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Introduction to Transfusion Medicine

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1 Introduction to Transfusion Medicine
Yara Park, MD and Araba Afenyi-Annan, MD, MPH Department of Pathology and Laboratory Medicine

2 Scenario 1 45 year old man with no significant PMH presents to the ED with 2 day history of coffee ground emesis and dark stools He also reports dizziness on standing and DOE Vitals: T 37.1, P 113, BP 102/59, R 24 CBC: WBC 8.4, Hgb 7.3, Hct 22%, plts 243K Does he need blood?

3 pRBC Transfusion AVOID Transfusion based on Lab Values alone
Indications: PROVIDE O2 carrying capacity Symptomatic anemia Tachycardia >100 bpm Mental status changes ECG signs of cardiac ischemia Angina Shortness of breath, light headedness or dizziness with mild exertion AVOID Transfusion based on Lab Values alone

4 pRBC Transfusion ALWAYS exercise sound clinical judgment
Assess tolerance of low Hgb Acute anemia: rapid onset Chronic anemia: gradual onset, +/- physiologic adjustment Increased risk of ischemia - pulmonary disease, coronary artery disease, cerebral vascular disease, etc.

5 UNC Indications for pRBC transfusion
Hgb < 8 in asymptomatic patient Hgb < 11 in symptomatic patient Acute/anticipated blood loss > 15% TBV Chronic transfusion regimen Neonate with blood loss > 10% TBV Neonate with respiratory distress and Hct < 45%

6 pRBC Transfusion RBCs suspended in Volume= 250 to 300 mL Expiration
anticoagulant (citrate based) Additive Solution - AS Provides nutrients to support RBC metabolism Volume= 250 to 300 mL 65% RBCs, 35% plasma and AS contains WBC’s and some platelets Expiration 42 days = Shelf life stored at 1-6° C 4 hrs of release from Blood Bank, must use within 30 minutes

7 pRBC Transfusion Transfuse slowly
Indications: PROVIDE O2 carrying capacity Transfuse slowly within 4 hours release from Blood Bank 1 unit pRBC will increase the average adult recipient’s (70 kg) Hemoglobin by 1 g/dL Hematocrit by 3% 5 ml/kg will increase the pediatric patient’s Hemoglobin by 1 gm/dl, Hematocrit by 3%

8 pRBC Transfusion RBCs should be infused alone or with
0.9% NaCl through a 170µm clot-screen filter NEVER mixed with Calcium containing solutions May cause clumping or clots Dextrose Hypotonic,may cause hemolysis or clumping Medications Hypertonic solutions AVOID infusing with Lactated Ringers

9 Next Step – Scenario 1 What do we order next? Type Type and screen
Type and cross

10 Blood Type WHAT IS IT? Determination of the ABO and Rh (D) types
Performed at room temperature FRONT TYPE –what’s on the cells? Mix 2 drops of patient cells with 2 drops of reagent antibodies to A, B and D antigens in different test tubes Agglutination indicates presence of antigen BACK TYPE – what’s in the serum? Mix 2 drops patient serum with both A and B reagent cells Agglutination indicates presence of antibody Reciprocal relationship: front and back types must match

11 Blood Type FRONT TYPE –what’s on the cells?
Mix 2 drops of patient cells with 2 drops of reagent antibodies to A, B and D antigens in different test tubes, Agglutination indicates presence of antigen

12 Blood Type BACK TYPE – what’s in the serum?
Mix 2 drops patient serum with both A and B reagent cells. Agglutination indicates presence of antibody

13 ABO System A Anti B B Anti A O -- Anti A, anti B Anti A,B AB A and B
Blood Type Front Type Antigen on cells Back Type Antibody in serum A Anti B B Anti A O -- Anti A, anti B Anti A,B AB A and B

14 Antibody Screen Determines if pt has antibodies to other major blood groups Requires Combining pt serum with 3 different RBCs with known blood group phenotype Incubate at 37 C to detect IgG antibodies Addition of Coombs serum Anti-human IgG : enables in vitro agglutination if IgG present If screen is +, antibody specificity is determined by a more extensive panel of testing RBCs Includes an autocontrol Does not include a a DAT (Direct Coombs)

