3Since antiquity, mankind has hypothesized there are bad substances called “humors” that accumulate in the blood of sick patients and that the removal of these humors would . make patients feel better
4Bloodletting, the practice of draining blood from sick patients,has been around since theEgyptians, dating back 1000 years BC. Thepractice of bloodletting peaked in the18th century and evolves with moderntechnology to this day.
5Apheresis is a procedure that is used in the treatment of patients with a variety of illnesses. The term apheresis comes from theGreek origin meaning “removal of”. All apheresis procedures involveremoving components from the blood.Efficient apheresis procedures have been developed over the last 15 years.
6Blood has 4 major components: red blood cells, white blood cells, platelets, and plasma. With modern machinery, blood can be separated into each of these 4 components. Thus, if a particular blood component is causing harm, it can be selectively removed andreplaced with the same blood component from healthy donors.
7History of modern plasmapheresis 1909 Fleig / FranceAuto & heterotransfusion of washed corpuscles1914 Abel / U.S.Use the term of Plasmapheresis in his paperProlonged the life of dog with bilateral nephrectomy by plasmapheresis1959 Michael Rubinstein was the first person to use plasmapheresis to treat an immune-related disorder when he "saved the life of an adolescent boy with thrombotic thrombocytopenic purpura (TTP) at the old Cedars of Lebanon Hospital in Los Angeles1970 -Invention of cell separator machine
9Apheresis in Clinical Practice Sickle Cell Dis.MalariaThrombocytosisRBCWBCPLTPlasmaLeukemiasCell TherapiesTTPGuillain Barre Syn.Myasthenia GravisGoodpasture’s Syn.Waldenstrom’s
10Plasmapheresis is an apheresis procedure that separates and removes the plasma component from a patient. Plasma exchange is when plasmapheresis is followed by replacement with fresh frozen plasma infusion
11To apply this treatment to patients appropriately it is essential to understand:1-the methods to remove plasma2- its effects on normal plasma constituents3-the role of replacement fluids in the treatment4-and the risks associated with the procedure.
12Mechanism of action of plasma exchange Removes pathologic substances such as pathologic Abs, immune complexes,and cytokines is the major mechanism of action of TPETPE may have an immunomodulatory effect beyond the removal of Ig:Reported effects of TPE on immune function include:T-cell modulation with a shift from in the Th1/Th2 balance with a shift toward Th2suppression of IL-2 and IFN- γ production
13Possible mechanisms of TPE Mechanism of actionDisordersRemoval of autoantibodyMyasthenia gravisRemoval of alloantibodyRh alloimmunization in preg.Removal of immune complexSystemic lupus erythemotosusRemoval of monoclonal proteinHyperviscosity syndromeRemoval of toxinMushroom poisoningReplacement of specific plasma factorThrombotic thrombocytopenic purpura
15TECHNIQUES OF SEPARATING PLASMA FROM WHOLE BLOOD Plasmapheresis is performed by 2 fundamentally different techniques: Devices separating based on density:centrifugationorDevices separating based on size: filtration
16centrifugation apheresis whole blood is spun so that the 4 major blood components are separated out into layers by their different densities. Centrifugation apheresis is commonly .performed by blood bankers
17centrifugation apheresis Advantages:1-Capable of performing cytapheresis2-No heparin requirement More efficient removal of all plasma componentsDisadvantages: 1-Expensive 2-Requires citrate anticoagulation 3-loss of platelets 4-usually requires a consultation to another service such as a blood banker
19Filtration plasmapheresis whole blood passes through a filter to separate the plasma components from the larger cellular components of red blood cells, white blood cells,and platelets.commonly performed by nephrologists andintensivist
20Membrane apheresis Advantages: 1-fast and efficient 2-No citrate requirementsDisadvantages:1-Removal of substances limited by sieving coefficient of membrane 2-Unable to perform cytapheresis3-Requires high blood flows , central venous access, heparin Limiting use in bleeding disorders
232010, ASFA published its updated comprehensive “Guidelines • Category I: “Disorder for which apheresis is accepted as first-line therapy,either as a primary stand-alone treatment or in conjunction with other modes of treatment.” • Category II: “Disorders for which apheresis is accepted as second-line therapy,either as a stand-alone treatment or in conjunction with other modes of treatment.” • Category III: “Optimum role of apheresis therapy is not established. Decision -making should be individualized.” • Category IV: “Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful. Internal Review Board approval is desirable if apheresis treatment is undertaken in these circumstances.”
