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Plasmapheresis DR KAMRAN FAZEL.MD.FCCM DR KAMRAN FAZEL.MD.FCCM.

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Presentation on theme: "Plasmapheresis DR KAMRAN FAZEL.MD.FCCM DR KAMRAN FAZEL.MD.FCCM."— Presentation transcript:

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2 Plasmapheresis DR KAMRAN FAZEL.MD.FCCM DR KAMRAN FAZEL.MD.FCCM

3 Since 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 Since 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

4 Bloodletting, the practice of draining blood from sick patients,has been around since the Egyptians, dating back 1000 years BC. The practice of bloodletting peaked in the 18 th century and evolves with modern technology to this day. Bloodletting, the practice of draining blood from sick patients,has been around since the Egyptians, dating back 1000 years BC. The practice of bloodletting peaked in the 18 th century and evolves with modern technology to this day.

5 Apheresis is a procedure that is used in the treatment of patients with a variety of illnesses. The term apheresis comes from the Greek origin meaning “removal of”. All apheresis procedures involve removing components from the blood. Efficient apheresis procedures have been developed over the last 15 years. Apheresis is a procedure that is used in the treatment of patients with a variety of illnesses. The term apheresis comes from the Greek origin meaning “removal of”. All apheresis procedures involve removing components from the blood. Efficient apheresis procedures have been developed over the last 15 years.

6 Blood 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 and replaced with the same blood component from healthy donors. Blood 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 and replaced with the same blood component from healthy donors.

7 History of modern plasmapheresis 1909 Fleig / France – Auto & heterotransfusion of washed corpuscles 1914 Abel / U.S. – Use the term of Plasmapheresis in his paper – Prolonged the life of dog with bilateral nephrectomy by plasmapheresis 1959 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 Angeles Invention of cell separator machine 1909 Fleig / France – Auto & heterotransfusion of washed corpuscles 1914 Abel / U.S. – Use the term of Plasmapheresis in his paper – Prolonged the life of dog with bilateral nephrectomy by plasmapheresis 1959 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 Angeles Invention of cell separator machine

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9 Apheresis in Clinical Practice RBCPlasmaWBCPLT Sickle Cell Dis. Malaria Leukemias Cell Therapies Thrombocytosis TTP Guillain Barre Syn. Myasthenia Gravis Goodpasture’s Syn. Waldenstrom’s

10 Plasmapheresis 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 Plasmapheresis 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

11 To apply this treatment to patients appropriately it is essential to understand: 1 -the methods to remove plasma 2 - its effects on normal plasma constituents 3 -the role of replacement fluids in the treatment 4 -and the risks associated with the procedure. it is essential to understand: 1 -the methods to remove plasma 2 - its effects on normal plasma constituents 3 -the role of replacement fluids in the treatment 4 -and the risks associated with the procedure.

12 Mechanism of action of plasma exchange Removes pathologic substances such as pathologic Abs, immune complexes,and cytokines is the major mechanism of action of TPE TPE 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 Th2 suppression of IL-2 and IFN- γ production

13 Mechanism of actionDisorders Removal of autoantibodyMyasthenia gravis Removal of alloantibodyRh alloimmunization in preg. Removal of immune complexSystemic lupus erythemotosus Removal of monoclonal protein Hyperviscosity syndrome Removal of toxinMushroom poisoning Replacement of specific plasma factor Thrombotic thrombocytopenic purpura Possible mechanisms of TPE

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15 TECHNIQUES OF SEPARATING PLASMA FROM WHOLE BLOOD Plasmapheresis is performed by 2 fundamentally different techniques: Devices separating based on density: centrifugation or Devices separating based on size: filtration

16 centrifugation 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 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

17 centrifugation apheresis Advantages: 1-Capable of performing cytapheresis 2-No heparin requirement 3-More efficient removal of all plasma components Advantages: 1-Capable of performing cytapheresis 2-No heparin requirement 3-More efficient removal of all plasma components Disadvantages: 1-Expensive 2-Requires citrate anticoagulation 3-loss of platelets 4-usually requires a consultation to another service such as a blood banker Disadvantages: 1-Expensive 2-Requires citrate anticoagulation 3-loss of platelets 4-usually requires a consultation to another service such as a blood banker

