[Antithrombotic treatment in acute coronary syndrome and atrial fibrillation]. / Antithrombotische Therapie bei akutem Koronarsyndrom und Vorhofflimmern.

The number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and indications for oral anticoagulation (OAC) for the prevention of stroke, who need dual antiplatelet treatment (DAPT) with acetylsalicylic acid (ASA) plus a P2Y12 inhibitor because of an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is also increasing. In the past these patients received a triple therapy (TT) for 3-12 months. This TT has never been studied for efficacy; however, the rate of bleeding complications in comparison to a simple OAC or DAPT is significantly higher. Registries and smaller trials showed that DAPT with an OAC plus a platelet inhibitor may be sufficient to prevent stroke and stent thromboses/myocardial infarctions. These questions were investigated in various prospective and randomized studies involving all four non-vitamin K oral anticoagulants (NOAC) approved for stroke prevention in AF. The NOACs were tested against vitamin K antagonists (VKA) involving single antiplatelet therapy without using DAPT. The trials with rivaroxaban (PIONEER AF-PCI) and dabigatran (RE-DUAL PCI) have already been published but the investigations involving apixaban (AUGUSTUS) and edoxaban (ENTRUST-AF PCI) are still ongoing. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with VKA with respect to bleeding complications without any obvious disadvantage due to increases in stroke cases or cardiac ischemia. The international guidelines already permit treatment without TT in cases where the bleeding risk is prevalent. In this situation it is recommended to prescribe a NOAC plus a single antiplatelet therapy. Thus, TT no longer seems to be indicated for most patients with AF and after ACS or PCI.

[Haemostatic testing prior to elective surgery? Yes!]. / Laboranalytischer Ausschluss einer hämorrhagischen Diathese vor elektiven Eingriffen? Ja!

Haemorrhagic disorders must be excluded prior to any operation or other invasive procedure that has the potential to involve serious bleeding. When assessing the individual risk of bleeding, screening tests of hemostasis must be combined with the patient's clinical history and symptoms, and any history of bleeding must be explored under direct medical supervision using a standardized questionnaire. However, this bleeding history is neither very specific, nor is it particularly sensitive. Screening tests that have been found to be useful include platelet count, activated partial thrombo plastin time (aPTT), prothrombin time (PT) and clottable fibrinogen. No reliable, sensitive and specific screening test is however available today to screen for platelet dysfunction or von Willebrand disease. A specialized coagulation laboratory should be involved when the bleeding history or laboratory screening indicate a potential haemorrhagic disorder.

e-Health-based management of patients receiving oral anticoagulation therapy: results from the observational thrombEVAL study.

Essentials e-Health based health care by an expert centre may advance management of oral anticoagulation. Outcome of patients was compared between an e-health based coagulation service and regular care. Patients in the coagulation service cohort experienced a significantly better clinical outcome. Lower risk for adverse events was related to anticoagulation-specific and non-specific outcome. SUMMARY: Background Management of oral anticoagulation (OAC) therapy is essential to minimize adverse events in patients receiving vitamin K-antagonists (VKAs). Data on the effect of e-health-based anticoagulation management systems on the clinical outcome of OAC patients are limited. Objectives To compare the clinical outcome of OAC patients managed by an e-health-based coagulation service (CS) with that of patients receiving regular medical care (RMC). Methods The prospective multicenter cohort study thrombEVAL (NCT01809015) comprised 1558 individuals receiving RMC and 760 individuals managed by a CS. Independent study monitoring and adjudication of endpoints by an independent review panel were implemented. Results The primary study endpoint (composite of thromboembolism, clinically relevant bleeding and death) occurred in 15.7 per 100 patient-years (py) with RMC and in 7.0 per 100 py with the CS (rate ratio [RR], 2.3; 95% confidence interval [CI], 1.7-3.1). Rates for major and clinically relevant bleeding were higher with RMC than with the CS: 6.8 vs. 2.6 and 10.1 vs. 3.6 per 100 py, respectively. Thromboembolic events showed an RR of 1.5 (95% CI, 0.8-2.6) comparing RMC with the CS. Hospitalization (RR, 2.6; 95% CI, 2.3-3.0) and all-cause mortality (RR, 4.6; 95% CI, 2.8-7.7) were markedly more frequent with RMC. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, treatment characteristics and sociodemographic status, hazard ratios (HR) for the primary endpoint (HR, 2.2; 95% CI, 1.5-3.4), clinically relevant bleeding (HR, 3.1; 95% CI, 1.7-5.5), hospitalization (HR, 2.2; 95% CI, 1.8-2.8) and all-cause mortality (HR, 5.6; 95% CI, 2.9-11.0) favored CS treatment. Conclusions In this study, e-health-based management of OAC therapy was associated with a lower frequency of OAC-specific and non-specific adverse events.

