Bronchoalveolar Activation of Coagulation and Inhibition of Fibrinolysis during Ventilator-Associated Lung Injury.

Background and Objective. Bronchoalveolar coagulopathy is a characteristic feature of pulmonary inflammation. We compared bronchoalveolar and systemic levels of coagulation in patients who did and patients who did not develop ventilator-associated lung injury (VALI). Methods. Secondary analysis of a randomized controlled trial evaluating the effect of lower tidal volumes versus conventional tidal volumes in patients without acute lung injury or acute respiratory distress syndrome at the onset of mechanical ventilation. Results. Ten patients with VALI and 10 random control patients without lung injury during the course of mechanical ventilation, but all ventilated with conventional tidal volumes, were compared. Patients who developed VALI showed both bronchoalveolar activation of coagulation (increase in thrombin-antithrombin complex levels P < 0.001 versus baseline) and inhibition of fibrinolysis (decline in plasminogen activator activity P < 0.001 versus baseline). The later seemed to be dependent on higher levels of plasminogen activator inhibitor type 1 (P = 0.001 versus baseline). Patients who developed VALI also showed elevated systemic thrombin-antithrombin complex levels and decreased systemic plasminogen activator activity levels. Conclusions. VALI is characterized by bronchoalveolar coagulopathy. Systemic and bronchoalveolar coagulopathy at the onset of mechanical ventilation may be a risk factor for developing VALI in patients ventilated with conventional tidal volumes.

Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management.

The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. Heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralised by administration of vitamin K or prothrombin complex concentrates. The antihaemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are currently being evaluated in clinical studies, showing promising results. The new-generation anticoagulants include specific inhibitors of factor IIa or factor Xa (including pentasaccharides) and antiplatelet agents belonging to the class of thienopyridine derivatives. A limitation of the new class of anti-IIa and anti-Xa agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option.

Hip surgery sequentially induces stress hyperglycaemia and activates coagulation.

BACKGROUND: A frequent complication of orthopaedic procedures is venous thromboembolism (VTE ). Hyperglycaemia has been shown to activate the coagulation system and is associated with postoperative morbidity and mortality. Therefore, we hypothesised that glucose levels increase during orthopaedic surgery and are associated with an activation of the coagulation system. METHODS: Nine adult patients undergoing elective hip replacement were included. Venous blood samples were taken before, during and after surgery. Plasma glucose levels, factor VIII clotting activity (fVIII:c), von Willebrand ristocetin cofactor activity, von Willebrand factor antigen and prothrombin fragment 1+2 were measured. RESULTS: Immediately after induction of anaesthesia, plasma glucose levels started to increase until the second day postoperatively (peak 8.0 mmol/l). After seven weeks glucose values had returned to baseline (6.1 mmol/l), p<0.001 with ANOVA. All coagulation parameters increased during surgery, subsequent to the rise in glucose. The change in mean FVIII:c and von Willebrand ristocetin cofactor activity was significantly correlated with mean glucose values. CONCLUSIONS: These observations indicate that total hip replacement surgery causes an increase in glucose levels that precedes the proportional rise of the measured coagulation parameters. This suggests a possible role of glucose in the activation of the coagulation system during hip surgery.

[Coagulation abnormalities and the dentist]. / Stollingsstoornissen en de tandarts.

Defects in the coagulation system increase the risk of excessive bleeding during and after invasive dental procedures. This increased risk of bleeding is irrespective whether the coagulation disorder is inherited or acquired, for example by using anticoagulant medication. However, the cause of the coagulation disorder dictates preventive measures to be taken. Therefore, a careful medical history is crucial to identify and characterize patients with coagulation abnormalities. Recently, the insight in the mechanism of coagulation has increased considerably. This has resulted in specific procedures to adapt the level of coagulation required for specific invasive dental procedures. The dentist must discuss this temporary alteration of the coagulation level with the medical specialist of the patient.

Blood coagulation in anhepatic pigs: effects of treatment with the AMC-bioartificial liver.

