Heme Flashcards
Pathogenesis of anemia of chronic disease
- Hypoproliferative anemia
- Release of cytokines from T cells and monocytes that stimulate the uptake an storage of iron in macrophages/monocytes
- Hepcidin is also stimulated, which contributes to more iron storage
- Suppresses EPO production by the kidneys
- Results in iron-deficient erythropoeisis despite marrow replete with iron
Presentation
- Normochromic
- Normocytic
- Usually mild/mod (Hb 80 - 95)
- Low retic count
Iron studies
- Low serum iron
- Low TIBC (elevated in Fe deficiency)
- Low % iron sat
- Normal or elevated ferritin
Chronic blood loss - lab workup
Chronic
- Low ferritin (low iron stores)
- Normal serum iron early, then falls with time
- Normal % iron sat early, then falls over time
- Hb typically preserved until severe iron deficiency occurs
- Target cells and pencil cells in severe deficiency
Treatment of anemia from chronic blood loss
- Source control
- Stop the bleeding if possible (surgical, endoscopically, radiation) - Iron supplementation
- If iron deficiency is present
- PO iron salts taken in 3-4 separate doses 1 hr prior to meals (cheaper)
- polysaccharide iron complex (expensive, no evidence they are better tolerated or provide better treatment than iron salts)
- Consider IV iron if patients are intolerant of PO iron, have intestinal malabsorption, or are losing iron more quickly than can be replaced with PO supps
3. Blood transfusion if severe anemia
IV iron formulations
- Calculate required dose
dose (mg) = hemoglobin deficit (g/dL) x body weight (lbs)
- In practice, no benefit over 1000mg of IV iron (give in divided doses)
- Typical to give 1000mg over multiple infusions as this will correct anemia without causing iron overload
Iron sucrose vs Iron dextran
- Iron dextran is associated with anaphylaxis in less than 1%, but not as commonly used for that reason
Megaloblastic anemia
- May be related to nutritional deficiencies in folate or B12
- Folic acid level often decreased compared to general elderly population in cancer patients, especially in major weight loss - anemia appears 4 months following inadequate intake
- Folic acid level may be an insensitive marker of deficiency
- Supplementation of folic acid 1mg PO daily
Anemia due to bone marrow infiltration
- Less common than anemia of chronic disease, iron deficiency, or nutritional deficiencies
- All malignancies can metastasize to marrow, but more common with lung, breast and prostate
Presentation:
- Leukoerythroblastic (immature nucleated RBCs, myeloid WBC precursors, teardrop red cells)
- If mild/mod infiltration, minimal changes to CBC
- If marrow significantly affected, may see severe anemia, high WBCs, and any variation of platelet numbers
Diagnosis
- Smear
- Can use a marrow bx to confirm, but may not be clinically necessary
Thrombocytopenia
- Commonly occurs in the context of pancytopenia due to MDS or heme malignancies
- Spontaneous bleeding unlikely until below platelet count of 20
- ICH unlikely until below platelet count of 10
Neuropenia
- most commonly due to bone marrow failure from myelosuppressive chemo, disease infiltration of bone marrow, or intrinsic bone marrow failure
- Definition: ANC < 1.5 (severe is < 0.5)
Febrile neutropenia: Definition, work up, management
Febrile neutropenia:
- Single or temp > 38.3 or sustained temp >38 for one hour
AND neuts <0.5 or <1 with predicted nadir of 0.5
- Nadir typically occurs 7-14 following administration of each cycle of treatment
- Source of infection often not identified (only in 20-30% of patients), and may be due to patient’s own flora
Investigations: Blood cultures, urine, sputum, any skin/mucosal lesion, stool, CXR, basic blood work including liver panel
Treatment:
- No routine use of G-CSF, but start broad spectrum abx immediately
Treatment of FN (specifics)
High risk patient:
- Hemodynamically unstable
- Altered mental status
- New pulm infiltrate
- Hepatic or renal dysfunction
- Underlying chronic lung disease
- Mucositis
- Inpatient at time of dx
- Prolonged neutropenia
- Expected neutropenia >7 days (generally in induction chemo for SCT or leukemia)
- Heme malignancy
- Comorbidities
- Higher intensity chemo
High risk patients Rx:
- Antipseudomonal beta lactam (Pip-tazo, mero, consider ceftaz).
