CONTENTS

• diagnostic approach to dropping hemoglobin
• gradual anemia:  the ICU drift
• transfusion targets for patients not exsanguinating
• managing Jehovah's Witness patients
• podcast
• questions & discussion
• pitfalls
• PDF of this chapter (or create customized PDF)

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diagnostic approach to dropping hemoglobin

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The standard internal medicine approach to anemia is shown above.  This is a nice algorithm, but it is designed for the evaluation of chronic anemia.  Evaluating a patient with acutely dropping hemoglobin is actually much simpler for the following reason:  bone marrow failure cannot cause an acutely dropping hemoglobin.

• Erythrocytes have a half-life of 120 days.
• If the bone marrow shut down completely, the hemoglobin would fall by only about ~1% per day (e.g. from 7 mg/dL to 6.9 mg/dL the next day).
• Any drop in hemoglobin faster than this must be due to blood loss or hemolysis.

This allows us to simplify the above algorithm as follows:

causes of acute hemoglobin drop

• Hemorrhage (usually)
  • External
    • GI bleed
    • Phlebotomy
    • Trauma/surgery
  • Internal
    • Hemoperitoneum
    • Hemothorax
    • Retroperitoneal hemorrhage, rectus sheath hematoma
    • Bleeding into thigh (common after hip fracture)
• Hemolysis
  • Malfunctioning intravascular prosthesis:  Impella device, mechanical heart valve, vascular graft/shunt
  • Microangiopathic hemolytic anemia (e.g. DIC, TTP)
  • Infection (clostridia, babesia, malaria)
  • G6PD deficiency
  • Autoimmune hemolytic anemia (transfusion reaction, drugs)

lab evaluation of acute hemoglobin drop

• Repeat CBC to verify that hemoglobin is truly falling.
• Labs to evaluate for hemolysis
  • Hemolysis screen:  Haptoglobin, lactate dehydrogenase (LDH), blood smear.
  • Sorting out cause of hemolysis:  Direct antiglobulin (Coombs) test
• Labs to assist in management of hemorrhage
  • Type & screen (or type & cross-match if hemoglobin rapidly falling)
  • Check coagulation factors and fibrinogen

imaging evaluation of hemoglobin drop 

• Bedside ultrasonography (including FAST scan) should allow for exclusion of hemothorax or hemoperitoneum.
• CT abdomen/pelvis may be indicated to evaluate for retroperitoneal hematoma, particularly if there was a recent procedure that may have caused this.
  • If there is a high index of suspicion for retroperitoneal hematoma or hemoperitoneum, consider CT angiography as this may guide a subsequent procedure by interventional radiology.

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gradual anemia- the ICU hemoglobin drift

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defining ICU hemoglobin drift

• Most ICU patients experience gradual decrease in hemoglobin over time.  This is probably multifactorial, with the following contributory factors:
• 1) Suppression of hematopoiesis due to inflammation (similar to anemia of chronic disease).
• 2) Phlebotomy for laboratory studies.
• 3) Minor, subclinical stress ulceration in the GI tract.

interventions to avoid

• Checking an extensive anemia panel (iron, folate, B12, reticulocyte count) isn't helpful, as discussed above.
• Iron supplementation is generally unhelpful.  Oral iron is poorly absorbed and may irritate the stomach.  Intravenous iron doesn't seem to affect blood transfusion requirements in the ICU.¹  Patients with systemic inflammation may have suppressed hematopoiesis regardless of their iron stores.
• Erythryopoietin has been trialed several times for this, with disappointing results.²  For most patients, this isn't worth the expense and work involved.  Erythropoietin should be considered, however, for the Jehovah's Witness patient (see below).

management of hemoglobin drift

• Minimize phlebotomy
  • Avoid unnecessary labs.
  • For patients at increased risk from anemia (e.g. ARDS patients with limited oxygen delivery), draw labs in pediatric tubes.
• Conservative transfusion strategy (more on this below)
• Discontinue unnecessary anticoagulants.  For example, some patients are on chronic aspirin for primary prevention – this should be discontinued.
• Prevention/treatment of stress ulceration
  • Prevention of stress ulceration:  enteral nutrition if possible, possibly proton pump inhibitor (more on this to come).
  • For patients who are consistently losing more hemoglobin than is usual, initiation of a proton pump inhibitor may be considered for empiric treatment of gastrointestinal erosions.

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transfusion targets for patients not exsanguinating

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transfusion should be used carefully and judiciously

• Transfusion may cause numerous problems:
  • Transfusion associated circulatory overload (TACO) – fancy name for volume overload.
  • Transfusion reactions including transfusion-related acute lung injury (TRALI) and anaphylaxis.
  • Immunosuppression.
  • Hyperkalemia, hypocalcemia.
• More liberal administration of blood products has been shown to be non-beneficial or harmful in most studies of critically ill patients.

transfusion target for the patient who is not acutely hemorrhaging

• The transfusion target for nearly all ICU patients is 7 mg/dL (70 g/L).  However, a target of >8 mg/dL (80 g/L) is preferable for patients recovering from CABG surgery or patients with active myocardial ischemia (NSTEMI or unstable angina).³
• Blood should generally be transfused one unit at a time.⁴  Avoid transfusion of more than one unit blood unless the patient is actively hemorrhaging or the hemoglobin is extremely low.  This is done for two reasons:
  • 1) Hemoglobin bounces around a bit from day to day.  Over-reacting to a “low” hemoglobin with two units blood transfusion will often over-correct the anemia.
  • 2) Blood transfusion tends to cause pulmonary edema (more so than crystalloid).   Two units of blood is a significant volume bolus for a patient who may have euvolemic or hypervolemic anemia.

