Papers by Marianne Schoorl
Scandinavian Journal of Clinical & Laboratory Investigation, 2008
During haemodialysis treatment, blood flows from the body to the extracorporeal circuit and vice ... more During haemodialysis treatment, blood flows from the body to the extracorporeal circuit and vice versa. In this study, pathophysiological defects in platelets indicated by alterations in RNA content and aberrations in platelet volume and morphology are detected before and during haemodialysis treatment. In subjects receiving haemodialysis treatment, qualitative interpretation of platelet characteristics with application of light microscopic evaluation reveals only 19¡11 % of platelets with appropriate staining density of the granulecontaining cytoplasm. On the contrary, a reference group of apparently healthy subjects shows 70¡12 % platelets with appropriate staining density of the granule-containing cytoplasm. During haemodialysis treatment, mean values for platelet volume, platelet distribution width and platelet large cell ratio demonstrate a tendency to decrease by 10 %, 11 % and 6 %, respectively, from the mean initial value to the value at t5150 min. Reduction of the platelet volume parameters just mentioned is hypothesized to be due to platelet degranulation as a result of platelet activation.
Scandinavian Journal of Clinical & Laboratory Investigation, 2003
Despite systemic heparinization, extracorporeal circulation will induce activation of blood coagu... more Despite systemic heparinization, extracorporeal circulation will induce activation of blood coagulation. Thrombogenicity is associated with biocompatibility of dialysis membranes. Investigation of procoagulatory and fibrinolytic activity is performed prior to and during treatment with haemodialysis. In this study fluctuations of plasma coagulation factor XII, thrombin antithrombin complexes, prothrombin fragment 1 + 2 and thrombus precursor protein were monitored in 10 subjects during treatment with haemodialysis. Subjects were treated with both polysulphone high-flux dialyser membranes (F-60) and low-flux poly-methyl-methacrylate (PMMA) membranes. Immediately after start of treatment, blood in contact with artificial membrane surfaces resulted in a marked decrease in factor XII activity amounting to a mean reduction of 80% in the case of PMMA and a reduction of 40% in the case of F-60. In due course, a steady, on-going generation of thrombin antithrombin complexes was observed in several subjects, especially after treatment with F-60 membranes, amounting to increases exceeding 100% of initial values. Establishment of fibrinogen, prothrombin fragment 1 + 2 and thrombus precursor protein plasma concentrations yielded enhanced results for PMMA compared with the results for treatment with F-60 dialysis membranes. In order to prevent activation of clotting during several stages of haemodialysis, supplementation of anticoagulant can be established on the basis of analytical results of coagulation parameters.
European Journal of Internal Medicine
Clinical Chemistry and Laboratory Medicine, 2009
Query-fever (Q-fever) is a zoonotic infection caused by the intracellular Gram-negative coccobaci... more Query-fever (Q-fever) is a zoonotic infection caused by the intracellular Gram-negative coccobacillus Coxiella burnetii. A large ongoing outbreak of Q-fever has been reported in the Netherlands. We studied various markers of infection in inpatients (hospitalised) and outpatients (treated by a general physician) with acute Q-fever in relation to disease severity. Leukocyte counts, C-reactive protein (CRP) and procalcitonin (PCT) concentrations were measured in 25 inpatients and 40 outpatients upon presentation with acute Q-fever. Chest X-rays, if available, were analysed and confusion, urea, respiratory rate, blood pressure-age 65 (CURB-65) scores, indicating severity of pneumonia, were calculated. CRP was the only marker that significantly differentiated between inpatients and outpatients. It was increased in all patients from both groups. Leukocyte counts and PCT concentrations did not differ between inpatients and outpatients. Overall, only 13/65 patients had an increased leukocyte count and only 11/65 patients presented with PCT concentrations indicative of possible bacterial respiratory tract infection. Infiltrative changes on the chest X-ray were observed in the majority of patients. CURB-65 score was 0+/-1 (mean+/-SD). Acute Q-fever, a relatively mild pneumonia with low CURB-65 scores, specifically induces a response in CRP, while PCT concentrations and leukocytes are within the normal range or increased only marginally.
