["Cryptogenic" coronary embolism - Case 4/2011]. / "Kryptogene" Koronarembolie - Fall 4/2011.

HISTORY AND ADMISSION FINDINGS: We report on a 42-year-old patient who presented with acute chest pain which occurred during defaecation. History revealed no cardiovascular risk factors. INVESTIGATIONS: ECG and laboratory testing showed an non-ST-elevation myocardial infarction (NSTEMI). DIAGNOSIS, TREATMENT AND COURSE: Coronary angiography revealed an embolic occlusion of the ramus intermedius. As origin of the embolus a deep vein thrombosis and a persistent foramen ovale (PFO) was diagnosed. We occluded the PFO with an Amplatz occluder. Because of the traumatic deep vein thrombosis phenprocoumon and clopdiogrel were given for 6 months. CONCLUSIONS: Patients with no cardiovascular risk profile, who present with typical chest pain, an embolic cause is an important differential diagnosis. Especially history is very helpful for the correct diagnosis. Interventional occlusion of PFO is a simple and safe approach for patients with symptomatic PFO regarding no permanent antithrombotic medication.

Prevalence of aspirin resistance in patients with type 2 diabetes.

Aspirin resistance has been recognised to occur in patients with cardiovascular disease and is associated with poor clinical prognosis. The purpose of the present study was to evaluate the prevalence of aspirin resistance in 172 patients with diabetes mellitus type 2 (DM-2). Platelet function of 172 consecutive patients with type 2 diabetes on chronic aspirin therapy was evaluated. The effect of aspirin was assessed using the platelet function analyser (PFA-100) system, reporting platelet-dependent thrombus formation as the time required to close a small aperture in a biologically active membrane. Resistance to aspirin was defined as a normal collagen/epinephrine-induced closure time (82-165 s). Aspirin responders were defined when closure time was > or =300 s. Thirty-seven (21.5%) of the type 2 diabetic patients were found to be resistant to chronic aspirin therapy, 29 (16.9%) were semi-responders and 106 (61.6%) were responders. Univariate analysis revealed that aspirin non-responders were significantly younger (p<0.05) compared to aspirin responders. A significant number of type 2 diabetic patients are resistant to aspirin therapy. Aspirin resistance can be evaluated by point-of-care testing and should be recognised in diabetic patients that are treated for primary or secondary prevention.

[Multimodal computed tomography in acute cerebral infarction. Experience with a standardized protocol in 100 patients]. / Multimodale Computertomographie beim akuten Hirninfarkt. Erfahrungen mit einem standardisierten Untersuchungsprotokoll bei 100 Patienten.

Computed tomography (CT) is the standard method of brain imaging in acute stroke. To an experienced examiner, nonenhanced CT will exclude hemorrhage and may indicate early ischemic signs. Reliable description of an ischemic area and the underlying vascular disease is not possible in the acute phase but is possible, particularly within the first hours, when therapeutic decisions on matters such as systemic thrombolysis are to be made. For such rapid decision-making, imaging must provide more information. Novel, contrast-enhanced CT techniques can provide this information. Perfusion CT (CTP) can show brain perfusion, allowing one to distinguish between reversible and irreversible damage in an ischemic area. Also, CT angiography (CTA) can detect occlusion or stenosis in the relevant vasculature. Using a modern, multislice CT scanner, it is now possible to combine these modalities of imaging. In a fast protocol for emergency evaluation, all three methods can be performed and evaluated to provide the crucial information within 15 min. In the first 102 patients examined within 6 h of symptom onset using this protocol, multimodal CT contributed substantially to therapeutic decisions, even though there are some limitations in these methods.

Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: Inflammation and hypercoagulability contribute to the development of acute cerebral ischemia. Both can be mediated by the CD40 system. This study investigated whether the CD40 system and related mediators are upregulated in patients with transient ischemic attack (TIA) or stroke. METHODS: Seventeen patients with TIA, 60 patients with complete stroke, and 15 control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 on monocytes during and 3 months after acute cerebral ischemia by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. RESULTS: Our main findings are as follows: (1) patients with acute cerebral ischemia showed a significant increase of CD154 on platelets and CD40 on monocytes compared with controls; (2) plasma levels of soluble CD154 were significantly higher in these patients; (3) these patients had significantly higher numbers of prothrombotic platelet-monocyte aggregates; (4) the chemoattractant MCP-1 was significantly elevated in cerebral ischemia; and (5) at 3 months' follow-up, upregulation of CD154 still persisted in patients with previous acute cerebral ischemia. CONCLUSIONS: Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy.

