Severe ARDS induced by fusobacterial infections: a rare clinical presentation of Lemierre syndrome.

Acute respiratory distress syndrome (ARDS) poses a major challenge in intensive care settings. The main underlying causes of ARDS are trauma, pancreatitis, and pulmonary manifestation of systemic inflammatory response syndrome/sepsis.Lemierre syndrome represents a nearly forgotten entity arising from oropharyngeal infections with Fusobacterial species, and it is of renewed and increasing interest because of evolving antibiotic resistances.We report two cases of young female patients afflicted by Lemierre syndrome with additional severe ARDS and present an overview of the current literature.

Rotation thromboelastography for the detection and characterization of lipoteichoid acid-induced activation of haemostasis in an in vitro sepsis model.

OBJECTIVES: In gram-positive sepsis, lipoteichoic acid (LTA) can induce alterations of haemostasis, potentially leading to disseminated intravascular coagulation. PATIENTS AND METHODS: Here, we demonstrate the effects of LTA on haemostasis in an in vitro model of gram-positive sepsis based on rotation thromboelastrography (ROTEM). RESULTS: In this model, LTA leads to time- and dose-dependent shortening of the clotting time (CT), whereas other ROTEM parameters are unaffected. Following heat shock simulation, the LTA effect was blunted with equal CTs in the presence and in the absence of LTA. In addition, the shortening of CT by LTA was inhibited by addition of the protein synthesis inhibitor. CONCLUSION: Our work demonstrates that the ROTEM system is capable of detecting the LTA effect on haemostasis and provides a sensitive in vitro tool for research into the links between gram-positive sepsis and coagulation.

Prone and ECMO - a contradiction per se?

Acute respiratory distress syndrome (ARDS) still represents a serious problem in clinical routine and is associated with a high mortality. Several concepts are known for special treatment, but, in some instances, the application of an extracorporeal membrane oxygenation (ECMO) is necessary for both the improvement of oxygenation and the elimination of carbon dioxide (CO(2)). One basic aspect in lung protective ventilation in this context is alveolar recruitment, which can be achieved by different approaches, such as "the open lung concept", according to Lachmann, or by additional kinetic therapy. The most exposed feature of this entity is 'prone', which may be quite challenging in patients requiring extracorporeal support or organ replacement therapy under ongoing critical illness. We report two outstanding cases of prone under conditions of a veno-venous ECMO therapy which improved significantly under this position. Furthermore, we reflect critically possible risk factors and adverse events of such procedures and afford a current view from the literature.

[Spontaneous hematoma and hip pain in a 65-year old patient]. / Spontane Hämatomneigung und Hüftschmerzen bei einer 65-jährigen Patientin.

The case of a 65-year-old woman with acquired hemophilia is reported. Acquired hemophilia is characterized by the development of inhibitors directed against coagulation factors. Impairment of plasmatic hemostasis leads to a severe bleeding tendency in individuals without a preexisting coagulation defect with considerable mortality. Pathophysiology, diagnostic work-up, and treatment are summarized and discussed.

Platelet function analyzer (PFA-100) as a useful tool for the prediction of transfusion requirements during aortic valve replacement.

BACKGROUND: Shear stress-induced hemostatic abnormalities, particularly loss of the hemostatically most competent, highest molecular weight von Willebrand factor multimers, are common in patients with aortic valve stenosis. Although controversially discussed, these hemostatic defects might be associated with an increased risk of bleeding during aortic valve replacement. Since the determination of closure times with a platelet function analyzer is sensitive for the detection of defects of primary hemostasis including shear stress-induced von Willebrand factor abnormalities, this study was performed to evaluate a method to predict intraoperative transfusion requirements in this setting. METHODS: Fifty patients (mean age ± SD: 68 ± 9 years, range 40-85 years) admitted for aortic valve replacement were enrolled in the study. Closure times of epinephrine/collagen and ADP/collagen cartridges were determined with a platelet function analyzer in the absence of antiplatelet agents. Results were compared to those obtained in healthy individuals without medication. The probability that a patient would require a transfusion of packed red cells (RBC) and fresh frozen plasma (FFP) was calculated for each obtained closure time using a multiple regression model. RESULTS: Compared to controls, patients undergoing aortic valve replacement had a significantly higher incidence of prolonged closure in the platelet function analyzer. The prolonged closure time of both epinephrine/collagen and ADP/collagen cartridges was significantly correlated with intraoperative transfusion of RBC, but not FFP. CONCLUSIONS: In patients undergoing aortic valve replacement, prolongation of closure times as determined by a platelet function analyzer is frequently observed, indicating the presence of shear stress-induced defects of primary hemostasis. Since the prolongation of closure times is significantly correlated to the probability of intraoperative transfusion, this method might offer a significant contribution to the preoperative risk stratification of patients.

