Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

University Medical Centre Ljubljana

Status and phase: Completed; Phase 4

Conditions: Anticoagulation; Apheresis

Treatments: Drug: Sodium Citrate; Drug: unfractionated heparin

Study type: Interventional

Funder types: Other

Identifiers

NCT05191290

0120-310/2017/3

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

heparin anticoagulation

Active Comparator group

Description:

standard heparin anticoagulation during plasmapheresis

Treatment:

Drug: unfractionated heparin

citrate anticoagulation

Experimental group

Description:

sodium citrate anticoagulation during plasmapheresis

Treatment:

Drug: Sodium Citrate