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Forsberg, U., Jonsson, P. & Stegmayr, B. (2019). Air contamination during medical treatment results in deposits of microemboli in the lungs: an autopsy study. International Journal of Artificial Organs, 42(9), 477-481
Open this publication in new window or tab >>Air contamination during medical treatment results in deposits of microemboli in the lungs: an autopsy study
2019 (English)In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 42, no 9, p. 477-481Article in journal (Refereed) Published
Abstract [en]

Introduction: Microbubbles of air may enter into patients during conventional hemodialysis, infusions of fluids, or by injections. The aim of this study was to investigate whether the air that enters the patient during hemodialysis can be detected in the lungs after death, and if so, whether this may be related to tissue damage. Methods: The material consisted of lung tissue from five chronic hemodialysis patients who died either during (two) or after hemodialysis (range 10 min from start until 3333 min after the last hemodialysis session); as reference group tissue was taken from seven patients who died due to amyotrophic lateral sclerosis. The lung tissue was investigated by microscopy after autopsy using a fluorescein-marked polyclonal antibody against fibrinogen as a marker for clots preformed before death. Results: All five hemodialysis patients had microbubbles of air in the lung tissue, whereas two of seven amyotrophic lateral sclerosis patients had such findings (Fisher's test p = 0.0278, relative risk = 3.5, confidence interval: 1.08-11.3). There were more microbubbles of air/10 randomly investigated microscopic fields of tissue in the hemodialysis patients than the amyotrophic lateral sclerosis patients (Student's test, p < 0.05). All hemodialysis patients had a medium graded extent of pulmonary fibrosis that was not found in any of the ALS patients. The microbubbles of air were surrounded by fibrin as a sign of development of clots around the air bubbles while the patients were still alive. Conclusion: Exposure to microbubbles of air during various treatments such as hemodialysis may result in microemboli. Future studies should clarify whether microbubbles of air contribute to tissue scarring. We suggest preventive measures against the exposure to microbubbles of air during especially repeated exposures such as hemodialysis.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
Microbubbles, microemboli, hemodialysis, pulmonary fibrosis, air bubbles
National Category
Biomedical Laboratory Science/Technology Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-162833 (URN)10.1177/0391398819840363 (DOI)000480759400001 ()30973284 (PubMedID)
Available from: 2019-09-13 Created: 2019-09-13 Last updated: 2019-09-13Bibliographically approved
Hadimeri, U., Wärme, A., Nasic, S., Fransson, S.-G., Wigelius, A. & Stegmayr, B. (2019). Angiography and phlebography in a hemodialysis population: A retrospective analysis of interventional results. International Journal of Artificial Organs
Open this publication in new window or tab >>Angiography and phlebography in a hemodialysis population: A retrospective analysis of interventional results
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2019 (English)In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040Article in journal (Refereed) Epub ahead of print
Abstract [en]

Objective: To clarify the reasons and beneficial effects and duration of arteriovenous fistula patency after radiological interventions in arteriovenous fistula. The patients investigated were referred due to arteriovenous fistula access flow problems.

Material and methods: In 174 patients, 522 radiological investigations and endovascular treatments such as percutaneous transluminal angioplasty were analyzed, retrospectively. All investigations were performed due to clinical suspicion of impaired arteriovenous fistula function.

Results: Arterial stenosis was significantly more frequent among patients with diabetic nephropathy (p < 0.001) and interstitial nephritis (p < 0.001). According to the venous stenosis, the diagnosis did not affect the frequency (p = 0.22) or the degree (p = 0.39) of stenosis. The degree of stenosis prior to percutaneous transluminal angioplasty correlated significantly with the degree of remaining stenosis after intervention (p < 0.001). Of the 174 patients, 123 (71%) performed a total of 318 investigations including percutaneous transluminal angioplasty. Repeated percutaneous transluminal angioplasty was performed significantly more often in patients with diabetic nephropathy. The median times to the first percutaneous transluminal angioplasty and to the subsequent percutaneous transluminal angioplasties were 9.5 and 5 months, respectively. Arteriovenous fistula in patients with diabetic nephropathy performed similar to most other diagnoses, although performing more percutaneous transluminal angioplasty/patient than most other diagnoses.

