Plasmapheresis and hemofiltration in poisonings

Mubeena Anjum

ER – Consultant, Kauvery Hospital, Salem, Tamil Nadu

Background

Terminologies

  • Apheresis is the general term used for technique of extracorporeal removal of a blood constituent.
  • Plasmapheresis is the process of obtaining plasma from blood.

Plasma exchange is using plasmapheresis to replace someone’s plasma, then adding the replacement fluid to the blood and returning the blood to the person receiving treatment.

Difference Between Hemodialysis, Hemofiltration and Hemodiafiltration

Haemodialysis: Hemodialysis removes solute, toxins (Urea, creatinine and other small molecular toxins), from the blood by diffusion.

Haemofiltration: Hemofiltration removes solute and solvent, water and toxins (β2-MG and other middle molecules), by convection.

Haemodiafiltration: Hemodiafiltration uses both diffusion and convection to cleanse blood. It can efficiently remove small and medium molecule metabolic waste in the patient’s body.

Haemoperfusion: Blood flows through a device containing adsorbent material (like charcoal or resin) that binds to and removes toxins from the blood.

Mechanism of TPE

Removal of pathogenic immunoglobulins in plasma – IgG in MG/IgM in WM/ or immune complexes Ig G/M in ABO incompatibility, non-antibody toxins like LDL.

Delivery of deficient factors – ADAMTS 13 in TTP

Types of TPE

The underlying mechanism of this procedure is accomplished by either centrifugation or filtration using semipermeable membranes

While centrifugation is based on the principle of separation using different specific gravities of various blood components, membrane plasma separation filters blood components based on their particle size.

Membrane filtration TPE can only separate plasma, whereas centrifugation TPE can fractionate any of the blood components (eg, erythrocytes, platelets, plasma).

MF TPE extracts a smaller fraction of plasma (30%) per unit of time than CTPE (80%), requiring longer treatment times, higher blood flow rates, and increase the risk for circuit clotting.

In CTPE, filtered plasma is discarded, and replacement fluid (donor plasma or colloids) are returned.

MPE allows selective removal of undesired macromolecules; hence, filtered, processed plasma is returned to the patient, eliminating the need for replacement fluids.

Centrifuge TPE

The centrifuge is the functional unit of this continuous-flow extracorporeal circuit and does not require a blood-membrane interface.

By spinning at 2,000-2,500 rpm, it separates the components of anticoagulated blood according to density.

Consequently, the blood separates around the axis of rotation, with plasma in the innermost layer, then granulocytes (ie, buffy coat), monocytes, lymphocytes, platelets, and finally red blood cells in the outermost layer

Centrifugation can pack RBC to a hematocrit level of≥80%, allowing for removal of larger plasma volumes and shorter sessions.

Because lower blood flow rates are sufficient, peripheral vein access can be used for centrifugation

MFTPE

Similar to UF in HD, plasma constituents are non-selectively removed across a semipermeable membrane. The separation efficiency depends on plasma filtration rates, membrane properties such as pore size and surface area, and the sieving coefficients. Serum protein adsorption to the membrane will lead to filter clogging and decreased separation.

Similar to CKRT modalities that rely on convective clearance, high UF rates lead to high filtration fractions, and RBC damage and filter clotting may occur as the hematocrit level increases. Therefore, MFTPE is limited to a FF of 30%-35% of the plasma, requiring longer treatment sessions and higher blood flow rates. MF TPE requires central venous access.

Unlike hemodialysis or hemofiltration, which removes substances of low to medium molecular weight from serum, TPE targets larger-molecular-weight substances present in plasma

Access

Large-Bore Peripheral Intravenous Access

In adults, 17-19–gauge needles are used; these are used to supply blood flow rates ranging from>80 to 60mL/min.

In children, 19-22–gauge needles are used.

Routinely, blood is withdrawn from the basilic or cephalic vein and returned with replacement fluid to smaller veins in the hands. One plasma volume is processed in 2hours.

Anticoagulation

Similar to HD, UFH is commonly used for systemic anticoagulation in MSPE and given as a single bolus of 3000–5000 IU or 40–60 U/kg, followed by 1000 IU/h as needed.

Citrate is commonly used in CTPE for anticoagulation, but it is rarely used in MSPE due to higher risk of toxicity and hypocalcemia from increased citrate exposure because higher volumes of blood are processed in the MSPE.

70-80 % of the citrate infused in MSPE is retained by the patient due to reduced removal because plasma extraction ratio is only 20–30% compared with 80% in CPE.

