Hematology Exam 1 - Comprehensive

What are the three primary functions of blood?

1) Transportation (carries O₂/nutrients)

2) Regulation (regulates temp/pH/volume)

3) Prevention (prevention of blood loss/infection)

What are the main components of blood?

Plasma and formed elements (RBCs, WBCs, platelets).

What is the primary function of erythrocytes (RBCs)?

Oxygen transport via hemoglobin.

What are the normal hemoglobin types in adults?

HbA1 (95–98%)

HbA2 (1.5–3.5%)

HbF (<2%)

What is the significance of HbF persisting beyond infancy?

Suggests a hemoglobinopathy (e.g., thalassemia).

Describe hemoglobin structure.

4 globin chains - 2α + 2β + 4 heme groups (each with iron)

Where does hematopoiesis occur in adults vs children?

Adults: red bone marrow (axial skeleton, long bones)

Children: ^^ + spleen/liver.

What drives hematopoiesis?

Cytokines and growth factors (EPO, G-CSF, IL-2, IL-3).

What nutrients are essential for normal hematopoiesis?

Iron, folate, B12, zinc, copper.

What are the key RBC indices and their meanings?

MCV = RBC size

MCH = amount of Hgb per RBC

MCHC = Hgb concentration per RBC volume

What does a peripheral smear evaluate?

RBC/WBC morphology, shape, size, color, and presence of abnormal cells.

What does a high RDW indicate?

Increased variability in RBC size (anisocytosis).

What happens to haptoglobin in hemolysis?

Decreases, as it binds free hemoglobin.

Which lab confirms abnormal hemoglobin types?

Hemoglobin electrophoresis.

What does a positive Coombs (DAT) test indicate?

Autoimmune hemolytic anemia (antibodies bound to RBCs).

Definition of anemia?

Decrease in RBCs or hemoglobin, reducing oxygen transport.

Hemoglobin thresholds defining anemia?

Men: <14 g/dL, Women: <12 g/dL.

Three key questions for anemia evaluation?

1. Etiology (production/destruction/loss)

2. RBC size (MCV)

3. Bone marrow response (retic count).

How is MCV used to classify anemia?

Microcytic = <80 fL

Normocytic = 81–99 fL

Macrocytic = ≥100 fL.

What does a high vs low reticulocyte count indicate?

High = marrow responding → destruction/blood loss

Low = marrow failure or lack of substrate

Major causes of microcytic anemia?

1. Iron deficiency

2. Thalassemia

3. Sideroblastic anemia

4. Lead poisoning

Pathophysiology of Iron Deficiency Anemia (IDA)?

Iron depletion → ↓ heme synthesis → ↓ Hgb → microcytic, hypochromic RBCs.

Most common cause of anemia worldwide?

Iron deficiency.

Common etiologies of IDA?

1. Chronic blood loss (GI, menses)

2. Malabsorption

3. Increased demand (pregnancy, growth)

4. Poor intake

Classic unique manifestations of IDA?

1. Glossitis

2. Angular cheilitis

3. PICA

4. Koilonychia (spoon nails)

IDA lab pattern?

Overall = microcytic/hypochromic anemia w/ Fe depletion

↓ Hgb, ↓ MCV, ↓ MCH

↑ RDW

↓ Ferritin, ↓ Serum iron, ↓ Iron saturation

↑ TIBC

↓ Retic count

IDA peripheral smear?

Microcytic, hypochromic RBCs.

IDA treatment?

1. Oral (ferrous sulfate 325 mg QD/QOD)

2. IV for refractory or urgent; transfuse if Hgb < 7 g/dL.

What is the key defect in thalassemia?

Decreased or absent globin chain production, disrupting 1:1 α:β ratio → unstable Hb → hemolysis

Classic lab clue for thalassemia?

Microcytosis out of proportion to anemia.

Where is thalassemia most common?

Malaria endemic regions (Mediterranean, Asia, Africa)

Gold-standard diagnostic test for thalassemia?

