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Anemia – Overview
Approach to the anemic patient Definition Manifestations, symptoms, and signs Causes Acute management Peripheral smears
Transfusions Indications and when to transfuse What to transfuse Ordering and documentation Transfusion reactions
Definition
What values define anemia? Values more than 2 standard deviations below the mean Hgb < 13.5 g/dL or Hct < 41% in men Hgb < 12.0 g/dL or Hct < 36% in women
Don’t forget…Hgb is a concentration! May be modified by its content May be modified by its dilutent (plasma) Assess the patient’s volume status!
Hemoconcentrated – dehydration Hemodiluted – after receiving significant IVF Falsely appearing normal – acute hemorrhage
Assess the patient History, Physical, Laboratory evaluation Stable vs. Unstable
Acute anemia due to hemorrhage Signs/Symptoms of intravascular volume depletion
•Pallor•Diaphoresis•Tachypnea•Cold, clammy extremities
•Hypotension•Tachycardia•Shock
Anemia that develops slowly May be recent, subacute, or lifelong Not usually accompanied by signs of intravascular
volume depletion, and symptoms subtle
Common Symptoms and Signs
Symptoms Fatigue Dyspnea Palpitations Worsening angina
symptoms or claudication GI disturbances –
anorexia, nausea, bowel irregularity
Abnormal menstrual patterns
Signs Pallor Tachypnea Tachycardia Wide pulse pressure Hyperdynamic precordium Jaundice or splenomegaly
Physical Exam
Sign HgbLoss of palmar creases 7 g/dL
Sublingual pallor of mucous membranes 8 g/dL
Conjuctival pallor 9 g/dL
Other Clues Glossitis – iron, folate, B12 deficiency Jaundice or Scleral icterus – hemolysis Splenomegaly – severe thalassemia, chronic hemolytic anemia,
leukemia/lymphoma, myeloproliferative syndrome Neurologic Abnormalities - paresthesias/ataxia B12 deficiency
Blood Loss
Obvious bleeding Trauma Melena Hematemesis Menometorrhagia
Occult bleeding Slowly bleeding ulcer or
carcinoma
Induced bleeding Repeated lab testing Hemodialysis losses
Post-surgical bleeding Retroperitoneal space Upper thigh
Most common cause of anemia
Blood Loss
Iron DeficiencyWith loss of RBCs, loss of iron will eventually
lead to iron deficiency anemia Iron Stores Depleted
1200 mL of blood loss – Males 600 mL of blood loss – Females
25% of menstruating females have no iron stores Any amount of blood loss could result in anemia
Decreased RBC Production
Rate of production < rate of destructionReticulocyte count < 2%Three morphologies
Microcytic (MCV < 80) Normocytic (MCV 80 – 99) Macrocytic (MCV ≥ 100)
Decreased RBC Production: Microcytic
Iron deficiency Anemia of chronic disease Copper deficiency Lead poisoning Congenital or acquired sideroblastic anemia
Decreased RBC Production: Normocytic
Early B12 or folate deficiency Dietary loss
Pernicious anemia, sprue, iron deficiency Anemia of chronic disease
Infection (ie. TB), Inflammation, Malignancy Bone marrow suppression
Aplastic anemia, acquired red cell aplasia, irradiation Chronic Renal Insufficiency Endocrine
hypothyroidism, hypopituitarism Meds
sulfa drugs, penicillins, anti-epileptics
Decreased RBC Production: Macrocytic
B12 or folate deficiency Myelodysplastic syndrome Aplastic Anemia or Pure Red Cell Aplasia MEDS: Hydroxyurea, zidovudine, ARA-C,
methotrexate, azathioprine, 6-MP Hypothyroidism EtOH abuse Multiple Myeloma or other plasma cell disorders Liver disease / Cirrhosis
Increased RBC Destruction
Hemolysis RBC life span < 100 days Occurs when bone marrow cannot keep up with
replacement of 5% RBC mass per day RBC survival ~ 20 days Reticulocyte count > 3% Elevated indirect bilirubin Elevated LDH Decreased haptoglobin
Increased RBC Destruction
Inherited Hereditary spherocytosis Sickle cell disease Thalassemia major
Antibodies Viruses Drugs AI connective tissue
diseases cancer
(leukemia/lymphoma) AIHA
Acquired Coombs’ positive AIHA TTP/HUS DIC MAHA PNH Malaria Prosthetic heart valves Trauma Hypersplenism Liver disease
Management
Admitting patients overnight? What happens when you’re on call? The middle of the night phone call…
Think of differential diagnoses on your way Address for most serious life-threatening possibility first
Bedside assessment of patient Rapid visual assessment of patient’s condition Vitals Selective H&P, chart review Management Document
Why would they call you for anemia?