Antidiabetic medications in overdose: a comparison of the inquiries made to a regional poisons unit regarding original sulfonylureas, biguanides and insulin.

OBJECTIVE: The drugs most commonly used to treat diabetes mellitus are sulfonylureas, biguanides and insulin. The most serious effects seen in overdose with these agents are hypoglycemia or lactic acidosis which may be fatal or cause cerebral defects. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with sulfonylureas, biguanides and insulin. PATIENTS AND METHODS: A total of 218,070 made inquiries between 1995 and 2004 were evaluated. The inquiries were received by telephone and a standardized questionnaire was sent subsequently to the physicians calling for follow-up information. The cases were analyzed with regard to gender, age, etiology, symptoms and clinical outcome. RESULTS: 263 inquiries concerning sulfonylureas (48.3% female, 49.4% male, 2.3% sex unknown, average age 39.1 +/- 26.8 years), 172 concerning biguanides (60.5% female, 37.2% male, 2.3% sex unknown, average age 41.5 +/- 24.1 years), and 191 concerning insulin (53.9% female, 41.9% male, 4.2% sex unknown, average age 44.6 +/- 16.7) were made. In cases involving sulfonylureas, the etiology was deliberate self-poisoning in 62.7% and accidental in 31.9% (biguanides 60.5% and 29.1%, insulin 85.3% and 9.4%). Using the Poisoning Severity Score, no symptoms were observed in 41.4% of the patients with sulfonylurea overdose (biguanides 40.1%, insulin 22.5%), minor symptoms in 37.6% (biguanides 32.6%, insulin 33.5%), major symptoms in 14.4% (biguanides 13.4%, insulin 26.2%) and serious symptoms in 4.6% (biguanides 12.2%, insulin 14.7%). Returned questionnaires reporting clinical outcomes showed that a full recovery occurred in most patients (sulfonylureas 97.4%, biguanides 93.0%, insulin 94.4%), cerebral defects persisted in 1.8% of the cases involving sulfonylureas (biguanides 1.5%, insulin 2.4%), and that 0.9% of the patients with sulfonylurea overdose died (biguanides 6.1%, insulin 3.6%). CONCLUSIONS: Sulfonylureas were the most frequently observed medication in cases of overdose with antidiabetic agents. Insulin overdose caused the highest number of major and serious symptoms. Overdose with biguanides led to the most deaths.

Hemodynamics during PEEP ventilation in patients with severe left ventricular failure studied by transesophageal echocardiography.

The effects of mechanical ventilation with PEEP were investigated in five patients with normal cardiopulmonary function (group A) and in 11 patients with severe left ventricular failure (group B). Cross-sectional area of the right and left atrium (RA/LA), left ventricle (LV), and right ventricle (RV) was determined at EDA/ESA using transesophageal echocardiography. Hemodynamic parameters and transesophageal pressure were measured simultaneously at PEEP levels 0, 4, 8, 12, and 16 cm H2O. End-diastolic area of the right atrium decreased significantly in both groups. The RA pressure increased, while transmural pressure remained unaltered. The CI decreased in both groups. The decrease in cardiac output by PEEP ventilation was related to the decrease in RV filling volume by external compression. In patients with congestive heart failure, PEEP ventilation with 8 to 10 cm H2O did not worsen LV function.

Acute dialysis: PMN-elastase as a new parameter for controlling individual anticoagulation with low molecular weight heparin (Fragmin).

Despite the improvements in the development of dialyzer membranes with greater hemocompatibility, an activation of the coagulation system occurs when blood comes into contact with exogenous surfaces. The large number of heparin dosage regimens demonstrated the difficulty to adapt general therapeutic guidelines. Low molecular weight heparin (Fragmin) was administered as a single bolus dose for anticoagulation during 58 acute dialyses. Anti-Xa-activity, the plasma levels of the lysosomal elastase of the polymorphonuclear granulocytes ("PMN-elastase") and of the thrombin-antithrombin III-complex (TAT) were measured at hourly intervals. Therapeutic anti-Xa-levels did not show evidence of sufficient inhibition of thrombin formation. The PMN-elastase increased by 180 ng/ml 3 h after administration of the bolus dose, with no further increase occurring (plateau phase). This was considered to reflect adequate anticoagulative activity. Where anticoagulation was inadequate, the elastase values rose consistently. After 2 h the increase of the PMN-elastase showed that--and to what extent--coagulation had been activated. The determination of PMN-elastase, using the IMAC-principle, is a method which can be performed quickly with any conventional autoanalyzer. It makes it possible to monitor adequate anticoagulation, but PMN-elastase results must be proven during routine use before recommendation as a routine test.