Rotation thromboelastography (ROTEM) parameters are influenced by age, gender, and oral contraception.

Rotation thromboelastography (ROTEM) is a screening method that allows the rapid detection of plasma- and platelet-related haemostatic abnormalities. To use this procedure more efficiently, reference values depending on gender, age, and oral contraception are required. In this study, five cohorts of healthy subjects were examined by ROTEM upon activation of the extrinsic or intrinsic pathway of coagulation, or recalcification alone. The cohorts comprised male subjects below (1) and above (2) 45 years of age, female subjects below 45 years of age with (3) or without (4) oral contraception, and female subjects above 45 years (5) without hormone replacement therapy. A significant influence of gender, age, and oral contraception on parameters determined by ROTEM was observed. Thus, adjustment for age, gender, and oral contraception is required when ROTEM is used to screen for distinct abnormalities of haemostasis.

Platelet-function analyzer closure times indicate shear stress-induced hemostatic abnormalities in patients with aortic valve stenosis and correlate with perioperative transfusion requirements.

BACKGROUND: Shear stress-induced hemostatic abnormalities are highly prevalent in patients with aortic valve stenosis. In this study, we determined closure times with a platelet-function analyzer (PFA-100, Dade Behring, Marburg, Germany) in patients admitted for aortic valve replacement to assess the correlation with the severity of aortic valve stenosis, blood loss, perioperative transfusion requirements, and need for re-thoracotomy. PATIENTS AND METHODS: Fifty consecutive patients (mean age [+/- SD] 68 +/- 9 years) were enrolled. Closure times of epinephrin/collagen and adenosine diphosphate (ADP)/collagen cartridges were determined at least ten days after discontinuation of antiplatelet medication and compared to those of healthy control subjects without medication. RESULTS: Closure times of epinephrin/collagen (210 +/- 69 sec vs. 140 +/- 50 sec, p < 0.0001) and ADP/collagen (145 +/- 58 sec vs. 108 +/- 45 sec, p < 0.0001) cartridges were prolonged in patients with aortic valve stenosis. Intraoperative transfusion of red blood cell units was associated with the closure times of epinephrin/collagen (r = 0.28, p = 0.04) and ADP/ collagen cartridges (r = 0.28, p = 0.04). Total transfusion of red blood cell units was associated with ADP/ collagen closure times (r = 0.31, p = 0.02), but not epinephrin/collagen closure times (r = 0.26, p = 0.07). No significant association of closure times with intraoperative, postoperative and total transfusion of fresh frozen plasma units was observed. CONCLUSIONS: Prolongation of closure times determined with a platelet-function analyzer is highly prevalent in patients with aortic valve stenosis and appears to reflect shear stress-induced hemostatic abnormalities. Since prolonged closure times are associated with increased perioperative transfusion of red blood cell units, the assay could significantly contribute to the identification of individuals at risk.

[Oral anticoagulation : Current overview and perioperative management in ophthalmic surgery]. / Orale Antikoagulation : Aktuelle Übersicht und perioperatives Management in der Ophthalmochirurgie.