“Doctor, this patient is bleeding from…” “Doctor, this patient’s H/H came back and
it’s 6 and 18…”
What do you do?
Management: Hypovolemic patients Notify resident Two large-bore IVs (16 gauge) Type and crossmatch for packed RBCs
May take up to an hour
IV fluids (crystalloid) Normal Saline or Lactated Ringers
Wide open if in shock 500 mL to 1000 mL NS bolus if mild/moderate volume
depletion Serial exams are important! for volume status and cardiac exam Be careful not to put patient in pulmonary edema
Management: Hypovolemic patients Determine site of hemorrhage
Look for obvious signs of bleeding IV sites, skin lesions, hematemesis, menstruation
Occult blood loss? Rectal exam for melena Flank swelling, flank or periumbilical ecchymosis post-op Pelvic exam in reproductive age women Ruptured aneurysm?
Review chart – PMH, meds, recent labs Surgical consult when appropriate
Management: Normovolemic patients Exclude active hemorrhage
If Hgb <10 g/dL, consider repeat measurement to exclude lab error
Even if Hgb 10-12 g/dL and normal vitals patients may become unstable quickly if bleeding
What is the patient’s baseline? Check graphic in Easy-CHCS If Hgb is more than 0.1-0.2 g/dL less than baseline,
assume underlying cause has worsened or secondary factor
Has chronic anemia been evaluated in the past?
Management: Normovolemic patients
Patient is comfortable, normal cardiovascular exam, no suspicion of bleeding…
Baseline studies for further evaluationMCV (microcytic, normocytic, macrocytic)RDW - representation of anisocytosisReticulocyte countPeripheral smear
Laboratory Evaluation
Reticulocyte countHigh (>3-5)
Increased erythropoietic response to continued hemolysis or blood loss
Low (<2) Deficient production of RBCs (reduced marrow
response) Concurrent disorder that impairs production (infxn,
prior chemotherapy)
Peripheral Smear
Normal peripheral smearNormal RBC diameter ~ 8-9 microns
About the size of a nucleus of a small lymphocyte Central pallor ~ 1/3 the RBC diameter
Peripheral Smear Polychromatic macrocytes
Young reticulocytes with RNA and ribosomes
• Slightly larger than other RBCs by 1-2m
• Grayish-blue in color
• Lacks normal biconcave shape
Represent shift out of marrow into circulation Can be used to estimate adequacy of erythropoietin
response to anemia
He who would cross the Bridge of Death
Must answer me
These questions three
Ere the other side he see….
Peripheral Smear Microcytic anemia – Two examples
• Microcytic/Hypochromic
• Pronounced aniso- and poikilocytosis
• Presence of cigar-shaped RBCs
• Absence of target cells
• Microcytic/Hypochromic
• Prominent target cells
• Marked deficit of Hgb – flattened appearance
?
Peripheral Smear
Macrocytosis Larger than normal RBCs Often oval shaped and well
hemoglobinized
Hypersegmented neutrophils Larger than normal neutrophils Five or more nuclear lobes
Two commonly seen types of anemia ?
Peripheral Smear
Myelofibrosis - When would you see this
Tear drop cells Nucleated RBCs Leukoerythroblastic
smear Seen with immature
WBCs
?