transfusion target for the patient with a gastrointestinal hemorrhage

• For patients who don't have a massively exsanguinating bleed, a conservative transfusion target (>7 mg/dL) was shown to improve mortality compared to a liberal transfusion target (>9 mg/dL).⁵
• If you're worried that the patient might suddenly open up, the safest approach is to order blood to be typed & crossed and placed on hold in the blood bank.   Make sure the patient has good intravenous access.   Then, if the patient starts exsanguinating, you're all set – just request that the blood be infused.  The vast majority of the time the patients won't bleed, allowing you to avoid exposing them to the risk of excessive transfusion.
• The harms from over-transfusion are probably greatest for patients with variceal hemorrhage, where over-transfusion can push patients into a death spiral:

contraindications to transfusion

• Transfusion may be especially problematic in:
  • Patients with increased blood viscosity (e.g. due to hyperleukostasis in uncontrolled AML).
  • Patients with thrombotic thrombocytic purpura (TTP) – may increase hemolysis.
  • Uncontrolled hypervolemia (especially dialysis patients).
  • Hyperkalemia (potassium leaks out of RBCs in storage, potentially increasing serum potassium levels).
• In these contexts, it may be reasonable to hold transfusion in patients with a hemoglobin <7 mg/dL in the absence of signs of organ hypoperfusion.
  • It is often wise to transfuse dialysis patients during hemodialysis, to avoid volume overload or hyperkalemia.

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managing Jehovah's Witness patients

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getting started: clarify goals

• Discuss with patient and/or family whether they would accept blood transfusion if necessary.
• Clarify whether some blood products may be acceptable (for example, some patients may accept coagulation factor concentrates).
• If at all possible, these discussions should occur early, when the patient is stable.  When in doubt, ethics consultation may be helpful.

avoid blood loss

• Avoid hemoglobin drift:  The major threat to these patients isn't necessarily an acute hemorrhage, but rather gradual blood loss which is commonly seen in ICU patients (see above: “hemoglobin drift”).  Gradual blood loss can easily become a major problem over a 1-2 week ICU stay.   The following measures may be used to avoid this:
  • Begin aggressive efforts to conserve blood immediately upon arrival to the ICU (don't wait until the patient's hemoglobin has dropped to 5 mg/dL).
  • Draw labs in pediatric tubes.
  • Discontinue all scheduled blood draws (no “cycling” of labs).  Every blood draw should represent a deliberate decision by the treatment team.  Consider giving patients “lab holidays” (e.g. checking basic labs q48hr or q72hr).
  • Lab draws should be strictly limited to mission-critical tests which are absolutely required for patient care.
• Adequate stress ulcer prophylaxis.
  • NSAIDs should be avoided to reduce the risk of peptic ulceration (as is the case for most critically ill patients).
  • Stress ulcer prophylaxis should be considered.
• Avoid coagulopathy
  • Whenever possible, avoid or minimize anticoagulation.
  • When anticoagulation is necessary, use the lowest dose possible of a reversible agent.  Avoid direct-acting oral anticoagulants.
  • Be aware of coagulation labs and act accordingly – especially for patients with active bleeding or when prescribing an anticoagulant.
• Avoid unnecessary procedures which pose a risk of bleeding.
• Aggressive management of any acute hemorrhage
  • Early operative intervention (e.g. prompt endoscopy for GI hemorrhage)
  • Use of pro-coagulants (e.g. tranexamic acid) may be rational.

promote blood synthesis

• The use of erythropoietin hasn't been shown to be beneficial in most patients, but it may improve hemoglobin levels.  Among Jehovah's Witness patients, this is a rational therapy.  This may be achieved as follows:
• 1) sq erythropoietin 300 U/kg/day for two weeks if necessary, then three times per week.^6 7
• 2) IV iron sucrose as needed to maintain ferritin >> 100 ng/mL and transferin saturation >20%.²  Erythropoietin won't work without adequate iron stores.
• 3) Give empiric folate and vitamin B12 to support hematopoiesis.

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Ordering iron studies on ICU patients to evaluate the etiology of acute-onset anemia.  As discussed above, acute anemia can never be due to iron deficiency.
• Over-transfusion of blood remains a considerable problem in the ICU, despite repeated studies showing that this is dangerous.  When in doubt, it's generally better to err on the side of not transfusing blood.
• A transfusion target of 7 mg/dL means that you don't transfuse unless the hemoglobin is actually below seven.
• Trying to transfuse blood to improve a patient's dyspnea is generally ineffective or harmful, unless the patient is severely anemic.

Going further:  

• Transfusion Literature Summaries (Chris Nickson, LITFL)
• Blood transfusion in ICU (Chris Nickson, LITFL)
• Blood Transfusion Strategies in the Modern Era (Giora Netzer, Maryland CC project)
• Anemia in the ICU (PulmCCM)
• The TRICC trial (Kent Lavery, INTENSIVE blog)
• Iron?
  • IRONMAN trial – TheBottomLine
  • IV iron in emergency medicine (Anton Helman, Emergency Medicine Cases)
• Severe anemia in Jehovah's Witness patients (Kevin Claire et al, WikEM)

References: