Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

Study Overview
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Brief Summary
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Membrane plasmapheresis is one of the methods for treating immune diseases. Plasmapheresis removes autoantibodies and immune complexes, paraproteins, lipoproteins and reduces the concentration of cytokines. In membrane plasmapheresis, plasma is separated from blood cells by a highly permeable membrane. The filtered plasma is then discarded and replaced with replacement fluid. During the procedure, there is an activation of the coagulation system, because of the extracorporeal blood circulation. The anticoagulation during the procedure is therefore necessary.

Detailed Description
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Standard heparin or citrate is routinely used as a method of anticoagulation in plasmapheresis. Citrate provides effective anticoagulation that is completely limited to extracorporeal circulation. Patients who are at increased risk for bleeding, anticoagulation with citrate is a more appropriate method than standard heparin, while in other patients both methods are equivalent. Citrate anticoagulation is performed by infusing citrate into the arterial line of the extracorporeal system. Citrate binds to plasma calcium and thus inhibits coagulation in the system. Calcium is added to the venous line of the system (when blood returns to the patient) to maintain a normal plasma ionized calcium concentration. Lowering the ionized calcium in the blood in the extracorporeal circulation inhibits the coagulation and activation of other systems (platelets, leukocytes, complement), which affects the biocompatibility of the artificial material and the whole procedure. Biocompatibility is extremely important, since the contact of blood with artificial material activates both the humoral and cellular systems. As part of the humoral immune system, complement is activated by the production of C3, C4 and C5, factor XIIa, there is also an increase in the production of bradykinin, kallikrein, quinine and plasmin, and some proteins are denatured (gamma globulins, fibrinogen, albumins). When the cellular immune system is activated, lymphocytosis can occur and the is also change in function of phagocytes. All previous studies show that regional anticoagulation with citrate improves biocompatibility in hemodialysis procedures (compared to heparin anticoagulation), but no direct comparison in plasmapheresis has been observed in the literature so far. Therefore, the investigators want to conduct a prospective randomized study comparing several parameters of heparin and citrate anticoagulation biocompatibility during plasmapheresis. The aim of the study is to demonstrate better biocompatibility in citrate anticoagulation compared to heparin.

Official Title
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Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

Conditions
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Apheresis, Anticoagulation

Intervention / Treatment
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* Drug: unfractionated heparin
* Drug: Sodium Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: older than 18 years an indication for plasma exchange (plasmapheresis) with albumin solution as a replacement solution Exclusion Criteria: contraindication for systemic heparinisation acute bleeding known active malignancy severe infection anticoagulant therapy at therapeutic dose

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: heparin anticoagulation<br>standard heparin anticoagulation during plasmapheresis | Drug: unfractionated heparin<br>* standard heparin at 2500 IU i.v. bolus and then 2000 IU/h continuously i.v. for anticoagulation during plasmapheresis<br>|
| Experimental: citrate anticoagulation<br>sodium citrate anticoagulation during plasmapheresis | Drug: Sodium Citrate<br>* 8% sodium citrate at approx. 27 mmol/h i.v. for anticoagulation during plasmapheresis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in serum thrombin-antithrombin complex from baseline to 30 minutes | thrombin-antithrombin complex | 30 minutes after start of plasmapheresis | 
| change in serum thrombin-antithrombin complex from baseline to the end of plasmapheresis | thrombin-antithrombin complex | at the end of plasmapheresis procedure | 
| change in serum platelet factor 4 from baseline to 30 minutes | platelet factor 4 | 30 minutes after start of plasmapheresis | 
| change in serum platelet factor 4 from baseline to the end of plasmapheresis | platelet factor 4 | at the end of plasmapheresis procedure | 
| change in serum C5a from baseline to 30 minutes | complement component C5a | 30 minutes after start of plasmapheresis | 
| change in serum C5a from baseline to the end of plasmapheresis | complement component C5a | at the end of plasmapheresis procedure | 
| change in serum myeloperoxidase from baseline to 30 minutes | myeloperoxidase | 30 minutes after start of plasmapheresis | 
| change in serum myeloperoxidase from baseline to the end of plasmapheresis | myeloperoxidase | at the end of plasmapheresis procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting) | complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting) | during plasmapheresis | 
| comparison of measured platelet factor 4 in patients' serum and filtered plasma | A Bland-Altman agreement analysis | 30 minutes after start of plasmapheresis | 
| comparison of measured thrombin-antithrombin complex in patients' serum and filtered plasma | A Bland-Altman agreement analysis | 30 minutes after start of plasmapheresis | 
| comparison of measured C5a in patients' serum and filtered plasma | A Bland-Altman agreement analysis | 30 minutes after start of plasmapheresis | 
| comparison of measured myeloperoxidase in patients' serum and filtered plasma | A Bland-Altman agreement analysis | 30 minutes after start of plasmapheresis |