Anemia

Certified, card-carrying HATER - I'm making a separate deck for reference ranges because that's stupid

Anemia

A reduction in RBC mass leading to decreased O2 delivery to tissues

Folate deficiency, anemia of chronic disease, thalassemia, pernicious anemia, iron deficiency, G6PD deficiency, sickle cell

Classic anemia causes

low Hgb, Low Hct, low RBC count

Labs for basic anemia - get a CBC

Anisocytosis

Variation in sizes of RBCs (wide RDW)

Poikilocytosis

Variation in the SHAPE of RBCs

MCHC (mean corpuscular Hgb Concentration)

Average Hgb concentration per RBC (basically how dark the cells are)

Mean cell volume (MCV - micro under 80, macro over 100)

A measure of the average RBC size

Mean Corpuscular Hgb (MCH)

Average amount of Hgb per RBC (a measure of weight)

Reticulocytes (0.5-1.5%)

A measure of immature RBCs which indicate that the bone marrow is working to put out RBCs

Serum Iron

A measurement of circulating iron (bound and unbound)

Serum Ferritin

A measurement of circulating iron storage (increase = increase in body iron stores)

Total Iron Binding Capacity (TIBC)

A measurement of circulation transport protein for iron (increases as stores are depleted, calculated from serum transferritin)

CBC w/ diff, Retic count, Blood smear, Iron studies, hemolysis labs, bone marrow biopsy

Labs to order for an anemia workup (in order of when to do them)

B12, folate

What are the macrocytic (100+ MCV) anemias?

Megaloblastic (AKA pernicious)

An anemia with large, structurally abnormal, immature RBCs - due to lack of B12 and folic acid

Intrinsic factor (IF - produced in the stomach, absorbed in the terminal illeum)

What is required for B12 to be absorbed?

Defective myelin in the CNS (neurologic dysfunction)

B12 is required for DNA synthesis, what might a deficiency lead to

Inability to absorb (loss of IF or the Ileum), inadequate intake (vegans), fish tapeworm, metformin, cholestyramine, neomycin, colchicine

Causes of B12 deficiency

Paresthesias, loss of vibratory sense, ataxia, weakness, AMS, glossitis, cheilosis, diarrhea, anorexia

Clinical findings of B12 deficiencies

Macrocytosis (MCV 100+ - maybe normal in Fe is low), decreased serum B12, hypersegmented neutrophils, Macroovalocytes (large, oval RBCs), Increased RDW, Elevated MMA and homocysteine

Lab findings in B12 defiencies

MMA, homocysteine (inversely proportional)

Okay team so the labs are giving B12 deficiency, but we want to be sure, what can we check?

IM/PO/patch B12 (1x weekly until corrected)

Management of B12 deficiencies - neurologic symptoms can be reversed if treated promptly

citrus fruits, leafy greens, meat, egg, liver

Sources of Folic Acid

DNA Synthesis (presents without neuro changes)

Folic acid is required for

Inadequate dietary intake (most common), EtOH intake, Dialysis, TMP-SMX, Sulfasalazine, methotrexate, phenytoin, Increased requirements (pregnancy, hemolytic anemia, malignancy), Celiac disease, IBD, small bowel lymphoma, small bowel resections, 5-methyltetrahydrofolate transferase deficiencies

Causes of Folate deficiencies

Anemia symptoms, glossitis, cheilosis, diarrhea, anorexia, NORMAL neuro exam, neural tube defects (if low during pregnancy)

Findings in folate deficiencies

Anemia stuff, MCV (100+), hyper-segmented neutrophils, decreased serum folate, normal B12, normal MMA, elevated homocysteine

Lab findings in Folate deficiencies

PO/IV Folic acid (1-5 mg), prenatal vitamins for pregnant patients

Management of Folate deficiencies

Iron deficiencies, thalassemia, sideroblastic

Types of Microcytic Anemia

Iron deficiency anemia

What is the most common cause of anemia worldwide and can occur at any age, usually if scarce or if there is a supply-demand mismatch

Blood loss (most common - menstruation, GI/GU ulcers/cancer, blood donation), Poor intake, Pregnancy/lactation (increased need), malabsorption (celiac disease, crohn’s, surgical resection)

Causes of Iron deficiency anemia

meat, poultry, fish, iron fortified breads/cereals, dried fruits, tofu, dark leafy green veggies

Sources of iron (1-1.5 mg/day)

Fatigue, pallor, tachycardia, exertional dyspnea, glossitis, cheilosis, koilonychia (spoon-shaped nails), pica, dry/rough skin (late stage), FOBT + (if GI loss), restless leg syndrome, esophageal webs, ecchymosis

Findings in iron deficiency

Anemia, Low MCV (under 80), hypochromic (low MCHC/MCH), Increase RDW, decrease reticulocytes (bone marrow ain’t got the goods), Decreased serum Fe, decreased ferritin, increased TIBC, decreased transferrin

