Hemostatic Disorder, Hyperfibrinogenemia
Conditions
Keywords
Double Filtration Plasmapheresis, Single Plasma Exchange
Brief summary
Therapeutic plasmapheresis causes changes in haemostasis by purifying many of the circulating factors involved. Few reliable data are available on these changes and most studies are limited to coagulation factor assays before and after the session, with little data documenting the kinetics of regeneration of these factors. It is recognized that haemostasis disorders caused by therapeutic apheresis must be corrected in cases of active bleeding. However the methods of correcting these disorders are debatable. Finally, it is unclear when changes in haemostasis associated with coagulation factor deficiency should be corrected. Haemostasis is probably not based solely on the level of blood fibrinogen, but it is most often its threshold that is used to trigger replacement therapy to prevent a supposed risk of haemorrhage. No studies are available on the kinetics of haemostasis disorders and the risk of haemorrhage following a therapeutic plasmapheresis session, according to session type and fibrinogen level at the end of the session. The hypothesis of this research is that the link between fibrinogen level and thrombin generation capacity, post therapeutic plasmapheresis, will enable us to better assess the risk of haemorrhage and propose preventive measures.
Detailed description
Therapeutic plasmapheresis causes changes in haemostasis by purifying many of the circulating factors involved. Some data are available on changes in circulating haemostasis factors with the Single Plasma Exchange technique and the Double Filtration Plasmapheresis; however, most often these studies are carried out in specific clinical situations where other haemostasis disorders may be present, such as severe renal failure. Furthermore, in these studies, assessment of changes in haemostasis is often limited to coagulation factor assays before and after the session, with little data documenting the kinetics of regeneration of these factors, whose molecular weight and half-life vary widely. To date, there is no clear consensus/recommendation on the management of haemostasis disorders secondary to therapeutic apheresis. The need to correct haemostasis disorders caused by therapeutic apheresis also appears to be consensual in cases of active bleeding.The methods of correcting haemostasis disorders can also be discussed between infusion of coagulation factor and fresh frozen plasma. Finally, apart from these clinical situations, it is not clear when changes in haemostasis associated with coagulation factor deficiency should be corrected. There are no studies available on the kinetics of haemostasis disorders and the risk of haemorrhage following a therapeutic plasmapheresis session, depending on the type of session and the fibrinogen level at the end of the session. The hypothesis of our research is that the existence of a link between fibrinogen level and thrombin generation capacity, post therapeutic plasmapheresis, will enable us to better assess the risk of haemorrhage and to propose preventive measures.
Interventions
PROCEDURESingle Plasma Exchange followed by Double Filtration Plasmapheresis
Double Filtration Plasmapheresis followed by Single Plasma Exchange
Sponsors
Centre Hospitalier Universitaire de Nīmes
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Patients being monitored for chronic therapeutic plasmapheresis with regional citrate anticoagulation will be recruited from the Nephrology Department at Nîmes University Hospital. After receiving written informed consent (inclusion visit), patients will be randomized to determine the nature of their first cycle (single plasma exchange or double filtration plasmapheresis. The next cycle will vary accordingly: DFPP if the first cycle was single plasma exchange, and single plasma exchange if the first session was DFPP.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients without renal failure treated with chronic therapeutic plasmapheresis with a minimum treatment interval of 10 days and who can be treated with single plasma exchange (SPE) or double filtration plasmapheresis (DFPP) in accordance with the international recommendations. * Therapeutic plasmapheresis with regional citrate anticoagulation. * Patients over 18 years of age. * Patient affiliated to or benefiting from a social security scheme. * Free, informed and written consent, signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).
