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We report on a female patient with confirmed secondary antiphospholipid syndrome (APS) due to underlying systemic lupus erythematosus (SLE). Despite a thromboplastin time within the normal range (international normalized ratio, INR) under treatment with a vitamin K antagonist (VKA), a recurrent thrombotic event occurred, this time as pulmonary embolism due to bilateral deep vein thrombosis. Despite an INR value in the therapeutic range, clotting factors II, VII, IX and X were found to be insufficiently decreased suggesting inefficient anticoagulation. Thus, the anticoagulation regimen was changed to the direct oral anticoagulant dabigatran. This case demonstrates that the INR in APS patients may be artificially prolonged in rare cases, despite a normal activated partial thromboplastin time (aPTT) and cannot be used for monitoring VKA anticoagulant therapy. Suspicion of ineffective anticoagulation despite VKA therapy should prompt measurement of the individual clotting factors.

A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients.In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution.We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution.Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

Acquired hemophilia is a rare but severe bleeding disorder caused by autoantibodies mostly against factor VIII. Clinically it mostly presents with soft tissue and muscular bleeding. Diagnostics include a prolonged aPTT, antibodies against FVIII and a reduced FVIII titre. Acute bleeding is controlled with recombinant factor VIIa (NovoSeven(®)) or activated prothrombin complex (FEIBA(®)), as both bypass FVIII in the coagulation pathway. Treatment to reduce the inhibitor consists of immunosuppression with corticosteroids, cyclophosphamid and can be extended with rituximab.Die Hemmkörperhämophilie ist eine seltene Erkrankung mit hoher Mortalität. Sie wird durch Autoantikörper meist gegen den Gerinnungsfaktor VIII verursacht und ist häufig idiopathisch. Klinisch imponieren Weichteilblutungen. Diagnostisch von Bedeutung ist eine isoliert verlängerte aPTT, niedrige Faktor-VIII-Aktivität und Antikörper gegen den Faktor VIII. Die Therapie besteht einerseits aus einer Gerinnungsaktivierung unter Umgehung des Faktors VIII mittels rekombinantem Faktor VIIa (NovoSeven®) oder aktivierter Prothrombinkomplex (FEIBA®) sowie einer immunsuppressiven Therapie (Kortikosteroide, Cyclophosphamid, Rituximab) zur Elimination des Antikörpers.

A 70-year-old man with a past history of COPD stage GOLD D with home oxygen therapy and tracheotomy due to long-term ventilation (898 hours) 6 years ago was admitted for investigation of haemoptysis during oral anticoagulation. He suffered from peripheral arterial disease (PAD) with bypass and repeated thrombectomy due to recurrent bypass caps, despite effective warfarin therapy. He had all cardiovascular risk factors.The suspicion of a bronchial carcinoma was confirmed by CT. Bronchoscopically a 2 cm lesion in the left upper lobe was biopsied. Additionally, bronchoscopy revealed an approximately erythematous, bloody discolored lesion (diameter 7 mm) at a tracheotomy scar.The biopsies revealed an adenocarcinoma in the left upper lobe and an oncocytic adenoma of the trachea - an extremely rare adenoma. The staging result was cT1b cN0 cM0 G2 IASLC Ia. Because of his severe multiple diseases the patient was in an inoperable condition. An interdisciplinary tumor conference recommended an individualized approach with a definitive radiotherapy of the adenocarcinoma. Endoscopic control of the macroscopically completely removed oncocytic adenoma of the trachea shall be performed one year later.Oncocytoma is an extremely rare adenoma (of the trachea), which in this case, has caused haemoptysis in addition to lung cancer during anticoagulation. For tumor genesis a reactive or hyperplasic response after tracheotomy 6 years ago is considered. Resection is the treatment of choice because of the potential for infiltrative growth. But the decision to treat always depends on individual benefit.

