Apheresis 092909 Hames

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Apheresis -- Review

Apheresis -- Review

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  • S.G is density compared to water
  • Inhibit conversion of angiotensin I to angiotensin II but also inhibition of the breakdown of bradykinin Bradykinin is produced as the blood is exposed to the extracorporeal surface With build-up of bradykinin, may have anaphylaxis: vasodilatation, hypotension, flushing, bradycardia Generally occurs within the first few minutes of the procedure; resolves when procedure stopped Don’t return blood in line Withold ACE-I 24-48 hours prior to pheresis
  • Absorption of mestinon occurs in 30-60min, peaks in 2 hrs and declines after 4 hours; usually dosed every 4-6 hrs
  • If pheresis precipitates cholinergic crisis, be prepared to suction patient, evaluate for need to intubate, once stabilized, tensilon test can differentiate between MC and CC. Tensilon will relieve MC but will have little effect or worsen a CC
  • von Willebrand factor (vWf) is synthesized in endothelial cells and assembled in larger multimers that are present in normal plasma. The larger multimers, called unusually large von Willebrand factor (ULvWf), are rapidly degraded in the circulation into the normal size range of vWf multimers by a specific von Willebrand factor-cleaving protease (or cleaving metalloproteinase) Nature: October 2001 Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients. However, the identity of the responsible protease and its role in the pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis in four pedigrees of humans with congenital TTP and mapped the responsible genetic locus to chromosome 9q34. A predicted gene in the identifed interval corresponds to a segment of a much larger transcript, identifying a new member of the ADAMTS family of zinc metalloproteinase genes (ADAMTS13). Analysis of patients' genomic DNA identified 12 mutations in the ADAMTS13 gene, accounting for 14 of the 15 disease alleles studied. We show that deficiency of ADAMTS13 is the molecular mechanism responsible for TTP, and suggest that physiologic proteolysis of VWF and/or other ADAMTS13 substrates is required for normal vascular homeostasis.
  • TBV: infant-child 100-75ml/kg teen 70-75ml/kg adult 65-80ml/kg Example: RBC volume in a 36kg child with Hct 22% TBV=36kg x 80ml/kg=2880ml RBCV=TBV x Hct = 2880ml x .22 = 633.6ml Unit of leukopoor RBC with 300cc and Hct 55% has RBCV of 165cc so for this child, 3.8 units of PRBCs would be needed for exchange
  • TBV: infant-child 100-75ml/kg teen 70-75ml/kg adult 65-80ml/kg Example: RBC volume in a 36kg child with Hct 22% TBV=36kg x 80ml/kg=2880ml RBCV=TBV x Hct = 2880ml x .22 = 633.6ml Unit of leukopoor RBC with 300cc and Hct 55% has RBCV of 165cc so for this child, 3.8 units of PRBCs would be needed for exchange

Transcript

  • 1. Apheresis Fellowship lecture series 9/29/09
  • 2.
    • Components of blood
    • Apheresis definitions
    • Methods of apheresis
    • Indications for apheresis
    • Dose of plasmapheresis/exchange
    • Anticoagulation
    • Routine medications
    • Complications of apheresis
    • Disease states
    • RBC exchange
  • 3. Components of blood
    • 45% cellular elements
    • 55% plasma
      • 92% water
      • 8% solutes
        • Proteins, non-protein nitrogen substances, food substances, regulatory substances, respiratory gases and electrolytes
          • Plasma proteins include albumin, globulins, prothrombin and fibrinogen
  • 4. Apheresis
    • Apheresis originates from Greek roots meaning “to take away from”
    • Apheresis = the separation of whole blood into its components
      • A selected component of blood is removed and the remaining elements are recombined and returned to the donor or patient
    • Concept of apheresis has been applied to blood donation as well as patient treatment
  • 5. Apheresis
    • 2 categories
      • Plasmapheresis
        • Plasma exchange – large quantities of plasma are removed and replaced with a suitable replacement solution during a therapeutic procedure
      • Cytapheresis
        • Leukapheresis
        • Thrombocytaphereis
        • Erythrocytapheresis
  • 6. Methods of Apheresis
    • Utilize peripheral or central line
    • Centrifugation
      • Continuous or discontinuous
    • Non-centrifugal based on sieving or “filtration technology”
      • Hollow-fibers or membranes
    • Combination of both
    *** PCMH uses a continuous centrifugation device
  • 7. Separation of blood by centrifugal force
    • Each blood component has a specific density and specific gravity
    Constituent Specific Gravity (g/ml) Plasma 1.025-1.029 Platelets 1.040 White Blood Cells B-Lymphocytes 1.050-1.060 T-Lymphocytes 1.050-1.061 Blasts/Promyelocytes 1.058-1.066 Monocytes 1.065-1.066 Myelocytes/Basophils 1.070 Reticulocytes 1.078 Metamyelocytes 1.080 Bands and Segmented Neutrophils 1.087-1.092 Erythrocytes 1.078-1.114
  • 8. Separation of blood by sieving
    • Filtration technology separates plasma and the cellular components by sieving the cells from plasma
    • Limited to plasmapheresis or donor platelet apheresis
    • Pore size of the membrane separator is 6 microns
    Component Diameter in Microns Platelets 3 microns Erythrocytes 7 microns Lymphocytes 10 microns Granulocytes 13 microns
  • 9.  
  • 10.  
  • 11.  
  • 12. Indications for Apheresis
    • Category I – primary or 1 st line adjunct to other treatments
    • Category II – generally beneficial
    • Category III – available trials insufficient to establish efficacy
    • Category IV – available trials show lack of efficacy; should be done only w/an approved research protocol
  • 13. Dose of Therapeutic plasma exchange
    • TBV = wt in kg x 70ml/kg (for adult)
    • TBV x (100 – hct%) = plasma volume
    TBV = total blood volume Estimated TBV is determined from wt/ht/age: infant-child 100-75ml/kg teen 70-75ml/kg adult 65-80ml/kg Plasma volume exchanged Plasma removed 0.5 39% 1.0 63% 1.5 78% 2.0 86% 2.5 92% 3.0 95%
  • 14. Anticoagulation for apheresis
    • Regional anticoagulation
      • Citrate
        • Used most commonly, enters the extracorporeal circuit at the first available opportunity
        • Metabolized by the liver, kidney and muscles
        • Because citrate is plasma bound, only 15-18% is returned
    • Systemic anticoagulation
      • Heparin
        • Used in liver failure, pediatrics
  • 15. Anticoagulation in Apheresis
    • Citrate
      • Binds to or “chelates” ionized calcium to produce a soluble complex; this makes calcium unavailable for calcium-dependent clotting
      • Remains active as long as the blood is in the extracorporeal circuit
  • 16. Anticoagulation in Apheresis
    • Citrate
      • Citric acid, citrate salts, citrate dextrose
      • Formulations:
        • Anticoagulant citrate dextrose (ACD)
          • Contains citric acid, sodium citrate and dextrose
          • Solution A 3% citrate concentration (21.4mg/ml)
          • Solution B 2% citrate concentration (12.9mg/ml)
        • Sodium citrate highly concentrated
          • 46.7% Trisodium citrate
    • For comparison, FFP is 4.10mg/ml and RBC with a Hct of 70% is .71mg/ml
  • 17. Side-effects of Anticoagulation
    • Citrate
      • Hypocalcemia is related to:
        • Rate at which citrated blood is returned to the donor/patient
        • Length of the procedure
        • Use of FFP as replacement fluid
        • Metabolism (i.e. hepatic function)
      • Infusion rates
        • 1mg/kg per minute or less harmless to most
        • > 1.7mg/kg per minute assoc. with mod to severe rxn
        • Limit for citrate infusions suggested as 4mg/kg per minute in extreme circumstances
  • 18. Side-effects of Anticoagulation
    • Citrate infusion rates:
      • Cellular collections
    • Citrate infusion rate = [Cit] / Body wt. x [TFR/ n+1 – CFR / n- (n x Hct) +1] (mg/kg/minute)
      • Plasma exchanges
    • Citrate infusion rate = {[Cit] / Body Wt} X [TFR/ n+1 – PFR / n- (n x Hct) + 1] (mg/kg/minute)
    • TFR = the total flow rate into the system, including AC, in ml/min
    • [Cit] = citrate concentration of anticoagulant in mg/ml
    • CFR = the collection pump flow rate in ml/min
    • Hct = the hematocrit expressed as a decimal
    • n = the ratio of the rate of donor whole blood withdrawn to the rate of AC
  • 19. Side-effects of Anticoagulation Hypocalcemia
    • Mild Circumoral paresthesia
    • Sneezing
    • Chewing on the lips
    • Moderate paresthesia progressing to hands, feet, and/or chest
    • chills despite the use of a blood warmer
    • nausea and vomiting, abdominal cramping
    • vibrating sensation
    • lightheadedness and mild hypotension
    • restlessness
  • 20. Side-effects of Anticoagulation Hypocalcemia
    • Severe muscle cramps, severe abdominal cramping
    • tremors
    • bladder and/or bowel incontinence
    • fear of impending doom
    • loss of consciousness
    • blurred or double vision
    • severe hypotension (BP < 90mmHg)
    • cardiac: arrhythmia, bradycardia, prolonged QT
    • interval, PVCs
    • Neuromuscular irritability
    • - chvostek’s sign
    • - trousseau’s sign
    • - seizure
  • 21. Side-effects of Anticoagulation Treating hypocalcemia
    • Keep pt warm with blankets
    • Blood warmers
    • Decrease BF rates