Labs for Iron deficiency anemia

Treat the underlying, PO Fe therapy (30-60 mg elemental Fe OR 325 mg Fe sulfate, continue 4-6 months after Hgb normalizes), Monitor retic count (1 week later), monitor ferritin/Hgb, IV iron and heme referral if refractory

Treatment plan for Iron deficiency anemia

qod dosing improves absorption and reduces constipation, avoid enteric coated forms, take on an empty stomach

Patient education measures for Fe supplementation

Thalassemia

An autosomal recessive disorder that causes gene deletion/point mutations more common in Southeast Asian, Mediterranean, and African American populations

Alpha Thalassemia

Deficiency/Absence of the alpha-globin chains

Beta Thalassemia

Deficiency/Absence of the beta-globin chains

imbalance of globin chains (2 alpha, 2 beta normally - point mutation) → effective erythropoiesis and hemolysis

What is the pathophys for Thalassemia

2 genes chromosome 16 (for a total of 4 since its recessive)

What chromosome is affected in alpha Thalassemia - severity depends on the amount of deletion

hydrops fetalis/hemoglobin barts

If there is NO normal alpha chains →

Hemoglobin H disease

If there is 1 normal alpha chain →

Alpha thalassemia minor (clinically normal, microcytic mild anemia)

If there is 2 normal alpha chains →

Alpha thalassemia minima/silent carrier (clinically and hematologically normal)

If there is 3 normal alpha chains →

Chromo 11 (2 genes exist)

What chromosome is affected in beta Thalassemia - production can range from near normal to completely absent

Transfusion dependent (major/intermedia), Non-transfusion dependent, Minor, trait

Categories of Beta Thalassemia

Severe microcytic anemia, hepatosplenomegaly, bony deformities, osteopenia, fractures

Findings in Transfusion Dependent Beta Thalassemia

Microcytic, hemolytic anemia, hepatosplenomegaly, bony deformities, osteopenia, fractures

Findings in Non-Transfusion Dependent Beta Thalassemia

Anemia, decreased MCV/MCHC, target cells, acanthocytes, poikilocytosis, basophilic stippling, nucleated RBCs, normal Fe studies, elevated levels of HbA2 and HbF in beta

Labs for Thalassemia

the vibes of beta thalassemia, but the exclusion of beta

How do you diagnose alpha Thalassemia?

Nothing

Management plan for alpha-thalassemia trait or beta minor

genetic counseling for prospective parents

Management plan for carriers of the alpha/beta thalassemia

Refer to Hematologist (especially NTDT, TDT, HbH), splenectomy, transfusion with chelation, folic acid, vitamin C, bone marrow transplant (curative for beta - especially if done early)

Management plan for severe thalassemia cases

Fe overload → cardiomegaly (restrictive), CHF, hepatosplenomegaly, death ☠

Consequences of frequent transfusions in thalassemia

Sideroblastic anemia

An anemia due to the inability to incorporate iron into heme, leading to the accumulation of iron in the mitochondria - either congenital or acquired

subtype of myelodysplasia, excessive EtOH, isoniazid, linezolid, Cu deficiency, lead poisoing

Acquired causes of Sideroblastic anemia

Lead impairs enzymes (cell death), abnormal heme synthesis

Pathophys for lead poisoning induced Sideroblastic anemia

pale, abdominal pain, fatigue, learning disabilities, neurologic/behavioral issues (ataxic, slurred speech, seizures, comatose, foot/wrist drop), lead line along the gum line

Features of Lead poisoning

Microcytic, hypochromic anemia, basophilic stippling, increased serum lead, increased serum Fe, normal/decreased TIBC, increased transferrin/ferritin, Lead lines on X-rays of the long bones

Diagnostic findings in Lead poisonings

Bone marrow examination - a prussian blue iron stain showing ring sideroblast (due to iron load)

Definitive diagnosis of lead poisoning

remove lead source, transfusion MAYBE, chelation therapy, consult heme and toxicology

Management of lead poisoning

Anemia of chronic disease

Which types of anemia can be Micro or Normocytic?

Chronic infection/inflammation, liver disease, chronic kidney disease, RA, malignancy

Underlying causes of Anemia of chronic disease

Decreased RBC life, block in the release of iron from macrophage, cytokine inhibition of EPO

Patho for Anemia of chronic disease

Anemia (Hbg is typically higher than 9), normocytic normochromic (most common - but can be hypochromic, microcytic), normal/low retics, decreased serum Fe, Decreased TIBC, Normal/elevated ferritin

Lab findings for Anemia of chronic disease

Treat the underlying cause, EPO (30,000 units SQ/week), Darbepoetin (300 mcg/2-3 weeks), in severe cases consider multiple anemia types (poor diet or GI bleeding)

Management of Anemia of chronic disease

MI, CVA

Excessive EPO (stimulation of RBC creation) increases the risk of

Aplastic, hemolytic anemia, hereditary spherocytosis, sickle cell anemia

Types of Normocytic anemia

Aplastic anemia

A failure of the bone marrow which if left untreated can lead to death ☠

Pancytopenia with bone marrow hypoplasia/aplasia, loss of hematopoietic stem cells (defining factor)

