Presentation on theme: "Introduction to Transfusion Medicine Yara Park, MD and Araba Afenyi-Annan, MD, MPH Department of Pathology and Laboratory Medicine."— Presentation transcript:
Introduction to Transfusion Medicine Yara Park, MD and Araba Afenyi-Annan, MD, MPH Department of Pathology and Laboratory Medicine
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?
pRBC Transfusion Indications: PROVIDE O 2 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
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%
pRBC Transfusion RBCs suspended in anticoagulant (citrate based) Additive Solution - AS Provides nutrients to support RBC metabolism Volume= 250 to 300 mL 65% RBCs, 35% plasma and AS contains WBCs 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
pRBC Transfusion Indications: PROVIDE O 2 carrying capacity Transfuse slowly within 4 hours release from Blood Bank 1 unit pRBC will increase the average adult recipients (70 kg) Hemoglobin by 1 g/dL Hematocrit by 3% 5 ml/kg will increase the pediatric patients Hemoglobin by 1 gm/dl, Hematocrit by 3%
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
Next Step – Scenario 1 What do we order next? Type Type and screen Type and cross
Blood Type WHAT IS IT? Determination of the ABO and Rh (D) types Performed at room temperature FRONT TYPE –whats 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 – whats 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
Blood Type FRONT TYPE –whats 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
Blood Type BACK TYPE – whats in the serum? Mix 2 drops patient serum with both A and B reagent cells. Agglutination indicates presence of antibody
ABO System Blood Type Front Type Antigen on cells Back Type Antibody in serum AAAnti B BBAnti A O--Anti A, anti B Anti A,B ABA and B--
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)
Screen Patient serum + 3 cells of known phenotype
Crossmatch Electronic 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 If patient has an active screen, can get blood w/i minutes Full Crossmatch For patients with antibodies Requires incubation and Coombs serum to confirm the patients IgG will not react with donor RBCs Takes ~45 minutes to complete
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
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
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?
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, O 2 99%RA CBC: WBC 8.4, Hgb 7.3, Hct 22%, plts 243K Does she need blood?
Scenario 2 pRBCs are only indicated to provide oxygen carrying capacity The patient is stable and doing well Has high tolerance for anemia
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, O 2 92%RA CBC: WBC 8.4, Hgb 5.3, Hct 16%, plts 443K Does she need blood?
Scenario 2 – Results Type: A positive Screen: Positive and the patient has a history of multiple alloantibodies (anti-C, K, Jk a, Fy a, 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
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
Scenario 3 65 year old woman with GIB Transfused during CABG 5 years ago and has 2 children
Warm autoantibodies In routine testing, usually all cells react with patients serum May appear to have specificity but not necessary to determine specificity of the WAA for transfusion purposes Rule out underlying unexpected alloantibodies
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
Conditional Release Card
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
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
Transfusing WAA patients Usually well tolerated Transfused cells may not survive any longer than the patients own cells
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?
Platelets Pooled platelet concentrates (PCs) 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!!!
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)
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)
Apheresis Separators Automated apheresis blood separators may be used for donation or therapeutic applications
Platelets PLT surface ABO antigens but not Rh Platelet specific Ags HLA- A and HLA-B Contain trace amounts RBCs making Rh type important Rh- female gets Rh- PLT
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
Platelets One therapeutic dose of PLTs Apheresis or 6 pooled platelet concentrates platelet count 30-50k
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 KTransfused 1 apheresis plt Tuesday 3 AMplts 11KTransfused 1 apheresis plt Weds. 4 AMplts 10KTransfused 1 apheresis plt
Is he responding to plts? ANSWER: Need to check 1 hour post counts Differentiate increased consumption from refractoriness Wednesday 4AMplts 10K Transfused 1 apheresis platelet at 6AM Post-count Wednesday 7:30AMplts 11K Appears to not be responding appropriately= Refractory
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
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)
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
Scenario 5 (continued) Labs: 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?
Fresh Frozen Plasma FFP 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
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
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
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 Patients weight and hematocrit : plasma volume Desired increase in Factor level
Scenario 5 (continued) For this patient, cryoprecipitate is the appropriate product Can provide large doses of fibrinogen in a small volume
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
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
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
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?