Background. The sum of undesirable side effects, occurring during haemodialysis (HD), is called b... more Background. The sum of undesirable side effects, occurring during haemodialysis (HD), is called bioincompatibility. Concerning platelets, both an increase in the expression of the cell surface marker Pselectin (CD62p) and release of the intracellular granule product platelet factor 4 (PF4) have been described. However, as PF4 is also abundantly present on endotheliumbound proteoglycans, it is questionable whether the HDinduced increase is exclusively attributable to release from platelets. With respect to the cause of HD-induced bioincompatibility, interest has been focused mainly on the extracorporeal circuit (ECC), especially the dialyser, whereas only little attention has been paid to other parts of the ECC and the mode of anticoagulation applied. To address the cause and origin of platelet activation and PF4 release during clinical HD, two complementary clinical studies were performed. Materials and methods. In study I, the relative influence of the various parts of the ECC was evaluated by measuring the expression of CD62p, platelet aggregation and levels of PF4 and serotonin at various sampling points. In study II, low-molecular-weight heparin (LMWH) was administered 10 min before the actual start of HD, in order to separate the effects from LMWH and the ECC on platelet activation. Results. In study I, CD62p expression increased across the entire length of the ECC, including the roller pump and dialyser (median at t 5 from 26% to 43%, P = 0.008; median at t 30 from 28% to 48%, P = 0.007). Increments in PF4 and aggregation of platelets were relatively modest. Platelet serotonin content, which was below reference values in healthy controls, and plasma serotonin concentration, which was above reference values, did not change. In study II, PF4 levels increased markedly after the injection of LMWH (from 12 IU/ml at t −10 to 75 IU/ml at t 0 , P = 0.018), whereas CD62p expression remained stable until the start of HD.
Blood Purification, 2009
Although platelet (PLT) activation and degranulation are well-known phenomena during hemodialysis... more Although platelet (PLT) activation and degranulation are well-known phenomena during hemodialysis (HD), controversies still exist about their nature and origin.
Nephrology Dialysis Transplantation, 2009
Background. Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage... more Background. Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Platelet (PLT) dysfunction, which is a wellknown phenomenon in advanced chronic renal failure, corresponds positively with CVD in these patients. The accumulation of retained uraemic toxins might play an important role in this respect. During haemodialysis (HD), both an increase in the expression of the platelet (PLT) cell surface molecule P-selectin (CD62p) and the release of intra-granular substances, such as platelet factor 4 (PF4) and B-thromboglobulin (BTG), have been described. As the removal of uraemic toxins is superior during haemodiafiltration (HDF), this form of treatment may have quite another impact on PLTs than HD. Methods. Nineteen chronic HD patients who were treated with low-flux HD for at least 2 months were included in the Dutch CONvective TRAnsport STudy (CONTRAST). After randomization, 10 patients continued low-flux HD and 9 patients switched to post-dilution HDF. The present study describes various parameters of PLT activation and degranulation at baseline (during HD) and after 3 months (during HDF) in the latter group of patients. At both time points, multiple blood samples were drawn. During the first 30 min of treatment, differences over the extracorporeal circuit (ECC) were calculated by taking samples from both afferent (arterial) and efferent (venous) lines. Correlations between various parameters were calculated in the total group of patients after 3 months.
Nephron Clinical Practice, 2007
alysate temperatures and during HD with citrate. Results: Citrate strongly reduced platelet activ... more alysate temperatures and during HD with citrate. Results: Citrate strongly reduced platelet activation, but did not improve IDH. The blood pressure was best preserved during cool-temperature HD, despite manifest platelet activation. Platelet activation was not accompanied by a rise in the plasma serotonin concentration. Conclusions: Three major conclusions can be drawn: (1) it is unlikely that platelet activation and subsequent serotonin release underlie IDH in the clinical situation; (2) the protective effects of cool dialysate on IDH appear to be independent of HD-induced platelet activation, and (3) extrapolating results from rat experiments to the human situation requires uppermost prudence.