Citrate toxicity is still possible in MSPE even when heparin is used for anticoagulation if FFP (contains 14% citrate by volume) is used for replacement fluid in a patient with kidney or hepatic failure. Citrate-induced hypocalcemia can be avoided with prophylactic administration of calcium.

Calculation of Plasma Volume

For the TPE prescription, the patient’s plasma volume is estimated on the basis of the hematocrit and weight of the patient in kilograms. A formula to estimate plasma volume is (0.065× weight [kilograms]) × (1− hematocrit).

Kaplan Formula for EPV= TBV*(1-hct)

  • Total blood volume – 70ml/kg in males & 65ml/kg in females
  • 70kg male patient with 40% HCT
  • TBV= 70*70= 4900ml
  • EPV= 4900 (1-0.40) = 2940ml

Exponential decay – if only 1 TPV = reduction of 35% of initial value, whereas if 2 TPV = further 15% reduction

Plasma exchange volume is usually prescribed as 1–1.5× estimated plasma volume, removes 60-75% of IV material.

Replacement Fluids

Replacement fluid is infused into the patient during PE to prevent hemodynamic collapse. The replacement fluid replaces the lost volume and exerts oncotic pressure to avoid hypotension.

Replacement choices are 5% albumin or FFP; 5% albumin is isosmotic, and its oncotic pressure is close to plasma Or add 50 g of 25% albumin to a litre of NS or RL to get a final concentration of 5% albumin for replacement solution.

Albumin derived from human plasma is highly purified with negligible risk of allergic reaction, but albumin replacement does not compensate for the depletion of clotting factors.

FFP replacement is mandated in certain diseases, such as TTP, to replace ADAMTS13 or if there is increased risk of bleeding because plasma exchange depletes the clotting factors.

Complications

  • Magnesium because replacement fluid lacks these electrolytes.
  • Depletion coagulopathy
  • Access-associated complications
  • Reaction to FFP.
  • Citrate in FFP can lead to hypocalcemia, metabolic alkalosis with high-volume transfusion.
  • Thrombocytopenia is L/C but can occur in MSPE, probably due to entrapment in the filter.
  • Use of the Plasma flow OP-05W is associated with a potential for increased bradykinin levels, and it would be wise to discontinue ACE inhibitors in any patient who is to be treated with this membrane.

Increased risk of bleeding due to removal of CF and fibrinogen can occur with >3 exchanges/ week with albumin infusion. To prevent this, the last 500 ml can be replaced with FFP instead of 5% albumin

ASFA Classification

  • Category 1: Includes disorders where plasmapheresis can be done as a first-line treatment,
  • Category 2: Includes disorders where plasmapheresis can be done as a second-line treatment in addition to the existing standard of care,
  • Category 3: Includes disorders in which the evidence of the benefit of plasmapheresis is minimal, and therapy must be individualized,
  • Category 4: Includes disorders in which the evidence suggests that plasmapheresis is either ineffective or harmful.
Category 1Category 2Category 3
AIDP/GBS/CIDPAIDPAcute liver failure
Myasthenia gravisCardiac transplantation: DesensitizationANCA-associated rapidly progressive glomerulonephritis (dialysis independent)
NMDA + encephalitisCatastrophic APLAAnti-glomerular basement membrane disease, Goodpasture syndrome (dialysis-dependent, no DAH)
MSCryoglobulinemiaAplastic anemia, pure red cell aplasia
Progressive multifocal leukoencephalopathy associated with natalizumabDCMAutoimmune hemolytic anemia
Hyperviscosity in monoclonal gammopathies/ CryoglobulinemiaHashimoto encephalopathy: Corticosteroid responsive encephalopathy associated with autoimmune thyroiditisBurn shock resuscitation
Renal & Liver transplantation: Desensitization and antibody-mediated rejectionHematopoietic stem cell transplantation, ABO-incompatibleCardiac neonatal lupus
ANCA-associated RPGN / FSGSLambert-Eaton myasthenic syndromeCardiac transplantation: Antibody-mediated rejection
Goodpasture syndromeMSChronic focal encephalitis (Rasmussen encephalitis)
Thrombotic microangiopathy (Factor H autoantibodies and ticlopidine)Myeloma cast nephropathyComplex regional pain syndrome; chronic
TTPNMOErythropoietic porphyria, liver disease
Wilson disease (fulminant)Overdose, envenomation, and poisoning, such as mushroomHemolysis liver enzymes low platelet (HELLP) syndrome (postpartum)
PANDASHematopoietic stem cell transplantation, HLA desensitization
SLEHemophagocytic lymphohistiocytosis; hemophagocytic syndrome; macrophage activating syndrome
IgA nephropathy; crescentic
Henoch-Schonlein purpura
Heparin-induced thrombocytopenia and thrombosis
Hypertriglyceridemic pancreatitis
Immune thrombocytopenia; refractory
Lung transplantation: Desensitization and antibody-mediated rejection
Paraneoplastic neurological syndromes
Pemphigus Vulgaris; severe
Pruritus due to hepatobiliary diseases
Scleroderma (systemic sclerosis)
Sepsis with multiorgan failure