The aim of the perioperative management of anticoagulation in patients with long-term oral anticoagulation is to minimize bleeding complications of surgical interventions.We aimed to give a summary of current data and to give practical recommendations for colleagues practicing surgery.This article gives a narrative overview of available data from 31 publications between 2000 and 2013.Every perioperative decision on whether to continue oral anticoagulation is preceded by an assessment of the risk of bleeding and embolism. In cases with a low risk of bleeding, oral anticoagulation can usually be continued. In contrast, for larger interventions with a moderate to high risk of bleeding, a discontinuation of phenprocoumon with temporary bridging is required. In this case it is common practice to discontinue phenprocoumon 7-9 days preoperatively and administer heparin mostly in the form of low molecular weight heparin (LMWH) depending on the international normalized ratio (INR). In contrast perioperative management of direct oral anticoagulants (DOAC) is discussed controversially. Based on the pharmacokinetics of the DAOC, the recommendations are to minimize the anticoagulation-free interval to 2-4 half-lives (HWZ) preoperatively (1-5 days) and early postoperative restart. In this case no bridging is necessary. On the other hand, an early interruption of DOAC 5 days prior to surgery to a minimum of 2 days postoperatively is favored by some surgeons to assure an adequate perioperative hemostasis. Depending on the risk of thromboembolism, bridging is required. These recommendations are justified by limited clinical experience and the absence of antagonism.The perioperative management of coagulation is still a challenge. While there are consolidated decision aids for phenprocoumon, the approach under DOAC treatment is still controversial due to limited data.

Venous thromboembolism (VTE) is a common complication in patients with cancer. Because of their improved subcutaneous bioavailability and reliable antithrombotic efficiency low-molecular-weight heparins (LMWH) are preferably used for prevention and treatment of cancer-related VTE. Thromboprophylaxis with LMWH is well established in patients undergoing cancer surgery and hospitalized cancer patients, while outpatient prophylaxis remains contentious. LMWH are recommended over unfractionated heparins and vitamin K antagonists for initial treatment and secondary prophylaxis (3-6 months) after cancer-related VTE. Long-term secondary prophylaxis should be considered for patients with ongoing active malignancy and low bleeding risk. Due to absence of clinical studies in cancer patients, the use of novel oral anticoagulants is currently not recommended.

During perioperative treatment of coagulopathic patients the so-called Point-of-Care (POC) analyses enable more rapidly available and more comprehensive hemostatic analyses compared to routinely performed conventional coagulation testing, such as activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen concentration and platelet count. In this review article a hemotherapy algorithm is presented which is based on viscoelastic and aggregometric POC measurements. The algorithm was designed double sided and consists of a general and a special part. The general part contains boxes and fields for sociodemographic data and gives general recommendations for coagulation management and therapy specifications for particular patient collectives and presents proposals for emergency reversal of anticoagulation therapy. The special part refers to basic physiological conditions for hemostasis and asks for measurement results of clot initiation, clot firmness, clot stability and platelet function analyses. Reference values were defined for each parameter and therapeutic options are presented. In cases of persistent coagulopathy despite algorithm-conform therapy, the algorithm could be run through once again. Finally, the algorithm presents therapeutic options for an ultima ratio therapy approach.

Electrical cardioversions are performed to restore sinus rhythm in patients with non-valvular atrial fibrillation to improve symptoms. It has been known for decades that cardioversion without adequate anticoagulation for 3-4 weeks prior to and for 4 weeks after cardioversion results in thromboembolic complication of about 5%. It is much less known that cardioversion is also associated with a higher risk of thromboembolism (stroke, peripheral embolism) in patients treated with usual anticoagulation. The control arms (warfarin) of the three studies with the new anticoagulants dabigatran, rivaroxaban, and apixaban for the prevention of thromboembolism in non-valvular atrial fibrillation report a monthly thromboembolic risk of 0,13-0,2%. The risk for thromboembolic complication in the month following cardioversion is about three to six times higher than without cardioversion in patients with non-valvular atrial fibrillation treated with usual anticoagulation. Since most cardioversions are performed by DC shock it is not known whether electrical and pharmacological cardioversions carry the same risk for thromboembolism. Although thromboembolic complications do not often occur following cardioversion the increased risk due to this procedure should be acknowledged. Strict anticoagulation (e. g. INR value2,5) in the first 10-14 days following cardioversion could possibly minimize the risk of thromboembolism.

Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients.Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.

Peripheral arterial occlusive disease is one manifestation of the systemic disease atherosclerosis. The initial therapy for every arteriosclerotic disease is aimed at reducing cardiovascular risk factors by lifestyle modification and medication. Patients who require surgical revascularisation need long-term antiplatelet therapy or anticoagulation. This therapy has to be differentiated according to the vascular territory involved and the method used for revascularisation. After local thrombendarterectomy, alloplastic bypass graft surgery of the aortic, aorto-iliac, aorto-femoral or femoro-popliteal region above the knee, long-term ASA 100 mg/d or clopidogrel 75 mg/d should be initiated. After alloplastic bypass grafting below the knee the combination of ASA 100 mg/d and clopidogrel 75 mg/d should be used. In contrast, after venous grafts the patency rate is improved by anticoagulation with vitamin K antagonists (INR 2-3), if there is a low risk of bleeding. If there is a contraindication to vitamin K antagonists, ASA 100 mg/d should be used. After revascularisation, a structured surveillance programme should be implemented aiming at controlling cardiovascular risk factors and monitoring the vascular state, as well as the anticoagulation and the antiplatelet therapy.

For many decades Vitamin K antagonists were the standard orally given medication for primary and secondary prevention of thromboembolism in patients with atrial fibrillation and stroke. Three compounds, dabigatran, rivaroxaban, and apixaban, are now challenging this well established prescription, as they showed similar effect in preventing thromboembolism with a lower bleeding rate in recently published well designed, controlled randomised, non-inferiority trials. Their advantages of each are to have a fixed dosage, no need to monitor coagulation factors, and fewer interactions with food and other drug intake. The therapeutic effect is estimated overall similar between the three compounds. Who is a candidate for one of the new drugs: Patients with atrial fibrillation and the clear indication to get a future oral anticoagulation are potential candidates to receive one of the new drugs. Further this may be patients where the treatment with Vit K antagonists was difficult to optimise, patients who are not willing to have blood controls done regularly or where blood controls are difficult to obtain. This will also be an option in patients who had a stroke due to atrial fibrillation and had no history of cerebral bleeding. Who should not receive the new anticoagulants: patients who present stable blood coagulation values in the treatment range and no complications should not be merged to the new drugs. Patients with severe renal insufficiency or receiving a medication that interacts with the new drugs (e. g. ketoconazole) or with synthetic heart valves will not be candidates to receive the new drugs.

A rare cause of acute liver failure is adult onset Still's disease (AOSD), a systemic inflammatory disorder. We present the case of a 24-year-old woman who presented with acute liver failure necessitating high urgency liver transplantation. The diagnosis of AOSD was established in accordance with the Yamaguchi classification criteria, including arthralgia, fever, sore throat, rash and hepatosplenomegaly. The early detection and therapy of AOSD can possibly avoid the development of liver failure with a poor prognosis.