15 Screen Patient serum + 3 cells of known phenotype



18 Crossmatch Electronic Crossmatch Immediate Spin Crossmatch
For patients without antibodies If patient has an active screen, can get blood w/i minutes Immediate Spin Crossmatch Rapid, room temp mixing of patient serum with donor RBCs to confirm ABO compatibility Full Crossmatch For patients with antibodies Requires incubation and Coombs serum to confirm the patient’s IgG will not react with donor RBCs Takes ~45 minutes to complete

19 Sample Requirements Know hospital approved policy ! Patient ID
Accuracy is Critical #1 cause of fatalities is human error Primary ID: 2 unique identifiers Full name and MR number Must match exactly with requisition and Information system Special armband may be required Secondary Info Date, time of collection, initials of phlebotomist Unacceptable: unlabeled or hemolyzed

20 Sample Requirements Sample reflects current immune system status of patient > 1 sample per hospitalization may be required Sample may be used for up to 72 hours Exception: Pre-care sample which may be used for up to 14 days as long as patient has not been transfused or pregnant in the previous 3 months P

21 Scenario 1 (continued) Type: O negative Screen: Positive
Suddenly, patient has another episode of bloody emesis Patient is now difficult to arouse, pulse is 140 and he is hypotensive The blood bank says it will be at least one hour before XM blood available What are your options?

22 Emergency Release

23 Scenario 2 8 year old girl with Hgb SS disease who presents to clinic for routine follow-up Reports no new problems and is doing well in school Vitals: T 37.1, P 88, BP 110/78, R 18, O2 99%RA CBC: WBC 8.4, Hgb 7.3, Hct 22%, plts 243K Does she need blood?

24 Scenario 2 pRBCs are only indicated to provide oxygen carrying capacity The patient is stable and doing well Has high tolerance for anemia

25 Scenario 2 (continued) Three weeks later, the same patient presents to the ED with pain in her right leg and back. Is also SOB. Vitals: T 37.6, P 113, BP 102/59, R 24, O2 92%RA CBC: WBC 8.4, Hgb 5.3, Hct 16%, plts 443K Does she need blood?

26 Scenario 2 – Results Type: A positive
Screen: Positive and the patient has a history of multiple alloantibodies (anti-C, K, Jka, Fya, s) With this combination of antibodies, only 0.25% of available units will be compatible The Blood Bank has 2 units of compatible blood but both are frozen

27 Frozen Units pRBCs can be frozen using glycerol and stored up to 10 years Often only resource for patients with multiple allo- antibodies To use, must thaw and wash Washing Takes ~1.5 hours per unit Can only wash one unit at a time Decrease recovery of red cells After thawed and washed, unit expires in 24 hours and cannot be re-frozen

28 Scenario 3 65 year old woman with GIB
Transfused during CABG 5 years ago and has 2 children


30 Warm autoantibodies In routine testing, usually all cells react with patient’s serum May appear to have specificity but not necessary to determine specificity of the WAA for transfusion purposes Rule out underlying unexpected alloantibodies

31 Next Steps Direct Coombs (DAT)
Start with polyspecific If +, then perform the DAT split Find out transfusion and pregnancy history Additional testing Low Ionic Strength Solution (LISS) Eluations and Adsorptions Patient phenotype Selected cell screens

32 Conditional Release Card

33 Transfusing WAA patients-Risks
Difficult to exclude alloantibodies Transfusion may stimulate alloantibody production Transfusion may intensify the autoantibody Transfusion may suppress erythropoiesis Destruction of transfused cells may increase hemoglobinuria and hemoglobinemia

34 Transfusing WAA patients
For patients who are rapidly hemolyzing, transfusion is often required as a life-saving measure Can be challenging due to the complex laboratory work-up and the acute clinical needs Transfusion should not be held solely because of serologic incompatibility Transfuse the smallest amount possible to maintain an adequate oxygen level, not to reach an arbitrary number

35 Transfusing WAA patients
Usually well tolerated Transfused cells may not survive any longer than the patient’s own cells

36 Scenario 4 17 year old male with AML, s/p 2 rounds of chemotherapy presents for next treatment During therapy, platelet count falls to 18,000 and patient experiences hematuria What are the transfusion options?