Peripheral Smear Hemolytic anemia Inerent defects
Membrane structure, Hgb stability, metabolic fxn Environmental
trauma, infection, autoimmune
• Microspherocytes• Bite Cells• Fragmented RBCs• Abnormal inclusion bodies
Can you name 2 types of inclusion bodies ?
Peripheral Smear Membrane defects
• Uniform elliptical shape
• Normal cell indices
• Caused by deformation through capillary beds
• Cytoskeletal abnormality that prevents recovery of normal shape • Small, dense RBCs
• Lack central pallor of normal RBCs
• Lack of cell water Higher MCHC
• Hereditary spherocytosis
• Autoimmune hemolitic anemia
Blood Transfusions
Decision making in a bleeding patient…Rapid, acute hemorrhageEBL > 30 – 40%, symptomaticEBL < 25 – 30%, no uncontrolled hemorrhage
When do patients need PRBCs?Hgb < 7 g/dL ?Hgb < 10 g/dL ?
Blood Transfusions
Rapid, acute hemorrhage
EBL > 30 – 40%, symptomatic
EBL < 25 – 30%, no uncontrolled hemorrhage
Transfuse PRBC May require uncrossmatched
or type-specific blood
Transfuse PRBC May require uncrossmatched
or type-specific blood
Crystalloid/Colloid resuscitation Proceed to PRBC for recurrent
signs of hypovolemia
Blood Transfusions What is your transfusion threshold? How about some help from EBM?
Hebert, et al. (NEJM 1999) looked at critically ill euvolemic patients 418 transfused for Hgb < 7 g/dL, 420 transfused for Hgb < 10 g/dL 30-day mortality was similar These results suggest transfusing at Hgb < 7 g/dL is at least as effective as, and
possibly superior to, transfusing at Hgb < 10 g/dL in critically ill patients Possible exception for patients with AMI and UA
Hebert, et al. (Crit Care Med 2001) did a multi-center trial in critically ill pts with CV disease
357 pts were randomly assigned to be transfused for Hgb < 7 or < 10 g/dL There was no differences in overall mortality for the entire group There was a higher mortality in the subgroup of 257 patients with severe ischemic
heart disease who were transfused for Hgb < 7 g/dL (not statistically significant) Rao, et al. (JAMA 2004) – retrospective study of transfusion in pts ≥ 65 with AMI
30-day mortality reduced when pts received transfusions for Hct ≤ 30 percent Possible effectiveness in pts with a Hct ≤ 33 percent
Blood Transfusions
What about transfusing… Platelets
< 50,000 if acutely bleeding < 20,000 if not bleeding and febrile < 10,000 if not bleeding and afebrile
Cryoprecipitate If patient is in DIC and fibrinogen < 100 Some say 175 if acutely bleeding
FFP Emergency reversal of warfarin therapy in bleeding patient Factor replacement in DIC
Blood Transfusions
What to transfuse and expected increase PRBC’s:
1 unit raises Hct by 3 – 4% and Hgb by about 1 gm/dl unless there is continued bleeding
Platelets: 1 “six pack” should raise the platelet count by 25,000/mcL
FFP: Prepared from a single unit of whole blood, contains all coagulation
factors and proteins in 1 unit of blood Cryoprecipitate:
Concentrated preparation of FFP containing only Factors VIII (100 units), XIII, fibrinogen (200 mg) and vWF – final volume is 10-15 mL
Ten bags of cryo (2g fibrinogen) will raise fibrinogen level about 70 mg/dL
Blood Transfusions
Compatability testing Fully crossmatched RBCs (T&C)
Patients requiring elective transfusion of RBCs Type, antibody screen, major crossmatch of each unit
Indirect antiglobulin test for minor blood group antibodies Tests donor cells against patient serum for ABO compatibility
May take several hours
Type and Screen (T&S) Surgical procedures when blood is occasionally needed ABO and Rh type Serum tested for RBC antibodies
If none, typed blood set aside, but not crossmatched If patient requires transfusion, crossmatched RBC can be made
available quickly If emergency, type-specific blood transfused, crossmatch after
Blood Transfusions
Compatability testing Emergency crossmatch
Urgently needed blood Type and crossmatch of RBCs in 15-30 min once pt’s blood is
received If pt has already been transfused, they usually have a sample
already
Uncrossmatched/type-specific RBCs If pt cannot wait 15-30 min for crossmatched or type-specific blood
or if pt’s blood type is unknown Type O-(Rh)negative
Once O-negative is exhausted, O-positive may be substituted with little risk
Conversion to type-specific, crossmatched blood should occur as soon as possible
Risk of inducing antibody only important in women of childbearing age
Blood Transfusions
Leukoreduced RBCs HLA alloimmunization against class I antigens does not occur Leukoreduced RBCs do not transmit CMV Indicated for chronically transfused patients, potential transplant
recipients, patients with previous febrile nonhemolytic reactions and CMV negative patients at risk
Irradiated RBCs Eliminates immunologically competent lymphocytes Prevents the occurrence of GVHD in patients who have
hereditary immune deficiency states Washed RBCs
Should be considered in patients in whom plasma proteins may cause a serious reaction
IgA deficiency, anaphylaxis with previous transfusions
X
XX
ANEMIA
The Black Knight20/123-45-6789
Document, document, document!