    • Decrease the AC:WB ratios to decrease citrate delivery
    • Calcium replacement
      • Tums
      • Oral calcium wafers
      • IV calcium gluconate (1gm – 94mg Ca++)
      • IV calcium chloride (1gm – 273mg Ca++)
    • Terminate procedure
    • Consider conditions that might exacerbate a citrate reaction: hyperventilation, hyperthermia, hypomagnesemia, hypoalbuminemia, using FFP as replacement fluid
  • 22. Side effects of anticoagulation
    • Other side effects of citrate
      • Hypomagnesemia
      • Hypokalemia
      • Decreased Ca/Mg can increase parathormone
  • 23. Other medications
    • Medications that are free in the plasma and NOT bound to plasma protein are NOT efficiently removed during plasmapheresis
    • Medications that are highly protein bound and slowly metabolized ARE more readily removed during plasmapheresis
      • If predominantly in the intravascular space, 70-80% of drug will be removed in a 1 to 1.5 plasma volume exchange
    • Not as big a problem with cytapheresis unless large volumes are processed
  • 24. Other medications
    • Irregardless, whenever possible, dose medications after pheresis
  • 25. Apheresis - complications
    • Early signs of a developing adverse reaction
      • Irregular breathing patterns
      • Hyperventilation
      • Tachycardia
      • Cold and clammy hands
      • Flushed or pale face
      • Restlessness
      • Abdominal cramping
  • 26. Apheresis - complications
    • Hypocalcemia related to citrate toxicity (most common)
    • Vasovagal and hypovolemic reactions
    • ACE-Inhibitors
      • Bradykinin is produced as the blood is exposed to extracorporeal surface
      • ACE-I decrease the rate of degradation of bradykinin
      • Potentiate allergic rxn (vasodilatation, hypotension, flushing, bradycardia) due to increased levels of kinins
      • Usually this rxn occurs within minutes; procedure should be terminated without blood return and rescheduled in 24-48hours
      • Withhold ACE-I 24-48 hours prio to treatment or choose alternative agent
  • 27. Apheresis - complications
    • Transfusion reactions (immediate within 15min or delayed up to 12 hours)
    • Coagulopathy
      • Removal of coagulation factors
      • A problem with albumin replacement
      • Fibrinogen level may decrease by 25-70% following a 1 to 1.5 plasma volume exchange
        • Recovers to baseline over 48-72 hours
      • PT/PTT may be abnormal post pheresis
        • Recovers 4-24 hours
      • 1-4 units of cryoprecipitate or FFP can be given at the end of the procedure as part of replacement fluids
    • Air embolism (acute SOB, chest pain, diaphoresis, confusion, shock, syncope)
  • 28. Apheresis - complications
    • Catheter complications
    • Mechanical hemolysis
    • Aluminum bone deposits (albumin may be contaminated with aluminum and other trace elements)
    • Thrombocytopenia
      • Up to a 30-50% decrease in platelet count has been reported
        • Removed with the plasma in plasma exchange
        • Removed with the red cells in RBC exchange
        • Become aggregated and caught in the machine centrifuge chamber, tubing and filters
  • 29. Disease states – Guillian Barre
    • Benefit in controlled and uncontrolled studies
    • North American Guillian Barre study group: Series of 5 exchanges compared to no exchanges but otherwise identical care
      • Plasma exchange has a role in tx of acute GBS
      • Greatest benefit w/disease duration < 1 wk and who are not on a ventilator
    • 5% Albumin replacement
  • 30. Disease states – CIDP
    • Regimen similar to North American Guillian Barre study group
      • 4-6 exchanges of 40 to 60 mL/kg in the 1 st 2 weeks
      • Some follow with 1-2 exchanges weekly or at larger intervals as needed to achieve maximal or stable response
    • 5% Albumin replacement
  • 31. Disease states – myasthenia gravis
    • An autoimmune disease where pts have antibodies to the acetylcholine receptor (AChR)