18 Centrifugal Separation

19 Filtration 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 and intensivist 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 and intensivist

20 Membrane apheresis Advantages: 1-fast and efficient 2-No citrate requirements Advantages: 1-fast and efficient 2-No citrate requirements Disadvantages: 1-Removal of substances limited by sieving coefficient of membrane 2-Unable to perform cytapheresis 3-Requires high blood flows, central venous access, heparin 4-Limiting use in bleeding disorders

21 Membrane Separation

22 Dialysis & Transplantation 2009 February: 1-4

23 2010, 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.”

24 Diseases and disorders treated with plasma exchange. ASFA categoryI Acute inflammatory demyelinating polyradiculopathy (Guillain-Barré Syndrome) ANCA-associated rapidly progressive glomerulonephritis/vasculitis (Wegener granulomatosis) Dialysis independent Alveolar hemorrhage Antiglomerular basement membrane disease (Goodpasture syndrome) Dialysis independent Alveolar hemorrhage

25 Diseases and disorders treated with plasma exchange. ASFA categoryI Chronic inflammatory demyelinating polyradiculopathy Cryoglobulinemia Focal segmental glomerulosclerosis (recurrent) Hemolytic uremic syndrome Autoantibody to factor H Hyperviscosity in monoclonal gamopathies Symptomatic Prophylactic for rituximab treatment

26 Diseases and disorders treated with plasma exchange. ASFA categoryI Paraproteinemic polyneuropathies IgG/IgA IgM Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) Renal transplantation, Ab-mediated rejection Thrombotic thrombocytopenic purpura

27 TPE & removal of plasma Significant declines in factor V (FV), FVII, FVIII, FIX, FX, and VWF activity occurs. Activities of FVIII, FIX, and VWF return to normal within 4 hours after TPE whereas 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

28 Additional substances removed include: inhibitors of coagulation such as antithrombin and the pseudocholinesterase necessary for metabolism of some drugs Theoretically, the removal of inhibitors of coagulation could predispose patients to thrombosis, but this has not been demonstrated definitively Reports of prolonged neuromuscular blockade due to decreased pseudocholinesterase activity have been reported

29 The 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

30 American Society of Hematology 2012 Medications reportedly removed by TPE Basiliximab Ceftriaxone Ceftazidime Chloramphenicol Cisplatin Diltiazem α IFN- IVIG Palivizumab Propoxyphene Propranolol Rituximab Tobramycin Verapamil Vincristine

31 American Society of Hematology 2012 For each plasma volume exchanged, approximately 60%-70% of substances present in the plasma at the start of that.plasma volume will be removed routine practice is to exchange only plasma volumes during a TPE. For each plasma volume exchanged, approximately 60%-70% of substances present in the plasma at the start of that.plasma volume will be removed routine practice is to exchange only plasma volumes during a TPE.

32 American Society of Hematology 2012 Treating volumes beyond 1.5 plasma volumes removes smaller, less clinically important amounts of pathologic substance present in the plasma while prolonging the procedure and exposing the patient to more replacement fluid and anticoagulant,increasing : risk 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 the plasma while prolonging the procedure and exposing the patient to more replacement fluid and anticoagulant,increasing : risk of complications without increasing benefit to the patient.

33 one-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.

34 Exchange Fluids 5% Albumin – Best choice – Dilute only with saline Combination of saline and albumin FFP Cryopoor plasma 5% Albumin – Best choice – Dilute only with saline Combination of saline and albumin FFP Cryopoor plasma

35 Albumin Advantages: 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 mediators Advantages: 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 mediators Disadvantages: 1-Expensive 2-No coagulation factors 3-No immunoglobulins Disadvantages: 1-Expensive 2-No coagulation factors 3-No immunoglobulins

36 70% albumin and 30% saline. majority of the albumin being given at the end of the procedure to avoid hypovolemia from redistribution of the crystalloid 70% albumin and 30% saline. majority of the albumin being given at the end of the procedure to avoid hypovolemia from redistribution of the crystalloid

