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Background and Purpose: The aim of this survey was to characterize the current diagnostic and therapeutic strategies for thrombosis of the cerebral sinus and veins (CVT) performed in German stroke units (SU)., Methods: Between September 2015 and January 2016 all clinical heads of certified SUs in Germany were invited to participate in a standardized online survey. The survey concentrated on the basic characteristics of SUs, diagnostic and therapeutic procedures and was made anonymous if so desired. Frequencies were expressed as percentages and differences between regional stroke units (RSU) and supraregional (i. e. comprehensive) SUs (SRSU) were compared with the χ 2 -test or Fisher's test RESULTS: A total of 107 SU heads participated (response rate 42.8%) and 55.1% of these were RSUs. In 77.2% the diagnosis is made by magnetic resonance imaging angiography (MR-A, RSU 81.1% vs. SRSU 72.3%; p = 0.29). Of the SUs 79.1% determined d‑dimer if CVT is suspected (79.3% vs. 78.7%; p = 0.94) and 88.5% carried out screening for thrombophilia (89.5% vs. 87.2%; p = 0.72). Intravenous unfractionated heparin (67.2% vs. 70.2%; p = 0.74) or subcutaneous low molecular weight heparin (32.8% vs. 29.8%; p = 0.74) are first line therapy in all SUs. Invasive procedures, such as hypothermia (3.7% vs. 10.6%; p = 0.25), hemicraniectomy (26% vs. 63.9%; p = 0.0001), endovascular techniques (11.1% vs. 40.4%; p = 0.0007) and systemic thrombolysis (5.5% vs. 10.6%; p = 0.47) are performed more frequently in SRSUs. Of the SUs 18.5% already use new oral anticoagulants (10.7% vs. 27.7%; p = 0.027). Most of the SUs organize a follow-up visit (70.9% vs. 76.6%; p = 0.52) with a MRI (94.2% vs. 91.1%; p = 0.7) within the first 6 months., Conclusion: The survey revealed substantial homogeneity between RSUs and SRSUs and standards are mostly in line with the guidelines. Non-established procedures, such as invasive therapeutic procedures and the administration of new oral anticoagulants were used significantly more often in SRSUs.

Venous thromboembolism [TE] is a multifactorial disease and protein C deficiency [PCD] constitutes a major risk factor. In the present study the prevalence of PCD and the clinical presentation at TE onset, including neonatal purpura fulminans, in a cohort of children are reported. In 367 unselected children (0·1-19 years) recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. Twenty-five of 338 children (7·4%) had PCD. Mean age at first TE onset was 10 years (range 0·1-18). Leading thromboembolic manifestations were neonatal purpura fulminans (n = 5), TE of cerebral veins (n = 3), stroke (n = 2) deep veinthrombosis (DVT) of the leg (n = 10), DVT & pulmonary embolism (n = 2) and DVT & pelvic veins (n = 3). Concomitant risk factors for TE were identified in 12 patients, whereas 13 children spontaneously developed TE. A positive family history of DVT was found in 10 children. In this unselected cohort of paediatric patients with symptomatic TE the overall prevalence of PCD was 7·4%; 1·5% presented with neonatal purpura fulminans. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high-risk population., (© 2014 John Wiley & Sons Ltd.)

Inhibition of thrombin by endogenous inhibitors plays a central role in the spatiotemporal control of clot formation. A failure to adequately inactivate thrombin such as in antithrombin deficiency generates a strong prothrombotic phenotype. To study if and to what extent delayed thrombin inactivation rates beyond antithrombin deficiency contribute to the prothrombotic phenotype we measured thrombin inhibition profiles in plasma samples obtained from 16 healthy individuals and 39 thrombophilic patients, including 17 patients diagnosed positive for anti-prothrombin/phospholipid antibodies. To test thrombin inhibition, thrombin was added to plasma, and endogenous thrombin inhibition stopped by addition of the reversible thrombin inhibitor argatroban. Subsequently, the amount of argatroban-complexed thrombin was measured using an oligonucleotide-based enzyme capture assay. In normal human plasma thrombin at concentrations up to 4 ng/ml (109 pM) became inactivated with an average half-life time of 56.4 ± 4.7 seconds (s). In antithrombin-deficient plasma the thrombin half-life was prolonged to 168.2 ± 14.9 s. Among the thrombophilic patients, only one with mild antithrombin deficiency showed impaired thrombin inactivation rates, whereas all other patients including the antiphospholipid positive patients showed thrombin inhibiting capacities within the normal range. We conclude that thrombin added to normal human plasma at subthreshold levels of ~100 pM or below becomes inactivated with a half-life time below 1 minute. Antiphospholipid antibodies do not prolong thrombin half-life times, making it unlikely that delayed thrombin inactivation contributes to the thrombotic phenotype of the antiphospholipid syndrome. In contrast, plasma levels of antithrombin falling below 80% of normal markedly prolong the thrombin half-life.