37 Platelets Pooled platelet concentrates (PC’s) from several whole blood donations 6 pack, 4 pack, 10 pack Multiple donors = One therapeutic dose Platelets, apheresis one donor, one donation, one or more therapeutic doses Suspended in citrated plasma Stored at 20-24º C up to 5 days only Very susceptible to shortages!!!

38 Blood Collection/ Manufacturing
Whole Blood Donation Donor whole blood centrifuged Separated in after collection by centrifugation into pRBC Platelet rich plasma (platelet concentrate) Plasma (FFP)                               

39 Blood Collection/ Manufacturing

40 Blood Collection/ Manufacturing
Apheresis Automated centrifugal blood separator Donor whole blood separated on line to collect one or more components pRBC Platelet, apheresis = 6 platelet concentrates Plasma (FFP)

41 Apheresis Separators                                               Automated apheresis blood separators may be used for donation or therapeutic applications

42 Platelets PLT surface ABO antigens but not Rh Platelet specific Ags HLA- A and HLA-B Contain trace amounts RBC’s making Rh type important Rh- female gets Rh- PLT

43 Indications for PLT Transfusion
Thrombocytopenia: quantitative defects Prophylactic transfusion for PLT <10k For invasive procedure, trauma , bleeding with PLT count <50k Rapidly falling PLT count with bleeding Platelet dysfunction: qualitative defects Uremia Aspirin ingestion Post- Cardiopulmonary Bypass

44 Platelets One therapeutic dose of PLTs  platelet count 30-50k
Apheresis or 6 pooled platelet concentrates  platelet count 30-50k

45 Scenario 4 (continued) The patient undergoes his third round of chemo and requires multiple pRBC and platelet transfusions He now is in his fourth round of chemo and is again thrombocytopenic Monday 4 AM plts 9 K Transfused 1 apheresis plt Tuesday 3 AM plts 11K Transfused 1 apheresis plt Weds AM plts 10K Transfused 1 apheresis plt

46 Is he responding to plts?
ANSWER: Need to check 1 hour post counts Differentiate increased consumption from refractoriness Wednesday 4AM plts 10K Transfused 1 apheresis platelet at 6AM Post-count Wednesday 7:30AM plts 11K Appears to not be responding appropriately= Refractory

47 Platelet Refractoriness
Monitor efficacy of transfusion by measuring PLT count within 1 hour of transfusion Conserve precious resources Minimize transfusions and risks Assist in recognizing platelet alloimmunization vs. consumption Common causes of “refractoriness” Bleeding Fevers Hepatosplenomegaly Alloimmunization

48 Platelet Alloimmunization
Seen in patients who receive many transfusions Usually caused by HLA Class 1 antibodies Order HLA antibody screen (PRA) to test for antibodies and also order HLA type If PRA is positive, blood bank will order HLA-matched platelets Other option, platelet drip (also used for ITP patients with life/organ threatening bleeds)

49 Scenario 5 63 year old man presents to the ED with fevers and AMS
Wife reports flu-like symptoms for previous 48 hours, now confused and difficult to arouse PMH: Prostate CA, HTN Vitals: T 39.2, P 108, BP 76/45, R 22 PE: Altered man in moderate distress

50 Scenario 5 (continued) Labs: What is the best product for him?
WBC 23K, Hct 42%, plts 107K PTT 37.7s, INR 1.3, fibrinogen 68 D-Dimer 13,000 Blood cultures: gram negative rods What is the best product for him?

51 Fresh Frozen Plasma FFP Contents: 200-300 mL +
Frozen within 8 hrs of collection Stored -18º C for up to 1 year Once thawed, can be kept at 1-6º C for 24 hrs Contents: 1 unit/mL of all clotting factors including labile Factors V and VIII ~400 mg fibrinogen Citrate as anticoagulant

52 FFP Indications Treatment of multiple coagulation factor deficiencies
Massive transfusion Trauma Liver disease DIC Unidentified deficiency Warfarin reversal prior to emergent invasive procedures (5-8 ml/kg) PT/PTT > 1.5x normal DOSE: ml/kg to attain 30% Factor level

53 Cryoprecipitate Cold insoluble white precipitate that forms when FFP is thawed at 1-6º C Removed from FFP by centrifugation and refrozen at – 20º C Once thawed, kept at room temperature CONTAINS: 80 to 150 IU Factor VIII:C (antihemophilic factor) 150 mg fibrinogen Von Willebrand Factor Fibronectin Factor XIII