Hemoglobin electrophoresis.

What is the difference between β-Thalassemia major vs minor?

Minor = mild anemia, no transfusion

Major = severe anemia, transfusion-dependent

Effects of α-Thalassemia gene deletion?

1 gene → silent carrier

2 genes → trait (mild anemia)

3 genes → HbH disease

4 genes → hydrops fetalis (Hb Bart’s, not compatible w/ life)

Thalassemia smear findings?

Target cells, basophilic stippling, elliptocytes.

Treatment for severe thalassemia?

Chronic transfusion, iron chelation, folic acid, ± splenectomy, gene therapy (Zynteglo), or allogeneic transplant.

Characteristic smear finding in lead poisoning?

Basophilic stippling.

Pathophysiology of lead poisoning?

Lead inhibits enzymes in heme synthesis → microcytic, hypochromic anemia.

Key symptoms of lead poisoning?

Irritability, learning issues, constipation, vomiting, abdominal pain, severe = encephalopathy, seizures.

Diagnostic test for lead poisoning?

Elevated blood lead level.

Treatment for lead poisoning?

Chelation (succimer PO, dimercaprol IM), remove exposure, supportive care.

What causes sideroblastic anemia?

Failure to incorporate iron into heme → iron accumulates around nucleus.

Common causes of sideroblastic anemia?

Lead, alcohol, isoniazid, chloramphenicol, malignancy.

Key diagnostic test for sideroblastic anemia?

Bone marrow biopsy showing ringed sideroblasts.

Lab finding in sideroblastic anemia?

↑ Serum iron (unlike IDA).

Treatment for sideroblastic anemia?

Remove offending agent; transfuse PRN.

Main causes of normocytic anemia?

Blood loss, hemolytic anemia, chronic disease, CKD, bone marrow failure.

First test to assess normocytic anemia?

Reticulocyte count (marrow response).

Lab hallmark triad in hemolytic anemia?

↑ LDH, ↑ bilirubin, ↓ haptoglobin.

What is the retic count in hemolysis (low/high)?

High (marrow compensation).

Inheritance pattern of G6PD Deficiency?

X-linked (mostly affects males)

Pathophysiology of G6PD Deficiency?

Oxidative stress → Heinz bodies → splenic removal → bite cells.

Triggers for G6PD Deficiency?

Fava beans, infection, oxidative drugs (sulfa, dapsone, nitrofurantoin, quinolones, methylene blue).

Diagnosis and treatment for G6PD Deficiency?

Quantitative G6PD assay; avoid triggers, transfuse if severe.

What are the types of antibodies in Autoimmune Hemolytic Anemia (AIHA)?

Warm (IgG) – 70%, splenic destruction; Cold (IgM) – complement-mediated.

What are warm AIHA causes?

Idiopathic or secondary (SLE, CLL, lymphoma, viral infection, drugs).

Labs for warm AIHA?

↑ LDH, ↑ retic, ↑ bili, ↓ haptoglobin, DAT positive.

What is the treatment for warm AIHA?

Steroids (first-line) → IVIG, splenectomy, or rituximab if refractory.

What is a common association with cold AIHA?

B-cell neoplasms or post-infection (EBV, MAC).

Key clinical clue for cold AIHA?

Acral cyanosis in cold temps.

What is the treatment for cold AIHA?

Avoid cold, rituximab; steroids less effective.

Pathophysiology of Anemia of Chronic Disease (ACD)?

Inflammatory cytokines trap iron in stores → marrow can’t use it.

Lab pattern for Anemia of Chronic Disease?

↓ Retic count

↓ Serum iron

↓ TIBC

Normal/↑ Ferritin.

Treatment for Anemia of Chronic Disease?

Treat underlying disease, EPO if symptomatic.

Main cause of Anemia of Chronic Kidney Disease (CKD)?

↓ Erythropoietin from declining GFR (<30 mL/min).