The liver has an excellent regenerative capacity after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSC) to participate in liver regeneration. Here we report our experience with portal vein embolisation (PVE) and CD133+ BMSC administration to the liver, compared with PVE alone, to augment hepatic regeneration in patients with critically low FLRV or impaired liver function.Eleven patients underwent PVE of liver segments I and IV-VIII to stimulate hepatic regeneration prior to extended right hepatectomy. In these 11 patients with a FLRV below 25% and/or limited quality of hepatic parenchyma, PVE alone did not promise adequate proliferation. These patients underwent additional BMSC administration to segments II and III. Two radiologists blinded to patients' identity and each other's results measured liver and tumour volumes with helical computed tomography. Absolute, relative and daily FLRV gains were compared with a group of patients that underwent PVE alone.The increase of the mean absolute FLRV after PVE with BMSC application from 239.3 mL±103.5 (standard deviation) to 417.1 mL±150.4 was significantly higher than that from 286.3 mL±77.1 to 395.9 mL±94.1 after PVE alone (p0.05). Also the relative gain of FLRV in this group (77.3%±38.2%) was significantly higher than that after PVE alone (39.1%±20.4%) (P=0.039). In addition, the daily hepatic growth rate after PVE and BMSC application (9.5±4.3 mL/d) was significantly superior to that after PVE alone (4.1±1.9 mL/d) (p=0.03). Time to surgery was 27 days±11 in this group and 45 days±21 after PVE alone (p=0.02). Short- and long-term survival were not negatively influenced by the shorter waiting period.In patients with malignant liver lesions, the combination of PVE with CD133+ BMSC administration substantially increased hepatic regeneration compared with PVE alone. This procedure bears the potential to allow the safe resection of patients with a curative intention that would otherwise carry the risk post-operative liver failure.

A total of 4 g of paracetamol repeated daily may be hepatotoxic in malnourished adults with low body weight

In numerous situations stroke physicians face a lack of evidence during their daily practice. In this report the authors address some of the difficult treatment decisions encountered in acute therapy and secondary prevention. Examples include off-label thrombolysis and prevention in high-risk situations. The available data from trials and registries are discussed, and personal views and recommendations are expressed.

An overview is given on the method and the applications of thrombin generation assays. Thrombin generation assays provide a tool which can be used to trace the entire thrombin formation and inactivation of a plasma sample. Therefore they are principally different from traditional global assays like PT and aPTT and promise new opportunities for the assessment of bleeding or thrombotic risks.

The case of a 78-year-old female patient who suffered atrial fibrillation and persistent thrombus in the left atrial appendage despite sufficient anticoagulation is reported. The case is chosen to demonstrate the complexity inherent in prophylaxis as well as risk evaluation of thromboembolism on the basis of clinical and echocardiographic criteria. We also discuss transesophageal echocardiography as the standard diagnostic procedure for detection of intracardiac thrombi prior to cardioversion as well as cardiac computer tomography as an alternative.

The recommendations for anticoagulation in over 80 years old patients are based on the thromboembolic/bleeding risk relation. They add to the published recommendations for the specific indications. Low-molecular-weight heparin (LMWH) is used to prevent thromboembolism postoperatively. Compression stockings and/or intermittent pneumatic compression are used if bleeding risk is very high. The dose is increased starting at day two if the thromboembolic risk is very high. Bleeding and thromboembolic risks are re-evaluted daily. The antithrombotic therapy is adjusted accordingly. Prophylaxis of thromboembolism in patients with acute illnesses and bedrest is performed according postoperative care. Two-thirds of therapeutic doses of low-molecular-weight heparin are used to treat acute venous thromboembolism. Reduced renal function (creatinine clearance30 ml/ min for most LMWHs or20 ml/min for tinzaparin) should result in a further reduction of dose. Intensity and duration of prophylaxis of recurrent events with vitamin K antagonist or LMWH in malignancy follow current or herein described recommendations. Patients with atrial fibrillation are treated with vitamin K antagonists adjusted to an INR of 2-3 for prophylaxis of embolism. Further details of anticoagulant therapy should be in agreement with the national or international recommendations.

Thromboses in the lower extremities are common. Non-invasive examination techniques, such as compression sonography and color-coded duplex sonography, have a high sensitivity and specificity. Relevant complications are in particular post-thrombotic syndrome and pulmonary arterial embolisms. The gold standard in treatment of phlebothrombosis of the leg is immediate anticoagulation therapy and compression treatment with early mobilization whereas lysis therapy, operative thrombectomy or implantation of cava filters are indicated only in isolated cases.

