Prevalence of heparin-induced PF4-heparin antibodies in hemodialysis patients.
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Adult↗
Biomedical subjects
M Spannagl
Publications and source records attributed to M Spannagl.
Reduction of acquired high titer factor VIII antibodies by extracorporeal antibody-based immunoadsorption without additional immunosuppressive therapy.
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Antibodies, Anti-Idiotypic↗
Delayed treatment with desulfato-hirudin prevents fibrin formation in lipopolysaccharide-induced shock.
Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfato-hirudin prevented fibrin formation and respiratory dysfunction in porcine lipopolysaccharide shock. We examined the effects of delayed administration of recombinant desulfato-hirudin in bacterial lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h) for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5 nmol/ kg/h); 10 randomised control animals received saline instead of recombinant desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were significantly lower in bacterial lipopolysaccharide+recombinant desulfato-hirudin animals than in controls. Both groups displayed a similar rise in pulmonary vascular resistance and other parameters of lung dysfunction; only lung tissue wet/dry ratio was lower in recombinant desulfato-hirudin-treated than in control animals. Both groups had similar circulatory alterations. Recombinant desulfato-hirudin interrupted coagulation activation during ongoing bacterial lipopolysaccharide-induced shock in pigs even when administered with a delay of one hour after start of the bacterial lipopolysaccharide infusion. A protective effect of delayed recombinant desulfato-hirudin administration on bacterial lipopolysaccharide-induced acute lung injury and alterations in the systemic circulation could not be demonstrated in this experiment.
Animals↗
Autoantibodies against the protease inhibitor calpastatin: a new risk factor for venous thrombosis?
Autoantibodies reactive against human calpastatin were detected by screening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected antiphospholipid syndrome. When further sera were analyzed it could be shown that > 90% of calpastatin autoantibodies, detected by Western blotting against the partial calpastatin clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin was developed and 205 healthy blood donors and 138 random sera from hospital patients were analyzed. A total of 11 sera (3.2%) were positive with no significant difference between the two groups (7/205 and 4/138). In 80 consecutive patients with a history of venous thrombosis 9 positive sera (11.3%; p < 0.01 vs. blood donors, p < 0.02 vs. hospital patients) were detected. Our results indicate that autoantibodies against calpastatin may constitute a so far unknown risk factor for venous thrombosis.
Adolescent↗
Urticaria haemorrhagica profunda.
Substantial subcutaneous haemorrhage without preceding trauma or underlying bleeding disorder is a rare occurrence in dermatological practice, essentially restricted to early childhood (acute haemorrhagic oedema of childhood). We report an adolescent with a morphologically unique bleeding manifestation. A 16-year-old boy presented with two episodes of massive subcutaneous haemorrhage in association with urticarial vasculitis. There was no history of preceding trauma or haemorrhagic disorder. Haemorrhage was observed in areas typically affected by angioedema, such as the periorbital, perioral, lingual, sublingual and laryngeal areas. History revealed an atopic diathesis with hay fever and examination showed alopecia areata. An antinuclear antibody titre and the presence of lupus anticoagulant indicated transient antiphospholipid antibodies. As urticaria corresponds to urticaria profunda angioedema, we hypothesize a pathophysiological relationship between superficial urticarial vasculitis and the deep variant of urticarial vasculitic disease, leading to the unique morphology present in our patient.
Adolescent↗
[Preoperative withdrawal of Marcumar].
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Anticoagulants↗
Evaluation of atherosclerosis in patients with central retinal vein occlusion by carotid artery duplex scanning and echocardiography: a prospective case-control study.
