Alex M. Blaicher

The Role of Oxytocin in Relation to Female Sexual Arousal

Oxytocin is clearly involved in human reproduction and serves an important role in sexual arousal. Oxytocin serum levels were measured before and after sexual stimulation in 12 healthy women. Values of oxytocin 1 min after orgasm were significantly higher (p < 0.05) than baseline levels. This finding supports the hypothesis that oxytocin plays a major part in human sexual response both in neuroendocrine function and postcoital behavior.

Endogenous Heparin-Like Substances Significantly Impair Coagulation in Patients Undergoing Orthotopic liver Transplantation

Orthotopic liver transplantation (OLT) is associated with severe bleeding, especially after reperfusion of the grafted liver.Heparin released from the liver graft contributes to postreperfusion coagulopathy. Although patients with liver cirrhosis have increased levels of endogenous heparinoids, the role of these substances during liver transplantation is unclear. Therefore, we performed native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping of the vena cava, 10 min before and 10 min after graft perfusion, and at the end of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin activity. In contrast to other investigations, we found significant heparin effects before reperfusion, although patients received no exogenous heparin. These heparin effects were greater in patients with cirrhosis compared with patients with cancer as the underlying disease leading to OLT. Administration of coagulation factors is the usual treatment of coagulopathies during OLT. The comparison of native versus heparinase-modified TEG can distinguish between heparin activity or coagulation factor deficiency as a cause of bleeding complications and provides a rational approach to the treatment of bleeding during OLT. Implications: Impaired coagulation function, contributed to by heparin or heparin-like substances, is frequently observed after reperfusion of a transplanted liver. This study demonstrates that a heparinase-modified thrombelastography can identify significant heparin effects in the absence of exogenous heparin administration in patients undergoing liver transplantation. (Anesth Analg 1998;86:691-5)

The effect of hydroxyethyl starch on platelet aggregation in vitro

The effect of hydroxyethyl starch (HES) on hemostasis seems to be minimal when it is used in recommended amounts.A number of studies have investigated the effect of HES on platelet function when administered in vivo, but there has been no study investigating the effect on the isolated platelet function when administered in vitro. A photometrical method to assess platelet function in platelet-rich plasma (approximately 250 x 109 platelets/L) was used with platelet aggregation induced using either collagen, epinephrine, adenosine diphosphate, or ristocetin. We found a dose-dependent decrease of platelet aggregation in vitro with either collagen or epinephrine, but not with adenosine diphosphate or ristocetin. However, the changes of HES on platelet aggregation were detected only in doses larger than those routinely used in the clinical setting. Therefore, we conclude that the influence of HES at the recommended doses on initial platelet aggregation may not be clinically relevant. Implications: The effect of hydroxyethyl starch on platelet function and coagulation is discussed. This study showed no influence on platelets in clinically relevant doses in an in vitro model. (Anesth Analg 1998;86:1318-21)

Effect of non‐selective, non‐steroidal anti‐inflammatory drugs and cyclo‐oxygenase‐2 selective inhibitors on the PFA‐100 closure time

The place of cyclo‐oxygenase (COX)‐2 selective non‐steroidal anti‐inflammatory drugs (NSAIDs) in the peri‐operative period remains under discussion. Due to the absence of COX‐2 in platelets, the risk of bleeding in patients who use selective NSAIDs is thought to be decreased. We studied the influence of aspirin, diclofenac, lornoxicam and rofecoxib on the in vitro bleeding time using the platelet function analyser (PFA‐100). The PFA‐100 simulates the process of platelet adhesion and aggregation after vascular injury in vitro. Measurements in 43 volunteers were performed at three time points: before, 3 h, and 12 h after oral ingestion of one of the randomly assigned study medications. Aspirin, diclofenac and lornoxicam had a significant effect on the in vitro closure time, while rofecoxib did not show this effect. This supports the use of COX‐2 selective drugs in the peri‐operative period to minimise the risk of bleeding.

Consensus use of desmopressin and antifibrinolytics in three university clinics.