54 Cryoprecipitate Each unit =10-15 mL Pool 10 units = typical adult dose
Indications: Deficiency of fibrinogen, Factor VIII or XIII Improve platelet function in uremia Dose calculation based on Patient’s weight and hematocrit : plasma volume Desired increase in Factor level

55 Scenario 5 (continued) For this patient, cryoprecipitate is the appropriate product Can provide large doses of fibrinogen in a small volume

56 Component Modifications
Pooling Split Cryopreservation (freezing) Leukocyte Reduction Washing Irradiation

57 Leukocyte reduction Filtration with specialized leukocyte removing filters Pre-storage vs. Post-storage Indications: Prevent CMV transmission Prevent alloimmunization to leukocyte antigens in patients who will require chronic transfusion Prevent recurrent febrile non-hemolytic transfusion reactions May require special request depending on hospital policy At UNCH, all pre-storage leukocyte reduced RBCs/PLTs

58 Washing Removal of plasma by washing RBC or platelets with saline
Indicated : For prevention of severe allergic reactions Anaphylaxis IgA deficiency Time consuming, labor intensive, delays transfusion, decreases transfusion increment slightly, changes expiration date (24 hours) Does not substitute for leukocyte reduction

59 Irradiation Prevent graft versus host disease (GVHD)
Blood products from blood relatives and HLA matched products must be irradiated due to similar HLA antigens Indicated in severe immunodeficiency settings (lymphopenia) BMT Hematopoietic malignancies undergoing chemotherapy Premature infants and IUT Severe combined immunodeficiency Disadvantages Changes product expiration date (28 days from irradiation) Increased potassium

60 Scenario 6 6 year old boy with AML and neutropenic fevers is given a unit of pRBCs for Hgb of 7.6 g/dL and SOB 30 minutes into the transfusion, the patient complains of chills and back pain What is the next step?

61 STOP THE TRANSFUION Do Not Restart the Unit

62 Scenario 6 (continued) The differential includes:
Hemolytic transfusion reaction Febrile non-hemolytic transfusion reaction Bacterial contamination/sepsis Underlying disease

63 Suspected Reaction Hemolytic reaction symptoms are not specific and include: Fever Chills Hypotension Oozing from IV site Back pain Hemoglobinuia If any of these occur STOP transfusion, provide appropriate supportive care, notify blood bank Send repeat samples for blood bank evaluation DO NOT restart the unit

64 Blood Bank Work-Up Serum color check DAT (Direct Coombs) Culture
Determines if antibody is coating red cells Culture Retype patient

65 Adverse Effects of Transfusion
Acute Transfusion Reactions < 24 hours Immune Allergic Hemolytic Febrile, non-hemolytic Anaphylactic Transfusion related acute lung injury (TRALI)

66 Adverse Effects of Transfusion
Delayed Transfusion Reactions > 24 hours Immune Hemolytic GVHD Platelet refractoriness Post transfusion Purpura Development of anti-platelet antibodies

67 Adverse Effects of Transfusion
Transfusion Reactions Non-Immune Acute Circulatory Overload (Volume excess) Septic shock from bacterial contamination of blood product Delayed Iron Overload Infectious Disease transmission

68 Transfusion Transmitted Disease Risks
Infectious Agent or Outcome Estimated Risk per Unit Transfused Estimated % of Infected Units that transmit or cause clinical sequelae Virus HIV-1 and -2 1:1,400,000-1:2,400,000 90 HTLV-1 and –II 1:256,000-1:2,000,000 30 HAV 1:1,000,000 HBV 1:58,000-1:147,000 70 HCV 1:872,000-1:1,700,000 WNV ? B19 parvovirus 1:3,300-1:40,000 Low

69 Scenario 7 45 year old man with colon cancer, currently undergoing chemotherapy Presents to clinic with epistaxis and platelet count of 15,000 Given one unit of platelets

70 Scenario 7 (continued) Five minutes into the transfusion, the patient develops SOB O2 saturation drops from 99% to 82% on room air What is in the differential

71 Differential Diagnoses
Transfusion Related Acute Lung Injury (TRALI) Allergic/anaphylaxis Transfusion Associated Circulatory Overload (TACO)