Antithrombotic treatment with oral anticoagulants and antiplatelet agents can increase the risk for perioperative bleeding. In contrast to other surgical fields, the optimal perioperative management in ophthalmic surgery has not yet been exactly defined and, thus, is not standardized. In this contribution, we provide an overview of currently available oral anticoagulants and discuss potential strategies for the management of these agents in different ophthalmic surgical procedures.

Rotational thrombelastometry for the bedside monitoring of recombinant hirudin.

BACKGROUND: Recombinant hirudin is used as an alternative anticoagulant, particularly in patients with heparin-induced thrombocytopenia type II. However, bedside monitoring for hirudin is not available. The present study aims to evaluate rotational thrombelastometry regarding its suitability to detect the effects of recombinant hirudin on whole blood coagulation. Hirudin was added to whole blood samples from healthy donors (n=5) and thrombelastometry variables resulting from activation of samples with tissue factor, ellagic acid, and ecarin were determined. METHODS: Hirudin (0.1-10 microg/ml) was added to citrated blood. Thereafter, rotational thrombelastometry was performed by initiating coagulation via recalcification and addition of tissue factor, ellagic acid, and ecarin, respectively, using the commercially available assays. RESULTS: In the absence of hirudin, clotting times (CT) induced by ellagic acid, tissue factor, and ecarin, respectively, were 141.7+/-18.0, 54.0+/-7.6, and 64.5+/-4.1 s. Increasing concentrations of hirudin led to dose-dependent prolongation of the clotting time with the three activators. All assays were capable to detect hirudin concentrations in the range of 0.5-5 microg/ml. At a final hirudin concentration of 1 microg/ml, clotting time increased to 268.0+/-25.1, 84.0+/-9.3, and 107.5+/-9.9 s, respectively, with the above-mentioned activators. The other thrombelastographic variables, including clot formation time, angle alpha, and maximum clot firmness, were not altered by hirudin at concentrations up to 5 microg/ml. CONCLUSIONS: Our study demonstrates the suitability of rotational thrombelastometry to detect anticoagulant effects of recombinant hirudin.

[Thrombophilia in pregnancy: venous thromboembolism, fetal loss, preeclampsia, intrauterine growth restriction]. / Thrombophile Hämostasestörung in der Schwangerschaft: Thrombose, Abort, Präeklampsie, intrauterine Wachstumsretardierung.

Women with acquired and hereditary thrombophilia are at increased risk of developing venous thromboembolism and other associated gestational vascular complications like fetal loss, preeclampsia, intrauterine growth restriction, and placental abruption during pregnancy. These complications are a major cause of maternal and fetal morbidity and mortality. In view of the data showing an association between thrombophilia and these adverse pregnancy outcomes, clinicians are increasingly using antithrombotic therapy in women at risk of these complications. Aside from recurrent pregnancy loss in antiphospholipid syndrome and prevention of venous thromboembolism, there is limited evidence on the benefit of antithrombotic interventions to guide therapy. The data in favour of antithrombotic therapy in women with hereditable thrombophilia and vascular placental complications consist predominantly of small uncontrolled trials or observational studies. Randomized, placebo-controlled trials are lacking as most patients do not accept placebo. Further randomised controlled trials are urgently required to explore this therapeutic option.

[Management of anticoagulants in ophthalmic surgery-a survey among ophthalmic surgeons in Germany]. / Umgang mit gerinnungshemmenden Substanzen in der Ophthalmochirurgie ­ eine Umfrage unter Ophthalmochirurgen in Deutschland.