Conclusion: Many patients could maintain long-term patency of arteriovenous fistula, including those with diabetic nephropathy, with repeated interventions; this motivates a closer follow-up for these patients. Clinically significant stenosis should be dilated as meticulously and as soon as possible. Occlusions of the arteriovenous fistula in most instances can be successfully thrombolyzed or dilated upon early diagnosis.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
Arteriovenous fistula, angiography, hemodialysis, percutaneous transluminal angioplasty, fistulography, phlebography
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-161902 (URN)10.1177/0391398819863429 (DOI)000476206500001 ()31303134 (PubMedID)2-s2.0-85069887785 (Scopus ID)
Available from: 2019-08-08 Created: 2019-08-08 Last updated: 2019-08-08
Wärme, A., Hadimeri, U., Hadimeri, H., Nasic, S. & Stegmayr, B. (2019). High doses of erythropoietin stimulating agents may be a risk factor for AV-fistula stenosis. Clinical hemorheology and microcirculation, 71(1), 53-57
Open this publication in new window or tab >>High doses of erythropoietin stimulating agents may be a risk factor for AV-fistula stenosis
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2019 (English)In: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 71, no 1, p. 53-57Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A native AV-fistula (AVF) for access in hemodialysis (HD) is preferable. Stenosis, a major hurdle, is associated with older age and diabetes mellitus. PURPOSE: This case-control study aimed to clarify if any medical and/or laboratory factors, that can be altered, could be associated to AVF stenosis.

METHODS: 33 patients with a patent AVF without need of intervention during a two year period (Controls) were matched by diagnosis and age with 33 patients (Cases), that had at least one radiological invasive examination/intervention due to suspected AVF malfunction (case-control mode 2:1).

RESULTS: Cases had higher weekly doses of Erythropoietin-Stimulating Agent (ESA) than Controls both before intervention (mean 8312 +/- 7119 U/w versus 4348 +/- 3790, p = 0.005) and after the intervention (7656 +/- 6795, versus 4477 +/- 3895, p = 0.018). Before intervention serum phosphate was higher in Cases while there was no significant difference in blood hemoglobin, weekly standard Kt/V, parathyroid hormone, calcium, albumin, C-reactive protein, smoking habits, BMI or other medication.

CONCLUSION: Higher doses of ESA were administered in patients with AVF stenosis. Since ESA may cause local hypertrophic effects on the vascular endothelium, we should prescribe lower doses of ESA in patients at risk. Further studies should clarify such connection.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Arterio-venous fistula, hemodialysis, erythropoietin, stenosis, uremia
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-158771 (URN)10.3233/CH-180381 (DOI)000463644100007 ()29914013 (PubMedID)
Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-05-08Bibliographically approved
Ramsauer, B., Graaff, R., Sikole, A., Trajceska, L., Lundström, S., Arsov, S., . . . Stegmayr, B. (2019). Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Decreases During the Summer in Dialysis Patients. Artificial Organs, 43(2), 173-180
Open this publication in new window or tab >>Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Decreases During the Summer in Dialysis Patients
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2019 (English)In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 43, no 2, p. 173-180Article in journal (Refereed) Published
Abstract [en]

Tissue advanced glycation end products (AGEs) are a measure of cumulative metabolic and oxidative stress and cytokine-driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation of AGEs and rises with age. SAF is one of the strongest prognostic markers of mortality in these patients. The content of AGEs is high in barbecue food. Due to the location in northern Sweden, there is a short intense barbecue season between June and August. The aim of this study was to investigate if seasonal variations in SAF exist in HD patients, especially during the barbecue season. SAF was measured noninvasively with an AGE Reader in 34 HD-patients (15 of those with diabetes mellitus, DM). Each time the median of three measures were used. Skin-AF was measured before and after each one HD at the end of February and May in 31 patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of August and March in 25 (19 m/6 w). Paired statistical analyses were performed during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There was at a median 5.6% increase in skin-AF during the winter period (February-May, P = 0.004) and a 10.6% decrease in the skin-AF during the summer (May-August, P < 0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin-AF decreased significantly during the summer. Future studies should look for favorable factors that prevent skin-AF and subsequently cardiovascular diseases.