You must write a note regarding the indication of transfusion or at least comment on it in your daily progress note
Transfusion Reactions Acute Hemolytic Transfusion Reaction Due to ABO incompatibility Incidence 1:250,000-1:1,000,000 with mortality
17-60% Sx include: fever, chills, vomiting, flank pain,
dyspnea, hypotension, tachycardia Pink plasma and red urine due to intravascular
hemolysis May lead to DIC, shock, and acute renal failure
due to ATN
Transfusion ReactionsDelayed Hemolytic Transfusion Reaction Caused by anamnestic antibody response to specific transfused
RBC antigens previously encountered by transfusion, transplantation, or pregnancy
Clinical presentation Usually asymptomatic Hct slight fever unconjugated bilirubin spherocytosis on peripheral smear
Hemolysis is usually extravascular, gradual, and less severe than with acute reactions
Rapid hemolysis can occur Incidence 1:1000
Transfusion Reactions Febrile nonhemolytic transfusion reaction
Most common transfusion reaction Occur within 1 – 6 hrs after transfusion RBCs or
platelets Fever, with or without chills or dyspnea Sx may mimic AHTR or infection – don’t ignore Incidence: 1% of PRBC transfusions and 30%
of platelet transfusions
Transfusion Reactions Transfusion-related Acute Lung Injury TRALI is a pulmonary agglutinin reaction
Pathogenesis – 2 stimuli needed primes neutrophils and activates endothelial cells, leading to increased
expression of adhesion molecules Ex. recent surgery, cytokine administration, massive blood transfusion, or active
infection activates neutrophils causing release of toxic mediators, endothelial
damage, and increased capillary permeability lipid-soluble species that is formed during the storage of banked blood
Causes acute respiratory distress, hypoxemia, hypotension, fever, and pulmonary edema, initially without signs of left ventricular failure
Occurs within 2 – 4 hrs of beginning the transfusion Incidence 1:2000 More favorable prognosis than ARDS
Mortality in ≤ 10% of cases of TRALI Recovery is generally complete within 96 hrs of onset
Transfusion ReactionsAnaphylaxis and Allergy
Allergic reactions Common – typically see urticarial rash Only transfusion rxn in which the blood product can be continued
Anaphylaxis Abrupt onset of hypotension, respiratory distress, angioedema,
nausea, abdominal cramping, diarrhea Incidence 1:20,000 – 50,000
Transfusion-associated GVHD Immunocompromised patients Sx include rash, elevated LFTs, and pancytopenia Mortality of 80% Prevent by irradiation of blood
Transfusion Reactions Septic Reactions
Secondary to asymptomatic donor bacteremia or skin “plugs”
Confined to blood products stored at room temp (platelets)
Incidence 1:12,000 platelet transfusions, 25% fatal Incidence 1:500,000 PRBC transfusions, 71 % fatal Most commonly implicated in bacterial contamination of
red cells is Yersinia enterocolitica
Management
Important things to find out on the phone What symptoms does the patient have?