Exclusion criteria
* Patients treated with oral anticoagulants or anti-platelet agents. * Patients treated for hypercholesterolaemia or hypertriglyceridaemia; hyperviscosity, acquired haemophilia or nephrotic syndrome. * Indication for substitution with fresh frozen plasma (FFP) for the treatment of the disease. * Patient in an exclusion period determined by another study. * Patient under court protection, guardianship or curatorship. * Patient unable to give consent. * Patient for whom it is impossible to give informed information. * Pregnant or breast-feeding patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of fibrinogen levels with Génésia® after the first plasmapheresis session with double filtration plasmapheresis | Day 0, end of session | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels with Génésia® after the plasmapheresis session with double filtration plasmapheresis | Month 1, Day 1, 1 hour after the session | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels after the plasmapheresis session with double filtration plasmapheresis | Month 1, Day 1, 1 hour after the session | Clauss functional method, g/L |
| Determination of fibrinogen levels after the first plasmapheresis session with double filtration plasmapheresis | Day 0, end of session | Clauss functional method, g/L |
| Determination of fibrinogen levels with Génésia® before the plasmapheresis session with double filtration plasmapheresis | Day 1 | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels before the plasmapheresis session with double filtration plasmapheresis | Day 1 | Clauss functional method, g/L |
| Determination of fibrinogen levels before the first plasmapheresis session with single plasma exchange | Day 0, before the session | Clauss functional method, g/L |
| Determination of fibrinogen levels with Génésia® before the first plasmapheresis session with single plasma exchange | Day 0, before the session | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels after the first plasmapheresis session with single plasma exchange | Day 0, end of session | Clauss functional method, g/L |
| Determination of fibrinogen levels with Génésia® after the first plasmapheresis session with single plasma exchange | Day 0, end of session | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels after the plasmapheresis session with single plasma exchange | Day 0, 1 hour after the session | Clauss functional method, g/L |
| Determination of fibrinogen levels with Genesia® after the plasmapheresis session with single plasma exchange | Day 0, 1 hour after the session | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels before the plasmapheresis session with single plasma exchange | Day 1 | Clauss functional method, g/L |
| Determination of fibrinogen levels with Genesia® before the plasmapheresis session with single plasma exchange | Day 1 | Automated thrombin generation test on Génésia®. |
| Determination of fibrinogen levels before the first plasmapheresis session with double filtration plasmapheresis | Day 0, before the session | Clauss functional method, g/L |
| Determination of fibrinogen levels with Génésia® before the first plasmapheresis session with double filtration plasmapheresis | Day 0, before the session | Automated thrombin generation test on Génésia®. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete blood count before the plasmapheresis session with single plasma exchange : Eosinophils | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Eosinophils | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Basophils | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Basophils | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Hematocrit | Day 0, Hour 0 | Quantitative, % |
| Complete blood count after the plasmapheresis session with single plasma exchange : Hematocrit | Day 0, Hour 1 | Quantitative, % |
| Complete blood count before the plasmapheresis session with single plasma exchange : Mean Corpuscular Volume | Day 0, Hour 0 | Quantitative, % |
| Complete blood count before the plasmapheresis session with single plasma exchange : Mean Corpuscular Hemoglobin | Day 0, Hour 0 | Quantitative, in pg |
| Complete blood count after the plasmapheresis session with single plasma exchange : Mean Corpuscular Hemoglobin | Day 0, Hour 1 | Quantitative, in pg |
| Complete blood count before the plasmapheresis session with single plasma exchange : Mean Corpuscular Hemoglobin Concentration | Day 0, Hour 0 | Quantitative, in g/L |
| Complete blood count after the plasmapheresis session with single plasma exchange : Mean Corpuscular Hemoglobin Concentration | Day 0, Hour 1 | Quantitative, in g/L |
| Serum albumin before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | Quantitative, in g/dL |
| Serum albumin after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | Quantitative, in g/dL |
| Prothrombin Time Test and International Normalized Ratio (PT/INR) before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | In seconds |