Place, publisher, year, edition, pages
Wiley Periodicals, Inc., 2019
Keywords
Skin autofluorescence, Hemodialysis, Seasonal variations, Advanced glycation end products
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-157223 (URN)10.1111/aor.13320 (DOI)000459167900010 ()30229953 (PubMedID)
Available from: 2019-03-22 Created: 2019-03-22 Last updated: 2019-03-22Bibliographically approved
Skagerlind, M. & Stegmayr, B. (2018). An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis. European Journal of Clinical Pharmacology, 74(3), 267-274
Open this publication in new window or tab >>An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis
2018 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 74, no 3, p. 267-274Article in journal (Refereed) Published
Abstract [en]

Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Haemodialysis, Haemorrhage, Priming, Anticoagulation
National Category
Hematology Pharmacology and Toxicology Nursing
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-132227 (URN)10.1007/s00228-017-2389-x (DOI)000424708300002 ()29198062 (PubMedID)
Note

Originally included in thesis in manuscript form with title "An evaluation of four modes of low-dose anticoagulation during haemodialysis".

Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2019-08-15Bibliographically approved
Duranton, F., Palma, A., Stegmayr, B., Wauthier, M., Torres, A. & Argilés, A. (2018). Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of Different Latitudes. Kidney and Blood Pressure Research, 43(5), 1529-1538
Open this publication in new window or tab >>Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of Different Latitudes
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2018 (English)In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 43, no 5, p. 1529-1538Article in journal (Refereed) Published
Abstract [en]

Background/Aims: Climate influences the regulation of blood pressure (BP). Our objective was to precisely estimate BP seasonality in hemodialysis (HD) patients from five European cities with marked climate differences. Methods: Stable prevalent HD patients from 5 European facilities (Santa Cruz de Tenerife (Spain), Seville (Spain), Montpellier (France), Ottignies (Belgium), Umea (Sweden)) present over the years 1995-1999 were included in this historical longitudinal observational study. Individual monthly averages of pre-dialysis BP level were computed from all facility BP measurements (>90 000 observations). The association between BP level and location, seasons and meteorological measurements was analyzed by mixed models. Results: 261 patients were included and followed-up for a median duration of 2 years (6903 monthly observations). Pre-dialysis SBP and DBP were minimal in summer (July) and maximal in winter (November and December), and mean changes were respectively 4.2 [3.0;5.4] and 2.0 [1.3;2.7] mmHg. Seasonality was confirmed in 4 locations (P-season <= 0.0010.001 for SBP and DBP), but not in Umea (both P-season >0.05). Seasonal changes in DBP were larger in southern locations (P-interaction =0.02). BP level was associated with climate parameters: in a positive manner with humidity or rainfall, and inversely with sunshine duration or temperature. The effects of temperature and rainfall on DBP varied with latitude (P-interaction <0.02) and were greater in southern locations. Conclusion: BP varies with seasons and climate in different European areas and seasonality can be more important in southern locations. These changes in BP deserve attention as they may be responsible for a significant increase in cardiovascular risk which may be preventable.

Place, publisher, year, edition, pages
S. Karger, 2018
Keywords
Chronic renal failure, Blood pressure, Weather, Geography, Chronic hemodialysis
National Category
Urology and Nephrology Physiology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-156349 (URN)10.1159/000494019 (DOI)000456656400011 ()30286451 (PubMedID)
Available from: 2019-02-12 Created: 2019-02-12 Last updated: 2019-02-12Bibliographically approved
Peters, B., Hadimeri, H., Mölne, J., Nasic, S., Jensen, G. & Stegmayr, B. (2018). Desmopressin (Octostim®) before a native kidney biopsy can reduce the risk for biopsy complications in patients with impaired renal function: a pilot study. Nephrology (Carlton. Print), 23(4), 366-370
Open this publication in new window or tab >>Desmopressin (Octostim®) before a native kidney biopsy can reduce the risk for biopsy complications in patients with impaired renal function: a pilot study
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2018 (English)In: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 23, no 4, p. 366-370Article in journal (Refereed) Published
Abstract [en]

AIM: To evaluate if the administration of desmopressin alters the risk for renal biopsy complications.