Electrical cardioversion ist often the treatment of first choice for restoring sinus rhythm in patients with atrial fibrillation. This article reviews the management of patients undergoing electrical cardioversion. As risk of formation of an intra-atrial thrombus formation is low after a short duration of AF (less than 48 h), immediate cardioversion can be performed in these patients (except those with a high risk for thrombembolic events). However, if the AF has lasted for more than 48 hours, patients have to be treated either with anticoagulants for at least three weeks or an atrial thrombus has to be excluded by transesophageal echocardiography. Both options achieve the same short- or long-term success rate for cardioversion. Cardioversion is probably safe even if there are spontaneous echocardiographic contrasts as signs of potential thrombogenic slowing of atrial blood flow, but individual factors of risk/indication have to taken into account. Success rate of cardioversion depends on various patient characteristics as well as on some technical variables, biphasic instead of monophasic shocks being more effective. If there is an early recurrence of AF after initially successful cardioversion, administration of amiodarone (for 4 weeks) increases the success rate of subsequent cardioversion. After successful cardioversion subsequent antiarrhythmic therapy can reduce recurrence of AF. Thrombembolic complications are more frequent within the first few days after cardioversion. Indication for and duration of post-cardioversion anticoagulation depends on individual characteristics (CHADS(2) score) as well as on the duration of the preceding episode of AF.

Use of oral anticoagulants is common in elderly persons. Oral anticoagulation can be used safely in the elderly if careful titration of the loading dose, careful changes in maintenance doses as well as consideration of drug interactions are taken into account. Frequent monitoring of the INR is essential, especially with changes in medical status and in co-medication. Correction of elevated INRs can be done following the recommendations. If vitamin K is used in stable patients, only small doses are required. In patients with atrial fibrillation, ischemic stroke risk and bleeding risk are predicted by overlapping factors. So patients who profit most from stroke risk reduction also show high bleeding risk. Risk stratification for ischemic stroke can be done easily with CHADS2-Score. Fall risk tends to be overestimated as a contraindication, whereas cognitive decline in combination with an unstable social network argues against anticoagulation. In the end, the decision to start or withhold anticoagulation has to be taken individually.

In contrast to heparins and oral anticoagulants, anti IIa inhibitors (thrombin inhibitors) are able to directly inhibit the protease activity of thrombin and can thereby precisely control the blood coagulation process. Direct thrombin inhibitors are either biosimilars (r-hirudin) or synthetically produced substances (bivalirudin, argatroban, dabigatran). In 1997 r-hirudin was introduced into clinical practice, however due to its narrow therapeutic range and the necessity of drug monitoring it has not gained widespread clinical use by now. Since 2004 and 2005 the synthetic thrombin inhibitors bivalirudin and argatroban, respectively, are available. With dabigatran the first oral synthetic thrombin inhibitor followed in 2008. These four drugs can inhibit even clot bound thrombin and show low plasma protein binding. They differ in respect to route and duration of application as well as elimination from the body, thereby offering a precise inhibition of blood coagulation adjusted to the individual case and without danger of HIT II. These advantages shall be used and advanced by the development of further direct thrombin inhibitors.

An overview is given on the clinical picture and therapy of the haemophilias A and B as an example for congenital coagulopathies. The survey deals with the special problems of today's "treated haemophilia" and its recommendations on diagnosis and treatment regimens. A special focus is put on the pathogenesis of the haemophilic joint arthropathy, that is affecting most haemophiliacs earlier or later during life. Safe plasma derived and recombinant clotting factor concentrates allow an efficient on-demand and also a prophylactic treatment for the prevention of bleeding sequelae. As a consequence life quality and life expectancy of today born haemophiliacs have nearly normalised. The problems of haemophilia with inhibitors and future therapeutic options are discussed. The development of inhibitors at start of therapy with factor VIII concentrates represent the nowadays most serious complication of haemophilia treatment. The only way to a long lasting eradication of the inhibitor ist the induction of immune tolerance that can be achieved by various protocols. A successful immune tolerance therapy (ITT) is the precondition for a regular prophylactic treatment regime. The Guidelines of the Federal Chamber of Physicians, the German recommendations for ITT and the consensus recommendations of an international working group provide an important lead for the conduction of immune tolerance therapy.