BACKGROUND: Transplant vasculopathy is the main limiting factor of the long-term success of heart transplantation. We sought to establish the role of platelets in the development and progression of transplant vasculopathy. METHODS AND RESULTS: Platelet analysis and intracoronary ultrasound examination were performed in 78 heart transplant recipients. Quantitative intracoronary ultrasound was used to define the severity of disease at baseline (48.8+/-4.5 months after transplantation) and at 1-year follow-up. Platelet activation was assessed with the use of immunological surface markers of activation (ligand-induced binding site 1 [LIBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1 immunoreactivity was significantly increased in patients with diffuse disease when compared with focal transplant disease (median [quartile], 27[14, 64] versus 18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an independent predictor for the presence and progression of diffuse transplant vasculopathy (P=0.04). Patients with enhanced LIBS-1 levels (>75% quartile) had a 3.3-fold increased relative risk (95% CI 1.8 and 18.9, P=0.002) for the presence of diffuse transplant vasculopathy. When a cutoff value of 16.5 for the level of LIBS-1 was used, patients had a 4.8-fold increased relative risk (95% CI 1.9 and 12.5, P<0.01) for the progression of transplant vasculopathy. CONCLUSIONS: Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Understanding the underlying pathophysiological mechanisms might contribute to the development of treatment strategies to prevent transplant vasculopathy.

Stress echocardiography in special groups: in women, in left bundle branch block, in hypertension and after heart transplantation.

The non-invasive diagnosis of coronary artery disease by exercise electrocardiography is less accurate in women than in men, with a high rate of false-positive results in women. In contrast, recent studies have demonstrated that stress echocardiography in women is more accurate than exercise echocardiography and that the significantly higher specificity of stress electrocardiography may have the benefit of avoiding unnecessary angiography in women. Exercise-induced changes in the electrocardiogram are non-diagnostic in the presence of left bundle branch block or basal ST changes. In these patients, stress echocardiography can be used instead of conventional scintigraphy for the detection of coronary artery disease, but further echocardiographic studies are needed to confirm the promising results. Exercise electrocardiography and exercise echocardiography have been reported to be disappointing in the early detection of cardiac allograft vasculopathy after heart transplantation, and dobutamine stress echocardiography overestimates the incidence of angiographic evidence of cardiac allograft vasculopathy. However, compared to intravascular ultrasound imaging, dobutamine stress echocardiography seems to be a suitable non-invasive method for detecting cardiac allograft vasculopathy.

Platelet function in septic multiple organ dysfunction syndrome.

OBJECTIVE: Altered platelet function plays a role in the pathophysiology of multiple organ failure in sepsis. The purpose of the present study was to evaluate various aspects of platelet adhesive function in septic patients and its putative relevance for prognosis. DESIGN: Prospective clinical study. SETTING: Intensive Care Unit of the University Hospital. PATIENTS AND METHODS: A total of 41 patients admitted to the medical Intensive Care Unit were studied. On the day of admission, patients were evaluated by intensive care scoring systems (Elebute, APACHE II) to assess the severity of sepsis and multiple organ dysfunction syndrome (MODS), and platelet function tests were performed. All patients were observed for 28 days to assess their clinical outcomes. Eleven patients revealed septicemia without MODS (Elebute > or = 12, APACHE II < 20) and 20 septic patients suffered from MODS (Elebute > or = 12, APACHE II > or = 20). Ten non-septic patients without MODS served as a control group (Elebute < 12, APACHE II < 20). Flow cytometric determination of the activated fibrinogen (fg) receptor GPIIb-IIIa and as well as thrombospondin (TSP) on platelets and platelet-neutrophil adhesion (CD 41 immunofluorescence) ex vivo was performed using monoclonal antibodies. The effect of plasma obtained from patients on normal platelet aggregation in vitro, and adhesion to cultured endothelial cells was evaluated. RESULTS: The surface expression of TSP on platelets was increased in septic patients with MODS compared to controls (p < 0.03). Platelet-neutrophil adhesion was not significantly altered in septicemia (p < 0.09) but decreased significantly in the presence of MODS (p < 0.05) when compared to controls. Logistic regression analysis showed that platelet-neutrophil adhesion was an independent predictor for poor clinical outcome (p < 0.01). Plasma from septic patients sensitized normal platelets to hyperaggregate and to adhere to cultured endothelium (p < 0.01). CONCLUSION: In septic patients platelets become activated and are hyperadhesive to other vascular cells including neutrophils and endothelium. This may induce sequestration of platelets and microcirculatory arrest, thus the development of MODS.

Hemostatic parameters in sepsis patients treated with anti-TNF alpha-monoclonal antibodies.