Background. During haemodialysis (HD), polymorphonuclear cells (PMNs) and platelets are activated... more Background. During haemodialysis (HD), polymorphonuclear cells (PMNs) and platelets are activated and release various granule products, including myeloperoxidase (MPO) and platelet factor 4 (PF4). MPO triggers the generation of reactive oxygen species, leading to irreversible protein, carbohydrate and lipid modification. PF4 probably also contributes to oxidative stress. As previously shown, HD-induced PMN degranulation is almost completely abolished during citrate anticoagulation, most probably due to its calcium chelation ability. Methods. In the present study, apart from HDinduced PMN and platelet degranulation, oxidative stress was analysed during three modes of anticoagulation. Heparin, dalteparin and citrate (HD hep , HD dal and HD cit ) were compared in a randomized, crossover fashion in eight chronic HD patients. Multiple blood samples were taken during the third HD session of each modality, from both the afferent and efferent line. Besides the degranulation markers MPO and PF4, various markers of oxidative stress were measured, including oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) and carboxymethyllysine (CML). Results. During HD hep and HD dal , marked degranulation was observed shortly after the start of HD. In contrast, during HD cit , PF4 and MPO levels remained unaltered, suggesting no release at all. After 1 week of HD cit , ox-LDL levels were markedly reduced [median 26% (3-65%), P ¼ 0.01], if compared with HD hep and HD dal . As regards MDA and CML, no differences were found.
Background. Hyperleptinaemia in chronic haemodialysis (CHD) patients has been associated with mal... more Background. Hyperleptinaemia in chronic haemodialysis (CHD) patients has been associated with malnutrition, which is an independent predictor of morbidity and mortality in this patient group. Methods. To assess the influence of HD on plasma leptin, 10 CHD patients were crossover randomized to low-flux polysulfone (PS: F 6HPS), high-flux PS (F 60S), super-flux PS (F 500S) or super-flux cellulose-tri-acetate (CTA: Tricea 150G) for 12 weeks each. Blood samples were collected at the start of the study and each 12-week period. In addition, the relationship between patient characteristics, inflammation and leptin was analysed. Results. At baseline, all groups showed similar leptin concentrations (mean 33.6±21.7 ng/ml). After a single HD session, a significant (P<0.01) decrease was observed with all three high permeable devices (Tricea 150G À52.7±6.4%; F 60S À63.1±5.7%; F 500S À68.7±8.2%), whereas leptin remained stable with low-flux PS. After 12 weeks, a marked increase was observed with low-flux PS (week 1, 30.4±23.0; week 12, 40.5±5.4 ng/ml, P ¼ 0.05), no change with super-flux CTA and high-flux PS (Tricea 150G week 1, 29.4±23.7; week 12, 32.0±27.9 ng/ml, P ¼ ns; F 60S week 1, 36.0±31.8; week 12, 33.0±31.2 ng/ml, P ¼ ns), and a significant decrease with super-flux PS (week 1, 38.3±33.0; week 12, 29.5±31.9 ng/ml, P ¼ 0.02). The change in leptin after 12 weeks was significantly different between super-flux PS, and both low-flux PS (P ¼ 0.009) and super-flux CTA (P ¼ 0.01). Besides interleukin-6 (IL-6) at the start of the study (P ¼ 0.006), no correlations were observed between patient characteristics, parameters of inflammation and plasma leptin levels.
Kidney International, 2002
Intercurrent clinical events are predictive of plasma C-reactive sistance [1, 2], dialysis relate... more Intercurrent clinical events are predictive of plasma C-reactive sistance [1, 2], dialysis related amyloidosis [3], malnutriprotein levels in hemodialysis patients.
Digestive Diseases and Sciences, 2001
Alterations in markers of coagulation have been found in patients with inflammatory bowel disease... more Alterations in markers of coagulation have been found in patients with inflammatory bowel disease. Our aim was to study the predictive value of coagulation and inflammatory parameters in the course of severe ulcerative colitis. Twenty-seven patients were included. The disease course was followed for one year. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratio, as well as the clinical predictive value of laboratory variables were calculated. Inflammatory variables, such as ESR, CRP, and leukocyte and platelet count showed poor diagnostic accuracy. Several coagulation parameters, such as fibrinogen and fibrin(ogen) degradation products, were increased in patients with active ulcerative colitis, whereas coagulation factor XIII was decreased. No significant relationship between clinical course and coagulation parameters was demonstrated, though both inflammatory and coagulation parameters were useful in the assessment of disease activity in patients with active ulcerative colitis.