Five million operations were carried out in 2400 clinics in Germany in 1996. Perioperative haemorrhage occurred in approximately 10-20% of these operations (1 000 000), of which 75% were surgically related and 25% as a result of disorders of haemostasis. In general, treatment of these haemorrhages mvolved two erythrocyte concentrates (EC), one Gesh Gozen plasma (FFP) and administraaon of thrombocyte concentrates (TC) in every tenth case. This means admirustraaon ofEC in every eighth case, a total of 500 000 EC, an FFP unit in every 16th case, a total of 250 OOO units of FFP. and a T C in every tenth case, a total of 25 000 TC. of haemostasis dependent peri-operative haemorrhaging in Germany. With an average cost of DM13O-150 (65-75 Euro) for EC, DMl00 (50 Euro) for FFP and DM1200 (600 Euro) for TC, a resultant cost is approximately DM125 OOO OOO (62 500 000 Euro) for the use ofblood products for haemostatic dependent pen-operative bleeding alone. Furthermore, the additional cost of approximately DM50 000 000 (25 OOO OOO Euro) for the increased use of antibioacs in the case of transfusion patients, presently three ames greater than patients not requinng transhion, must also be taken into account. Moreover, the potential risk ofinfection of HIV, HBV, HCV and also Lues-infection must be considered. Consequently differential diagnosis and treatment has gained particular Importance in peri-operative bleeding in prosthesis surgery, e.g. knee and hip jomt replacement and in surgery involving high blood loss. It is sensible to identify patients at hgh risk of bleeding prior to surgery and prepare for ths. In particular, identification of coagulopathies (primary or secondary, in particular due to acetyl salicylic acid (ASS), von Willebrand’s disease) is effective in minimising blood loss. Situations such as emergency surgery and acute patients must often be treated rationally without recourse to accurate haemostatic diagnosis. Simple schemes are essential for fast action.

The influence of VIP and epoprostenol on platelet CD62P expression and primary haemostasis in vitro.

Human vasoactive intestinal peptide (VIP) and epoprostenol (prostacyclin) have vasodilatative effects in the pulmonary circulation. Both VIP and epoprostenol are successfully used to treat pulmonary hypertension in humans and experimental animal models. The positive effects of epoprostenol on the course of this disease are achieved through vasodilatation and inhibitory effects on platelet activity. Since VIP also binds specifically to platelets, we compared the in vitro effects of VIP and epoprostenol on platelet P-Selectin (CD62P) expression and primary haemostasis. Anti-aggregative effects of VIP (10−6 mol and 10−8 mol) and epoprostenol (50, 5 and 0.5 ng/ml) on platelets were determined by agonist-induced CD62P expression and in vitro bleeding time (PFA-100™ system). Blood from healthy individuals was either incubated with epoprostenol, VIP or saline control and was analysed by whole blood flow cytometry and the PFA-100™. Prior to flow cytometric analysis, the platelets were stimulated with either arachidonic acid (AA) or adenosine diphosphate (ADP). Whole blood flow cytometry analysis showed that epoprostenol inhibited dose-dependently agonist-induced CD62P expression, whereas VIP did not inhibit CD62P expression. PFA analysis revealed substantial closure time prolongation by epoprostenol and again no effects of VIP. These results indicate that VIP, in contrast to epoprostenol, has no effect on platelet CD62P expression and primary haemostasis.

Platelet disorders in uraemia before and after haemodialysis under the influence of low dose aspirin

Thrombocyte dysfunction and increased bleeding time (BT) are well documented in uraemic patients. However, these patients are frequently medicated with low dose aspirin (ASA) in order to maintain shunt patency and prevent cardiovascular events. Recently, life- threatening gastrointestinal haemorrhage in an uraemic subject taking low dose aspirin has been reported. In this work ASA related bleeding risk in uraemic patients and the effect of haemodialysis on their bleeding tendency was studied by measuring in vitro bleeding time (BT) using the Thrombostat 4000 in 34 uraemic patients on chronic haemodialysis compared to 50 healthy subjects. Our results indicate that low dose aspirin does not influence uraemic thrombopathia 8 to 10h after ingestion but seems to increase bleeding risk shortly after ingestion. Moreover, haemodialysis alters uraemic in vitro BT with regard to the time after ingestion of ASA.