PubMed Health⌕ Search

Biomedical subjects

M Spannagl

Publications and source records attributed to M Spannagl.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phosphatidylethanolamine participates in the stimulation of the contact system of coagulation by very-low-density lipoproteins.

We have analyzed the influence of plasma lipoproteins on the activation of the contact pathway of blood coagulation in platelet-rich plasma (PRP). The formation of thrombin in PRP incubated in vitro was abolished by the factor XIIa antagonist corn trypsin inhibitor and by severe factor XII deficiency, indicating mediation by the contact system. Addition of VLDL to the PRP shortened the lag period and increased the generation of thrombin. There was no effect of HDL and LDL. In whole blood, VLDL accelerated the rate of fibrin formation, the procoagulant effect being prevented by factor XII deficiency and by corn trypsin inhibitor. The thrombin formation in the PRP was strongly increased by microemulsions of the VLDL lipids while it was reduced by the aqueous phase of the particles. Separation of the VLDL lipids indicated the phospholipid component as the major activating principle. Vesicles supplemented with all VLDL phospholipids but lacking specifically the fraction containing phosphatidylethanolamine (PE) prolonged the lag time. The PE containing fraction alone as well as vesicles enriched with egg PE shortened the lag period. In summary, VLDL stimulates the contact pathway of blood coagulation, ethanolamine phospholipids being the most active components of the particles.

Adult↗
PubMed2000

[The Bavarian Thromboembolic Risk Cohort Study (BATER). Study protocol, state of the investigation and first results].

OBJECTIVE: Familiar venous thromboembolic disease (VTE) is known to be related with factor V Leiden mutation (FVL), but also with other genetic markers. It is the objective to investigate of the BATER-study in a representative Bavarian cohort, and to assess whether they could predict VTE events. This paper shortly describes the study protocol, gives an overview of planned sub-studies, and provides first results of the historic cohort analysis. PATIENTS AND METHODS: The baseline survey of the cohort study of Bavarian women aged 18-49 years (random sample from the population) was performed in two samples in 1996 and 1997. It was planned to estimate a prevalence and predictive value of potential markers of VTE in a historic--prospective as well as concurrent approach with annual follow-up of the cohort. This representative cohort should build a basis for nested case-control studies and serve as a reference group for other analytical epidemiological studies in young women. 1685 women were ascertained (response rate 61%), underwent an inquiry, and provided blood samples for a blood bank; for this paper, complete data are available from 1650 women. Laboratory parameters were measured to determine APC resistance, FVL-mutation, antithrombin-, protein C and S deficiency, and were correlated to the results of a detailed, life-time history of thrombembolic events. RESULTS: The prevalence of FVL mutation in the sample was 5.7% (95% confidence interval 4.6-6.6%). Other genetic VTE risk markers were observed to be less frequent than 1%. The positive predictive value (pPV) of FVL mutation for a VTE event is about 7%, but for a positive family history of VTE (first grade relatives) 3% only. CONCLUSIONS: VTE events are rare in the German population of young women, even in cases of FVL mutation. A positive family history is rarely associated with the occurrence of VTE in women under 50 years of age, and the predictive value of FVL mutation is low. Therefore, a screening for FVL mutation is not justified unless there is suspicion of a high VTE risk for other reasons.

Adolescent↗
PubMed2000

Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?

BACKGROUND: Major concern was raised by an earlier study regarding oral contraceptive use in women with the factor V Leiden mutation. A more than 30-fold increase in relative risk for venous thromboembolism was reported; for homozygotes, the relative risk was as much as 100-fold or more. OBJECTIVE: To replicate the reported risk estimates with a new population-based case-control study. METHODS: Eighty women with a diagnosis of venous thromboembolism were consecutively identified and compared with population-based controls (n = 406). Factor V Leiden mutation was identified by genotype analysis. The evaluation was performed with conditional logistic regression (matched for 5-year age group). RESULTS: Matched, adjusted odds ratios (OR) for idiopathic venous thromboembolism in women without and with the factor V Leiden mutation who used oral contraceptives were 4.1 (95% confidence interval (CI) 2.1-7.8) and 10.2 (95% CI 1.2-88.4), respectively. The adjusted OR for factor V Leiden carriers was 2.0 (95% CI 1.0-4.4). The OR for women with the factor V Leiden mutation and oral contraceptive use versus no factor V Leiden mutation and no oral contraceptive use was 10.2 (95% CI 3.8-27.6). CONCLUSION: The results confirm the increased relative risk of idiopathic venous thromboembolism for users of oral contraceptives and factor V Leiden carriers. However, we suspect that the true risk for women who are factor V Leiden carriers may be increased two- to four-fold rather than seven-fold or more, and that the risk for the combination of factor V Leiden and oral contraceptive use may be increased in the order often- to 15-fold rather than over 30-fold.

