Hematology Unveiled - Didactic Med

🔴 Red Blood Cell Disorders

Anemias classified by Mean Corpuscular Volume (MCV)

MICROCYTIC ANEMIAS MCV < 80 fL

📊 Definition:

Small red blood cells with reduced hemoglobin content

🔍 Types:

Iron Deficiency Anemia: Most common cause worldwide. Low ferritin, high TIBC, low transferrin saturation
Thalassemia: Genetic disorder affecting hemoglobin production (α or β chains). Target cells on smear
Sideroblastic Anemia: Ring sideroblasts in bone marrow. Can be congenital or acquired
Lead Poisoning: Basophilic stippling on blood smear. Elevated blood lead levels
Anemia of Chronic Disease: Can present as microcytic or normocytic. Elevated ferritin, low TIBC

🎯 Key Labs:

CBC, Iron studies (serum iron, TIBC, ferritin, transferrin saturation), Peripheral smear, Hemoglobin electrophoresis

💊 Management:

Iron supplementation for IDA, Supportive care for thalassemia, Treat underlying cause

Clinical Pearl: "TAILS" mnemonic for microcytic anemia: Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic anemia

NORMOCYTIC ANEMIAS MCV 80-100 fL

📊 Definition:

Normal-sized RBCs but reduced count. Classify by reticulocyte count

🔍 Low Reticulocyte Count (Hypoproliferative):

Aplastic Anemia: Pancytopenia, hypocellular bone marrow. Can be acquired or inherited (Fanconi)
Anemia of Chronic Disease: Inflammation reduces EPO response. Common in CKD, cancer, autoimmune diseases
Chronic Kidney Disease: Reduced EPO production. Treat with ESAs
Pure Red Cell Aplasia: Selective absence of RBC precursors
Myelophthisic Anemia: Bone marrow infiltration (cancer, fibrosis). Teardrop cells on smear

🔍 High Reticulocyte Count (Hemolytic/Blood Loss):

Sickle Cell Disease: HbSS, vaso-occlusive crises. Sickled cells on smear
G6PD Deficiency: X-linked, hemolysis with oxidative stress. Bite cells, Heinz bodies
Hereditary Spherocytosis: Spherocytes, positive osmotic fragility test. Splenomegaly
Autoimmune Hemolytic Anemia: Warm (IgG) or Cold (IgM) antibodies. Positive DAT/Coombs
Paroxysmal Nocturnal Hemoglobinuria (PNH): Complement-mediated hemolysis. Flow cytometry for CD55/CD59
Microangiopathic Hemolytic Anemia: Schistocytes. Seen in TTP, HUS, DIC, malignant HTN
Acute Blood Loss: Trauma, GI bleeding, surgery

🎯 Key Labs:

CBC with reticulocyte count, Peripheral smear, LDH, Haptoglobin, Indirect bilirubin, Direct antiglobulin test (DAT)

Clinical Pearl: Corrected reticulocyte count >2% suggests hemolysis or blood loss. Elevated LDH, low haptoglobin, and elevated indirect bilirubin indicate hemolysis.

MACROCYTIC ANEMIAS MCV > 100 fL

📊 Definition:

Large red blood cells. Divided into megaloblastic and non-megaloblastic types

🔍 Megaloblastic (Impaired DNA Synthesis):

Vitamin B12 Deficiency: Neurological symptoms (paresthesias, ataxia, dementia). Elevated methylmalonic acid & homocysteine. Causes: pernicious anemia, malabsorption, dietary
Folate Deficiency: No neurological symptoms. Elevated homocysteine only. Causes: poor diet, malabsorption, pregnancy, medications (methotrexate, phenytoin)
Medications: Methotrexate, hydroxyurea, azathioprine, 5-FU, zidovudine

🔍 Non-Megaloblastic (Normal DNA Synthesis):

Alcoholism: Direct toxic effect on bone marrow. May have concurrent folate deficiency
Liver Disease: Impaired lipid metabolism affects RBC membrane. Cirrhosis, hepatitis
Hypothyroidism: Reduced EPO production and metabolism
Reticulocytosis: Young RBCs are larger (polychromasia)
Myelodysplastic Syndrome (MDS): Clonal disorder with dysplastic changes
Diamond-Blackfan Anemia: Congenital pure red cell aplasia. Macrocytic with low reticulocytes

🎯 Key Labs:

CBC with MCV, Vitamin B12, Folate, Methylmalonic acid, Homocysteine, Thyroid function, Peripheral smear (hypersegmented neutrophils)

Clinical Pearl: Methylmalonic acid elevated ONLY in B12 deficiency. Homocysteine elevated in BOTH B12 and folate deficiency. Hypersegmented neutrophils (>5 lobes) are pathognomonic for megaloblastic anemia.

⚪ White Blood Cell Disorders

Leukemias, Myeloproliferative & Myelodysplastic disorders

ACUTE LEUKEMIAS

🔍 Types:

Acute Myeloid Leukemia (AML): >20% myeloblasts in bone marrow. Auer rods. Median age 68 years. FLT3, NPM1, CEBPA mutations
Acute Lymphoblastic Leukemia (ALL): >20% lymphoblasts. TdT positive. Philadelphia chromosome (BCR-ABL) in 25% adults. More common in children
Acute Promyelocytic Leukemia (APL): AML subtype with t(15;17) PML-RARA. DIC risk. Treat with ATRA + arsenic trioxide

📊 Presentation:

Pancytopenia, fatigue, infections, bleeding, bone pain, hepatosplenomegaly

💊 Management:

Induction chemotherapy, consolidation, possible stem cell transplant. APL: ATRA + arsenic