Gastroenterology, 2000
Background: Activation of hemostasis has been demonstrated to be involved in the pathophysiology ... more Background: Activation of hemostasis has been demonstrated to be involved in the pathophysiology of ulcerative colitis (UC). Whether this hemostatic imbalance is due to coagulation or fibrinolytic disturbancies is unclear. Methods: Thirty-three patients with active UC were studied by determination of the thrombin-dependent generation of fibrin degradation products (FbDP) as a marker of coagulation and of the plasmin-dependent generation of fibrinogen degradation products (FgDP) as a marker of fibrinolysis. The balance of hemostasis was expressed as the ratio between FgDP and FbDP. Markers of inflammation (ESR, CRP, fibrinogen (Fg) and coagulation (fragment 1+2 (F1+2), thrombin-antithrombin (TAT» were also determined. Severity of disease was assessed by a 18-points endoscopic score, a 4-points pathohistologic score, and a 22-points patient score at baseline and at the third or fourth month of treatment. Reference values were determined in 22 healthy controls. Comparisons were performed by ANOVA and Student's T-test. Results: In active disease, all parameters differed significantly from healthy controls. During treatment, UC activity diminished from active to quiescent disease (endoscopically from 12.3 to 5.3; histopathologically from 2.21 to 0.75; patient score from 11.5 to 3.6). ESR, CRP and Fg also decreased significantly in the course of Uc. The hemostatic markers Fl +2, TAT, FgDP and FbDP decreased but not at a level of significance. In quiescent disease, all parameters of coagulation, including FgDP, were elevated in comparison with controls, indicating that activation of coagulation and fibrinolysis was persistent in the course of UC. The ratio between FgDP and FbDP was 0.69 in active UC, and was decreased in comparison with quiescent UC (1.12, p=O.Oll) and with controls (1.36, p < 0.0001). The FgDPIFbDP ratio in quiescent
Gastroenterology, 1998
Background: Decreased factor XIII (F XIII) levels, the fibrinstabilizing clotting factor, has bee... more Background: Decreased factor XIII (F XIII) levels, the fibrinstabilizing clotting factor, has been described in ulcerative colitis (UC). Consumption of F XIII due to activation of coagulation or fibrinolysis, slow (re)generation of F XIII and gut leakage may account for this decrease. Addition of FXIII may be beneficial in the course of severe UC. We performed laboratory tests concerning coagulation and fibrinolysis in the course of UC to assess their relation with F XIII levels. Methods: A cohort of 20 patients with severe UC was prospectively followed for 12 weeks. At intervals (t=0,2,4,8,12 weeks), symptoms were assessed by a patient score (NEJM 1994(NEJM , 1841) and blood samples were collected. Endoscopy was performed at baseline and at 12 weeks during which a disease activity score was calculated (J Clin Gastroenterol 1988, 169). This endoscopic score and laboratory findings were related to the patient score (PS) by application of Spearman rank correlation test. All patients were treated with 5-ASA and immunosuppressive therapy. Results: PS strongly correlated with the endoscopic score (r=0.68). A high PS, related with disease activity, was associated with decreasing levels of F XIII (r = -0.37), and increasing CRP (r = 0.52), fibrinogen (r = 0.44), TAT (r = 0.24), and fibrin degradation products (r = 0.30). Plasmin-dependent generation of fibrinogen degradation products was not associated with disease activity (r = -0.09). Low levels of F XIII were strongly associated with TAT (r = -0.65), and CRP (r = 0.52), but not with fibrinogen degradation products (r = -0.09). Conclusions: Activation of coagulation in active UC was demonstrated by positive correlations of PS with TAT and fibrin degradation products. F XIII was strongly correlated with parameters of coagulation, but not with fibrinolysis. We hypothesize that F XIII decrease is due to consumption. • G4521 OLEIC ACID IMPROVES DRUG ABSORPTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. G Van Citters and HC Lin.
Scandinavian Journal of Gastroenterology, 1995
Factor XIII (F XIII), the last coagulation factor in the clotting cascade, plays a role in mucosa... more Factor XIII (F XIII), the last coagulation factor in the clotting cascade, plays a role in mucosal repair. Beneficial effects of F XIII supplementation in severe ulcerative colitis (UC) have been observed. The aim of this study was to relate plasma F XIII activity to the severity of inflammatory bowel disease (IBD). A transversional and, in part, longitudinal study of F XIII activity and related clotting products was performed in 39 patients with UC, 31 patients with Crohn&amp;amp;#39;s disease (CD), and 20 controls. Disease activity was assessed with a combined activity score in UC and with the Dutch Activity Index in CD. F XIII activity was decreased in active UC (p &amp;amp;lt; 0.05) and active CD (p &amp;amp;lt; 0.05) and was inversely correlated with severity in both UC (r = -0.30) and CD (r = -0.46). In six patients with UC (15%) and six patients with CD (19%) F XIII activity was below the lower range of normal. In these patients apparent rectal bleeding was only found in severe UC. Hyperfibrinolysis was indicated by elevated levels of D-dimer (p &amp;amp;lt; 0.001) notwithstanding increased concentrations of alpha-2 antiplasmin (p &amp;amp;lt; 0.05). In active IBD we found decreased plasma F XIII activity and hyperfibrinolysis. Decreased F XIII activity was not associated with apparent rectal bleeding in IBD.
