Transcript Blood replacement therapy Methods and Complications

Hemostasis and Transfusion
Medicine
Scott Mollison
PGY2 Orthopedic Surgery
September 13, 2013
Outline
• Physiology of hemostasis
• Disorders of bleeding
– Congenital and acquired
• Blood Products
– Overview
– Indications
– Administration
– Complications
Local Hemostasis
• Significant surgical bleeding is usually caused
by ineffective local hemostasis
Mechanical Pressure
– Finger
– Extremity tourniquet
– Hemostatic clamp (Pringle maneuver) – usually
more damaging to the vessel than digital pressure
– Simple ligature for small vessels
– Transfixion suture and ligature for large arteries
with pulsation
– Bone wax
Heat
• Harmonic scalpel
• Vibration at 55kHz
• Denatures collagen
• Thyroidectomy, hemorrhoidectomy etc.
• Thermal Agents
• Heat denatures protein
• Electrocautery – A/C
• Direct current and argon gas to control diffuse bleeding
Hemostasis
FACTOR 2a
FACTOR 2
FACTOR 2!!
• THROMBIN
Coagulation Cascade
VWF
Platelets
EXTRINSIC – TF/7/9/10
Platelets
• NO NUCLEUS
• Fragments of MEGAkaryocytes
• 30% of platelets may be sequestered in spleen
• Spleen removes after 7-10 days
Hemostatic Plug
• STEP 1: Subendothelial collagen and vWF are exposed in the
injured intimal wall
Step 2
• GP I/IX/V on platelet membranes adhere to
collagen and vWF
Step 3 Degranulation
3. Platelets Release…
– ADP + serotonin – chemoattract platelets
– Fibrinogen bridges GP IIB/IIIa receptor on activated
platelets
– Thrombospondin strengthen fibrinogen-platelet bonds
– Ca2+
Cyclooxegynase
Screening Tests
Prothrombin Time
Prothrombin Time
– PT – play tennis outdoors – extrinsic cascade
– Factor V, VII, X, thrombin
– Warfarin therapy depletes vitamin K
dependent proteins (prothrombin, VII, IX, X,
protein C and S)
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Activated Partial Thromboplastin
Time
– aPTT – play table tennis indoors – intrinsic
cascade
– Factor XII, XI, IX, VIII
– Heparin causes prolongation by depleting the
intrinsic pathway factors
Hemophilias
• X-linked recessive
• A :: factor VIII
• B :: factor IX
– Mild disease between
5-30%
– Moderate bleeding
between 2-5%
– Severe bleeding with
factor levels <2%
Treatment
Factor VIII or IX concentrates
DDAVP for Hemophilia A (8)
Induces release of vWF from endothelial cells
raising the levels of VIII
Factor 8 stabilized by vWF
Von Willebrands Disease
• AD inheritance
• Most common
• 1% population
• Symptoms similar to hemophilia
• Treatment: Factor VIII // vWF replacement //
DDAVP
What vitamin?
Acquired Hemorrhagic Disorders
• Vitamin K deficiency
• Anticoagulant drugs
– Warfarin (Vitamin K)
– Heparin (protamine sulfate)
• Hepatic Failure – coagulation factors except VIII
• Renal Failure – platelet dysfunction
• Hypothermia
Disseminated Intravascular
Coagulation
– Systemic thrombo + hemorrhagic
– Coagulant activation = consumption of
coagulation factors and platelets
– Thrombin and plasmin circulate
– ↑ PT ↑ aPTT
– ↑ d-dimer
– ↓ fibrinogen, ↓ platelets
– Tx – underlying conditions, antithrombin
concentrates, blood products
Blood Groups
• Alloimmunization – production of antibodies
directed against the blood group antigens of
another individual
– From transfusion or pregnancy
– IgG antibodies -> hemolysis
– Directed against
• WBCs
• Platelets
• Plasma proteins
Structure
• Carbohydrate
• Gene on xsome 9p
Rheusus
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Antigen has no function?
