Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

Phase 4

Completed

• Conditions: Apheresis; Anticoagulation
• Interventions: Drug: Sodium Citrate; Drug: unfractionated heparin

• Registration Number: NCT05191290
• Lead Sponsor: University Medical Centre Ljubljana

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-12-12
• Study First Submitted QC: 2021-12-29
• Study First Posted: 2022-01-13
• Study Start: 2022-01-21
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
citrate anticoagulation	Sodium Citrate	sodium citrate anticoagulation during plasmapheresis
heparin anticoagulation	unfractionated heparin	standard heparin anticoagulation during plasmapheresis

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Medical Center Ljubljana; 🇸🇮 Ljubljana, Slovenia