PLASMA EXCHANGE J MANION NEPEAN HOSPITAL

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1 PLASMA EXCHANGE J MANION NEPEAN HOSPITAL

2 PLASMA The fluid portion of blood Normally approx 5% body weight or 3.5L in 70kg male Clots on standing unless anticoagulated Common plasma proteins are albumin, globulin and fibrinogen Normal osmotic pressure is ~25mmHg across the capillary wall Plasma proteins provide approx 15% of buffering capacity of blood due to ionised COOH and NH2 groups Other protein components include antibodies, coagulation factors, and hormones Majority of drugs are contained within plasma fraction of blood

3 TERMINOLOGY Therapeutic Plasma Exchange Removal of patient plasma and replacement with a different fluid Plasmapheresis General term used to describe the removal of plasma from blood Plasma Filtration A technique that separates plasma from cellular components using a highly permeable filter (plasma filter) using a dialysis/haemofiltration machine Nepean ICU uses the Aquarius Machine to perform Plasma Exchange

4 Dialysis machine fitted with plasma filter Allows passage of molecules and proteins up to 2 million Daltons Volume typically replaced with Albumin, however if many exchanges are needed, then 2 units FFP given at last procedure If patient is at risk of bleeding, then use 25% FFP If treating TTP then 100% FFP is the preferred replacement fluid initially

5 Dedicated apheresis machines can also use centrifugation to separate the plasma component from whole blood May be used for plasma exchange and for plasma donation #nofilter

6 RATIONALE FOR PLASMA EXCHANGE Can be used to treat any disorder where there is a pathogenic circulating factor responsible for the disease Other benefits include: Depletion of inflammatory mediators Altered immunoregulation Increased reticuloendothelial activity (mononuclear phagocyte system) Replacement (in some cases) of deficient plasma factors

7 INDICATIONS Removal of pathologic substances in plasma to reduce ongoing damage or reverse pathological process Immunoglobulins Multiple Myeloma, Waldenström macroglobulinaemia Autoantibodies Myasthenia Gravis, SLE, TTP, HUS, Factor VIII inhibitors Lipoproteins - Hypercholesterolaemia Leukocytes Hyperleukaemic leukostasis Platelets Severe Thrombocytosis Circulating immune complexes Immune complex glomerulonephritis, SLE, Systemic Vasculitis Protein bound substances and toxins Thyroid storm Hyperparasitaemia Malaria

8 PRINCIPLES OF TREATMENT The substance to be removed should be sufficiently large that it cannot easily be removed by less expensive techniques such as haemofiltration or haemodialysis The substance half life must be sufficiently long that removal is much more rapid than endogenous clearance pathways The substance must be acutely toxic and/or resistant to conventional therapy so that rapid elimination from extracellular fluid is indicated In some cases, TPE is the definitive therapy (TTP and acute Guillain Barre)

9 COMPLICATIONS Non-plasma replacement fluid: Hypokalaemia Depletion of coagulation factors and immunoglobulins Hypotension especially if patient taking ACEI Donor plasma as replacement fluid Anaphylaxis (possibly due to IgA in donor plasma) Allergy Transfusion related lung injury (antibodies in donor plasma against recipient cause leucoagglutination in pulmonary circulation) Infection

10 COMPLICATIONS Decreased concentrations of any drugs present at the time of exchange Altered pharmacokinetics even if drug is not removed (e.g. removal of antithrombin III reduced efficacy of heparin) Fluid and electrolyte imbalances requiring strict fluid monitoring and electrolyte replacement Citrate induced hypocalcaemia (paraesthesia, N+V, hypotension, muscle cramps, chest pain, tetany, arrhythmias such as long QT) Citrate induced metabolic alkalosis Changes in plasma oncotic pressure normally tolerated, but if pre-existing pulmonary or cerebral oedema decreased plasma oncotic pressure may increase oedema

11 ACQUIRED AUTOIMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) Thrombotic microangiopathy caused by deficiency of ADAMTS13 due to development of an autoantibody ADAMTS13 is a von Willebrand factor protease important in cleaving large vwf multimers ADAMTS13 deficiency results in: Small vessel platelet-rich thrombi Thrombocytopenia Microangiopathic haemolytic anaemia Sometimes associated with neurologic abnormalities, fevers, mild renal impairment Plasma exchange performed and volume replaced with plasma thereby removing autoantibody from circulation and replacing ADAMTS13 May benefit from Cryosupernatant plasma (depleted of vwf) if refractory after 5x exchanges Daily TPE until neuro status, LDH and platelet count are normal range

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13 GUILLAIN-BARRĒ Immune mediated progressive symmetric ascending weakness though to be triggered by preceding infection causing antigen cross reactivity. Peripheral nerve myelin is the target of cellular immune response Usually starts in legs. Loss of deep tendon reflexes. Commonly accompanied with paraesthesia of hands and feet % need ventilatory support.

14 GUILLAIN-BARRĒ TPE indicated within 24hours of presentation if patient has rapidly progressive symptoms. In moderately affected patients (no respiratory compromise yet) reduces need for intubation by ~50% Protocol adopted is 250ml/kg (5x50ml/kg) q2 nd daily for 1-2weeks. Shortens course of illness Not to be used in conjunction with IVIG

15 MYASTHENIA GRAVIS Autoimmune disorder characterised by weakness and fatigability of skeletal muscles Classically autoantibodies specific for acetylcholine receptor (AChR) cause inactivation and eventual destruction of AChR over time by complement mediated mechanism, but other targets have been identified. Rapid immunotherapies needed in Myasthenic crisis, prior to Thymectomy, as a bridge to long term immunotherapies or periodically for maintenance of remission for poorly controlled MG in spite of other chronic immunomodulators.

16 MYASTHENIC CRISIS Defined as life threatening weakness from acquired myasthenia gravis that is severe enough to necessitate intubation or to delay extubation following surgery Weakness of respiratory muscles often accompanied by bulbar muscle weakness which may result in upper airway obstruction or dysphasia with risk of aspiration. Generalised weakness may mask accessory muscle use and degree of respiratory compromise resulting in sudden respiratory collapse Precipitants: Infection Post surgery Pregnancy/child birth

17 PLASMA EXCHANGE IN MYASTHENIA GRAVIS Goal is to reduce autoantibodies Typical regimen is 4-6 exchanges of volume q2 nd daily. Replacement fluid is normally albumin