| Prothrombin Time Test and International Normalized Ratio (PT/INR) after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | In seconds |
| Factors VIII, IX, XI and XII before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | By 1-stage APTT-based Factor assay, in seconds |
| Factors VIII, IX, XI and XII after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | By 1-stage APTT-based Factor assay, in seconds |
| Factors X, V and II [Prothrombin] before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | Prothrombin assay, in seconds |
| Factors X, V and II [Prothrombin] after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | Prothrombin assay, in seconds |
| von Willebrand factor (vWF) activity - ristocetin cofactor test after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | Binding to platelet membrane glycoprotein Ib |
| D-dimers and circulating soluble fibrin monomers before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | By enzyme-linked immunosorbent assay (ELISA) method |
| D-dimers and circulating soluble fibrin monomers after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | By enzyme-linked immunosorbent assay (ELISA) method |
| Platelet function test before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | ADP/collagen and adrenalin/collagen cartridges. |
| Platelet function test after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | ADP/collagen and adrenalin/collagen cartridges. |
| von Willebrand factor (vWF) activity - ristocetin cofactor test before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | Binding to platelet membrane glycoprotein Ib |
| Thrombin generation test on Génésia® before the plasmapheresis session with single plasma exchange (hemorrhagic exploration version) | Day 0, Hour 0 | Triggered by 1 pM tissue factor |
| Thrombin generation test on Génésia® after the plasmapheresis session with single plasma exchange (hemorrhagic exploration version) | Day 0, Hour 1 | Triggered by 1 pM tissue factor |
| Automated thrombin generation test on Génésia® before the plasmapheresis session with single plasma exchange | Day 0, Hour 0 | Triggered by 5 pM tissue factor with response to purified thrombomodulin (thrombotic exploration version) |
| Automated thrombin generation test on Génésia® after the plasmapheresis session with single plasma exchange | Day 0, Hour 1 | Triggered by 5 pM tissue factor with response to purified thrombomodulin (thrombotic exploration version) |
| Complete blood count before the double filtration plasmapheresis session : White blood cells | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : White blood cells | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Red blood cells | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Hemoglobin | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Red blood cells | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Hemoglobin | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Platelets | Day 0, Hour 0 | Quantitative, % |
| Complete blood count after the double filtration plasmapheresis session : Platelets | Day 0, Hour 1 | Quantitative, % |
| Complete blood count before the double filtration plasmapheresis session : Neutrophils | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Neutrophils | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Lymphocytes | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Lymphocytes | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Monocytes | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Monocytes | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Eosinophils | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Eosinophils | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the double filtration plasmapheresis session : Basophils | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Basophils | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count after the double filtration plasmapheresis session : Hematocrit | Day 0, Hour 1 | Quantitative, % |
| Complete blood count before the double filtration plasmapheresis session : Mean Corpuscular Volume | Day 0, Hour 0 | Quantitative, fL |
| Complete blood count after the double filtration plasmapheresis session : Mean Corpuscular Volume | Day 0, Hour 1 | Quantitative, fL |
| Complete blood count before the double filtration plasmapheresis session : Mean Corpuscular Hemoglobin | Day 0, Hour 0 | Quantitative, pg |
| Complete blood count after the double filtration plasmapheresis session : Mean Corpuscular Hemoglobin | Day 0, Hour 1 | Quantitative, pg |
| Complete blood count before the double filtration plasmapheresis session : Mean Corpuscular Hemoglobin Concentration | Day 0, Hour 0 | Quantitative, g/L |
| Complete blood count after the double filtration plasmapheresis session : Mean Corpuscular Hemoglobin Concentration | Day 0, Hour 1 | Quantitative, g/L |
| Serum albumin before the double filtration plasmapheresis session. | Day 0, Hour 0 | Quantitative, g/L |
| Serum albumin after the double filtration plasmapheresis session. | Day 0, Hour 1 | Quantitative, g/L |
