New recommendations on cerebral venous and dural sinus thrombosis from the German consensus-based (S2k) guideline.

Over the last years, new evidence has accumulated on multiple aspects of diagnosis and management of cerebral venous and dural sinus thrombosis (CVT) including identification of new risk factors, studies on interventional treatment as well as treatment with direct oral anticoagulants. Based on the GRADE questions of the European Stroke Organization guideline on this topic, the new German guideline on CVT is a consensus between expert representatives of Austria, Germany and Switzerland. New recommendations include:• CVT occurring in the first weeks after SARS-CoV-2 vaccination with vector vaccines may be associated with severe thrombocytopenia, indicating the presence of a prothrombotic immunogenic cause (Vaccine-induced immune thrombotic thrombocytopenia; VITT).• D-dimer testing to rule out CVT cannot be recommended and should therefore not be routinely performed.• Thrombophilia screening is not generally recommended in patients with CVT. It should be considered in young patients, in spontaneous CVT, in recurrent thrombosis and/or in case of a positive family history of venous thromboembolism, and if a change in therapy results from a positive finding.• Patients with CVT should preferably be treated with low molecular weight heparine (LMWH) instead of unfractionated heparine in the acute phase.• On an individual basis, endovascular recanalization in a neurointerventional center may be considered for patients who deteriorate under adequate anticoagulation.• Despite the overall low level of evidence, surgical decompression should be performed in patients with CVT, parenchymal lesions (congestive edema and/or hemorrhage) and impending incarceration to prevent death.• Following the acute phase, oral anticoagulation with direct oral anticoagulants instead of vitamin K antagonists should be given for 3 to 12 months to enhance recanalization and prevent recurrent CVT as well as extracerebral venous thrombosis.• Women with previous CVT in connection with the use of combined hormonal contraceptives or pregnancy shall refrain from continuing or restarting contraception with oestrogen-progestagen combinations due to an increased risk of recurrence if anticoagulation is no longer used.• Women with previous CVT and without contraindications should receive LMWH prophylaxis during pregnancy and for at least 6 weeks post partum.Although the level of evidence supporting these recommendations is mostly low, evidence from deep venous thrombosis as well as current clinical experience can justify the new recommendations.This article is an abridged translation of the German guideline, which is available online.

Screening for lupus anticoagulants in patients treated with vitamin K antagonists.

INTRODUCTION: The dRVVT test for detecting lupus anticoagulants (LA) is difficult to interpret when patients are treated with vitamin K antagonists (VKA). METHODS: We performed LA testing in 33 VKA-treated patients with definite antiphospholipid syndrome (APS) and compared the results with 100 controls subjects not receiving VKA and 110 APL-negative patients anticoagulated for reasons other than APS. RESULTS: Compared with the dRVVT ratio before the initiation of VKA therapy, a higher cutoff value, defined as the 99th percentile, was established for VKA-treated patients with INR values between 2.0 and 3.5. A dRVVT ratio of >1.7 yielded a sensitivity of 81.3%, specificity of 99.1%, and positive and negative predictive values of 98.7% and 85.8%, respectively, for detecting LA. Cohen's kappa coefficient indicated good agreement for the dRVVT ratio obtained from testing with and without VKA treatment (κ = 0.813; 95% CI: 0.773-0.853), which was higher (κ = 0.941; 95% CI: 0.917-0.965) when the LA diagnosis was based on the results of both the dRVVT and a second test system (i.e., Mixcon-LA assay). CONCLUSIONS: Lupus anticoagulants testing in VKA-treated patients with APS according to current guidelines appears to be possible for the majority of patients without discontinuing anticoagulant therapy.

[Management of catheter-related upper extremity deep vein thrombosis]. / Management bei katheterassoziierter Armvenenthrombose.

