First Things First
- Inherited hemoglobinopathies caused by disordered Hb synthesis
- Name is based on which chain subunit is underproduced; however, this underproduction leads to overproduction of other subunits.
- So a pt with beta-thalassemia may have excess alpha, delta, gamma subunits
- Anemia is a consequence of ineffective erythropoiesis and hemolysis combined.
- Often the complications of iron overload syndromes prompt the complication leading to ICU admission.
- The overall contribution of these two processes differs in various forms of thalassemia.
- Cooley’s anemia is a severe form of beta-thalassemia that may be seen in ICU care.
- Globin reduction contributes to diminished hemoglobin molecules (hypochromasia) and small structure (microcytosis).
- Development of unchecked accumulation of subunits causes unstable molecules, leading to apoptosis and hemolysis and poor iron acclimation.
- Anemia causes excess erythropoietin, but this is counteracted by ineffective production.
- Accelerated apoptosis is major factor in dysfunctional erythropoiesis, caused by excess chain deposition in erythroid progeny.
- Beta-thalassemia is common in Mediterranean countries, North Africa, Middle East, India, and Europe.
- Alpha-thalassemia: usually of Asian origin but also seen in India, the Middle East, and Africa; pts with severe types rarely survive (hydrops fetalis)
- Both types can co-exist, usually lessening the severity of disease.
History and Physical
- Remember, vital signs are vital signs!
- Check for tachycardia, bradycardia, fever, respiratory rate and SaO2.
- Often, exam is complicated by co-existing disease state.
- Specifically ask about medicines, OTC drugs, herbal remedies, EtOH and recreational drug use.
- Ask about PMH and concurrent treatments, including chemotherapeutic drugs.
- Inquire about ethnic, familial, and geographical background.
- Ascertain menstrual variations and amounts, bleeding from various body sites (GI, vaginal, epistaxis, gums, bruising).
- Exposures to toxic and marrow effective agents
- Examine for infection, lymphadenopathy, stool blood, spleen enlargement, liver size, petechiae, purpura, murmurs, pale membranes and skin.
- Cardiovascular, GI, skin, neuro, lymph, organ systems exam
- Examine groin, flanks, chest and extremities for anatomical blood loss, hematomas, compartment syndromes.
- Rectal and NGT exam of upper GI tract if melena/hematochezia exists
- Ask specifically about RUQ pain from cholecystic disease.
- Order standard CBC with differential, peripheral smear for schistocytes, reticulocyte count, PT/PTT, LFTs, metabolic profile, TSH, iron, TIBC, folate, ferritin, B12, transferrin, blood type/screen, ESR, CRP, lactate, DIC panel, haptoglobin, LDH.
- Try to obtain these before blood is given.
- Serum iron level is unreliable, with ~78% sensitivity and 36% specificity in ICU management.
- Reticulocyte index (see “Anemia” chapter for specifics)
- Iron levels and other serum studies may be inaccurate if recent transfusions have been given.
- Pan-culture for infection
- Urine analysis, creatinine, BUN, glucose
- CPK and troponin (for rhabdomyolysis and ongoing ischemia from anemia)
- CXR, EKG, ABG, SvO2 (if CVC above diaphragm)
- Low MCV with high reticulocyte count may be the first indirect evidence for thalassemia.
- Hb-electrophoresis evaluation usually confirms the diagnosis in beta-thalassemia but can be normal in alpha-subtypes, transfusions or acute anemia.
- Hemoglobin/hematocrit (H/H): In worse forms levels can be extremely low (< 5 g/dL) but usually levels are 8-9 g/dL.
- Indices (MCV/MCH): Considerably low
- RDW: Thalassemia trait normal, major has marked elevation from notable anisocytosis
- Reticulocytes: High
- WBC: Leukocytosis with left shift and bands usually present in beta-thalassemia major from both the hemolysis-induced cell shift and inappropriate counting of excess RBC types by automated machines
- Platelets: Often low, reflective of concomitant disease state or splenic enlargement, but can be normal
- Serum iron studies: High, with extremely elevated saturation levels, >70-80%; TIBC elevated
- Ferritin: High, but levels need to be taken into consideration in face of acute illness. Some patients may have iron overload.
- Peripheral smear: Usually done by automated systems in lab, but ask for specific hemolysis and anemia profiling. Great source for identification of abnormal cell types, inclusion bodies (Heinz), morphology.
- Other: Complete RBC phenotype, hepatitis screen, folic acid level, and human leukocyte antigen (HLA) typing are recommended before initiation of blood transfusion therapy.
- Hemoglobin electrophoresis: Patients with silent carrier genotypes may have “normal” levels and usually don’t have an ICU presentation based on their genotype.
- Both alpha-thalassemia and beta-thalassemia trait are similar. Both should be differentiated from iron deficiency anemia (IDA; see below).
- Elevated levels of Hb A2, F, or both are seen in beta-thalassemia.
- Alpha-thalassemia, electrophoresis is usually normal; other tests may be needed to differentiate IDA or AAI from thalassemia.
- EZP levels are usually elevated in patients with IDA or AAI, not with thalassemia.
- Soluble transferrin receptors levels are high in patients with IDA but not in those with AAI or thalassemia.
- Adequate H&P usually allows for proper identification of thalassemia patients when labs are inconclusive.
- Hemoglobin levels are usually ≥9 g/dL. Levels less than this indicate a confounding process.
- RBC count is usually higher in patients with thalassemia compared with IDA.
- RDW is normal.
- May have stippling pattern (basophilic)
- Mentzer index: In non-critical care settings, to differentiate IDA from thalassemia
- Not generally useful in an acute setting, especially if multifactorial anemias present
- Divide the MCV by RBC count (MCV/RBC).
- 13 suggests thalassemia, < 13 indicates IDA.
General Management Principles
- Pts usually present with overwhelming infections, cardiomyopathy or endocrine failures.
- Depending on the geno- and phenotypical profile, patients may have low-grade, asymptomatic, compensated anemia, or symptomatic, decompensated disease.
- Patients may have admission associated with thalassemia or concomitant disease processes; this makes treatments and diagnosis difficult.
- Endocrine dysfunction
- Cardiomyopathy from iron overload or chronic hyperdynamic state
- Thrombophilia with DVT/PE
- Pulmonary hypertension
- Proclivity for severe overwhelming infections secondary to splenic dysfunction or loss, transfusion-related infections, including Yersinia
- Severe forms of alpha-thalassemia and beta-thalassemia intermedia (Hb H disease) can be characterized by moderately severe anemia, splenic enlargement, jaundice, bone changes due to expansion of marrow. In these situations, Hb electrophoresis is diagnostic.
- Unstable and dysfunctional Hb can be detected on peripheral smears as Heinz bodies.
- Remember, Hb electrophoresis will be inaccurate if transfusions have been given in face of IDA.
- Directed toward specific complications as above
- Transfuse only when necessary
- Desferal (chelation therapy) -- pts may have a pump to deliver
- Splenectomy may be necessary.
- IDA depresses production of all Hb molecules. Consider repeating confirmatory tests when acute illness is over.
- Check for iron overload.
- Evaluate for common complications as noted above.
- Source control for sepsis
- CI, hemodynamic monitoring for cardiac decompensation
- As disease progresses, pt can suffer from the consequences of long-term therapy, notably iron overload syndromes, infections, gallstones.
- Typical ICU complications
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