BACKGROUND AND PURPOSE: Central retinal vein occlusion (CRVO) is a common cause of retinal vascular visual loss second to diabetic retinopathy. Atherosclerotic risk factors are thought to affect vascular flow or cause retinal vascular wall abnormalities, thereby contributing to development of CRVO. Previous studies did not fully evaluate the degree of atherosclerotic disease. The purpose of this study was to determine the degree of atherosclerosis of the carotid artery by duplex scanning and to investigate cardiac manifestations of atherosclerotic risk factors by echocardiography in patients with CRVO. MATERIAL AND METHODS: 39 patients (age 63.1 years [50-84 years], 21 men, 18 women) with CRVO were compared with a control group consisting of 39 individuals (age 59.3 years [49-81 years], 19 men, 20 women) in whom echocardiography was performed to rule out endocarditis. Clinical examination, laboratory testing, carotid artery duplex scanning and echocardiography were performed in all patients. RESULTS: Echocardiography revealed significantly increased prevalence of left ventricular hypertrophy (30.8% in CRVO patients, 5.1% in controls) as a typical sign of hypertensive heart disease in CRVO patients, which is consistent with the increased prevalence of hypertension (HTN) (46.2% in CRVO patients, 15.4% in controls). The prevalence of atherosclerosis of carotid artery and ascending aorta, and all other echocardiographic findings were comparable in CRVO patients and controls: regional wall motion abnormality, left ventricular dilatation, aortic valve calcification, and mitral valve calcification. CONCLUSION: Our study demonstrates that CRVO is not associated with atherosclerosis of large arteries, such as the carotid artery and the ascending aorta. We propose that the retinal artery atherosclerosis seen in most CRVO patients is caused by HTN.
Aged↗
Increased platelet and coagulatory activity indicate ongoing thrombogenesis in peripheral arterial disease.
In peripheral arterial disease (PAD) risk of thrombosis is high and systemic haemostatic derangement thought contributory. We investigated platelet and coagulatory activity in patients with PAD and sought to find the best disease indicator. Stagnation point flow adhesion-aggregometry (SPAA) enables real-time quantitative assessment of platelet adhesion and aggregation under well-defined flow conditions. SPAA and agonist-induced aggregometry (Born method) were performed and concentrations of fibrinogen, fibrin monomer (FM), D-dimer, and thrombin-antithrombin complex (TAT) measured in 92 PAD patients and 70 healthy volunteers. Agonist-induced aggregometry detected no differences between patients and controls. SPAA-measured platelet adhesion and spontaneous aggregation (p < 0.001), and concentrations of fibrinogen (p < 0.001), FM (p < 0.001), TAT (p < 0.02) and D-dimer (p < 0.001) were all significantly increased in patients. Neither platelet function nor coagulatory activity was altered in patients receiving aspirin. Sensitivity and specificity in detecting PAD were as follows: SPAA (95%, 93%), fibrinogen (36%, 91%), FM (48%, 84%), TAT (36%, 78%), D-dimer (73%, 80%). Our findings support the concept of ongoing thrombogenesis as being contributory to the progression and possibly to the initiation of PAD. Aspirin alone did not prevent haemostatic hyperreactivity in these patients and flow-mediated platelet function was the most sensitive and specific indicator of advanced disease. This technique thus appears to be valuable, not only for evaluating therapeutic strategies to prevent platelet activation, but also in elaborating platelet-related mechanisms involved in thrombogenesis and atheroma formation.
Adult↗
Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.
Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.
Adenosine Diphosphate↗
The value of quantitative fibrin monomer determination in the early diagnosis of postoperative deep vein thrombosis.
A new test for the determination of fibrin monomer in plasma was clinically evaluated in comparison to the plasma concentration of D-D, TAT and F1,2 for the early diagnosis of prethrombotic conditions. For this purpose 129 patients who underwent abdominal surgery were followed longitudinally. 12 patients developed DVT postoperatively, proved by phlebography. The identical specificity level 73.2% was chosen for all 4 tests. At this specificity, FM had the highest sensitivity (91.7%), followed by D-D (75.0%), TAT (41.7%) and F1,2 (33.3%). All FM-positive DVT-patients had pathological FM-values at least one day prior to the clinical manifestation of thrombosis. In a group of 255 obviously healthy persons the cut-off value for the new FM test was determined at 3.6 mg/l (95th percentile). No clinically relevant influence of gender, age, smoking habits or oral anticonception could be observed. It is concluded that FM is a valuable diagnostic tool for the early diagnosis of prethrombotic conditions.
Abdomen↗
Increased platelet and coagulatory activity in peripheral atherosclerosis flow mediated platelet function is a sensitive and specific disease indicator.