What is the smear finding in CKD?

Burr cells.

What is the treatment for Anemia of Chronic Kidney Disease?

ESA (Procrit/Aranesp) or HIF-PH inhibitors (Daprodustat, Vadadustat).

Examples of Bone Marrow Failure Syndromes?

Aplastic anemia, Pure Red Cell Aplasia, PNH, Myelofibrosis.

Mechanism of Aplastic anemia?

Autoimmune destruction of hematopoietic stem cells → pancytopenia.

Bone marrow biopsy finding in Aplastic anemia?

Treatment for Aplastic anemia?

Immunosuppression (ATG, cyclosporine, steroids) or allogeneic transplant.

Pathophysiology of Myelofibrosis?

Marrow replaced by fibrotic tissue, causing extramedullary hematopoiesis (hepatosplenomegaly).

What is the treatment for Myelofibrosis?

JAK2 inhibitors or stem cell transplant.

What should you think when you see microcytic anemia?

Think iron, thalassemia, lead, sideroblastic.

What should you think when you see normocytic anemia?

Think hemolysis, acute loss, chronic disease, CKD, marrow failure.

What does high LDH + low haptoglobin indicate?

Hemolysis.

What does low ferritin indicate?

Iron deficiency.

What does high ferritin + low iron suggest?

Chronic disease.

G6PD leads to which RBC morphology?

Bite cells.

AIHA leads to what lab finding?

Positive Coombs test.

What is characteristic of thalassemia?

Microcytosis disproportionate to anemia.

What is the pathophysiology of Autoimmune Hemolytic Anemia (AIHA)?

Autoantibodies (IgG or IgM) form against RBCs leading to complement activation and premature RBC destruction.

What are the two major types of AIHA and their associated antibodies?

1. Warm AIHA: IgG, 70%, splenic macrophage-mediated

2. Cold AIHA: IgM, complement-mediated.

What are common causes of Warm AIHA?

Idiopathic, or secondary to CLL, lymphoma, SLE, HIV, viral syndromes, or drugs (PCN, methyldopa, quinidine).

What symptoms are associated with Warm AIHA?

Anemia symptoms, jaundice, splenomegaly, ± asymptomatic.

What lab findings are associated with Warm AIHA?

↑ LDH, retic, bilirubin

↓ haptoglobin

Direct Coombs positive

Anti-C3 positive.

What is the first-line treatment for Warm AIHA?

Corticosteroids.

What are the second-line treatments for Warm AIHA?

IVIG.

What treatments are used for refractory Warm AIHA?

Splenectomy or Rituximab; Folic acid for RBC turnover support.

Who are typical patients for Cold AIHA?

Older adults with B-cell neoplasm (CLL, Waldenstrom’s) or post-viral (EBV, Mycoplasma).

What clinical clue indicates Cold AIHA?

Acral cyanosis (blue fingers, toes, ears, nose) in cold environments.

What lab findings indicate Cold AIHA?

Similar to warm, but DAT positive for C3 only; Cold agglutinin test positive.

What is the recommended treatment for Cold AIHA?

Avoid cold exposure, Rituximab, supportive care; steroids often ineffective.

What is the pathophysiology of Anemia of Chronic Disease (ACD)?

Inflammation traps iron in macrophages, decreasing marrow availability despite adequate stores.

What are common underlying causes of ACD?

Malignancy, autoimmune disease, chronic infection, connective tissue disorders.

What is the typical lab pattern for ACD?

↓ Serum iron

↓ TIBC

normal/high ferritin

low retic count

How is ACD treated?

Treat underlying disease; consider EPO if symptomatic.

What mechanism leads to Anemia of Chronic Kidney Disease?

Low EPO due to decreased renal production when GFR <30 mL/min.

What smear findings are associated with CKD?

Burr cells as CKD progresses.

What is the lab pattern seen in CKD?

↓ Serum iron/transferrin

normal ferritin

↓ EPO

normal RDW