Central venous catheters (CVCs) are important tools in the care of patients with acute or chronic diseases, but catheter-related thrombosis and thrombotic occlusions are frequent complications, especially if CVCs are implanted for long-term use. In this review we focus on the management of these complications. Risk factors for catheter-related thrombosis include dislocation of the catheter tip, the presence of malignant disease and hypercoagulability. Catheter-related thrombosis is associated with catheter infection, pulmonary embolism and post-thrombotic syndrome. Catheter-related thromboses which most frequently involve the subclavian vein are usually diagnosed by duplex ultrasound examination and treated with anticoagulation therapy for a minimum of three months or longer if the catheter is left in place. Prevention of catheter-related thrombotic complications includes proper positioning of the CVC with the catheter tip lying in the proximal superior vena cava and regular flushing of the catheter with saline solution or unfractionated heparin. The use of anticoagulants for primary prevention is currently not recommended.

Acute and long-term outcome of Silverhawk assisted atherectomy for femoro-popliteal lesions according the TASC II classification: a single-center experience.

BACKGROUND: Directional atherectomy (DA) has become popular in some centers to remove atherosclerotic plaques in femoro-popliteal lesions. Although immediate and also short - term outcome data are promising, solid long-term data are warranted to justify the widespread use in daily practice. PATIENTS AND METHODS: In this prospective study de novo and restenotic lesions of the femoro-popliteal segments were treated with the Silverhawk device. 161 consecutive patients (164 lesions) with peripheral artery disease (PAD) Rutherford classes 2 to 5 were included from June 2002 to October 2004 and October 2006 to June 2007 (59 % male, mean age 67 +/- 11 years, range 40 to 88) and the outcome analyzed according to the TASC II classification. RESULTS: DA alone was performed successfully in 28 % (n = 46), adjunctive balloon angioplasty in 65 % (n = 107) and stenting in 7 % (n = 11). The overall technical success rate was 76 % (124 / 164) and the procedural success rate 95 % (154 / 164). At 12 months primary patency rate was 61 % (85 / 140) and the secondary patency rate was 75 % (105 / 140) in the entire cohort, being less favourable in TASC D compared to TASC A to C lesions (p = 0.034 and p < 0.001, respectively). Furthermore the restenosis rate differed trendwise (p = 0.06) between de novo and restenotic lesions. Changes in the ABI and the Rutherford classes were significantly in favour of TASC A to C lesions compared to TASC D after 12 months (p = 0.004). The event free survival (MI, TIA, or restenosis) was 48 % at 12 months and 38.5 % at 24 months. Predictor for restenosis in the multivariable analysis was only male gender (p=0.04). CONCLUSIONS: The results in TASC D lesions are inferior to those in the lesser stages. DA of femoro-popliteal arteries leads shows a trend to better long-term technical and clinical outcome in de novo lesions compared to restenotic lesions.

Alteration of pharmacokinetics of lepirudin caused by anti-lepirudin antibodies occurring after long-term subcutaneous treatment in a patient with recurrent VTE due to Behcets disease.

The direct thrombin inhibitor lepirudin is mainly applied in heparin-induced thrombocytopenia. We report here the case of a 37-year-old kurdish woman in whom Behcets disease was diagnosed in 1998 when she presented with a Budd Chiari syndrome (BCS) complicated by pulmonary embolism. Recurrent venous thromboembolism (VTE) occurred despite anticoagulant therapy with UFH, LMWH or phenprocoumon and various immunosuppressive therapy regimens. In 2001, when BCS recurred ultimately i.v. lepirudin was administered. When the patient improved and remained clinically stable lepirudin was applied subcutaneously. During long-term treatment with twice-daily 50 mg no further VTE was observed over the following years. Additionally, no bleeding complications occurred. In May 2005 anticoagulant therapy was switched to phenprocoumon. BCS reoccurred when INR values were suboptimal in February 2007, and lepirudin treatment was immediately restarted. After admission the patient received 50 mg b.i.d. lepirudin s.c. with plasma levels in the therapeutic range (0.5-1.0 mg / l). Over the following months, lepirudin levels repeatedly exceeded the upper limit of this range and the dosage was stepwise reduced. Finally, 20 mg b.i.d. were sufficient to obtain therapeutic levels. Renal function was normal, but lepirudin antibodies were present in high titer, as assessed by ELISA. We suppose that these antibodies reduce renal filtration of lepirudin thus leading to increased plasma levels. This case is an example for successful long-term therapeutic-dose anticoagulation with s.c. lepirudin in a patient with Behcets disease and recurrent VTE despite therapeutic anticoagulant therapy with LMWH or vitamin K antagonists. However, frequent measurement of lepirudin plasma levels is needed. If stepwise dose lowering is required over time, the presence of lepirudin antibodies should be considered.

Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary.

BACKGROUND: Light transmittance aggregometry (LTA) is considered to be the 'gold standard' of platelet function testing. As LTA has been poorly standardized, we analyzed the results of LTA in healthy subjects and patients with antiplatelet therapy using different concentrations of agonists and performing tests in non-adjusted and platelet count-adjusted platelet-rich plasma (PRP). METHODS: LTA was performed in 20 healthy subjects and in patients treated with aspirin (n = 30) or clopidogrel (n = 30) monotherapy, as well as in patients on combination therapy (n = 20), using arachidonic acid (ARA 0.25 and 0.5 mg mL(-1)) and adenosine diphosphate (ADP 2 and 5 microm) as agonists and performing platelet function tests in non-adjusted and platelet count (250 nL(-1) +/- 10%)-adjusted PRP. RESULTS: The overall platelet aggregation response is decreased after adjusting the PRP for platelet count compared with measurements in unadjusted PRP. The variability of aggregation results is high in adjusted PRP in the subgroup of healthy subjects, ranging from 9.2-95.3% (5th-95th percentile) relative to 77.6-95.5% in non-adjusted PRP when determining maximum aggregation to ARA 0.5 mg mL(-1). Late aggregation using ADP 2 microm ranges from 3.8-89.9% in adjusted PRP compared with 42.9-92.5% in non-adjusted PRP. Maximum aggregation using ARA 0.5 mg mL(-1) in non-adjusted PRP differentiates between aspirin-treated patients and healthy controls well, whereas late aggregation using ADP 2 microm in non-adjusted PRP offers the best discrimination between clopidogrel-treated patients and healthy controls. CONCLUSION: Adjustment of PRP for platelet count does not provide any advantage and therefore the time-consuming process of platelet count adjustment is not necessary.

C-reactive protein is a strong independent predictor of death in type 2 diabetes: association with multiple facets of the metabolic syndrome.

INTRODUCTION: It has been suggested that atherosclerotic vascular disease is a chronic inflammatory process. The aim of this study was to investigate the importance of C-reactive protein (CRP) as a cardiovascular risk marker and predictor of death, as well as its relation to other factors of the metabolic syndrome in a cohort of type 2 diabetic patients at high risk of severe macrovascular complications. MATERIAL AND METHODS: 592 patients, aged 55 to 74 years (311 men, 281 women), with signs and symptoms of circulation deficits were examined by duplex ultrasound for suspected cerebrovascular and peripheral arterial disease and followed over a period of 5 years. At baseline, 292 patients of the total group had type 2 diabetes (49.3%). Ischemic heart disease was present in 40.2%, internal carotid stenosis in 21.9% and peripheral arterial disease in 39.7% of the subjects. RESULTS: During the observation period, 104 patients had died, 72 (69.2%) due to cardiovascular causes. Non-fatal myocardial infarction occurred in 39 patients (7.4%), non-fatal stroke in 70 patients (13.3%) and amputations because of gangrene were unavoidable in 24 patients (4.6%). In Cox regression analysis, CRP was the strongest predictor of death and cardiovascular death in the total cohort (RR 3.7 [95% CI 1.86-7.50] and 5.4 [2.13-13.76]), as well as in the type 2 diabetic subgroup (RR 3.3 [1.27-8.70] and 5.4 [1.44-20.0]). In contrast neither the traditional cardiovascular risk factors nor the data of diabetic metabolic control were able to improve prediction. CRP was correlated positively with plasma levels of triglycerides (r=0.19, p=0.002), C-peptide (r=0.21, p=0.004), postprandial glucose (r=0.17, p=0.009), albuminuria (r=0.16, p=0.020), and inversely with HDL cholesterol (r=-0.20, p=0.002) in type 2 diabetic patients. CONCLUSIONS: CRP seems to be a better predictor of death and cardiovascular events than traditional risk factors or parameters of metabolic control in type 2 diabetic patients at high risk for cardiovascular endpoints. Additionally, CRP is associated with several facets of the metabolic syndrome.