25Diseases and disorders treated with plasma exchange. ASFA categoryI Chronic inflammatory demyelinating polyradiculopathyCryoglobulinemiaFocal segmental glomerulosclerosis (recurrent)Hemolytic uremic syndromeAutoantibody to factor HHyperviscosity in monoclonal gamopathiesSymptomaticProphylactic for rituximab treatment
26Diseases and disorders treated with plasma exchange. ASFA categoryI Paraproteinemic polyneuropathiesIgG/IgAIgMPediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)Renal transplantation, Ab-mediated rejectionThrombotic thrombocytopenic purpura
27TPE & removal of plasmaSignificant declines in factor V (FV), FVII, FVIII, FIX, FX, and VWF activity occurs.Activities of FVIII, FIX, and VWF return to normalwithin 4 hours after TPEwhereas the remaining coagulation factors achieve pre-TPE activity levels by 24 hours.The exception to this is fibrinogen, which reaches 66% of pre-apheresis levels by72 hours
28Additional substances removed include: inhibitors of coagulation such as antithrombin and the pseudocholinesterase necessary for metabolism of some drugsTheoretically, the removal of inhibitors of coagulation could predispose patients tothrombosis, but this has not been demonstrated definitivelyReports of prolonged neuromuscular blockade due to decreased pseudocholinesterase activity have been reported
29The removal of Abs from the patient can result in: false negative tests for: infectious diseases, autoantibodies, alloantibodies,and enzyme and coagulation factor activity. Samples for such testing should be collected before the initiation of TPE
30Medications reportedly removed by TPE Basiliximab Ceftriaxone CeftazidimeChloramphenicolCisplatinDiltiazemα IFN-IVIGPalivizumabPropoxyphenePropranololRituximabTobramycinVerapamilVincristineAmerican Society of Hematology
31For each plasma volume exchanged, approximately 60%-70% of substances present in the plasma at the start of that .plasma volume will be removedroutine practice is to exchange only plasma volumes during a TPE.American Society of Hematology
32risk of complications without increasing benefit to the patient. Treating volumes beyond 1.5 plasma volumes removes smaller, less clinically important amounts of pathologic substance present in theplasma while prolonging the procedure and exposing the patient to more replacement fluid and anticoagulant,increasing :risk of complications without increasing benefit to the patient.American Society of Hematology
33one-third of the replacement fluid administered at the beginning of the TPE will be present by the end, with the majority having been removed. Administering plasma as a replacement fluid at the beginning of a TPE results in exposure of the patient to blood products without benefit.
34Exchange Fluids 5% Albumin Combination of saline and albumin FFP Best choiceDilute only with salineCombination of saline and albuminFFPCryopoor plasma
35AlbuminAdvantages: 1-No risk of hepatitis 2-Stored at room temperature 3-Allergic reaction are rare 4-No concern about ABO blood group 5-Depletes inflammation mediatorsDisadvantages: 1-Expensive 2-No coagulation factors 3-No immunoglobulins
3670% albumin and 30% saline. majority of the albumin being given at the end of the procedure to avoid hypovolemia from redistribution of the crystalloid
37FFP Advantages: 1-Coagulation factors 2-Immunoglobulins Disadvantages: 1-Risk of hepatitis, HIV, transmission2-Allergic reaction3-Hemolytic reaction4-Must be ABO compatible5- citrate load
38vascular access ?central venous access Or peripheral vascular access
39Studies examining the complication rates of apheresis procedures : the frequency of complications due to the placement of central venous catheters exceed the frequency of complications directly related to the procedure. (hemopneumothorax) Central venous access has also been identified as a major risk factor for complications of TPE in other studies
40Complications of plasmapheresis 4-25%Minimal reactions 5%Mod reactions 5-10%Severe reactions <3%Mortality rate 3-6 per proceduresThe majority of deaths is anaphylaxis associated with FFP, PTE , vascular perforation
42Indications for emergency plasmapheresis Anti-GBM disease and /or/pulmonary hemorrhage in Goodpasture syn.Hyperviscosity syn with signs and symptoms suggesting impending stroke or loss of visionTTP/HUSFactor 8 inhibitor in patients requiring surgeryRespiratory insufficiency in G-B synMG with respiratory distress not responding to medicationAcute poisoning
44ASFA category for TPEI for :TTP and atypical HUS due to autoantibody to factor HII for :CAPSIII for :hematopoietic stem celltransplant–associated thrombotic microangiopathy
45TTP pathophysiologic process : classic “pentad”pathophysiologic process :deficiency ofADAMTS-13 (aka, von Willebrand factor[VWF]–cleaving proteinase)VWF- and platelet-rich microthrombicongenital and acquiredADAMTS-13 inhibitors and proteolytic inactivatorsincluding :interleukin-6, plasma-free hemoglobin, IgG autoantibody, Shiga toxin,plasmin, thrombin, and granulocyte elastase
46TPE in TTPremove the large and ultra-large VWF - ADAMTS-13inhibitors and proteolytic inactivators, and replenish ADAMTS-13. the recommended TPE replacement fluid is plasma or plasma with cryoprecipitate removed (ie, the plasma portion that is depleted with ultra-large VWF and large plasma VWF).
47HUS:Typical &Atypical The “triad” of HUS is thrombocytopenia, microangiopathic hemolytic anemia, and .renalFailure In atypical HUS, in addition to the typical “triad” , .patients have neurologic abnormalities Currently, the ASFA does not recommend TPE (category IV) for typical HUS
48We recommend consulting nephrology and hematology to send the appropriate ADAMTS-13, VWF, and complement studies.In addition, TPE should be initiated until the results of biomarkers can differentiate the diagnoses.Because the underlying pathology is the deficiency of complement H activity, the recommended TPE replacement fluid is either plasma or albumin. We recommend plasma as the replacement fluid since it has normal factor H activity.Crit Care Clin 28 (2012) 453–468
49DICMany case series and observational studies suggest that TPE might have a beneficial effect in DIC. TPE is thought to normalize the blood coagulation to homeostasis milieu by removing tissue factor and plasminogen activator inhibitors type I and by replacing antithrombin III, protein C,and coagulation factors. Currently, the ASFA does not have a specific recommendation for TPE in DIC.
50sepsisthe ASFA gives a category III recommendation DIC has been shown to be one of the major contributing mechanisms to multiorgan failure in critically ill patients. Thus, there is a biologic plausibility that the beneficial treatment effect of TPE in sepsis with multiorgan failure could be from reversing DIC .
51Systemic Lupus Erythematosus The ASFA gives a category II recommendation for TPE :in severe SLE such as with cerebritis or diffuse alveolar hemorrhage. The ASFA does not recommend TPE (category IV) for SLE-associated nephritis. TPE is thought to remove autoantibodies, complement, interferon alpha, and immune complexes. The recommended TPE replacement fluid is either plasma or albumin.
52NEUROLOGIC DISORDERSThe ASFA gives a category I recommendation for TPE in acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome), chronic inflammatory demyelinatingpolyradiculoneuropathy, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and Sydenham’s chorea, multiple sclerosis, and myasthenia gravis
53Frequency of procedures Duration of therapy Anti- GBM disease :2 plasma volume daily for 7 consecutive daysTTP-HUS :1.5 plasma v. for first 3 treatments followed by 1 plasma v. until plt is normalized and LDH level below 400iu/lCryuoglobulinemia:1 plasma v. 3 times weekly for 2-3 weeksRPGN: 4 days for the first weekHyperviscosity syn: daily 1 plasma v for 2-5 days (HAND BOOK OF DIALYSIS 2007)
54FUTURE VIEWHemophagocytic Lymphohistiocytosis: Pathologic Hyperactive Inflammation(HLH) HLH is a syndrome of pathologic hyperactive inflammation due to unchecked immune .activation
55multiorgan failure with the following clinical criteria (1) fever (2) splenomegaly (3) cytopenia (4) Hypertriglyceridemia (5) hemophagocytosis in bone marrow spleen, lymph nodes, or liver (6) low or absent NK-cell activity (7) ferritin greater than 500 ng/mL, and (8) elevated serum CD 25
56Secondary HLH &familial/primary Epstein-Barr virus is the most commonly recognized .infection associated with secondary HLH TPE has been reported in many small case series to be beneficial in calming the cytokine storm and to provide hematologic support in patients with primary and secondary HLH. Currently, the ASFA has not commented on the use of TPE in HLH.