Gastroenterology, 1998
Interleukin (IL)-5 expression, eosinophilia and eosinophil activation have been shown to be incre... more Interleukin (IL)-5 expression, eosinophilia and eosinophil activation have been shown to be increased early in the course of several gastrointestinal conditions including Crohn's disease, celiac disease and during enteric parasitic infections. However a functional role for eosinophils in either enteric host defense or in intestinal pathophysiology is unclear. IL-5 deficient (-/-) mice as well as their IL-5 +/+ controls were orally gavaged with 375 T. spiralis larvae for primary infections, and with a similar number for subsequent challenges. We measured isometric contraction of jejunal longitudinal muscle and counted adult worms as well as eosinophils within the infected small bowel, during both primary and challenge infections. In addition, as a measure of worm fecundity, we analyzed skeletal muscle larvae numbers.
American Journal of Gastroenterology, 2001
In healthy conditions, factors inducing or inhibiting coagulation and factors inducing or inhibit... more In healthy conditions, factors inducing or inhibiting coagulation and factors inducing or inhibiting fibrinolysis are in balance. In ulcerative colitis, hypercoagulation is presumed, which may explain part of the clinical features of this disease. Therapy strategies affecting hemostasis may improve the course of ulcerative colitis. This study was conducted to evaluate the balance of coagulation and fibrinolysis in the course of treatment of active ulcerative colitis. Patients with active ulcerative colitis were studied by serial determination of markers of the coagulation cascade (thrombin-antithrombin complexes and fibrin degradation products [FbDP]) and the fibrinolytic cascade (fibrinogen degradation products [FgDP]). Parameters of inflammation were also measured (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], albumin, platelet count, and fibrinogen). Disease activity was assessed by endoscopic and histopathological scores. Follow-up measurement was performed in the course of treatment at the third or fourth month after baseline. Measurements were compared with healthy controls. Thirty-three patients and 22 healthy controls were included. During active ulcerative colitis, inflammatory parameters (CRP, ESR, platelet count) and hemostatic parameters (thrombin-antithrombin complexes, fibrinogen, FgDP, and FbDP) were elevated in comparison with healthy controls. Albumin was decreased and antithrombin-III remained unchanged. During treatment, disease activity decreased significantly endoscopically and histopathologically (p &amp;amp;lt; 0.001). CRP, ESR, platelet count, and fibrinogen also decreased significantly. The hemostatic balance, expressed as the ratio between the plasmin-dependent generation of FgDP and coagulation-dependent generation of FbDP, increased from 0.69 to 1.12 during treatment, mainly because of a decrease of FbDP. In healthy controls, this ratio was The coagulation and fibrinolytic cascades were activated in active ulcerative colitis, with a hemostatic imbalance in favor of coagulation. This hypercoagulability persisted in 20% (7/33) of patients with ulcerative colitis in remission. The decrease of FbDP and the increase in the FgDP/FbDP ratio during reconvalescence of ulcerative colitis showed that the coagulation cascade was more activated than the fibrinolytic cascade in active disease.
Accreditation and Quality Assurance, 1999
An open mind is essential for the implementation and improvement of total quality management. Le... more An open mind is essential for the implementation and improvement of total quality management. Leadership, as such, is of no value without a vision concerning corporate culture and human resources. Therefore, constant communication between partners within a corporate body is the cornerstone for empowerment. The evaluation of ideas and complaints is considered to be essential for the identification of strengths and weaknesses of a system, whereas, competition and benchmarking may reveal surprising opportunities for improvement. We discuss the idea that customer-oriented efficiency in a hospital environment may be classified as a critical success factor.
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Papers by Marianne Schoorl