The importance of flow in both athero- and thrombogenesis is well established. In peripheral arterial disease (PAD) atherosclerosis is disseminated, thrombosis risk high and systemic hemostatic derangement believed contributory. We studied platelet and coagulatory activity in PAD patients, thereby evaluating the clinical efficacy of Stagnation Point Flow Adhesio-Aggregometry (SPAA). SPAA provides real-time quantitative assessment of platelet adhesion and aggregation under convective, low-shear flow conditions. 62 nondiabetic PAD patients and 66 healthy volunteers were examined, whereby SPAA and conventional aggregometry were performed and circulating fibrinogen, fibrin monomer (FM), the fibrin degradation product D-Dimer and thrombin-antithrombin-complex (TAT) assessed. Conventional aggregometry detected no differences between patients and controls. SPAA-measured platelet function (p < 0.001), fibrinogen (p < 0.001), FM (p < 0.001), TAT (p < 0.02) and D-Dimer (p < 0.001) were significantly increased in patients and not effected by aspirin therapy. Respective sensitivity and specificity in detecting PAD was as follows: SPAA (96%/95%), fibrinogen (36%/92%), FM (46%/88%), TAT (40%/73%), D-Dimer (75%/80%). Increased platelet and coagulatory activity was verified in PAD, whereby flow-mediated platelet adhesion and aggregation proved the most sensitive and specific parameter. These findings indicate the usefulness of SPAA for delineating platelet-related disease mechanisms and evaluating therapeutic strategies to prevent platelet activation.
Antithrombin III↗
Warfarin pretreatment does not lead to increased bleeding tendency during cardiac surgery.
OBJECTIVE: To study the influence of preoperative warfarin anticoagulation on postoperative blood loss and allogeneic blood requirement. DESIGN: Retrospective study with a matched control group. SETTING: University and community hospital, single institutional. PARTICIPANTS: 240 patients scheduled for cardiac surgery. INTERVENTIONS: Warfarin sodium was administered to 125 patients preoperatively to prevent thromboembolic complications of their underlying heart disease, 115 served as control. Approximately half of the patients in each group received aprotinin treatment during operation. MEASUREMENTS AND MAIN RESULTS: The international normalized ratio (INR) of the prothrombin time was preoperatively 2.4 (95% confidence interval [CI 0.95]: 2.3 to 2.6) in the warfarin group and 1.1 (CI 0.95: 1.0 to 1.1) in the control group (p < 0.05), and postoperatively 1.9 (CI 0.95: 1.8 to 2.1) (warfarin) and 1.5 (CI 0.95: 1.4 to 1.5) (control) (p < 0.05). The postoperative blood loss after 6 and 12 hours was 381 (CI 0.95: 329 to 434)/505 (CI 0.95: 439 to 571) mL (warfarin) compared with 472 (CI 0.95: 403 to 541)/612 (CI 0.95: 527 to 697) mL (control) (p < 0.05). This difference was blunted when the proteinase inhibitor aprotinin was used. Neither preoperative nor postoperative prothrombin time correlated with blood loss. Despite lower heparin consumption the activated coagulation time (ACT) during CPB was significantly prolonged in the warfarin group. CONCLUSIONS: Warfarin pretreatment does not lead to increased bleeding but may even have a beneficial anticoagulant effect that may lead to better preserved postoperative hemostasis and reduced blood loss.
Aprotinin↗
Influence of high-dose aprotinin on anticoagulation, heparin requirement, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open-heart surgery. A double-blind, placebo-controlled study.
BACKGROUND: Aprotinin causes a prolongation of the celite-activated clotting time (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of aprotinin. The current study was designed to test the efficacy of aprotinin to improve anticoagulation, and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate this antithrombotic effect of aprotinin, this study was done in patients prone to reduced intraoperative heparin sensitivity. METHODS: In a prospective, randomized, double-blind clinical trial, 30 male patients scheduled for elective primary coronary revascularization and treated with heparin for at least 10 days preoperatively, received either high-dose aprotinin (group A) or placebo (group C). The CACT and KACT were determined, but only CACT was used to control anticoagulation with heparin. Parameters of coagulation that are indicators of thrombin generation and activity (F1+2 prothrombin fragments, thrombin-antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D-dimers), aprotinin, and heparin plasma concentrations were measured. Postoperative blood loss and allogeneic blood transfused were recorded. RESULTS: Total heparin administered was 36,200 units (95% confidence interval: 31,400-41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05). Hemostatic activation during cardiopulmonary bypass (CPB) was significantly reduced in group A compared with group C. After 60 min of CPB, all parameters were significantly different (P < 0.05) between the groups (group C vs. group A): F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml; thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38) ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and 2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5 min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C and A, respectively (P < 0.05), whereas the KACT showed no differences between the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for groups C and A, respectively (P < 0.05). CONCLUSIONS: Aprotinin treatment in combination with heparin leads to less thrombin generation during CPB. Aprotinin has anticoagulant properties. Celite-activated ACT is reliable for monitoring anticoagulation in the presence of aprotinin, because the prolonged CACT in the aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not reflect this effect of aprotinin.