D antigen = Rh+
Chromosome 1
15% Rh –
Exposre (transfusion or pregnancy) = anti-D
alloantibody
BLOOD PRODUCTS
Packed Red Blood Cells
– Clinically used most
– Centrifuged to remove plasma
• Less reactions
– Decreased amount of Na,K,lactic acid, citrate
– Stored at 4 degrees C for 42 days
• Provide oxygen carrying capacity
Indications
– Acute blood loss
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Estimated/anticipated ongoing losses >15%
DBP < 60
SBP drop > 30
Tachycardia
Oliguria/anuria
Mental status changes
Base deficit
Lactic acidosis
Mixed venous sat. and oxygen delivery
Special Considerations
• Hg <100 in pts with ↑ risk for coronary artery
disease or pulmonary insufficiency
• Symptomatic anemia
Indications
– ? Hgb 70
– To maintain Hgb >100 in patients at risk
for/hx CAD or pulmonary insufficiency for
those patients where losses are anticipated
or have happened
– TRICC trial: <70 in ICU patients
– Risk of organ failure: <110
Classes of Blood Loss
Administration Considerations
– Type
• Same ABO and Rh group
– Crossmatch: recipient serum with donor RBC
– Transfuse within 35 days
• concers re: cell lysis => hyperkalemia, citrate chelating
calcium
– Infuse 2-4 hrs / unit
– < 4hrs due to bacterial growth
– Consider lasix
– One unit PRBCs increased Hct 4%
Leukocyte-Reduced and LeukocyteReduced-Washed RBC
– 99.9% of WBC and most platelets removed
– Prevents almost all
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febrile, nonhemolytic transfusion reactions
alloimmunization to HLA class I antigens
platelet transfusion refractoriness
CMV transmission
– Most evidence supporting is poor quality
Platelets
– Can be random donor, single donor or HLA
matched
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Random donor/pooled comes in 5 unit doses = 1 adult
dose
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Increase platelet count by 10-15 x 10^9/L
Single donor platelets for BMT recipients
HLA matched can be used for
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Alloimmunized (previous transfusion)
Refractory patients (sensitization)
Indications
• <50,000 with microvascular bleeding or
planned surgical procedure
• <10,000 for prophylaxis
• Complicated procedures which required > 10
units PRBCs and have bleeding (surgical
hemostasis)
• Platelet dysfunction with petechiae, purpura,
bleeding or surgical procedure
– Relative contraindications:
• TTP, HIT, HUS, PTP (post-transfusion purpura)
Platelets
– Stored at 20-24 degrees C
– Permeable storage bag: O2, CO2
– Shelf life 5 days
• Bacterial contamination risk 10x that of RBC
Granulocyte Concentrate
• Profound granulocytopenia (<500)
– With evidence of infection unresponsive to
antibiotic therapy
• Daily transfusion until infection controlled or
granulocyte count >1000
• Prepared from donors premedicated with
GCSF and corticosteroids
• Shelf life 24 hours
Fresh Frozen Plasma (FFP)
– Contains ALL factors and plasma proteins
• Fibrinogen, albumin, antithrombin and protein C+S
• Only source of Factor V
– Frozen within 8 hrs of collection
– Stored frozen ~ 1 year
– Multiple donors
Indications
– Depletions of multiple factors / acquired
• DIC
• Sepsis
• TTP/HUS
• Warfarin
• Vitamin K deficiency
• Liver disease
• Massive transfusion
• Specific factor unavailable
• Congenital deficiencies of antithrombin III, prothrombin, factors V,
VII, IX, XI, protein C or S
• Prophylaxis for deficiencies if surgical procedure is planned
Administration Considerations
– Infection transmission risk
• Acellular = no intracellular infections (CMV)
– 1 unit increases coagulation/clotting factors ~8%
– Up to 20% citrate
– Use within 4 hrs
– Not volume expander
Monitoring
• PT and aPTT
Cryoprecipitate
– Fibrinogen (Factor 1)
– Fibronectin
– vWF + F 8
– Factor 9
– Prepared from 1 unit of FFP
• thawed and re-frozen with 10-15cc plasma
• Stored frozen = 1 year
Indications
– Bleeding
– With fibrinogen or factor XIII deficiency
• Congenital (rare), severe liver disease, DIC, massive
transfusion