| Prothrombin Time Test and International Normalized Ratio (PT/INR) before the double filtration plasmapheresis session. | Day 0, Hour 0 | In seconds |
| Prothrombin Time Test and International Normalized Ratio (PT/INR) after the double filtration plasmapheresis session. | Day 0, Hour 1 | In seconds |
| Factors VIII, IX, XI and XII before the double filtration plasmapheresis session. | Day 0, Hour 0 | 1-stage APTT-based Factor assay |
| Factors VIII, IX, XI and XII after the double filtration plasmapheresis session. | Day 0, Hour 1 | 1-stage APTT-based Factor assay |
| Factors X, V and II [Prothrombin] before the double filtration plasmapheresis session. | Day 0, Hour 0 | Prothrombin assay, in seconds |
| Factors X, V and II [Prothrombin] after the double filtration plasmapheresis session. | Day 0, Hour 1 | Prothrombin assay, in seconds |
| Automated thrombin generation test on Génésia® after the plasmapheresis session with single plasma exchange (thrombotic exploration version) | Day 0, Hour 1 | Triggered by 5 pM tissue factor with response to purified thrombomodulin |
| D-dimers and circulating soluble fibrin monomers before the double filtration plasmapheresis session. | Day 0, Hour 0 | By enzyme-linked immunosorbent assay (ELISA) method |
| D-dimers and circulating soluble fibrin monomers after the double filtration plasmapheresis session. | Day 0, Hour 1 | By enzyme-linked immunosorbent assay (ELISA) method |
| Platelet function test before the double filtration plasmapheresis session. | Day 0, Hour 0 | ADP/collagen and adrenalin/collagen cartridges |
| Platelet function test after the double filtration plasmapheresis session. | Day 0, Hour 1 | ADP/collagen and adrenalin/collagen cartridges |
| von Willebrand factor (vWF) activity - ristocetin cofactor test before the double filtration plasmapheresis session. | Day 0, Hour 0 | Binding to platelet membrane glycoprotein Ib |
| von Willebrand factor (vWF) activity - ristocetin cofactor test after the double filtration plasmapheresis session. | Day 0, Hour 1 | Binding to platelet membrane glycoprotein Ib |
| Automated thrombin generation test on Génésia® before the plasmapheresis session with single plasma exchange (hemorrhagic exploration version) | Day 0, Hour 0 | Triggered by 1 pM tissue factor |
| Automated thrombin generation test on Génésia® after the plasmapheresis session with single plasma exchange (hemorrhagic exploration version) | Day 0, Hour 1 | Triggered by 1 pM tissue factor |
| Automated thrombin generation test on Génésia® before the plasmapheresis session with single plasma exchange (thrombotic exploration version) | Day 0, Hour 0 | Triggered by 5 pM tissue factor with response to purified thrombomodulin |
| Plasma Bank | Before Day 0, hour 0 | Storage of unused tube ends |
| Complete blood count before the double filtration plasmapheresis session : Hematocrit | Day 0, Hour 0 | Quantitative, % |
| Complete blood count after the plasmapheresis session with single plasma exchange : Neutrophils | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Mean Corpuscular Volume | Day 0, Hour 1 | Quantitative, % |
| Complete blood count before the plasmapheresis session with single plasma exchange : White blood cells | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : White blood cells | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Red blood cells | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Red blood cells | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Hemoglobin | Day 0, Hour 0 | Quantitative, grams per liter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Hemoglobin | Day 0, Hour 1 | Quantitative, grams per liter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Platelets | Day 0, Hour 0 | Quantitative, % |
| Complete blood count after the plasmapheresis session with single plasma exchange : Platelets | Day 0, Hour 1 | Quantitative, % |
| Complete blood count before the plasmapheresis session with single plasma exchange : Neutrophils | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Lymphocytes | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Lymphocytes | Day 0, Hour 1 | Quantitative, per microliter |
| Complete blood count before the plasmapheresis session with single plasma exchange : Monocytes | Day 0, Hour 0 | Quantitative, per microliter |
| Complete blood count after the plasmapheresis session with single plasma exchange : Monocytes | Day 0, Hour 1 | Quantitative, per microliter |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gender of patients | Day 0, Hour 0 | Recorded as Male, Female, Nonbinary |
| Patient's apheresis protocol | Day 0, Hour 0 | The apheresis protocol used, and parameters related to plasmapheresis will be recorded |
| Diagnostic history of patients | Day 0, Hour 0 | The patients' diagnostic history will be recorded |
| Height of patients | Day 0, Hour 0 | Recorded in centimeters |
| Weight of patients | Day 0, Hour 0 | Recorded in kilos |
| Age of patients | Day 0, Hour 0 | Recorded in years |
Countries
France
Contacts
Primary ContactOlivier MORANNE, Professor
Backup ContactAnissa MEGZARI
Outcome results
None listed