importance due to the rapidly increasing number of flights. Systematic data on haemostatic parameters in these patients are not available yet. PATIENTS AND METHODS: We were therefore analyzing the anamnestic, laboratory and clinical findings in 19 patients (17 males, 2 females, aged 33-75 years) with the final clinical diagnosis ECS. RESULTS: Symptoms commenced either immediately or up to 93 hours after disembarkation (mean 42.3 hours). In the great majority (84.2%) myocardial infarction was the initial diagnosis. No defect in the coagulation and/or prostaglandin system was discovered in either of the patients. Prevalence of smoking (26.3%) was even lower than in the normal population. No predisposing factors were found. Apparent anamnestic similarities were flu and fever (47.4%) while 4 of the patients (26.3%) had severe diarrhoea and dehydration before the flight. Almost all the patients (78.9%) were drinking alcohol during the flight and not actively moving their legs (84.2%). ECS occurred also in business and first class passengers. CONCLUSION: Surprisingly the onset of ECS is definitely not associated with haemostatic defects and not necessarily associated with the clinical risk factors reported.

Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial.

A randomized, double-blind multicenter trial was performed to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) (LU 47311, Clivarine) and standard unfractionated heparin for the prophylaxis of postoperative venous thromboembolism. Altogether 1351 patients scheduled to undergo abdominal surgery were included. Main outcome measures included the incidence of thromboembolic events (deep vein thrombosis, pulmonary embolism, or both) and bleeding complications, including wound hematoma. A total of 655 patients received 1750 anti-Xa IU of LMWH plus a placebo injection daily; 677 patients received 5000 IU of unfractionated heparin (UFH) twice a day. Both drugs were found to be equally effective, as 4.7% of patients in the LMWH group and 4.3% in the UFH group developed postoperative thromboembolic complications. However, the incidence of bleeding complications was significantly reduced in the LMWH group: 55 (8.3%) patients in the LMWH group and 80 (11.8%) in the UFH group developed bleeding complications, a relative risk (RR) of 0.70 (95% CI 0.51-0.97;p = 0.03); wound hematoma occurred in 29 (4.4%) of the LMWH group compared with 55 (7.7%) in those in the UFH group for an RR of 0.57 (95% CI 0.37-0.88;p = 0.01). This study confirmed that a very low dose of 1750 anti-Xa IU daily of this new LMWH is as effective as 10,000 IU of UFH for preventing postoperative deep vein thrombosis. At this dose its administration is associated with a significant reduction in the risk of bleeding including wound hematoma.

Low haemoglobin in haemophilia children is associated with chronic immune activation.

Anaemia is a frequent complication in patients with human immunodeficiency virus type 1 (HIV-1) infection. We tested 14 children with severe haemophilia (9 HIV-1 antibody seropositive CDC stage IIA, 5 seronegative) for haemoglobin and urinary neopterin concentrations and found a negative correlation between neopterin and haemoglobin (rs = -0.745, p = 0.007; Spearman's rank correlation). This finding suggests that chronic immune activation, possibly along with the release of specific cytokines such as interferon gamma and tumor necrosis factor alpha may be involved in the pathogenesis of anaemia.

Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and Fragmin.

In a double blind randomized trial on 250 patients undergoing elective abdominal surgery the effect of Fragmin was compared with heparin. Patients over 40 years of age except appendectomy and herniotomy were included. The dose of heparin was 5,000 IU b.i.d. whilst Fragmin was given in a dose of 2,500 U once per day and the second injection was a placebo. Prophylaxis started 2 h preoperatively and was maintained for 7 days. The fibrinogen uptake test was used as a screening method for thrombosis which was confirmed by phlebography. 124 patients were in the heparin group and 126 in the Fragmin group. Comparability between groups was found in: age, sex, Broca index, amount and type of risk factors, type of surgery. Thromboembolism was found in 10 cases in each group. Blood transfusions on the postoperative days 1 to 6 were required in 2 Fragmin and in 12 heparin patients. The total amount of blood given during that time was 6 units in the Fragmin and 37 units in the heparin group. These differences were significant.

Antithrombotic therapy in patients with known risk factors for thromboembolism.

In about 50% of the cases of spontaneous deep vein thrombosis a congenital deficiency of an inhibitor of coagulation or an insufficient fibrinolytic mechanism can be detected. In arterial thromboembolism a connection with hyperactive platelets or with a diminished availability of tissue plasminogen activator can be found in about 70%. However, in these cases the defect which provokes thrombosis is mostly acquired and is connected with hyperlipidemia and/or with atherosclerotic alterations of the vessel wall. A study on patients with thromboembolic tendency and detectable risk factors was carried out. A total of 470 patients could be observed for 2 years under an adequate antithrombotic prophylaxis. The occurrence of thromboembolic episodes 2 years prior to prophylaxis and 2 years under prophylaxis was compared. In venous cases thrombosis could be controlled almost completely by coumarins when the underlying cause was a deficient plasmatic inhibitor. In patients with diminished fibrinolysis there was only a partial effect of oral anticoagulants. A better result could be obtained when pentosan polysulfate was administered. In arterial thromboembolism the results of prophylaxis were less convincing. The efficacy of ASA in patients with an increased platelet function was only moderate. In addition, ASA hat to be discontinued in about 20% of the patients because of gastrointestinal problems. Pentosan polysulfate in patients with a diminished fibrinolytic capacity had a fairly good effect and resulted in a 60% reduction of thromboembolic manifestations. It is shown that an exact diagnosis of the underlying deficiency which is likely to cause thrombosis can also improve the efficacy and the specificity of prophylaxis.