Administration
– Given as “10 single units”
– Goal: maintain fibrinogen >1g/L
– May contain anti-A or anti-B antibodies
• Risk of rxn similar to FFP
Factor VIII / IX concentrate
– Hemophilia A/B
– For treatment and prophylaxis
• Enhanced viral clearance during purification
Activated Factor VII
– Congenital factor VII deficiency
– Hemophilia when refractory/sensitized to F8/9
– Safety concern: thrombosis
• 5% risk MI
Whole Blood
• O2 carrying capacity + volume expansion
• Sustained acute hemorrhage of ≥25% of total
blood volume loss
• Stored at 4◦C
• Not readily available /used
Autologous Transfusion
Substantial losses are anticipated
Removes transfusion reaction and disease transmission
EPO + FE supplementation blood can be donated 1/ week
– Up to 4 days prior to surgery
Expensive
Decreased Hgb prior to surgery
More likely to need a transfusion
Fibrin Sealant
– Tisseel, Crosseal
– Made from cryoprecipitate
Thrombin (F2) Products
– Floseal,Thrombostat, Thrombin-JMI
– No foreign body or inflammatory reactions
– Risk of DIC if product is introduced intravascularly
Topical Hemostatic Agents
– Gelfoam, Surgifoam
– Forms hydrated meshwork to promote clotting
– Can swell, and may cause granulomatous reaction
– Degrades over 4-6 weeks
Complications
Acute vs Delayed
• <24hrs VS >24 hrs
Transfusion Reactions
Immunologic reactions
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Febrile nonhemolytic transfusion reactions
Acute hemolytic transfusion reactions
Delayed hemolytic transfusion reactions
Anaphylactic transfusion reactions
Urticarial/Febrile transfusion reactions
Post transfusion purpura
TRALI
Non-Immunologic issues
Febrile Non-Hemolytic
• Most common
– WBC’s (HLA) + Host immune response
• Cytokines and TNF from storage
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Fever
+/- Chills
+/- Dyspnea (within 6 hrs)
Rise in temperature ≥1◦C
Treatment
– May continue transfusion unless patient
demonstrates signs of anaphylaxis
(hypotension) or other associated
symptoms
– Consider hemolysis or contamination
– Anti-pyretics and antihistamine
Acute Intravascular Hemolytic Rxn
• ABO incompatibility: Most common cause
of morbidity after RBC transfusion
Signs / Symptoms
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Fever
Chills,
Flank pain
Hemoglobinuria
DIC
ARF
Airway edema
Hypotension, shocklife-threatening
Labs show hemolysis (pink serum)
Coombs test (+)
Treatment
– STOP transfusion, re-check blood
– ABC’s!!
– Immune complexes cause renal dysfunction
• IV fluids and diuresis (mannitol, lasix, +/- low dose dopamine
– Monitor PT, aPTT, fibrinogen and platelet count
– Monitor renal function/avoid renal failure
– Tissue Factor released from lysed RBCs may
initiate DIC
– Labs for hemolysis – serum haptoglobulin, LDH,
and indirect bilirubin
– Majority = mislabeling / wrong patient
Delayed Transfusion Reaction
(Extravascular)
• Rh or Kidd Ab, … Kell, Dufy (Subclinical antibody)
• Antibody coated RBCs cleared by the reticuloendothelial
system
• day 2 to 10
• Malaise, jaundice, fever
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No specific therapy
Additional RBC transfusions may be necessary
Identify antibody if possible
Coomb’s
Avoid future transfusion with offending cause
Anaphylactic Transfusion reaction
• Severe reaction after transfusion of only a few mLs
– Cause
• usually IgA mediated in IgA deficient patients
– Clinical
• seconds to minutes from reaction
• SOB, coughing, N+V, hypotension, bronchospasm, LOC,
respiratory arrest and shock
– Prevalence
• 1 in 20,000
– Treatment
• STOP transfusion, maintain IV access
• ABC’s, epi, pressors, ranitidine, benadryl
• Wash RBCs/IgA free units in future
Post Transfusion Purpura
– Thrombocytopenia due to platelet alloantibodies
– 7-10 days post transfusion
– Usually women
– Treatment
• Plasmaphoresis OR IV IG
• Avoid additional platelet transfusions
Urticarial / Allergic
• Related to plasma proteins found in
transfused components
• Benign
• Antihistamines, steroids