Adolescent↗
PubMed2000

c7E3 Fab inhibits low shear flow modulated platelet adhesion to endothelium and surface-absorbed fibrinogen by blocking platelet GP IIb/IIIa as well as endothelial vitronectin receptor--results from patients with acute myocardial infarction and healthy controls.

The c7E3 Fab reduces ischemic complications in patients undergoing high-risk coronary angioplasty or atherectomy. The present study investigated how c7E3 Fab inhibition of the platelet receptor glycoprotein IIb/IIIa and the endothelial vitronectin receptor affected platelet adhesion to endothelium and surface adsorbed fibrinogen under flow conditions. Platelet adhesion was examined using a stagnation point flow device with shear stress and shear rates up to 2.2 dynes/cm2 and 170 s(-1), respectively. Ex vivo adhesion was compared between two groups of patients with acute myocardial infarction (AMI) treated with angioplasty and stent implantation and a group of healthy controls. Only one AMI group received c7E3 Fab therapy. Patients in both groups were administered acetyl salicylic acid (ASA) and heparin. In AMI patients c7E3 Fab reduced platelet adhesion to adsorbed fibrinogen by 79% compared to AMI patients without c7E3 Fab treatment and by 74% compared to healthy controls. Thirty hours after termination of c7E3 Fab infusion adhesion had slightly recovered with an inhibition of 61% and 52% still present, respectively. Additionally, in vitro platelet adhesion to intact endothelium and to adsorbed fibrinogen was measured during superfusion with ADP stimulated platelet rich plasma of healthy controls to which c7E3 Fab was added at a final concentration fc of 20 microg/ml. In spite of ADP stimulation c7E3 Fab completely blocked platelet adhesion to adsorbed fibrinogen and, moreover, to intact endothelium. Preincubation of endothelial cells with c7E3 (fc = 20 [microg/ml) blocked adhesion of ADP-stimulated platelets by approximately 50%. Apart from the inhibition of platelet aggregation, c7E3 Fab added in vitro and given therapeutically in patients effectively blocks platelet adhesion to components of the injured as well as intact vessel wall under stagnation point flow conditions.

Abciximab↗
PubMed1999

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation.

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and resemble third-generation contraceptives.

Activated Protein C Resistance↗
PubMed1999

Replacement of coagulation factors in liver or multiple organ dysfunction.

Due to the complexity of alterations in hemostasis, replacement therapy in multiple organ dysfunction is a domain for nonspecific replacement therapy by means of fresh frozen plasma. Refined methods of virus inactivation as well as the consequent declaration of the major components of plasma derivatives have led to an increasing use of high-purity blood coagulation factor concentrates. Furthermore, the problem of activated factors and their inherent thrombogenic effect is meanwhile considerably attenuated. In the future, the availability of high-purity blood coagulation factor concentrates with a defined amount and quality of their factor content will enable a specific replacement therapy in single or multiple organ dysfunction in addition to unspecific replacement therapy by fresh frozen plasma

Blood Coagulation Factors↗
PubMed1999

[Skin necrosis in the front foot area during anticoagulation with phenprocoumon].

HISTORY AND ADMISSION FINDINGS: A 52-year-old woman was admitted because of pain for several days in the lower left leg and increasing pretibial swelling with livid discoloration. Six months before she had undergone a bilateral adnexectomy with removal of the omentum and subsequent chemotherapy for ovarian cancer. INVESTIGATIONS: Duplex sonography on the day of admission revealed thrombosis of the left popliteal vein with an unobstructed femoral vein. Both the quick value (89%) and partial thromboplastin time (PTT, 35.9 s) were within normal limits. Computed tomography and sonography were highly suspicious of a local recurrence of the ovarian cancer with peritoneal carcinomatosis. TREATMENT AND COURSE: PTT-effective heparinization (heparin-Na) was initiated together with overlapping anticoagulation with phenprocoumon (thromboplastin time 20-30%). On the 9th day after starting phenprocoumon painful, black necrotic changes began to appear on the skin of the left first to fourth toes. Assuming these to be due to phenprocoumon, anticoagulation was switched to low-molecular heparin (Enoxaparin), and antithrombin III and protein C were administered. A few days later thrombosis of the right iliac vein occurred, probably caused by local recurrence of the ovarian cancer. No palliative chemotherapy was undertaken in view of the thrombotic complications. The patient died a few months later from the cancer. CONCLUSION: If there is an underlying malignancy, chemotherapy and therapeutic vitamin-K antagonism in the presence of thromboembolic complications increases the risk of lowering protein C activity and may cause the rare complication of skin necrosis, induced by phenprocoumon.

Anticoagulants↗
PubMed1999

Mechanisms underlying increased platelet reactivity in patients with peripheral arterial disease. Preliminary results.