Antithrombin substitution therapy.

Antithrombin (AT) is the most important inhibitor of the coagulation system. Due to the high cost of AT treatment, there must be rational arguments to justify its use. Established indications for AT substitution include hereditary homozygous AT deficiency in newborn babies and hereditary AT deficiency before or during certain situations, for example, surgery and pregnancy. AT substitution therapy can also be justified in the treatment of complex coagulation disorders, sepsis with disseminated intravascular coagulation and acute thromboembolic events with reduced AT activity. Administration of AT concentrates to patients with nephrotic syndrome or stable hepatopathy is not justified. To achieve an anti-inflammatory effect in patients with sepsis, it is thought that above-normal levels of AT activity (> 140% of the normal level) are probably needed. Although currently available data on the effect of AT in the treatment of sepsis are insufficient, results from controlled studies will soon become available and will show whether sepsis is an indication for AT substitution.

[Local fibrinolysis in renal artery occlusion]. / Die lokale Fibrinolyse bei Nierenarterienverschlüssen.

The indications and technique of local fibrinolysis therapy of acute renal artery occlusions are discussed in relation to four patients. Because of the short period for which ischaemia is tolerated by the kidney, the result of treatment depends largely on the time interval between occlusion and the beginning of treatment. Partial perfusion of the renal artery was obtained in three patients. Since the "ischaemia time" of the kidneys had been exceeded, it was not possible to obtain complete restitution of renal function in any of these patients.

[Radiologic follow-up of the thoracic organs in intensive care patients. The value of the thoracic picture correlated with the clinical and biochemical findings]. / Radiologische Verlaufskontrolle der Thoraxorgane beim Intensivpflegepatienten. Wertigkeit der Thoraxaumfnahme in Korrelation mit klinischen und biochemischen Befunden.

Correlation between chest radiographs and clinical indicators was studied in 212 patients in intensive care. 1. There was good correlation between raised pulmonary artery pressure and radiological signs of left heart insufficiency, but not with the value of central venous pressure. 2. Fever and leukocytosis nearly always precede radiological evidence of pneumonia; their persistence does not necessarily indicate persistent pneumonia. 3. Pneumonias, effusions, atelectases and emboli are more common on the right. 4. More than 70% of central venous catheters were incorrectly placed; most commonly, the catheter was placed too low. Life-threatening complications occurred in 1.3%.

Arterial embolism to the upper extremity in a patient with factor V Leiden mutation (APC resistance)--a case report and review of the literature.

Factor V Leiden mutation has emerged as one of the leading abnormalities in inherited blood coagulation disorders, resulting in a markedly increased risk for deep leg vein thrombosis. A 24-year-old woman presented with acute onset of critical ischemia of her left thumb and index finger. Intraarterial angiography revealed an embolus in the distal radial artery and a thrombotic occlusion of the digital artery of the thumb and index finger. Immediate therapy encompassed a selective surgical embolectomy of the distal radial artery followed by a local intraarterial lysis that was continued for 3 days. Additionally, therapeutic anticoagulation and vasodilating drugs (prostaglandin E) were administered. Within 2 days, capillary refill reappeared and the initial loss of sensory function at the tip of the thumb and index finger diminished. A screening test for thrombophilic disorders led to the diagnosis of a heterozygous mutation of factor V (Leiden mutation). Arterial thromboembolic events of factor V Leiden mutation are rare and have to date been described only in the supraaortic and coronary circulation. Therefore, the arterial embolism to the left hand presented in this report constitutes a rarity that could be successfully salvaged by the combined use of a vascular surgical procedure and intensified medical management.

[Cushing syndrome in ACTH-producing neuroendocrine tumor of the hepatic duct]. / Cushing-Syndrom bei ACTH-produzierendem neuroendokrinen Tumor des Ductus hepaticus.

We present a patient with an ACTH producing neuroendocrine tumor of the hepatic bile duct which was detected by chance during abdominal surgery for Cushing's syndrome. Diagnostic strategy and surgical therapy in patients with neuroendocrine tumors are discussed. The diagnostic problems caused by combination with an endocrine function disorder like Cushing's syndrome are pointed out.

Recurrent cerebral ischaemia in a pregnant woman with patent foramen ovale II° and thrombophilia.