72 Scenario 8 22 year old woman with menorrhagia who presents to clinic with SOB and dizziness Reports prolonged heavy bleeding Vitals: T 37.1, P 115, BP 85/60, R 20 PE: Pale, fatigued appearing woman; flow murmur

73 Scenario 8 You decide she needs pRBCs
How do you consent her for blood/blood products?

74 Basic Principles of Informed Consent
Consent is a process Requires comprehension by patient Voluntary & free from coercion Not legally binding May be revoked at any time Prospective

75 Elements of Informed Consent
Information to the patient Explanation of intervention Benefits Risks Alternatives Opportunity for questions/clarification Availability of choices (including refusal) Autonomous patient decision Documentation of process

76 Products Requiring Informed Consent
Consent Required Consent Variable Blood Components-whole blood or apheresis derived Plasma derived proteins HPCs- any source Recombinant Proteins Minimally processed tissues; femoral heads, corneas, heart valves, reproductive tissues Highly Processed Tissue: Bone plugs

77 Procedures Requiring Informed Consent
Consent Required Consent Variable Donor-Patient HPC collection, Preoperative Autologous donation Acute normovolemic hemodilution Therapeutic Phlebotomy Intraoperative blood recovery & reinfusion Therapeutic apheresis Postoperative blood recovery & reinfusion

78 Physician Responsibility
Formulate a course of action based on clinical expertise, judgment, and best available information Give the patient enough information about the plan to make an independent decision about whether or not to accept recommendation.

79 Information to Patient
Statement of patient’s medical condition Explanation of intervention Benefits Relief of symptoms, prevention of complications Likelihood of achieving goal Risks Alternatives Prognosis with or without intervention

80 Patient Discussion Points
Need for transfusion Benefits Treatment such as increase O2 carrying capacity Prevention such as preoperatively for potential coagulation factor or platelet loss Statement of the likelihood of success Risks Clinician to determine

81 Standards for Risk Disclosure
No national standard Professional organizations State laws Case Law Reasonable Patient Standard Simple Subjective Standard Reasonable Physician Reasonable Patient Standard; CA, NJ NY and WA physicians explain all medically reasonable courses of treatment and non-treatment option in a manner that a reasonable patient in the same or similar circumstances would require to make an informed choice. Does not apply to situations where unforeseeable condition arises. No duty to disclose every single detail of the proposed treatment or operation. Simple Subjective Standard: HA, LA, TX physicians to disclose “enough information for the paitent or guardian to make an informed decision, may have established disclosure panels for a given treatment/procedure.” Reasonable Physician: physician disclose information that other reasonable physicians in good standing within their community would give to their patients about the particular therapy or procedure; “professional custom and practice standard”; many have abandoned as too simplistic.

82 Risks of Transfusion: What to disclose?
Infectious disease risks-see table Noninfectious disease risks Most common include allergic, FNHTR Rare but potentially fatal Acute HTR, Bacterial contamination, TRALI Patient specific Coexisting morbidities, previous reactions How problems would be handled, potential long term impacts

83 Alternatives to Transfusion
Preoperative autologous donation Erythropoietin Intraoperative conservation techniques Acute normovolemic hemodilution Blood salvage and reinfusion Blood substitutes are not an option!

84 Right of Refusal Consequences of refusal Must complete separate form
Refusal to the Use of Blood or Blood Products

85 Scenario 9 35 year old woman with no PMH presents to the ED with fatigue, fever and petechiae Lab work reveals Hct 22%, platelet count 8K, LD 3100 On peripheral smear, many schistocytes Of note: BP normal, HIV negative, pregnancy test negative

86 Thrombotic Thrombocytopenic Purpura

87 Definition of TTP First described in 1924 by Moschowitz in a 16 year old female Classic pentad of symptoms Hemolytic anemia Thrombocytopenia Fever Renal failure Altered mental status

88 Diagnostic Criteria Many causes of microangiopathic hemolytic anemia (MAHA) For diagnosis of TTP Minimum criteria MAHA Thrombocytopenia Other causes excluded Only 34% of patients present with all features of pentad

89 Peripheral Smear

90 Autopsy Findings Picture courtesy of Dr. Mark Brecher

91 Classification of TTP Primary or idiopathic TTP Secondary TTP
Transplant Chemotherapy HIV Drugs Connective tissue disorders Hormonal (pregnancy)