METHODS: A multicenter registry containing 576 native kidney biopsies (NKb) with a serum creatinine above 150 µmol/L in 527 patients (372 men and 155 women, median age 61 years) was used. Most of the data were prospective. At one of the hospitals all biopsies with creatinine above 150 µmol/L received desmopressin before biopsies (NKb 204). These were compared to outcome of biopsy complications against other centres where desmopressin was not given (NKb 372). Fisher's exact test, χ2 analyses, univariate and multiple binary logistic regression were used. Data were given as Odds Ratio (OR) and Confidence Interval (CI). A two sided p-value of <0.05 was considered significant.

RESULTS: In NKb with creatinine >150 µmol/L, those with desmopressin had less overall (3.4% versus 8.4%, OR 0.39, CI 0.17-0.90) whereas major or minor complications were not different. While desmopressin did not exhibit difference in complications in men, women received less major (0% versus 8.6%, p = 0.03) and overall complications (0% versus 12.1%, p = 0.006). A multiple logistic regression revealed that, after adjusting for BMI, age and sex, prophylaxis with desmopressin showed less major (OR 0.38, CI 0.15-0.96) and overall complications (OR 0.36, CI 0.15-0.85).

CONCLUSION: Desmopressin given before a native kidney biopsy in patients with impaired renal function can reduce the risk for complications.

Keywords
desmopressin, kidney biopsy, renal biopsy, biopsy complications
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-131383 (URN)10.1111/nep.13004 (DOI)000427015500010 ()28107603 (PubMedID)
Available from: 2017-02-13 Created: 2017-02-13 Last updated: 2019-05-21Bibliographically approved
Toss, F., Edgren, G., Berlin, G., Stegmayr, B. & Witt, V. (2018). Does prophylactic calcium in apheresis cause more harm than good?: Centre heterogeneity within the World Apheresis Association Register prevents firm conclusions. Vox Sanguinis, 113(7), 632-638
Open this publication in new window or tab >>Does prophylactic calcium in apheresis cause more harm than good?: Centre heterogeneity within the World Apheresis Association Register prevents firm conclusions
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2018 (English)In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 113, no 7, p. 632-638Article in journal (Refereed) Published
Abstract [en]

Background and objectives: Symptomatic hypocalcaemia is common during apheresis procedures based on citrate‐based anticoagulants. As a consequence, patients often receive prophylactic calcium treatment. However, a recent publication based on the World Apheresis Association (WAA) register suggested harmful effects of such prophylactic calcium use. Recognizing possible limitations in the previous WAA register analyses, we critically re‐evaluate the data, to test whether a change in prophylactic calcium usage may be warranted.

Materials and methods: Using the WAA register, we reanalysed previous data by means of centre and treatment type stratification, to explore the role of prophylactic calcium as a risk factor for adverse events.

Results: There was large variability in adverse event rates dependent on the centre performing the apheresis procedure and dependent on the type of procedure. When this variability was accounted for, there was no clear effect of calcium administration on risk of adverse effects.

Conclusion: Shortcomings in the previous WAA register analyses may have failed to account for important confounding factors resulting in a substantial overestimation of the risk attributable to calcium usage. Overall our findings do not support a negative effect of prophylactic calcium administration in the apheresis setting.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
blood component removal, plasmapheresis, plasma exchange, cytapheresis, adverse events, calcium
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-153132 (URN)10.1111/vox.12698 (DOI)000447492200003 ()30079964 (PubMedID)
Available from: 2018-11-09 Created: 2018-11-09 Last updated: 2018-11-09Bibliographically approved
Jonsson, P., Lindmark, L., Axelsson, J., Karlsson, L., Lundberg, L. & Stegmayr, B. (2018). Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers. Artificial Organs, 42(5), 533-539
Open this publication in new window or tab >>Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers
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2018 (English)In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 42, no 5, p. 533-539Article in journal (Refereed) Published
Abstract [en]