Adult↗
Protection of single-chain urokinase-type plasminogen activator (scu-PA) in aprotinin treated cardiac surgical patients undergoing cardiopulmonary bypass.
Intraoperative high-dose aprotinin administration has been shown to reduce the intra-and postoperative blood loss in cardiac surgery. The haemostatic effect has been attributed to platelet preserving properties and to inhibition of contact activation reducing thrombotic and fibrinolytic activity during and after cardiopulmonary bypass (CPB). Here we report on the effects of aprotinin on urokinase-type plasminogen activator, especially on the protection of the zymogen single-chain urokinase-type plasminogen activator (scu-PA). scu-PA occurs cell associated as well as free in the circulation (concentration 50 pM, half-life 5 min), and is potentially activated by kallikrein and plasmin, both potent targets for aprotinin. The generated active two-chain u-PA (tcu-PA) is a powerful activator of fibrinolysis. Sixteen male patients undergoing myocardial revascularization were randomly assigned to aprotinin treatment (A) or control group (C). Plasma concentration of total u-PA antigen and of the specific forms scu-PA(zymogen) and tcu-PA(active enzyme) were measured at different stages intraoperatively and two hours postoperatively. After an initial drop due to haemodilution at the onset of CPB, the concentrations of circulating u-PA forms restored intraoperatively in A, but remained subnormal in C until the end of the observation period. The concentration of total u-PA antigen of shed mediastinal blood was both in A and C two-fold higher than in the circulation, but the antigen was preserved as the zymogen scu-PA in A and largely converted to an inactive, non activatable form in C. Intra- and postoperative blood losses were less than half the amount in A as compared to C.(ABSTRACT TRUNCATED AT 250 WORDS)
Aprotinin↗
Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells.
We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Effect of fibrinogen substitution in afibrinogenemia on hemorheology and platelet function.
Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced platelet aggregation from < 10% to 32%. Platelet adhesion, measured by Stagnation Point Flow Adhesio- Aggregometry, was not detectable prior to substitution but attained normal values thereafter. Scanning electron microscopy of adhering platelets revealed pseudopodia protrusion and spreading. Morphometry revealed two populations of spread platelets one of which demonstrated inhibited spreading as compared to healthy controls. Immunoelectron microscopy revealed normal GPIIb/IIIa receptor expression, both before and after substitution. Dynamic and kinematic viscosity of plasma and whole blood remained below the 99.9% confidence border of a healthy control group. In afibrinogenemia fibrinogen levels as low as 10% of normal concentration sufficed to normalize coagulation, platelet adhesion, and, partially, spreading.
Adult↗
[Heparin for therapy of ulcerative colitis: therapy of a concomitant phenomenon or indication of pathophysiology?].
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Adult↗
Delayed treatment with platelet activating factor receptor antagonist web 2086 attenuates pulmonary dysfunction in porcine endotoxin shock.
The triazolodiazepine WEB 2086, a specific platelet activating factor (PAF) receptor antagonist, has previously been shown to prevent pulmonary hypertension, hypoxia, and bronchoconstriction when given before bacterial lipopolysaccharide (LPS). The aim of the present study was to examine whether WEB 2086 reduced these changes even when given after the onset of LPS-induced shock. In a randomized trial LPS was given intravenously (i.v.) in a dose of 1 microgram/kg/h for 8 hours to anesthetized, ventilated pigs. Ten animals received LPS and WEB 2086, 10 mg/kg/h i.v. for 6.5 hours, beginning 1.5 hours after LPS. Ten control animals received LPS and saline. During treatment with WEB 2086, pulmonary hypertension was significantly attenuated compared with the findings in the control group. Gas exchange, airway pressure, extravascular lung water levels, intrapulmonary shunt, and cathepsin B levels in plasma showed a trend toward improvement but the group differences were not statistically significant. These data indicate that the PAF antagonist WEB 2086 can partially block pulmonary dysfunction and enzyme release from inflammatory cells when given during ongoing LPS shock in pigs, and that PAF may be an important mediator of the cardiopulmonary changes seen in septic shock.
Animals↗