Tumor necrosis factor-alpha (TNF alpha) is a central mediator in the pathogenesis of sepsis. It also interferes with the hemostatic system and exerts and a net procoagulant effect. Since TNF alpha may contribute to thrombotic complications in sepsis patients, we determined markers of thrombin activation, parameters of the fibrinolytic system (D-dimer, tissue plasminogen activator antigen (tPA) urinary type plasminogen activator antigen (uPA), plasminogen activator inhibitor antigen (PAI-1) and von Willebrand factor antigen (vWF) in 30 patients with sepsis or septic shock. All patients were treated with standard therapy, but 14 patients were treated additionally with an anti-TNF alpha monoclonal antibody (MAK 195F); 16 patients served as historical controls. No significant effect of the antibody on the parameters of the hemostatic system could be determined. Our data speak against a modulation of coagulation or the fibrinolytic system by the monoclonal anti-TNF alpha antibody MAK 195F in this cohort of sepsis patients.

Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure.

This study focuses on the role of platelet membrane glycoproteins and platelet-leucocyte adhesion in patients with sepsis and multiple organ failure (MOF). Specifically, the study raises the following issues: (1) the influence of sepsis and MOF on platelet activation as assessed by surface expression of platelet membrane glycoproteins GPIIb-IIIa and thrombospondin; and (2) the effect of sepsis and MOF on platelet adhesion to circulating leucocytes. In addition, platelet activation and platelet-leucocyte adhesion are evaluated according to clinical outcome. Forty-five patients with suspected sepsis or MOF were evaluated by intensive care scoring systems (APACHE II and Elebute) to assess severity of disease. Flow cytometric techniques were used to examine platelet membrane expression of various adhesion molecules on circulating platelets and the appearance of platelet specific antigen (CD41) on leucocytes as an index of platelet-leucocyte adhesion. The results were compared with severity of disease and according to outcome in patients. Twenty-eight patients of the total study population were septic and 17 were non-septic. Twenty-two of the 28 septic patients suffered from severe MOF (APACHE II > or = 20) whereas in six septic patients MOF was absent. Eleven of the non-septic group suffered from moderate MOF whereas in six, severe MOF was present. In septic patients fibrinogen receptor activity on platelets was significantly above normal values (P < 0.001). When MOF was present, thrombospondin surface expression on circulating platelets also increased significantly (P < 0.05). Concomitantly, platelet-leucocyte adhesion was increased in sepsis (P < 0.05) and decreased in patients with MOF (P < 0.05). Significant lower levels of circulating platelet-leucocyte aggregates occurred in non-survivors (P < 0.05). We conclude that sepsis is associated with increased surface expression of platelet adhesion molecules and an increased occurrence of circulating platelet-leucocyte aggregates. The decrease in circulating platelet-leucocyte peripheral sequestration. An increased platelet-leucocyte adhesion and sequestration might account for development of MOF in the course of sepsis.

Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation.

Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow cytometric techniques and platelet specific monoclonal antibodies, platelet surface expression of fibrinogen receptor on GPIIb-IIIa, of von Willebrand Factor receptor GPIb, and of granule glycoproteins (thrombospondin (TSP), GMP-140, GP53) was measured. Plasma membrane expression of GPIIb-IIIa and GPIb on circulating platelets was not affected by sepsis of MOF. Septic patients, however, showed a significantly elevated fibrinogen receptor activity (LIBS1 expression) (p < 0.05) that correlated with severity of disease (r = 0.597, p = 0.043). No significant change in surface expression of granule glycoproteins (TSP, GMP-140, GP53) was noted in septic patients. In contrast, degranulation of granule glycoproteins was significantly elevated in MOF (p < 0.05) which well with severity of MOF (GMP-140, r = 0.611, p = 0.013; TSP, r = 0.643, p = 0.026). We speculate that platelets in sepsis circulate in a hyperaggregable but still reversible state that results in increased risk of microthrombotic events. In the course of the disease, irreversible platelet degranulation of adhesion molecules occurs that may play an important role in the development of MOF.

Characterization of a phospholipase A2 in human serum.

Elevated catalytic activities of serum phospholipase A2 were measured in patients with inflammatory diseases. In contrast to human pancreatic phospholipase A2, the enzyme in serum of patients with non-pancreatic diseases was rather heat labile and showed a broad pH-optimum in the neutral range. Molecular sieving experiments revealed the existence of macro-molecular forms of the enzyme in serum which were cleaved into monomers of M(r) 14,000 in the presence of high salt concentrations. More than 100-fold purification was achieved by gel filtration chromatography on Sephadex G-100 in the presence of 2 mol/l KCl. Whether this serum phospholipase A2 and a secretory liver and platelet isoenzyme are identical remains to be established.