The function of a newly devised bioartificial liver (AMC-BAL) based on viable, freshly isolated porcine hepatocytes has been evaluated in anhepatic pigs. The aim of this study was to assess the contribution of BAL treatment on blood coagulation parameters. Pigs were anesthetized and a total hepatectomy was performed (n = 15). The infrahepatic caval vein and the portal vein were connected to the subdiaphragmatic caval vein using a three-way prosthesis. Animals received standard intensive care (control, n= 5), treatment with an empty BAL (device control, n= 5) or with a cell-loaded BAL (BAL-treatment, n= 5) for a period of 24 h starting 24 h after hepatectomy. Coagulation parameters studied concerned prothrombin time (PT), platelet count, the procoagulant system (factors (F)II, FV, FVII, FVIII and fibrinogen), anticoagulant system (AT III), fibrinolytic system (t-PA, PAI-1) as well as markers of coagulation factor activation (TAT complexes, prothrombin fragment F1 + 2). FII, FV, FVII, AT III and fibrinogen rapidly decreased after total hepatectomy in pigs in accordance with the anhepatic state of the animals. FVIII levels were not influenced by the hepatectomy. A mild drop in platelet count was seen in all groups. Treatment of anhepatic pigs with the cell-loaded BAL did not restore PT or clotting factor levels. TAT and F1 + 2 complexes, however, were significantly increased in this group. Levels of t-PA and PAI-1 were not influenced by cell-loaded BAL treatment. Treatment of anhepatic pigs with the AMC-BAL based on freshly isolated porcine hepatocytes does not result in an improved coagulation state due to extensive consumption of clotting factors. However, increased levels of TAT complexes and prothrombin fragments F1 + 2 during treatment of anhepatic pigs indicate synthesis and direct activation of coagulation factors, leading to thrombin generation. This demonstrates that this bioartificial liver is capable of synthesizing coagulation factors.

[Increased perioperative blood loss during treatment with paroxetine]. / Toegenomen peroperatief bloedverlies bij paroxetinegebruik.

A 63-year-old man who took paroxetine for depression developed massive peroperative haemorrhage during a pancreaticoduodenectomy as a result of paroxetine-induced thrombocytopathy. He lost 4 litres of blood. After administration of 8 units of fresh frozen plasma and 2 times 5 units of thrombocyte concentrate, hemostatic control was obtained and the operation could be continued. Paroxetine is a non-tricyclic serotonin reuptake inhibitor prescribed for the treatment of depression. Since this drug also blocks serotonin reuptake in platelets, a clinically significant platelet dysfunction can occur under certain conditions. Because serotonin promotes platelet aggregation, too low an amount of serotonin in the platelets can result in thrombocytopathy. Before major surgery, it is advised to perform extensive clotting tests if there is any hint of haemorrhagic diathesis in the anamnesis. In case of a prolonged bleeding time, paroxetine treatment should be stopped perioperatively.

Diagnosis of deep-vein thrombosis using an objective Doppler method.

STUDY OBJECTIVE: To determine the diagnostic criteria (phase I) and to assess the accuracy (phase II) of an objective Doppler-Valsalva pressure method as compared with contrast venography for the diagnosis of acute deep-leg-vein thrombosis in symptomatic outpatients. DESIGN: A two-phase prospective study in consecutive patients. Doppler ultrasound strip-chart recordings and venograms were independently analyzed by experienced observers. SETTING: Referral-based medical clinics at university medical centers. PATIENTS: One hundred and ten (phase I) and one hundred and fifty-five (phase II) patients who had clinically suspected venous thrombosis and were referred by their general practitioners were included. METHODS AND MEASUREMENTS: A normal Doppler test result was defined as a cyclic spontaneous signal (S-signal), a continuous S-signal with a Valsalva pressure of less than 6.5 mm Hg, or an absent S-signal with flow after cessation of the Valsalva maneuver. A continuous S-signal with a Valsalva pressure of 6.5 mm Hg or more or an absent S-signal without flow after cessation of the Valsalva maneuver were defined as abnormal test results. The accuracy indices for proximal vein thrombosis in phase II (155 patients; prevalence, 31%) were sensitivity, 91% (95% CI, 79% to 98%), and specificity, 99% (CI, 97% to 100%). All 3 patients with isolated calf-vein thrombosis had normal Doppler test results. CONCLUSIONS: The objective Doppler method is an accurate, reproducible, and simple method for detection of venous thrombosis in symptomatic outpatients.

Serum elastase inhibitor deficiency and alpha 1-antitrypsin deficiency in patients with obstructive emphysema.

A decreased inhibition of pancreatic elastase has been detected in the serums of six patients with alpha(1)-antitrypsin deficiency. Five have severe clinical and physiological pulmonary emphysema. This observation extends the defect of inhibition by serum to a second, biologically active proteolytic enzyme in this form of familial emphysema.