INTRODUCTION: As our population ages and comorbidities rise, ophthalmic surgeons are increasingly faced with patients on anticoagulant therapy or with clotting disorders. The ophthalmic surgeon has to weigh the perioperative risk of haemorrhage when anticoagulation continues against the risk of thromboembolism caused by discontinuation or changing the patient's medication (bridging, switching, cessation). There are currently no guidelines or recommendations. METHODS: A survey was sent to the DOG (German Ophthalmologic Society) divisions and associated surgical organizations to determine the status quo. A questionnaire was sent out and filled out by the different groups of specialists. RESULTS: All four divisions of the DOG and four associated organizations returned completed questionnaires. Surgical interventions were listed that are carried out during anticoagulant therapy without exceptions, as well as interventions that were classified to require medical adjustment. Although the assessments varied, general consensus was achieved regarding interventions not requiring adjustments due to anticoagulants (i. e., intravitreal injection, cataract surgery, laser and corneal operations, simple muscle surgery), and those interventions requiring adjustments in medications (glaucoma operations, complex retina surgery, eye socket surgery, complex surgery of the lid). CONCLUSION: Main result of this survey was the specification of serious bleeding complications which are permanent vision loss and re-operation. They could serve as endpoint parameters for essential future investigations. Nevertheless, this survey makes clear that the decision about an adjustment of anticoagulant medication in ophthalmic surgery is currently made individually and not based on established standards.

Platelet receptor HPA-1 polymorphism of alphaIIbbeta3 and 807 C/T polymorphism of alpha2beta1 and Buerger's disease.

Thromboangiitis obliterans or Buerger's disease is an episodic and segmental inflammatory and thrombotic process of the medium and small arteries of the lower extremities. Even though the disease was described 90 years ago, the etiopathogenesis is still under consideration. Afflicted patients are mostly young male cigarette smokers without signs of atherosclerosis or other risk factors for peripheral arterial occlusive disease. This indicates that hereditary thrombophilic factors could play a role in the etiopathogenesis. Recently, increasing evidence shows that platelet receptor polymorphisms (HPA-1 polymorphism of beta3 subunit of alphaIIbbeta3 and 807 C/T polymorphism alpha2beta1) are associated with early onset of arterial thrombosis (myocardial infarction, stroke). This case-control study was designed to assess whether the 807 C/T polymorphism or the HPA-1 polymorphism is involved in the pathogenesis of Buerger's disease or has any influence on the clinical course of Buerger's disease. Eighteen patients with Buerger's disease and 81 (sex and age matched) healthy control subjects (mean age 44 +/- 10 vs 45 +/- 8 years, respectively) were genotyped for platelet receptor HPA-1 and GPIa 807 C/T polymorphism. The gene frequency of HPA-1 and GPIa 807 C/T polymorphisms was identical in both groups. Prevalence of hetero- and homozygous carriers of the HPA-1b allel (1a1b and 1b1b genotype) as well as the prevalence of the 807 C/T and 807 T/T carriers did not differ significantly between the two groups, p >0.05. The grade of clinical disease manifestation as well as disease progression did not reveal any significant relationship with HPA-1 and 807 C/T polymorphisms. A relationship between the age at onset of the disease and HPA-1 polymorphism was not found. Otherwise analysis of the GPIa 807 C/T platelet receptor polymorphism showed that the average age of patients who are carriers of the T allele at early onset of disease was 32 +/- 6 years (range 27-48 years) compared to 42 +/- 6 years (range 34-53 years) of the C/C carriers (p <0.05). This indicates that the GPIa 807 C/T polymorphism does not represent a risk factor for Buerger's disease itself, but could be associated with premature onset of this disorder in predisposed individuals.

A rationale for positive selection of peripheral blood stem cells in multiple myeloma: highly purified CD34+ cell fractions of leukapheresis products do not contain malignant cells.

In multiple myeloma (MM), the presence of tumor cells in leukapheresis products (LP) has been demonstrated with highly sensitive molecular biological tools in up to 100% of cases. Therefore methods to reduce the tumor load of LP by CD34+ selection are envisaged. However, there is controversy as to whether the CD34+ cell is already involved in the malignant process. We have established a PCR assay with allele-specific oligonucleotide primers (ASO) complementary to the CDR3-hypervariable region of the immunoglobulin heavy chain gene of each patient's myeloma clone. Using this ASO-PCR, 43 LP of 10 patients with MM eligible for high-dose therapy were assessed for malignant cells. Furthermore, in an experimental setting we have examined 10 CD34+ and four CD19+ fractions obtained from PCR-positive LP by sequential preparative magnetic and fluorescence activated cell sorting (purity >96%) for the presence of the tumor-specific CDR3 region. The majority of LP harbored cells of the myeloma clone (93%), while all CD34+ fractions were PCR-negative. In all CD19+ fractions malignant cells were detected. These results confirm that CD34+ selection can be considered for LP in MM. The sensitivity of the ASO-PCR (up to 10[-5]) enables us further to monitor the efficacy of CD34+ enrichment protocols in the clinical setting.