Influence of blood collection techniques on platelet function.

For investigations of platelet function it is recommended that venipuncture should be performed using ordinary needle systems instead of butterfly cannulae systems. Platelets might be activated in the long plastic tubes of butterfly systems. The aim of this study was to investigate the dependency of platelet function results on blood sampling using different collection systems. Therefore, blood of 25 healthy volunteers was collected from both arms using at the same time on one side a 21-gauge needle and on the other side a 21-gauge butterfly cannula system. Both samples of each volunteer were analyzed on the PFA-100. Platelet aggregation was performed on the Behring Coagulation Timer (BCT) and the optical aggregometer PAP-4 using ADP, collagen and arachidonic acid to induce platelet aggregation in platelet-rich plasma. No significant prolongation of the closure times on the PFA-100 with the COL/EPI cartridge and the COL/ADP cartridge was observed when using butterfly cannulae. The results of optical aggregometry were not significantly different. The maximum aggregation response did not differ significantly for both collection systems. Aggregometry and the PFA-100 system are not affected by different blood collection systems. Therefore butterfly cannulae can be used for sample collection to investigate platelet function.

Prolonged QTc interval and elevated heart rate identify the type 2 diabetic patient at high risk for cardiovascular death. The Bremen Diabetes Study.

AIM: The Bremen Diabetes Study is an observation study to characterise type 2 diabetic patients at high risk for death and cardiovascular complications by routine metabolic and cardiovascular tests. The aim of the present analysis was to evaluate the prediction of QTc interval prolongation and/or heart rate for cardiovascular mortality in comparison to traditional cardiovascular risk factors. METHODS: We followed 475 type 2 diabetic patients (age 55 - 75 years; 304 women, 171 men) from a defined residential area, seen in our clinic primarily for metabolic control. Patients with coexisting micro- or macroangiopathic complications were not excluded. Outcome data were obtained for 423 subjects. QT intervals were measured in a 12 lead ECG and corrected for heart rate with Fridericia's equation [QTc = QT/RR1/3]. RESULTS: During the 5 year observation period 57 patients (13.5 %) died due to cardiovascular causes. In multivariate analysis we found that QTc interval prolongation (p = 0.0008), elevated heart rate (p = 0.0001), serum creatinine (p = 0.0260), smoking (p = 0.0056) and peripheral arterial disease (p = 0.0127) at baseline were independent predictors for cardiovascular death. The odds ratio was 2.7 (95 % CI 1.07 - 4.11) for QTc interval prolongation (> 421 ms) and 3.3 (95 % CI 1.33 - 8.19) for elevated heart rate (> 75/min). CONCLUSION: Easily established ECG criteria such as prolonged QTc time and elevated heart rate obviously are powerful predictors of cardiovascular death in type 2 diabetic patients and are possibly superior to the traditional cardiovascular risk factors. As heart rate itself is an independent risk indicator, QTc time should be calculated by a formula (e.g. Fridericia's equation) that more accurately corrects QT for heart rate than the widely used Bazett's formula.