92 Normal Processing Activity
ULvWF Stimulation: histamine, Shiga Toxin, tumor necrosis factor-alpha, IL-8, and IL-6 P-selectin Weibel-Palade Body

93 Normal Processing Activity
ADAMTS13 attaches A3 domains in the monomeric subunits of ULvWF multimers and then cleave Tyr Met peptide bonds in adjacent A2 domains Fluid shear stress may increase the efficiency of ADAMTS13 attachment and/or cleavage of ULvWF multimers

94 TTP Pathophysiology

95 TTP Pathophysiology

96 TTP Emergent plasma exchange (TPE) 1 PV daily
1.3 to 1.5 PV may be used in refractory patients or those severely affected Plasma is replacement of choice Platelet count >150 K (x 2-3 days) LDH “normal” Watch out for anemia (may need RBCs) FFP infusions if TPE delayed

97 Apheresis A Greek word that means to separate or remove

98 Apheresis Terms Therapeutic Procedures Cytoreductive Apheresis
Plasma Exchange, TPE, or Therapeutic Plasmapheresis Red Cell Exchange or Erythrocytapheresis Photopheresis Immunoadsorption

99 Methods of Separation Filtration Centrifugation Plasma removal only
WBC removal Platelet removal Red cell removal Plasma removal

100 Centrifugation Methods
Continous Flow Two access lines Faster Smaller extracorporeal volume

101 Centrifugation Methods
Discontinous Flow Single need acces Volume fluctuations

102 ASFA Treatment Categories
Category I Therapeutic hemapheresis is standard and acceptable therapy Category II Generally acceptable, considered to be more supportive to other treatment

103 Treatment Categories Category III Category IV
Evidence is insufficient to establish the efficacy Category IV Controlled trials have shown lack of efficacy

104 Emergent Indications TTP Hyperviscosity syndrome
Pulmonary Renal Syndrome Goodpasture’s, ANCA with DAH Sickle Cell Crises (Hgb SS, SC, S-Thal) ACS, Stroke/TIA, hepatic sequestration Cytoreduction for leukemia, essential thrombocytosis

105 Hypervisocity Syndrome

106 Hyperviscosity Syndrome
Whole blood viscosity related to Hct, RBC aggregation, plasma proteins, and interactions with the vasculature When viscosity increases, fragile endothelium can be damaged

107 Hypervisocity Syndrome
Waldenstroms Macroglobulinemia, IgM Myeloma Viscosity poor correlation with clinical symptoms Concurrent anemia may confound diagnosis Elevated total protein, total Ig, UPEP, SPEP Hydration trail, chemotherapy Certainty of diagnosis : risk vs benefit

108 IgG 300 KDa IgM 900KDa Torlonib 2000

109 IgM Intravascular Space Extravascular Space
outward forces IgM Inwards Forces colloid-osmotic pressure Intravascular Space Extravascular Space Torloni MD 2000 13

110 Role of TPE Category I Remove excess Ig to rapidly normalize viscosity

111 Practical Considerations
One plasma volume exchange Calculated PV will not equal actual PV Usually 1-2 TPEs will relieve symptoms Replacement fluid 5% albumin (with addition of crystalloid)

112 Be aware of BP fluctations!
Free water pulled into vessel Free water pulled out of vessel Inwards Forces Outwards Forces Outwards Forces Inwards Forces

113 Pulmonary-Renal Syndromes

114 Pulmonary renal syndrome
Goodpasture’s Syndrome (Category I) Wegener’s/ANCA (Category II) Daily with plasma (1 PV) until pulmonary hemorrhage subsides then every other day for a total of 6 – 9 procedures) 5% albumin once risk of bleeding subsides Anemia may require RBC transfusion

115 Goodpasture’s Syndrome
Results from the presence of an IgG anti-glomerular/ alveolar basement membrane antibodies (detected by radioimmunoassay in over 90% of cases). It represents a Type II immune reaction (cytotoxic antibody mediated). Males are affected more than females (9:1)

116 Goodpasture’s Syndrome
The majority of patients present in their mid-twenties with hemoptysis (75%- due to diffuse pulmonary hemorrhage), hematuria (due to glomerulonephritis), anemia, hepatosplenomegaly, and hypertension. Pulmonary symptoms will generally proceed the renal disease by weeks to months, many patients also have laboratory evidence of renal disease at the time of presentation (microscopic hematuria).