Fever, chills, dyspnea, back pain, diaphoresis What are the vital signs? Which blood product is being transfused? How long ago did the transfusion start? Why was the patient admitted to the hospital?
Orders Stop the transfusion for the following symptoms
Sudden hypotension, chest pain, back pain, tachypnea Any symptom starting within minutes of the start of the transfusion Fever in a pt who has never been transfused or never been pregnant
If the transfusion has been stopped keep IV open with NS
Management
Always consider the major threats to life first Acute hemolytic reaction Anaphylaxis
Quick look at the patient Comfortable, distressed, or critical?
Assess airway and vital signs Check that the patient’s wristband and
identification tag on the blood match
Management
Selective Physical Exam HEENT
Flushed face Facial Edema
Lungs Wheezes
Neuro Decreased consciousness
Skin Heat along vein being used Oozing from IV sites
Urine color Red/Brown
Selective History Any new symptoms since the
initial phone call? Fever/chills HA, CP, back pain,
diaphoresis Shortness of breath
Has the patient had previous transfusion reactions?
Chills and fever are common
ManagementAnaphylaxis Stop transfusion Epinephrine
1:10,000 – profound anaphylactic shock 0.2 mL/min IV up to total dose of 3 mL in 15 min May repeat q15 min
1:1000 – less severe situations 0.5 mL IM, may repeat q5 min
Hydrocortisone 500mg slow IV or IM, then 100mg IV or IM q6 hrs
Albuterol nebs Benadryl 50-75 mg slow IV or IM Intubation if necessary
ManagementAcute Hemolytic Reaction Stop transfusion Replace IV tubing NS 500mL bolus, goal UOP > 100mL/hr Lasix 40mg IV (4 mg/min) or Mannitol 25g IV over 5 min
Labs• Repeat crossmatch• Coombs’ test• Free Hgb• CBC, RBC morphology• Coags, FDP• Urea, Creatinine• Unclotted blood for stat spin demonstrates hemolysis when plasma remains pink
Urine dipstick• Hemoglobinuria
Labs on donor blood• Repeat crossmatch• Coombs’ test
ManagementUrticaria Do not stop the transfusion
Hives alone are rarely serious Hives with hypotension is anaphylactic rxn until
proven otherwise
Benadryl 50mg PO or IV Premedicate prior to future transfusions If that fails to prevent urticarial rxns, transfuse
with washed RBCs
ManagementFever Do not stop the transfusion unless hemolytic rxn
is suspected Ex. Fever developing within minutes of start
Tylenol 650mg PO if needed Premedicate with tylenol prior to subsequent
transfusions If that fails to prevent fever, transfuse with
washed RBCs
Management Pulmonary Edema Stop transfusion or slow rate unless
patient urgently needs blood Lasix 40mg IV with transfusion
Blood Transfusions
Risks of infection:Hep B ~ 1:63,000Hep C < 1:2,000,000HIV 1 & 2 < 1:2,000,000HTLV 1 ~ 1:250,000-2,000,000Parvovirus B19 ~1:10,000
References On Call Principles & Protocols, 4th Ed. Elsevier Saunders, Philadelphia 2004. Hematology in Clinical Practice, McGraw-Hill, New York 2001. Hebert, PC, et al. Is a low transfusion threshold safe in critically ill patients with
cardiovascular diseases? Crit Care Med 2001; 29:227 Hebert, PC, et al. A multicenter, randomized, controlled clinical trial of transfusion
requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999; 340:409
Rao, SV, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004; 292:1555
Valeri, CR, et al. Limitations of the hematocrit level to assess the need for red blood cell transfusion in hypovolemic anemic patients. Transfusion 2006; 46:365.
Dodd, RY, et al. Current prevalence and incidence of infectious disease markers and estimated window period risk in the American Red Cross blood donor population. Transfusion 2002; 42:975.
Stramer, SL, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 2004; 351:760
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