- Consider Vanco in SSTI or hemodynamic instability
Low risk patient Rx:
- Most patients receiving chemo for solid tumours are low risk for complications requiring hospitalization, in the absence of other signs or symptoms
- Cipro 750 BID (alternative levoflox) + Amox/clav
Factors making a patient high risk with FN
High risk patient:
- Hemodynamically unstable
- Altered mental status
- New pulm infiltrate
- Hepatic or renal dysfunction
- Underlying chronic lung disease
- Mucositis
- Inpatient at time of dx
- Prolonged neutropenia
- Expected neutropenia >7 days (generally in induction chemo for SCT or leukemia)
- Heme malignancy
- Comorbidities
- Higher intensity chemo
DIC
- Tissue factor released from vascular endothelial damage, trauma, cytokines, etc, triggering coag cascade
- Microthrombi formed in circulation which perpetuate cascade
- Over time, clotting factors consumed and then excessive bleeding occurs
May be acute (bleeding predominates b/c of depletion of platelets, fibrinogen, clotting factors)
May be chronic and somewhat compensated (thrombosis predominates b/c liver can keep up with coag factors)
Major causes:
- Sepsis
- Trauma/surgery
- Malignancy (especially APML and adenocarcinoma)
- Obstetrical complications
Diagnosis of DIC
- Thrombocytopenia
- MAHA (non-immune hemolysis with low Hb, schistocytes on smear, high bili)
- High INR/PTT
- Low fibrinogen (note may be normal in the context of malignancy)
- Elevated D-dimer
Management of DIC
- Supportive care i palliative patients - note that mortality ranges from 31-86%
- Treat underlying cause (especially infection)
- Platelets if Plt <20 or bleeding
- Cryo for Fibrinogen < 0.5
- FFP if INR elevated and bleeding
- May consider heparin for chronic DIC with thrombosis predominant
RBC Transfusions in palliative care
Indications
- Fatigue and dyspnea, but no RCTs to guide (observational data only)
- No guidelines, decision is individual
- In non-palliative patients, transfusion threshold is usually 70 in non-cardiac patients so long as there is no evidence of bleeding
Platelet transfusions in palliative care
- Prophylactic transfusion for patients with Plt < 10 given risk of ICH
- If actively bleeding, target Plt > 50
Transfusion reactions - frequency
Frequency of transfusion reactions:
- Urticaria (1 in 100)
- TACO (1 in 100)
- Fever (1 in 300)
- Delayed hemolytic reaction (1 in 7000)
- TRALI (1 in 10 000)
- Acute hemolytic reaction (1 in 40 000)
- Anaphylaxis (1 in 40 000)
- Bacterial sepsis (1 in 250 000)
- HBC (1 in 7.5 million)
- HCV (1 in 13 million)
- HIV (1 in 21 million)
Presentation of Acute hemolytic reaction
Hemolytic transfusion reaction
- Occurs within 24 hours after transfusion - Suspect with hypotension, hemoglobinuria, renal failure, back pain, chills, fever, signs of DIC.
Management:
- IV NS to promote diuresis and maintain BP
- Manage DIC and hemorrhage
Presentation of TRALI
TRALI
- Typical onset within 6 hours of transfusion, presents with dyspnea, bilateral lung infiltrates, fever, tachycardia, tachypnea, hypotension
- Note BNP will be low
Treatment:
- Stop transfusion
- Diuretics and steroids NOT helpful
- Mechanical ventilation PRN
- Typical resolution within 24-72 hours
Delayed hemolytic transfusion reaction
Presentation:
- Occurs 5-15 days post transfusion
- Coomb’s positive
- Antibodies result in sequestration and phagocytosis of RBCs in the liver and spleen. Often clinical silent, but may present with low grade fever or jaundice
- Indirect hyperbilirubinemia (jaundice)
- Hemoglobinuria
Criteria for minor blood transfusion reaction
- Hives or rash < 25% of body and no other symptoms
- Fever is associated with no other symptoms
Febrile non-hemolytic transfusion reaction
- Fever during transfusion or up to 4 hours after
- Chills, rigors, N/V, hypotension without fever
- Symptoms are self limited, respond to tylenol
If fever is the only symptom:
- Consider tylenol
- Consider restarting transfusion
If any symptom other than fever:
- Ensure investigations completed to rule out acute hemolysis (CBC, lytes, bili, INR/PTT, fibrinogen, LDH)
Use of erythropoeitin in palliative patients
- Most common use is in anemia associated with advanced renal disease
- May be used in some cancers, but there is concern that it can worsen tumour control
- Increased risk of hypertension and VTEs
VTE in palliative care (incidence, pathogenesis)
- 15% of patients with cancer will develop symptomatic VTE
- 10% of patients with idiopathic VTE will be diagnosed with cancer within a year
- Due to venous stasis, endothelial injury, and hypercoagulability