118 Anti–GBM/ Goodpasture’s Syndrome
Lung/kidney damage mediated by anti-GBM Two Goals: Two concurrent strategies Removal of anti-GBM TPE Suppress its synthesis Self-limited: 6-12 months Cyclophosphamide + steroids (pulse) Azathioprine

119 Anti–GBM/ Goodpasture’s Syndrome
PLAN for TPE: Recommendations vary 4 TPE exchanges (of at least 1 plasma volume) 1st week Then alternate days (qoD) Total of 6 –9 treatments over 2- 3 weeks Following titer pre and post exchange Immunosuppresive drugs should be continued longer Follow serum IgG as a surrogate: <200 mg/dL Consider risk of Ig removal and increased risk of infection

120 Wegener’s Granulomatosis, ANCA, etc.
Necrotizing granulomatous vasculitis, C-ANCA positive

121 ANCA, Wegener’s, other RPGN
Patients presenting with RPGN Anti-neutrophil cytoplasmic autoantibodies MPO or PR3 specificity +/-pulmonary hemorrhage Diffuse Alveolar Hemorrhage =DAH

122 ANCA/Wegener’s/RPGN With DAH Emergent TPE useful DAH can be fatal
Daily TPE with FFP replacement to prevent dilutional coagulopathy Once DAH subsides, complete TPE series qoD Generally 7 TPE procedures over 2 weeks

123 Sickle Cell Disease

124 Sickle Cell Disease Most commonly Hb SS
Sickled RBC have shortened life-spans, leading to hemolytic anemia and microvascular occlusions Patients can have vaso-occlusive events Pain crises Acute chest syndrome (ACS) Stroke Priapism Splenic, hepatic, and renal dysfunction

125 Indications for Erythrocytapheresis
Category I for life and organ threatening complications EMERGENT Stroke: CVA or prophylactic chronic RBC ex Acute Chest Syndrome with progressive respiratory insufficiency URGENT Priapism : as adjunct when primary therapy fails Pre-operative to minimize risk of SSD complications during anesthesia

126 Cerebrovascular Disease
Incidence of Stroke: 6-10% 11% of patients will have a CVA by age 20 50% will have a second stroke within 3 years without intervention 75% due to vascular occlusion 25% from hemorrhage

127 Stroke Risk Factors Transcranial Doppler
Measurement of Average Velocity Normal 130cm/sec Increase risk of Stroke > 200cm/sec High velocity may cause narrow vessel to collapse or clot to form.

128 Benefits of Exchange Rapid increase in Hemoglobin A Euvolemia
Simple Transfusion = Hyperviscosity Reduction in Fe Load Drop in platelet count Suppression of hematopoeisis

129 Practical Considerations
Determine goal : 70% Hgb A, Acute chest 70-90% Hgb A, stroke Final Hct Blood Units set up time consuming C, E, K negative, sickle trait negative Get type & screen and Hb/Thal panel sent stat Check on patient RBC phenotype/prior blood bank records here and afar

130 Therapeutic Apheresis in Leukemia/ Thrombocytosis

131 Cytoreduction Acute leukemias: leukostasis Usually high blast %
WBC when symptoms generally begin Myeloid >100,000 Lymphoid >400,000 Monocytoid > 50,000 Sxs: pulmonary and CNS Category I

132 Cytoreduction May be profoundly anemia due to marrow inflitration
RBC transfusion may be required Anemia can lead to similar CNS sxs as hyperleukocytosis May need to decrease WBC to safely transfuse

133 Cytoreduction Generally one time procedure
May need to repeat if patient becomes symptomatic again or chemotx delayed Central line usually required Hetastarch used to increase WBC removal efficiency

134 Thrombocytosis Seen with essential thrombocythemia and polycythemia vera At risk for thromboembolic events (plt count >^600K) Can have bleeding (plt count >1.5 million) Plateletpheresis is rarely used; must be used in conjunction with plt-lowering agents Category II

135 Resources Blood Bank Staff: 966-4011
TMS Attending/Fellow/Resident on call 24/7 McLendon Lab Website Always welcome to do a rotation on TMS!

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