Unlabelled: The clinical relevance of thrombophilia screening in stroke patients is still a matter of debate, and descriptions of larger patterns of genetic variability are rare. We assessed the frequency of hereditary hypercoagulability in young patients with cryptogenic stroke (n = 44) and in healthy blood donors (n = 282) without prior cardiovascular event. Furthermore, we focused on the impact of thrombophilia screening on secondary stroke prevention., Results: Compared to the control group (19-67 years; median 38.5 years; 64% women), there was a lower prevalence of the FVII-R353Q mutation (p = 0.033) in stroke patients (17-52 years; median 36 years; 59.1% women). Of note, the FVII-R353Q mutation lowers FVII plasma levels, probably reducing the risk of cardiovascular events. The prevalence of the remaining 13 gene polymorphisms did not differ significantly. However, the prevalence of FV Leiden mutation tended to be higher among stroke patients., Conclusion: Overall, extended screening for inherited thrombophilia had an impact on medical stroke prevention in every sixth patient with cryptogenic stroke.

Introduction: Whether thrombophilic disorders, which are established risk factors for venous thromboembolism (VTE), also increase the risk of arterial thrombosis is still unknown., Materials and Methods: We analyzed data from 1081 consecutive patients (649 F/432 M, 16-93 years of age) with previous VTE registered in the MAISTHRO (MAin-ISar-THROmbosis) database with regard to arterial thrombotic events and contributing risk factors. Screening for thrombophilia included testing for factor V Leiden and prothrombin G20210A mutation, antiphospholipid antibodies and activities of factor VIII, protein C, protein S and antithrombin., Results: Of the entire study cohort, 40 patients (3.7%) had a prior myocardial infarction (MI), and 41 (3.8%) suffered a stroke. Other arterial thrombotic events were rare. Elevated factor VIII levels were more prevalent in MI patients than in controls (44.4 vs. 25.9%, p=0.044), but after adjusting for the traditional cardiovascular risk factors, this relationship was no longer significant. We observed a higher rate of lupus anticoagulant in MI patients with an adjusted odds ratio of 3.3 (95%CI 0.84-12.8, p=0.090). No difference in any other tested thrombophilia was observed in patients with MI or stroke relative to those without., Conclusion: The cumulative incidence of arterial thrombotic events in VTE patients is low, and the inherited thrombophilias do not seem to substantially increase the risk of arterial thrombosis.

Patients with ischemic stroke are sometimes found to have an underlying inherited (deficiency of protein C, protein S, antithrombin III, activated protein C resistance, prothrombin gene mutation, hyperhomocysteinemia) or acquired thrombophilia (lupus anticoagulant and anticardiolipin antibodies, hyperhomocysteinemia). Patient selection for thrombophilia screening is, therefore, a frequent question in managing patients with ischemic stroke. In this review we discuss patient selection and timing for laboratory tests for thrombophilia screening in stroke patients based on a literature review and we calculated overall costs per year in Germany for testing patients older than 18 years with an ischemic stroke of undetermined cause. As there is a lack of studies comparing anticoagulation with antiplatelet therapy in patients with diagnosed thrombophilia, laboratory screening for thrombophilia even in a selected group of patients with cryptogenic ischemic stroke remains of questionable value at present. An exception appears to be testing for lupus anticoagulant and anticardiolipin antibodies in younger patients with suspected antiphospholipid syndrome (two positive test results necessary), because anticoagulation seems to be superior to aspirin in patients with antiphospholipid syndrome.

Prophylactic treatment against deep vein thrombosis has become a routine part of surgical treatment. The indications and the form of prophylaxis selected depend on the patient's individual risk profile, which is determined in turn by a combination of exposing and predisposing risk factors. The exposing risk factors depend on the type of surgery and trauma the patient is exposed to, while the predisposing risks are determined by factors peculiar to the patient. This review deals with the modalities of prophylaxis current-ly available, pharmacological details relating to these, and their clinical significance. In addition, evidence-based data, recommendations for the duration of prophylaxis derived from official guidelines, and medicolegal aspects are discussed. The development of new anticoagulants is expanding the range of prophylactic methods, which means further in-formation is needed.

Objectives: In this study the frequency of inherited thrombophilic risk factors in a population of German CVT patients and their influence on clinical outcome were evaluated., Material and Methods: Twenty-five patients (age 37.1 +/- 16.3 years) with CVT were screened for inherited coagulation disorders. All participants received a full clinical follow-up (mean follow-up period 4.8 +/- 6.4 years)., Results: Inherited thrombophilic risk factors were identified in 9 (36%) of the 25 patients studied. Four were found positive for the heterozygous factor V Leiden mutation, 2 were heterozygous carriers of the prothrombin-G20210A-polymorphism. APC resistance proved to be a reliable screening method for factor V Leiden mutation, whereas genetic evaluation for protein S and C deficiencies failed to demonstrate any mutations despite the identification of 1 patient with a protein C and protein S deficiency each. One patient suffered from a familial plasminogen deficiency. These 9 patients had a less favorable outcome (P < 0.05)., Conclusion: Our results demonstrate that screening for inherited thrombophilia should be an integral part in the diagnostic work up of CVT patients. Patients with inherited coagulopathies tended to have a less favorable outcome, corroborating recommendations for a longer period of oral anticoagulation.