A survey is given on pharmacology and indications for the treatment with vitamin K antagonists. The therapeutic handling and self control by the patient is described.

Nearly every second patient, who needs an oral anticoagulation with vitamin K antagonists, is feasible to perform INR-self-management after participation in a structured teaching program. Patient self-testing or measuring the INR value by relatives or nurses would increase this method of control by the aid of telemedicine systems. An accurately, weekly measurement leads to an optimal therapeutic control of anticoagulation intensity, which results in an impressive risk reduction up to 50%. This depends not on the underlying heart disease and had been demonstrated in patients older than 60 years. Due to the small INR variability and therefore a higher percentage in target range, a lower anticoagulation intensity in patients with mechanical heart valve prosthesis should be justifiable. For the next decade, INR self-management/self-testing should be the method of choice, even direct thrombin inhibitors or factor Xa antagonists would be available. An advantage of INR self-management is the control of drug adherence, which could be an unresolved problem for new anticoagulants.

There is little consensus on the optimal perioperative management for most patients on oral anticoagulation with vitamin K antagonists. Bridging therapy is not recommended for the majority of patients on oral anticoagulation as most are at low risk for perioperative stroke. Though most clinicians choose an aggressive perioperative strategy for patients with high thromboembolic risk (e.g., mechanical mitral valve replacement) by withholding warfarin perioperatively and the use of full-dose heparin, prophylactic dose heparin is given for lower risk cagegories (e.g., bileaflet aortic valve replacement and atrial fibrillation). The amount of increase in postoperative major bleeding when full-dose anticoagulation is administered soon after surgery is the factor in the decision with the least available data. The optimal method for returning the International Normalized Ratio (INR) to the desired range preoperatively depends upon its degree of initial elevation and whether or not clinically significant bleeding is present. Rapid reversal of excessive anticoagulation should be undertaken in patients with serious bleeding at any degree of anticoagulation. Vitamin K therapy is an effective treatment for INR prolongation in patients with vitamin K-associated coagulopathy; coagulation factor replacement is required, in addition, in patients with major bleeding or with an indication for immediate correction of their INR. Patients receiving prothrombin complex concentrate have a more rapid and more complete reversal of their anticoagulation as compared with fresh frozen plasma.

It has long been a standard procedure to replace coumarin by heparin if a patient using this oral anticoagulant had to undergo dental surgery. The Quick-Value had then to exceed a certain limit before surgery could be safely performed. Today this procedure has changed in that a switch to heparin is only made for invasive and large area surgery. Simple dental extractions, small biopsies and periodontal treatments are performed under continuous oral anticoagulation and local hemostyptic measures are applied. It has been shown that the likelihood of postoperative bleeding complications after adequate local hemostasis during dental surgery is much lower than is the risk of thrombosis or embolic complication following cessation of anticoagulant medication before surgery.

In December 2006 the allocation of livers from deceased donors in Germany and several other Eurotransplant countries was reset. The previous allocation system relied on CTP score to assess the need of transplantation, but it also assigned to waiting time a prominent role in prioritization. That system was replaced by the primarily urgency-oriented model of end-stage liver disease (MELD) allocation system. First experience with this classification in the U.S.A. shows that MELD scores are able to identify the urgency of liver transplantation correctly in most types of liver disease. Due to the MELD-based allocation, the growing waiting time and waiting-list mortality could be counteracted. At the same time it became evident however that MELD scores do not reflect mortality on the waiting list or thus the urgency for all types of liver diseases. Therefore the new allocation system introduced in the Eurotransplant countries contains standardized and flexible exceptions for these diseases. In addition the new allocation rules were created as a learning system. Repeated "fine tuning" of the allocation process based on continuous monitoring of daily allocation practice and clinical studies aim at just and effective distribution of the precious and limited supply of donor organs.