Characteristics of aplastic anemia

Cancer treatments, Anti-eplileptics, NSAIDs, sulfonamides, chloramphenicol, PTU, methimazole, gold, arsenicals, benzene, solvents, glue vapors, EBV, Seronegative hepatitis, HIV, other herpes viruses, eosinophilic fasciitis, SLE, GVHD, paroxysmal nocturnal hemoglobinuria, thymoma, pregnancy, anorexia

Causes of aplastic anemia

ANEMIA SYMPTOMS (SHOCKER), neutropenia, thrombocytopenia, purpura, petechiae

Findings in aplastic anemia

Pancytopenia (RBC down, retic down), normocytic anemia (mild macrocytosis), Bone Marrow biopsy 🏆 (hypocellular marrow, few residual hematopoietic stem cells are normal, NO megaloblastic maligannt cells/fibrosis is absent)

Diagnostics for aplastic anemia

Hematopoietic cell transplant (HCT), intensive immunosuppressive therapy (IST)

Management for aplastic anemia

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD)

A X-linked recessive disorder that leads to the loss of the HMP shunt that protects RBC from oxidative injury leading to hemolysis

Class I (severe enzyme deficiency, chronic anemia), Class II (severe enzyme deficiency with intermittent hemolysis), Class III, Class IV, Class V (no clinical significance - found on genetic testing)

Variant Classification of G6PD

infection, FQs, dapsone, nitrofurantoin, phenazopyridine, primaquine, sulfonylureas, methylene blue, fava beans, henna, naphthalene

Oxidative stressors of G6PD

jaundice, dark urine abd/low back pain

Findings of G6PD - depends on the severity and presence of hemolysis

Increased LDH, Normocytic Anemia, elevated retics, bite/blister cells, Heinz bodies, elevated indirect bili, hemoglobinuria; NADP assay (screening and confirmation), G6PD enzyme direct assay (will be a false neg during episodes)

Diagnostics for G6PD - can be normal between episodes

avoid triggers, transfuse in severe cases

Management of G6PD

Hereditary Spherocytosis

An autosomal dominant disorder that results as a defect in the RBC membrane (a scaffolding protein in the RBC cytoskeleton) and a decreased surface-to-volume ratio leading to a spherical shape

ANEMIA, jaundice, splenomegaly (hypertrophy due to RBC destruction), pigmented gallstones, neonatal hyperbilirubinemia

Clinical findings in Hereditary Spherocytosis

Normocytic/microcytic, hyperchromic Anemia, increase retics, spherocytes, increased indirect bili, increased LDH

Diagnostics for Hereditary Spherocytosis

Refer to hematologist, folic acid 1 mg/day (must haves), splenectomy (moderate to severe), vaccines prior to splenectomy, monitor for hemolytic and aplastic crises

Management of Hereditary Spherocytosis

Sickle Cell anemia

An autosomal recessive disorder of the hemoglobin S gene (mixed genotype is thought to be protective against malaria)

HbS is deoxygenated → sickle shape → leads to micro/macro vessel occlusion and hemolysis

Patho for Sickle Cell Anemia

vaso-occlusion, sequestration, aplastic

Components of a hemolytic crises of sickle cell anemia

Skin ulcerations, painful crises, retinopathy, ischemic necrosis of bones, renal dysfunction, hyposplenism, hepatic dysfunction, priapism, jaundice, gallstones, Pulmonary HTN, HF

Clinical findings in sickle cell anemia - starts at around 6 months (fetal hgb is replaced by S)

Acute vaso-occlusive crisis

What is the primary cause of hospitalization in sickle cell anemia

fever, dyspnea, hypoxia, chest pain, abdominal pain/swelling, HA, seizure, vision changes, priapism, pain refractory to home meds, AMI, stroke, organ failure

Signs and Symptoms of an Acute vaso-occlusive crisis - best indicator is hx

Acute chest syndrome

What clinical finding in Sickle Cell anemia presents with fever, cough, and infiltrate on a CXR

Universal newborn screening, Normochromic Normocytic anemia, sickled cells, Howell-jolly bodies, target cells, absent HbA and HbS on electrophoresis, increase indirect bili, hemoglobinuria, high performance liquid chromatography (preferred)

Diagnostics for Sickle cell anemia

folic acid (1mg day), daily vitamins, Pen VK until age 5, Vaccines, Hydroxyurea (increases NO, increased fetal Hgb, reduces leukocyte count)

Prevention of complications of sickle cell anemia

Pain control (NSAIDs to opioids), O2 (hypoxia/acute chest), blood transfusions for stroke prevention/treatment, acute chest, symptomatic anemia, Abx for infection, IV fluids, supportive care

Treatment of acute complications of sickle cell anemias

Allogeneic hematopoietic stem cell transplantation (HSCT), gene therapy (autologous transplant + editing of HbS gene)

Curative treatments of Sickle cell anemia