We were encouraged to investigate the reasons for large amounts of foam observed in bloodlines during hemodialysis (HD). Foam was visible in the venous air trap within the Artis Gambro dialysis device. Estimates of the extent of foam were graded (0no foam, 10extensive foam) by two persons that were blind to the type of dialyzer used. Thirty-seven patients were involved in the dialysis procedures. Consecutive dialyses were graded using dialyzers from Fresenius Medical Care (CorDiax dialyzers that were used for high flux HDFX80 and FX100, and for hemodiafiltrationFX1000). The extracorporeal circuit was primed automatically by dialysate using Gambro Artis software 8.15 006 (Gambro, Dasco, Medolla Italy, Baxter, Chicago, IL, USA). The priming volume recommended by the manufacturer was 1100 mL, whereas our center uses 1500 mL. Extensive amounts of blood foam were visual in the air traps. Although the manufacturer recommended extension of priming volume up to 3000 mL, this did not eliminate the foam. Microbubble measurement during HD revealed the air to derive from the dialyzers. When changing to PF210H dialyzers (Baxter) and using a priming volume of 1500 mL, the foam was significantly less (P<0.01). The extent of foam correlated with the size of the FX-dialyzer surface (P=0.002). The auto-priming program was updated to version 8.21 by the manufacturer and the extent of foam in the air trap using FX dialyzers was now reduced and there was no longer a difference between FX and PF dialyzers, although less foam was still visible in the venous air trap during several dialyses. In conclusion, this study urgently calls attention to blood foam development in the venous air trap when using Artis devices and priming software 8.15 in combination with Fresenius dialyzers. Updated auto-priming software (version 8.21) of Artis should be requested to reduce the extent of foam for the Fresenius dialyzers. Other interactions may also be present. We recommend further studies to clarify these problems. Meanwhile caution is warranted for the combined use of dialysis devices and dialyzers with incompatible automatic priming.

Keywords
dialysis, priming, foam, bubbles, air, blood
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-149031 (URN)10.1111/aor.13070 (DOI)000433563800012 ()29542180 (PubMedID)2-s2.0-85047846399 (Scopus ID)
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2019-05-20Bibliographically approved
Mahmood, D. & Stegmayr, B. (2018). Haemodialysis with Tinzaparin Versus Dialysate Citrate as Anticoagulation. Blood Purification, 46(3), 257-263
Open this publication in new window or tab >>Haemodialysis with Tinzaparin Versus Dialysate Citrate as Anticoagulation
2018 (English)In: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 46, no 3, p. 257-263Article in journal (Refereed) Published
Abstract [en]

Anticoagulation with citrate-containing haemodialysate (cHD) is an alternative to tinzaparin haemodialysate (tHD). The study investigated whether cHD would differ when changed from tHD. The same 18 patients were their own controls followed up with cHD for 5 months. LDL-cholesterol decreased at the end of a cHD session (p = 0.01). Neutrophils (p = 0.013) and monocytes (p = 0.007) dropped more during a cHD session. During the follow-up period of cHD, approximately 50% needed additional tinzaparin. Before the cHD session could start, there was a lower total cholesterol at 2 weeks (p = 0.014) and LDL-cholesterol at 1 month (p = 0.011) versus an increase of LDL at 5 months (p = 0.02). Only patients without additional tinzaparin had a reduction of C-reactive protein (CRP) at 2 months of cHD (p < 0.05) but not later. Solely cHD seems possible only in half of the patients. A greater reduction in granulocytes and monocytes during cHD indicates a more extensive blood membrane interaction, while CRP may be lower.

Place, publisher, year, edition, pages
S. Karger, 2018
Keywords
Biocompatibility, Blood purification, Citrate, Haemodialysis, Haemoglobin, Heparin
National Category
Hematology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-150401 (URN)10.1159/000490409 (DOI)000439389800012 ()29972824 (PubMedID)2-s2.0-85049885888 (Scopus ID)
Available from: 2018-08-06 Created: 2018-08-06 Last updated: 2019-05-21Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-2694-7035

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