[Use of antithrombin III concentrates]. / Einsatz von Antithrombin-III-Konzentraten.

Concentrates of antithrombin III (AT III) have been applied in congenital as well as in acquired AT III deficiency. Congenital defects only require substitution during surgery and in the case of pregnancy. Otherwise prophylaxis of thrombosis can be successfully carried out with oral anticoagulants. In acquired AT III deficiency substitution was found to be useful in cases of advanced DIC. When AT III activity was constantly kept around 100% the duration of DIC could be considerably shortened. No beneficial effect of additional administration of heparin was found. In cases of DIC due to septic shock the survival rate could be increased from an average of 20% without substitution to over 70% with AT III substitution as could be shown by different authors.

Immunological status and HIV antibodies in patients with haemophilia--a longitudinal study.

Various immunological parameters were investigated in 12 children suffering from severe haemophilia A or B receiving substitution therapy over a follow-up period of 3 1/2 years. At the beginning of the study, the therapy was changed to heat-treated concentrates of factors VIII or IX. Antibodies to HIV were found in 9 out of these patients. There were no AIDS-related clinical symptoms, but HIV antigen was detectable in one case. Abnormalities of immunological parameters were found independently of HIV infection, but were more pronounced in anti-HIV seropositive patients. Elevated levels of immunoglobulins gave evidence of polyclonal B-cell activation whilst increased levels of neopterin indicated activated T-cells and macrophages. There was no close association between these two types of activation. However, peak activation of both immune compartments was found approximately 1 year after changing the therapy. Thereafter a continuous tendency towards normalization of neopterin levels was observed. At the final visit immunoglobulin levels also tended to decrease. The HIV antigen seropositive child showed the highest neopterin levels during the whole study period. Our data indicate that the primarily high risk of developing AIDS in anti-HIV-seropositive haemophiliacs is declining.

[Clinical studies on the fibrinolytic action of pentosan polysulfate]. / Klinische Untersuchungen zur fibrinolytischen Wirkung von Pentosanpolysulfat.

The influence on fibrinolysis of the heparin-like substance Polyanion SP 54 is described. In vitro tests showed an increase of fibrinolysis by activation of the endogenous pathway via factor XII and prekallikrein. In vivo an increase of the availability of tissue plasminogen activator was assumed in addition. When different ways of administration of Polyanion SP 54 were tested an enhancement of fibrinolysis was also found after oral application of the substance. In a long term test the stimulation of fibrinolysis after oral therapy did not diminish within 12 months. A trial on patients with cerebral ischemic attacks and diminished fibrinolysis is not yet concluded but permits the assumption of a considerable diminution of ischemic attacks during therapeutic use of Polyanion SP 54.

[Early influence of acute preoperative haemodilution with human albumin and ringer's lactate on coagulation (author's transl)]. / Frühe Gerinnungsveränderungen bei akuter präoperativer Hämodilution mit Humanalbumin und Ringerlactat

Acute haemodilution was performed in 10 patients scheduled mainly for vascular surgery. Before induction to anaesthesia 910 +/- 29.1 ml whole blood was taken and simultaneously replaced as follows: 50% of that amount with 3,6% albumin solution, another 50% X 3 with lactated Ringer solution. The haematocrit was thus lowered from 39.8 +/- 1.71 to 28.4 +/- 1.7 vol%. Extensive clotting studies were performed to investigate the early influence of haemodilution on the clotting mechanisms in the time span between the end of blood collection and the point of surgical anaesthesia. The group of patients with normal clotting studies prior to haemodilution has shown a slight and short-lasting hypercoagulability. This has been proven by a shortening of r and k in TEG, by a shortening of non-activated Partial Thromboplastin Time (means activation of the XII and XI factor) and also, by the presence of an activated factor Xa and by an increase of maximum platelet aggregation and of platelet factor 3 availability. This mechanism of clotting activation is similar to the one observed after marked blood loss. It was assumed that this minor, early and short-lasting hypercoagulability has no further influence on the well known usual intra- and post-operative changes in clotting mechanisms (intra-op lowered, post-op enhanced coagulability). In contrast to the patients with normal clotting, a clotting defect due to preexisting liver-cell damage becomes worse during the haemodilution, which method in the presence of hepatic insufficiency therefore is contraindicted. A few additional data on input-output, serum and urine electrolytes and on 2,3 DPG have been gathered during our study. They indicate a positive fluid balance and the necessity for a close watch of electrolytes. The possible trend of 2.3 DPG elevation which has also been found might reflect a compensatory mechanism increasing oxygen transport capacity of haemoglobin if the above described method of haemodilution is used.

[The influence of hydroxyethyl starch on postoperative alterations of blood coagulation (author's transl)]. / Zur Beeinflussung postoperativer Anderungen der Blutgerinnung durch Hydroxyäthylstärke

The influence of hydroxyethyl starch (HES) on postoperative hypercoagulaemia was examined in a double blind study. One group of 10 patients received 500 ml HES during surgery and on the following three days. A comparable group received the same amount of isotonic saline solution. In some respects, hypercoagulaemia was significantly diminished in the HES-group. The diminution could, however, be mainly explained by the diluting effect of the plasma expander.