BACKGROUND: In peripheral arterial disease (PAD) atherosclerosis is disseminated and thrombosis risk is high. We have not only shown the platelets of PAD patients to by hyperreactive and aspirin resistant, but have recently verified them to be hypersensitive to heparin as well. In the present study we have begun to clarify the mechanisms underlying these regularly observed clinical findings. METHODS: Platelet function was tested with conventional, ADP-primed aggregation and with stagnation point flow adhesio-aggregometry (SPAA). SPAA permits real time, quantitative assessment of platelet adhesion and aggregation under biologically relevant flow conditions. The platelets from a female patient with congenital afibrinogenemia, were analyzed before and after intravenous fibrinogen substitution. In 14 PAD patients and 14 controls, platelet reactivity was assessed before and after incubation with the two platelet membrane glycoprotein (GP)-IIb/IIIa inhibitors Ro 43-8857 and 7E3. Lastly, experiments were performed before and after addition of plasma aliquots stemming from 4 PAD patients to platelet rich plasma and to solutions of gel-filtered platelets (GFP) stemming from 4 healthy volunteers. Before fibrinogen substitution, the platelets of the afibrinogenemic patient were unable to adhere in the SPAA-system and maximal ADP-primed aggregability was below 10%. After substitution, normal platelet adhesion was measured and primed aggregation increased three-fold. Mean baseline adhesion in the patient collective was twice that compared to controls (p<0.001). SPAA-measured, spontaneous aggregation was observed in ten patients and in none of the controls (p<0.001). RESULTS: Both SPAA-measured and primed aggregation were abolished at the lowest substrate concentrations (0.1 microM Ro 43-8857, 1 microg/ml 7E3). At these concentrations adhesion was reduced by 65% and 40% (respectively) in patients, and by 55% and 25% in controls. Total abolition of adhesion in both groups was seen with 0.5 microM Ro 43-8857 and 10 microg/ml 7E3. Platelet response to inhibitory agent was similar in patients and controls, as were the differences in dose-response between aggregation and adhesion. Upon addition of patient plasma to volunteer PRP, the platelets of all 4 healthy individuals aggregated spontaneously and the mean adhesivity in the group rose three-fold. The overall ability of the GFP to adhere when re-added to their own plasma was decreased, whereas, in the presence of patient plasma, adhesion increased significantly. CONCLUSIONS: On the basis of these findings we conclude that: 1) SPAA measures and quantifies platelet interactions with both fluid-phase (aggregation) and immobilized (adhesion) fibrinogen, 2) these reactions are mediated by the GP, IIb/IIIa receptor complex 3) the binding affinity, metabolic pathways and signal transduction underlying platelet adhesion differ from those involved in aggregation (possibly reflecting their varying roles in hemostasis), 4) the functionally normal platelets of patients with PAD are primed in vivo by a circulating plasma constituent, which leads to enhanced recruitment of activated GP, IIb/IIIa onto the platelet surface and, thereby, to an overall increase in reactivity.

Acetates↗
PubMed1998

Influence of high- and low-dose aprotinin on activation of hemostasis in open heart operations.

BACKGROUND: The protease inhibitor aprotinin reduces hemostatic activation and blood loss after cardiac operations. The aim of the present study was to investigate the influence of two different aprotinin doses on hemostatic activation and to identify the most effective dose to reduce the postoperative bleeding tendency. METHODS: In a prospective, randomized, double-blind clinical trial, 230 patients scheduled for routine open heart operations received either high-dose (group H) or low-dose (group L) aprotinin. Primary outcome measures were the level of F(1+2) prothrombin fragments as a marker of thrombin generation, the level of D-dimers as an indicator of fibrinolysis, and the amount of postoperative blood loss. Allogeneic blood transfusion was recorded as a secondary outcome measure. RESULTS: Aprotinin plasma concentrations 5 minutes after the onset of cardiopulmonary bypass were 166 +/- 45 kallikrein inactivator units per milliliter in group H and 118 +/- 30 kallikrein inactivator units per milliliter in group L (p < 0.05). Fibrinolytic activation was reduced significantly in group H compared with group L: the level of D-dimers at the end of CPB was 1,027 +/- 781 ng/mL and 1,977 +/- 1,001 ng/mL, respectively, in the two groups (p < 0.05). However, thrombin generation (F(1+2) fragments) did not differ between the two groups (7.4 +/- 3.5 nmol/L in group H and 8.6 +/- 4.3 nmol/L in group L). Twenty-four-hour postoperative blood loss was 663 +/- 461 mL in group H compared with 877 +/- 513 mL in group L (p < 0.05), and the corresponding allogeneic blood requirement was 1.3 +/- 1.9 U in group H and 1.9 +/- 2.3 U in group L (p < 0.05). CONCLUSIONS: A high-dose aprotinin regimen was significantly more effective than a low-dose regimen in attenuating fibrinolysis and reducing the bleeding tendency and allogeneic blood requirements, but not in reducing F(1+2) prothrombin fragments. High-dose aprotinin therapy appears to be superior to low-dose therapy.