This case report concerns a pregnant multipara (age: 27 years) in the 16th gestational week. She developed a sudden onset of paraesthesia in her left lower arm although injecting dalteparin 5000 IU once daily subcutaneously (s. c.) due to a heterozygous factor V Leiden mutation and a prior miscarriage in the first pregnancy and preeclampsia in her third pregnancy. After the miscarriage she delivered two healthy children under prophylactic anticoagulation with low molecular weight heparin (LMWH). Now via magnetic resonance imaging (MRI) she was diagnosed as having multiple cerebral ischaemic lesions. Further workup revealed the presence of a patent foramen ovale (PFO) II° but no venous thrombosis in her legs. She was then treated with dalteparin 5000 IU twice daily by subcutaneous injections. At 19th gestational week she developed paraesthesia in her left lower arm again. The MRI showed a cortical lesion in the territory of the right median cerebral artery. The anticoagulation dose was increased stepwise under surveillance of the anti-FXa-level 3-4 h after subcutaneous injections aiming to achieve the supratherapeutic range of 1.2-1.5 IU/ml anti-Xa-units. No more neurological symptoms appeared under this antithrombotic therapy. The patient delivered by induction of labor at the 38th gestational week.

Massive pulmonary embolism in a young boy with T-cell leukaemia. Successful thrombolytic therapy by recombinant tissue plasminogen activator (rtPA).

Acute pulmonary embolism (PE) is a serious complication in association with malignant diseases. We describe the successful treatment of PE applying a systemic thrombolytic therapy in a 4-year-old boy with acute lymphoblastic leukaemia. The thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) 0.1 mg/kg bodyweight per hour for six hours was continued for six days without important side effects. In particular no bleeding complications were observed. Computed tomography with contrast revealed a remarkable regression of the central PE. Without further delays the chemotherapy was resumed.

[Dabigatran therapy--perioperative management and interpretation of coagulation tests]. / Therapie mit Dabigatran. Periinterventionelles Management und Interpretation von Gerinnungstests.

UNLABELLED: Dabigatran, an oral, reversible direct factor IIa inhibitor, is approved in Europe for stroke prevention in atrial fibrillation and for the prevention of venous thromboembolism after elective hip and knee replacement. In contrast to vitamin K antagonists, a routine coagulation monitoring during the treatment with dabigatran etexilate is not necessary. However, in specific clinical situations such as invasive emergency procedures or serious haemorrhage, the actual anticoagulant status of dabigatran may be of importance for the treating clinician and can be assessed by clotting tests (aPTT, TT, ECT). The diluted thrombin time test (Hemoclot®), which is specifically calibrated for dabigatran, is useful for quantitative determination of the dabigatran serum concentration. In general, discontinuation of dabigatran etexilate 24 hours before standard elective surgery is sufficient to normalise the bleeding risk in patients with normal renal function. In patients with renal impairment and/or in the case of a high bleeding risk procedure the recommended duration of discontinuation is prolonged. If a bleeding episode occurs in a patient on dabigatran, further treatment should be based on the severity and localisation of the bleeding. A distinct feature of dabigatran is the possibility of effectively removing dabigatran from the circulation by haemodialysis. RECOMMENDATION: In the case of clinically minor bleedings, a delay in the administration of the next dabigatran etexilate dose is recommended. The length of the delay is based on the patient's individual thromboembolic risk. In minor bleedings the use of prothrombin complex concentrates is not indicated. In the case of moderate or major bleedings the main focus should be on stabilising the circulation by using fluids and blood products and, if a lesion can be identified, the local treatment thereof. If time and infrastructure is available, dialysis offers an effective and fast option to remove dabigatran out of the circulation. In the incidence of severe and life threatening bleedings, an additional, more complex haemostasis management is required. Besides haemodynamic stabilisation of the circulation, administration of prothrombin complex concentrates should not be delayed. It has to be kept in mind that standard laboratory coagulation parameters may not accurately reflect the effect of prothrombin complex concentrates in patients on dabigatran. Hence the effect of the prothrombin complex concentrate should be monitored clinically and adjusted by means of onset of coagulation in vivo.

Superficial thrombophlebitis in varicose vein disease: the particular role of methylenetetrahydrofolate reductase.

BACKGROUND: The purpose of this study was to compare the genetic background of superficial (SVT) and deep vein thrombosis (DVT). METHODS: Factor V (FV)-Leiden (G16891A)-, factor II(G20210A)-mutations, protein C- and S, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms at C677T and A1298C, and serum homocysteine levels (hcy) were determined in 29 patients with SVT and 26 with DVT. Findings FV- and -II-mutations were less frequent in patients with SVT (2/3) compared with DVT (9/5), respectively (P < 0.002 in case of FV). However, the frequency of the MTHFR C677T polymorphism was significantly higher in patients with SVT compared with DVT (CT 12 versus 10, and TT 7 versus 1, respectively, P << 0.001). The distribution of the MTHFR A1298C genotype and serum hcy levels was similar in both patient groups. Protein S-deficiency was recorded once (SVT). Interpretation These results suggest that the MTHFR C677T-mutant genetically predisposes its carriers to SVT which may contribute to hypercoagulation in pre-existing varicose vein disease.