    • Treatment options:
      • Meds to enhance neuromuscular transmission (=anticholinesterase drugs) -> facilitate more acetylcholine at the neuromuscular junction. i.e. mestinon=pyridostigmine, prostigmin=neostigmine
      • Long-term immunosuppression
      • Short-term plasma exchange with albumin replacement
      • IVIG
      • thymectomy
    • Indications
      • Not responding to drug therapy
      • In myasthenic crisis
      • Pre- and post- thymectomy
  • 32. Disease states – myasthenia gravis
    • Myasthenic crisis – exacerbation of myasthenia gravis
    • Cholinergic crisis – identical symptoms but caused by excess of anticholinesterase medications: plasma exchange can precipitate this as it removes antibodies
      • Main difference between the 2 is HR should increase with MC and should decrease with CC
      • Other symptoms of CC include abdominal cramps, pallor, sweating, hypotension, respiratory arrest
    • Pregnant pt
      • infant might be born with neonatal myasthenia gravis
      • can treat mom w/anticholinesterase drugs, steroids, plasma exchange
  • 33. Disease states – TTP
    • Plasma exchange with FFP replacement is treatment of choice
    • Should be an emergent transfer; utilize transfer to ED if beds full; tell outside hospital to hang 2-3 units of cryopoor (or regular if no cryopoor) FFP while awaiting emergent transfer
  • 34. Blood 98 (6) September 15 2001
  • 35. Indications for Red Blood Cell Exchange
    • Sickle cell disease
    • Falciparum malaria
    • Babesiosis
    • Thalassemia
    • CO poisoning
    • methemaglobinemia
  • 36. Red Blood Cell Exchange is used in sickle cell disease to:
    • Alleviate an acute process
      • Impending stroke
      • Acute chest syndrome
      • Priapism
      • Retinal infarction
      • Hepatopathy
      • Severe liver disease
      • Refractory hematuria
    • Prophylactic
      • To prevent a 2 nd stroke (goal HbS < 30-50%)
      • To alleviate chronic pain crises
      • To prevent iron overload
  • 37. Red Blood Cell Exchange sickle cell disease
    • Standard PRBC Hct is 70-80%
      • May be lower with leukoreduced (55%) or washed units
    • To calculate amt of RBCs to be exchanged need to know wt, TBV (total blood volume), Hct and these will allow you to determine the RBCV (RBC volume)
    • Pt’s with prior febrile transfusion reaction will need leukocyte-reduced RBCs
    • For pts with RBC alloantibodies, antigen-negative RBCs will be needed
    • Must use hemoglobin S negative blood
    • Must use standard blood filter on replacement line
  • 38. Red Blood Cell Exchange sickle cell disease
    • Example: RBC volume in a 36kg child with Hct 22%
    • TBV=36kg x 80ml/kg=2880ml
    • RBCV=TBV x Hct = 2880ml x .22 = 633.6ml
    • Unit of leukopoor RBC with 300cc and Hct 55% has RBCV of 165cc so for this child, ~3.8 units of PRBCs would be needed for exchange
    Estimated TBV is determined from wt/ht/age: infant-child 100-75ml/kg teen 70-75ml/kg adult 65-80ml/kg
  • 39. THE END!!
  • 40. History of Apheresis
    • Ancient practice of bloodletting
    • 1914 – first application of separation of blood components in uremic dogs
  • 41. History of Apheresis
    • During WWII, plasma needed
    • Edwin J. Cohn adapted cream separator to separate plasma from whole blood
  • 42. History of Apheresis
    • 1948 – Cohn developed a closed-system whole blood separation device
    • 1952 – sequential weekly plasma removal with red cell storage a week at a time
    • 1962 – Mr. G. Judson (IBM) Dr. Emil Freireich (NCI) developed a continuous-flow blood component centrifuge
  • 43. History of Apheresis
    • 1960’s – Allen Latham, Jr and the Arthur D. Little Company developed a discontinuous-flow apparatus -> Soon to be Haemonetics corporation
    • 1966 – 1 st manual plasmapheresis using centrifugation device connected to integrated bag/tubing system
    • 1984 – COBE bought IBM Biomedical systems division and eventually introduced COBE Spectra