Aprotinin↗
PubMed1998

Normalized activated protein C ratio itself not associated with increased risk of venous thromboembolism.

Recently, discussions focused on the question whether acquired activated (APC) resistance is a clue to the observed association between venous thromboembolism (VTE) risk and oral contraceptive (OC) use, especially with the so-called third-generation OC. The objective of our study was to check the validity of acquired APC resistance regarding VTE risk in a case-control study. Sixty-seven women with confirmed VTE diagnosis (n = 67) were consecutively ascertained in primary health care settings, interviewed and blood samples taken (at the earliest 6 months after VTE). Cases were age-matched to 290 population controls. Acquired APC resistance was measured as normalized APC ratio (APCRN). The effect of APC on tissue factor initiated thrombin generation was measured in plasma using alpha 2-macroglobulin attached thrombin activity as an endpoint. Higher risk (odds) ratio with 95% CI) of VTE for carriers of heterozygote Factor V Leiden mutation was confirmed [OR = 2.72 (CI:1.51-4.92)]. However, there is no association between VTE and the level of APCRN OR 0.65 (CI:0.35-1.22). We conclude that acquired APC resistance, measured with a tissue factor initiated test, is unlikely to have a direct association to the clinical outcome of venous thromboembolism.

Adolescent↗
PubMed1998

Resistance to activated protein C in women using oral contraceptives.

Resistance to activated protein C (APC resistance) is an important and common risk factor for deep vein thrombosis. The majority of patients with APC resistance carry a mutation on the factor V gene at nucleotide position 1691 (G/A), called factor V Leiden mutation. Besides the factor V Leiden mutation several acquired risk factors like lupus anticoagulant, elevated levels of acute phase proteins (increased plasma levels of factor VIII and fibrinogen), pregnancy, or the use of oral contraceptives are known to induce APC resistance in plasma. We studied the effect of oral contraceptives (OC) on hemostasis variables known to be risk factors for venous thromboembolism, especially looking for acquired APC resistance and the plasmatic factors of the protein C system. We studied 821 women, who were randomly selected and enrolled in the BATER- cohort study (Bavarian Thromboembolic Risk Study), which was carried out in Bavaria (Germany) from 1996 to 1997. Current use of any OC type compared with noncurrent use showed a significantly impaired response to APC. There was no difference in APC response among women currently using OCs of different generations. Coagulation factor VIII was the only factor of the protein C pathway that was not altered under OC use. All other plasmatic factors of the protein C system changed in the expected range as described before. On the other hand, coagulation factor VIII was the only factor of the protein C system which negatively correlated with the APC response in the assays applied. Thus, APC resistance is significantly lower in OC users than in nonusers but cannot be attributed to increased factor VIII levels. Whether a decreased response to APC in OC users is of clinical relevance has to be proven in further studies.

Activated Protein C Resistance↗
PubMed1998

Spreading of platelets: a morphological marker for platelet reactivity in peripheral arterial occlusive disease.

Platelet-surface contact is the first step in thrombus formation. Platelet spreading makes this initial contact irreversible. On the other hand plasma lipids and fibrinogen have been described to activate platelets or promote adhesion. We therefore investigated whether platelet spreading under stagnation-point flow conditions correlated with plasma concentrations of cardiovascular risk factors such as fibrinogen and high density lipoprotein (HDL)-cholesterol. Platelet rich plasma (PRP) from patients with peripheral arterial occlusive disease and healthy controls was examined by means of the Stagnation-Point Flow Adhesio- Aggregometer (SPAA). The SPAA comprises a microscopic setup with a flow chamber that permits direct observation and quantitation of platelet deposition onto standardized surfaces. After the flow experiments the deposited platelets were analyzed morphometrically for the degree of spreading expressed as inverse circularity (1/C). 1/C was correlated over 2 X 2 tables of fibrinogen combined with plasma levels of HDL-cholesterol, each of which was divided into a low and high value group. The patient and control group differed significantly with regard to 1/C, i.e. patient platelets demonstrated more adhesive platelets with a more extensive degree of spreading. 1/C was inversely correlated with HDL-cholesterol and showed significant differences between the patient and the control group. Increased 1/C values were found when associated with high fibrinogen levels and simultaneously with low HDL-cholesterol concentrations. Platelet spreading shows a correlation with increased levels of independent plasmatic risk factors for thrombosis in PAOD patients. Obtained during stagnation-point flow, spreading seems to be a morphological marker for platelet hyperreactivity.

Journal Article↗