[Arteriosclerosis and media sclerosis. A comparison of 2 calcifying vascular diseases]. / Arteriosklerose und Mediasklerose. Eine Gegenüberstellung zweier kalzifizierender Gefässerkrankungen.

PATHOGENESIS: Arteriosclerosis and Mönckeberg's mediasclerosis are vascular diseases associated with calcification of the artery wall. While mediasclerosis in most cases develops in type 2 diabetic patients, arteriosclerosis is the result of a combination of different vascular risk factors. Mönckeberg's mediasclerosis typically involves the tunica media, whereas arteriosclerosis-associated calcifications primarily involve the intima. CLINICS: Isolated mediasclerosis does not cause narrowing of the blood vessel. The disease is usually asymptomatic, specific therapy has not yet been established. The involvement of the intima in arteriosclerosis finally leads to a decreased circulation.

Continuous venovenous haemofiltration using a citrate buffered substitution fluid.

Different methods of regional anticoagulation using citrate in continuous renal replacement therapy have been described in the past. However, these procedures were usually very complex or did not reach modem requirements for effective continuous renal replacement therapy. Furthermore, little is known about long-term acid-base stability and citrate levels during the treatment. We describe a system in which citrate is used both as anticoagulant and as the sole buffer substance in continuous venovenous haemofiltration. Our citrate-containing, calcium-free substitution fluid was used in predilution mode with a constant ratio between blood flow (120 to 150 ml/min) and substitution flow (2400 to 3000 ml/hour). Anticoagulation was limited to the extracorporeal circuit. Twenty patients with acute renal failure on mechanical ventilation were treated, four for eight hours, four for 24 hours and 12 as long they needed continuous renal replacement therapy (9.6 +/- 5.0 days, range 4.0 to 39.3 days). We achieved stable acid-base and electrolyte balance in all patients. We observed no bleeding complications (patient activated clotting time 112.4 +/- 17.1 s, post-filter circuit activated clotting time 270.5 +/- 80.3 s) and achieved appropriate filter life times (48.6 +/- 13.2 h). Predilution, citrate-based substitution fluid provides both anticoagulation within the extracorporeal circuit and control of acid-base balance in critically ill patients at risk of bleeding in acute renal failure. It is easy to apply and safe. Clearance can be varied as long as a constant ratio between blood and substitution flow is maintained.

Intravenous iloprost: a new therapeutic option for patients with post-transplant distal limb syndrome (PTDLS).

The purpose of this study was to investigate the application of intravenous iloprost as a novel therapy for the treatment of post-transplant distal limb syndrome (PTDLS). PTDLS is a benign but disabling complication in the first year after renal transplantation. It is characterized by bilateral, often incapacitating pain in the feet and or knees on motion and a significant rise in alkaline phosphatase levels on laboratory evaluation. On MRI, bone marrow edema of the affected bone regions can be demonstrated. PTDLS differs from steroid induced osteonecrosis of the hip in terms of localization, an average cumulative steroid dosage within expected limits, and a benign outcome, as PTDLS does not progress to overt cell necrosis. From August 2003 to April 2005 we treated 10 patients with MRI-proven diagnosis of PTDLS following a standardized regimen of intravenous iloprost over 5 days. Iloprost led to prompt pain relief measured on a visual analogous scale (VAS) ranging from 1 to 10 (5.6 +/- 1.5 before vs. 2.1 +/- 1.3 after treatment, p = 0.0004). PTDLS represents a benign but disabling complication following renal transplantation. Intravenous iloprost might be a promising therapeutic concept leading to a quick relief of symptoms without relevant side effects.