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
Blood Bank Work-Up Serum color check DAT (Direct Coombs) Determines if antibody is coating red cells Culture Retype patient
Adverse Effects of Transfusion Delayed Transfusion Reactions > 24 hours Immune Hemolytic GVHD Platelet refractoriness Post transfusion Purpura Development of anti-platelet antibodies
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
Transfusion Transmitted Disease Risks Infectious Agent or OutcomeEstimated Risk per Unit Transfused Estimated % of Infected Units that transmit or cause clinical sequelae Virus HIV-1 and -21:1,400,000-1:2,400,00090 HTLV-1 and –II1:256,000-1:2,000,00030 HAV1:1,000,00090 HBV1:58,000-1:147,00070 HCV1:872,000-1:1,700,00090 WNV?? B19 parvovirus1:3,300-1:40,000Low
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
Scenario 7 (continued) Five minutes into the transfusion, the patient develops SOB O 2 saturation drops from 99% to 82% on room air What is in the differential
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
Scenario 8 You decide she needs pRBCs How do you consent her for blood/blood products?
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
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
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.
Information to Patient Statement of patients medical condition Explanation of intervention Benefits Relief of symptoms, prevention of complications Likelihood of achieving goal Risks Alternatives Prognosis with or without intervention
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
Standards for Risk Disclosure No national standard Professional organizations State laws Case Law Reasonable Patient Standard Simple Subjective Standard Reasonable Physician
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
Alternatives to Transfusion Preoperative autologous donation Erythropoietin Intraoperative conservation techniques Acute normovolemic hemodilution Blood salvage and reinfusion Blood substitutes are not an option!
Right of Refusal Consequences of refusal Must complete separate form Refusal to the Use of Blood or Blood Products
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
Thrombotic Thrombocytopenic Purpura
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
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
Autopsy Findings Picture courtesy of Dr. Mark Brecher
Classification of TTP Primary or idiopathic TTP Secondary TTP Transplant Chemotherapy HIV Drugs Connective tissue disorders Hormonal (pregnancy)
Normal Processing Activity P-selectin ULvWF Weibel-Palade Body
Normal Processing Activity
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
Apheresis A Greek word that means to separate or remove
Apheresis Terms Therapeutic Procedures Cytoreductive Apheresis Plasma Exchange, TPE, or Therapeutic Plasmapheresis Red Cell Exchange or Erythrocytapheresis Photopheresis Immunoadsorption
Methods of Separation Filtration Plasma removal only Centrifugation WBC removal Platelet removal Red cell removal Plasma removal
Centrifugation Methods Discontinous Flow Single need acces Volume fluctuations
ASFA Treatment Categories Category I Therapeutic hemapheresis is standard and acceptable therapy Category II Generally acceptable, considered to be more supportive to other treatment
Treatment Categories Category III Evidence is insufficient to establish the efficacy Category IV Controlled trials have shown lack of efficacy
Emergent Indications TTP Hyperviscosity syndrome Pulmonary Renal Syndrome Goodpastures, ANCA with DAH Sickle Cell Crises (Hgb SS, SC, S-Thal) ACS, Stroke/TIA, hepatic sequestration Cytoreduction for leukemia, essential thrombocytosis
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
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
IgG 300 KDa IgM 900KDa Torlonib 2000
colloid-osmotic pressure IgM Inwards Forces outward forces Extravascular Space Intravascular Space Torloni MD
Role of TPE Category I Remove excess Ig to rapidly normalize viscosity
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)
Inwards Forces Outwards Forces Outwards Forces Inwards Forces Free water pulled into vesselFree water pulled out of vessel Be aware of BP fluctations!
Pulmonary renal syndrome Goodpastures Syndrome (Category I) Wegeners/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
Goodpastures 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)
Goodpastures 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).
Anti–GBM/ Goodpastures 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
Anti–GBM/ Goodpastures Syndrome PLAN for TPE: Recommendations vary 4 TPE exchanges (of at least 1 plasma volume) 1 st 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
Wegeners Granulomatosis, ANCA, etc. Necrotizing granulomatous vasculitis, C-ANCA positive
ANCA, Wegeners, other RPGN Patients presenting with RPGN Anti-neutrophil cytoplasmic autoantibodies MPO or PR3 specificity +/-pulmonary hemorrhage Diffuse Alveolar Hemorrhage =DAH
ANCA/Wegeners/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
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
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
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
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.
Benefits of Exchange Rapid increase in Hemoglobin A Euvolemia Simple Transfusion = Hyperviscosity Reduction in Fe Load Drop in platelet count Suppression of hematopoeisis
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
Therapeutic Apheresis in Leukemia/ Thrombocytosis
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
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
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
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
Resources Blood Bank Staff: TMS Attending/Fellow/Resident on call 24/7 McLendon Lab Website Always welcome to do a rotation on TMS!