• Transfusion may be completed after the signs
and symptoms resolve
• History of allergic reactions? premedicate antihistamines
TRALI (Transfusion Related Acute
Lung Injury)
– Uncommon
– Cause
• anti WBC / anti HLA antibodies bind recipient leukocytes
• WBCs aggregate in pulmonary vasculature and cause
capillary permeability
/ damage
– Onset
• occurs within 6 hours of transfusion
– Symptoms/Signs
• pulmonary edema, dyspnea, hypoxemia, fever, hypotension
– Treatment
• Supportive, like ARDS, however resolves within 2 days
Other transfusion complications
• Circulatory overload
• Air embolism
• Coagulopathy
– Dilutional thrombocytopenia
• Citrate toxicity
• Thrombophlebitis
• Hypothermia
– Arrhythmia <32 degrees C
• Electrolyte toxicity
– Increased K if transfused greater than 100ml/min
• Acid/Base Imbalance
– citrate/lactate conversion to bicarb in liver after transfusion
• Decreased 2,3 DPG
• Hypotensive reactions - ACEi
Infectious
– Bacterial contamination (Gram negatives)
• Platelets 1 / 10,000 sepsis per dose
– HIV (1 / 5,000,000)
– Hepatitis C (1 / 3,000,000)
• Asymptomatic, chronic active hepatitis
– Hepatitis B (1 / 80,000)
• CMV, syphilis, others (Chagas’ dz, malaria,
brucellosis, yersinia )
Massive Transfusion
• Replacement of the patient’s blood volume
with packed RBCs in 24 hours or transfusion of
>10 units in a few hours
• Complications
– Acid-base change
– Hyperkalemia
– Hypocalcemia
– Dilutional thrombocytopenia
– Hypothermia
ANTIOCOAGULANTS
• Heparin activates ______
– UFH
• Requires monitoring via aPTT or anti-fXa activity
• Risk of HIT
– LMWH
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Tinzaparin, enoxaparin
more reliable therapeutic anticoagulation – inhibits fXa
Lower HIT risk
No monitoring unless patient has renal insufficiency or severe obesity
– Determine drug effect with an assay for anti-Xa activity
Fondaparinux
– Synthetic polysaccharide
– Inhibits fXa
– Injection
– Fixed dose, no monitoring
Direct thrombin (2a) inhibitors
– Argatroban, lepirudin, bivalirudin, dabigatran
• Injection
– Rivaroxaban
• PO
– Can be used in anticoagulation after HIT
– No need for monitoring
• If necessary, can test via ecarin clotting time
Warfarin
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Vitamin K antagonist
For long-term anticoagulation
Cytochrome p-450 system
Drugs that decrease the effect of warfarin
• Barbiturates, oral contraceptives, estrogen-containing compounds,
corticosteroids, adrenocorticotropic hormone
– Drugs that increase the effect of warfarin
• Phenylbutazone, clofibrate, anabolic steroids, L-thyroxine,
glucagons, amiodarone, quinidine, cephalosporins
Questions
• 14) Ideal time to donate autologous blood
before surgery
• a) less than 7 days
• b) 7-14 days
• c) 21-34 days
• d) 6-8 weeks
Which factor is decreased the most in stored
blood?
a) 3
b) 5
c) 10
which of the following bacteria can cause a
bacteremic infection from a blood transfusion?
a. pseudomonas
b. yersinia enterocolita
c. campylobacter
d. proteus mirabilus
e. staphylococcus epidermis
All of the following are true about autologous
blood donate except?
a) decreased viral transmission risk
b) decreased risk of getting a transfusion
c) it costs more than a regular transfusion
d) no proven benefit has been shown for using
autologous transfusions
21. Which of the following is the most infectious
agent for a blood transfusion?
Hepatitis A
Hepatitis B
Hepatitis C
HIV
CMV
57. What is the commonest cause of cardiac
arrest post blood transfusion?
a.
b.
c.
d.
Hypothermia
Circulatory overload
Hemolytic transfusion reaction
Anaphylaxis
Blood transfusion given in OR. Patient’s serum
subsequently turns pink and they become
hypotensive and tachycardic. Treatment
A.Give more blood
B.Administer fluids and mannitol
C. Cry
D. No biggie, probably traumatic foley
References
• Old talks
• Hoffman: Hematology Basic Principles and
Practice
• Schwartz: Principles of Surgery
• Canadian Blood Services
– http://www.transfusionmedicine.ca/resources/cli
nical-guide-transfusion