Category 4

  • Amyloidosis, systemic
  • Dermatomyositis/polymyositis
  • HELLP syndrome (antepartum)
  • Lupus nephritis
  • Thrombotic microangiopathy (gemcitabine and quinine)

Contraindications

  • Non-availability of central line access or large bore peripheral lines
  • Hemodynamic instability or septicemia
  • Known allergy to fresh frozen plasma or replacement colloid/albumin
  • Known allergy to heparin
  • Hypocalcemia (restricts the use of citrate as an anticoagulant during the procedure); relative contraindication
  • Angiotensin-converting enzyme (ACE) inhibitor used in last 24 hours; relative contraindication

Dialyzer Membrane Types

Filter Based – Hollow fiber and parallel plate.

Hollow fibre dialyzers are cylindrical shell-like structures, consisting of multiple polysulfone capillary fibres. Parallel plate dialyzers consist of layered membranes, with ridges and grooves which facilitate filtration.

Both these dialyzers allow plasma filtration based on particle size and pressure gradients. Hollow fibre dialyzers are more gentle as opposed to parallel plate dialyzers and are preferred for pediatric patients, whereas hollow fibre dialyzers use less blood volume, and hence require a reduced dose of citrate or heparin for anticoagulation.

Plex in Toxicology

The rationale for using plasmapheresis must be confirmed in each type of intoxication by evidence of effective clearance, as well as by high plasma protein binding and a low volume of distribution of the toxic substance.

TPE is not routinely recommended in the management of yellow phosphorus poisoning. TPE is provided only as a ‘bridge to liver transplantation’ when contemplated.

TPE improves overall hospital survival in patients with ALF by approximately 10%. TPE is recommended as a part of optimal treatment of ALF due to yellow phosphorus poisoning regardless of the need for liver transplantation.

The replacement fluids, that is, FFPs and albumin, replace the synthetic function of the liver. TPE removes toxic substances which may be responsible for hepatic coma, thus replacing the excretory function of the liver. LV-TPE showed improved haemodynamics comparable with the effects reported previously with high volume-TPE

Learning points.

  • Plasma exchange should be attempted in every case of yellow phosphorus poisoning with acute liver failure (ALF) even if liver transplantation is not possible.
  • Successful outcome also depends on early detection and management of life-threatening complications like hypoglycaemia, cerebral oedema, hepatic encephalopathy, hypocalcaemia and spontaneous bleeding.
  • Hypoglycaemia settles along with liver enzymes within the first 2 weeks of onset of ALF.
  • Bilirubin and prothrombin time take at least 6 weeks to normalise.
  • Urea levels are the last to recover.
  • Another productive area for future research includes the use of plasma exchange therapy for the treatment of acute endogenous intoxications.

Recent examples include the treatment of severe preeclampsia, extensive rhabdomyolysis, and life-threatening bleeding in a hemophiliac with inhibitors to clotting factors.

In conclusion

DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidaemia.

Hemoperfusion in Paraquat

Furthermore, neither early HP nor multiple secessions of HP were associated with survival. The use of hemoperfusion with a charcoal filter appears to be a very important therapeutic tool for the treatment of acute and severe forms of thyrotoxicosis due to l-thyroxine intoxication. Hemoperfusion is more effective at clearing protein-bound drugs

Hemoperfusion is also more efficient than hemodialysis at clearing lipid-soluble drugs Hemodialysis and hemodiafiltration are more efficient at clearing readily water-soluble substances and small molecules

If a substance is equally well removed by either hemodialysis or hemoperfusion, then hemodialysis is the modality of choice, because it has fewer complications.

The principal disadvantage of hemoperfusion is the saturation of the adsorbent cartridge, which occurs after 4–8 hr due to clotting and adherence of cellular debris and plasma proteins to the adsorbent, necessitating regular changes of the cartridge. In addition, hemoperfusion does not correct any acid-base or electrolyte abnormality, or fluid overload.

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