37 FFP Advantages: 1-Coagulation factors 2-Immunoglobulins Advantages: 1-Coagulation factors 2-Immunoglobulins Disadvantages: 1-Risk of hepatitis, HIV, transmission 2-Allergic reaction 3-Hemolytic reaction 4-Must be ABO compatible 5- citrate load Disadvantages: 1-Risk of hepatitis, HIV, transmission 2-Allergic reaction 3-Hemolytic reaction 4-Must be ABO compatible 5- citrate load

38 vascular access ? central venous access Or peripheral vascular access central venous access Or peripheral vascular access

39 Studies 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

40 Complications of plasmapheresis 4-25% Minimal reactions 5% Mod reactions 5-10% Severe reactions <3% Mortality rate 3-6 per procedures The majority of deaths is anaphylaxis associated with FFP, PTE, vascular perforation 4-25% Minimal reactions 5% Mod reactions 5-10% Severe reactions <3% Mortality rate 3-6 per procedures The majority of deaths is anaphylaxis associated with FFP, PTE, vascular perforation

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42 Indications 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 vision TTP/HUS Factor 8 inhibitor in patients requiring surgery Respiratory insufficiency in G-B syn MG with respiratory distress not responding to medication Acute poisoning Anti-GBM disease and /or/pulmonary hemorrhage in Goodpasture syn. Hyperviscosity syn with signs and symptoms suggesting impending stroke or loss of vision TTP/HUS Factor 8 inhibitor in patients requiring surgery Respiratory insufficiency in G-B syn MG with respiratory distress not responding to medication Acute poisoning

43 THROMBOTIC MICROANGIOPATHIES Thrombotic thrombocytopenic purpura (TTP) hemolytic uremic syndrome (HUS) disseminated intravascular coagulation (DIC) catastrophic antiphospholipid syndrome (CAPS)

44 ASFA category for TPE I for : TTP and atypical HUS due to autoantibody to factor H II for : CAPS III for : hematopoietic stem cell transplant–associated thrombotic microangiopathy

45 TTP classic “pentad” pathophysiologic process : deficiency ofADAMTS-13 (aka, von Willebrand factor[VWF]–cleaving proteinase) VWF- and platelet-rich microthrombi congenital and acquired ADAMTS-13 inhibitors and proteolytic inactivators including :interleukin-6, plasma-free hemoglobin, IgG autoantibody, Shiga toxin,plasmin, thrombin, and granulocyte elastase

46 TPE in TTP remove 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).

47 HUS: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

48 Crit Care Clin 28 (2012) 453–468 We 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.

49 DIC Many 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.

50 sepsis the 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.

51 Systemic 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.

52 NEUROLOGIC DISORDERS The 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

53 Frequency of procedures Duration of therapy Anti- GBM disease :2 plasma volume daily for 7 consecutive days TTP-HUS :1.5 plasma v. for first 3 treatments followed by 1 plasma v. until plt is normalized and LDH level below 400iu/l Cryuoglobulinemia:1 plasma v. 3 times weekly for 2-3 weeks RPGN: 4 days for the first week Hyperviscosity syn: daily 1 plasma v for 2-5 days ( HAND BOOK OF DIALYSIS 2007) Anti- GBM disease :2 plasma volume daily for 7 consecutive days TTP-HUS :1.5 plasma v. for first 3 treatments followed by 1 plasma v. until plt is normalized and LDH level below 400iu/l Cryuoglobulinemia:1 plasma v. 3 times weekly for 2-3 weeks RPGN: 4 days for the first week Hyperviscosity syn: daily 1 plasma v for 2-5 days ( HAND BOOK OF DIALYSIS 2007)

54 FUTURE VIEW Hemophagocytic Lymphohistiocytosis: Pathologic Hyperactive Inflammation(HLH ) HLH is a syndrome of pathologic hyperactive inflammation due to unchecked immune.activation Hemophagocytic Lymphohistiocytosis: Pathologic Hyperactive Inflammation(HLH ) HLH is a syndrome of pathologic hyperactive inflammation due to unchecked immune.activation

55 multiorgan 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

56 Secondary 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.

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