CHRONIC LEUKEMIAS

🔍 Types:

Chronic Myeloid Leukemia (CML): Philadelphia chromosome t(9;22) BCR-ABL fusion. Three phases: chronic, accelerated, blast crisis. Marked leukocytosis with left shift. Massive splenomegaly
Chronic Lymphocytic Leukemia (CLL): Most common leukemia in adults. Absolute lymphocytosis >5,000/μL with smudge cells. Autoimmune hemolytic anemia/ITP common. Richter transformation possible

💊 Management:

CML: Tyrosine kinase inhibitors (imatinib). CLL: Watch and wait vs chemoimmunotherapy vs targeted therapy (BTK inhibitors, BCL-2 inhibitors)

MYELOPROLIFERATIVE NEOPLASMS (MPN)

🔍 Types:

Polycythemia Vera (PV): ↑RBC mass, JAK2 V617F mutation (95%). Erythromelalgia, pruritis after hot shower. Risk of thrombosis
Essential Thrombocythemia (ET): ↑Platelets >450,000. JAK2, CALR, or MPL mutations. Risk of thrombosis and bleeding
Primary Myelofibrosis (PMF): Bone marrow fibrosis, teardrop cells, leukoerythroblastic smear. Massive splenomegaly

💊 Management:

Phlebotomy for PV, Aspirin, Hydroxyurea, JAK2 inhibitors (ruxolitinib) for advanced disease

MYELODYSPLASTIC SYNDROMES (MDS)

📊 Definition:

Clonal stem cell disorders with ineffective hematopoiesis and dysplasia. Risk of progression to AML

🔍 Features:

Cytopenias, macrocytosis, dysplastic changes in bone marrow (>10% dysplasia in ≥1 lineage), ring sideroblasts may be present

💊 Management:

Supportive care, growth factors, hypomethylating agents (azacitidine, decitabine), lenalidomide for del(5q), stem cell transplant

🟡 Platelet Disorders

Quantitative and qualitative platelet abnormalities

THROMBOCYTOPENIA (Low Platelets <150,000/μL)

🔍 Decreased Production:

Bone Marrow Failure: Aplastic anemia, MDS, leukemia, metastatic cancer
Nutritional: B12, folate deficiency
Medications: Chemotherapy, alcohol

🔍 Increased Destruction:

Immune Thrombocytopenic Purpura (ITP): Isolated thrombocytopenia, antiplatelet antibodies. First-line: corticosteroids, IVIG
Thrombotic Thrombocytopenic Purpura (TTP): Pentad: thrombocytopenia, MAHA, fever, renal dysfunction, neurologic changes. ADAMTS13 deficiency. Emergency: plasma exchange
Hemolytic Uremic Syndrome (HUS): Triad: MAHA, thrombocytopenia, acute kidney injury. Often post-diarrheal (E. coli O157:H7)
Heparin-Induced Thrombocytopenia (HIT): Paradoxical thrombosis. Stop heparin, start direct thrombin inhibitor
DIC: Consumption coagulopathy. ↓Platelets, ↓Fibrinogen, ↑PT/PTT, ↑D-dimer

🔍 Sequestration:

Hypersplenism (cirrhosis, portal hypertension)

🔍 Dilutional:

Massive transfusion

THROMBOCYTOSIS (High Platelets >450,000/μL)

🔍 Primary (Clonal):

Essential Thrombocythemia: JAK2, CALR, or MPL mutations. Risk of thrombosis and bleeding
Polycythemia Vera, CML, PMF: Can present with elevated platelets

🔍 Secondary (Reactive):

Inflammation, infection, iron deficiency, malignancy, splenectomy, acute bleeding, recovery from bone marrow suppression

PLATELET FUNCTION DISORDERS

🔍 Types:

Bernard-Soulier Syndrome: Giant platelets, deficiency of GPIb-IX-V complex
Glanzmann Thrombasthenia: Deficiency of GPIIb-IIIa complex
Storage Pool Defects: Dense granule or α-granule deficiency
Acquired: Uremia, medications (aspirin, NSAIDs, clopidogrel), myeloproliferative disorders

📊 Presentation:

Mucocutaneous bleeding, prolonged bleeding time, normal platelet count, abnormal platelet aggregation studies

🟣 Coagulation Disorders

Bleeding and thrombotic disorders

HEMOPHILIA

🔍 Types:

Hemophilia A: Factor VIII deficiency. X-linked recessive. Most common severe bleeding disorder
Hemophilia B (Christmas Disease): Factor IX deficiency. X-linked recessive

📊 Labs:

Prolonged PTT, normal PT, normal platelets, decreased factor VIII or IX levels

📊 Presentation:

Hemarthrosis, deep tissue bleeding, intracranial hemorrhage, excessive bleeding with surgery/trauma

💊 Management:

Factor replacement (recombinant or plasma-derived), desmopressin for mild hemophilia A, emicizumab for hemophilia A with inhibitors

VON WILLEBRAND DISEASE (VWD)

📊 Definition:

Most common inherited bleeding disorder. Deficiency or dysfunction of von Willebrand factor (vWF)

🔍 Types:

Type 1 (75%): Partial quantitative deficiency. Autosomal dominant
Type 2: Qualitative defects in vWF. Multiple subtypes (2A, 2B, 2M, 2N)
Type 3 (Rare): Complete deficiency. Autosomal recessive. Severe bleeding

📊 Labs:

Low vWF antigen, low vWF activity (ristocetin cofactor), may have prolonged PTT, may have low Factor VIII

💊 Management:

Desmopressin (DDAVP) for type 1, vWF/Factor VIII concentrates, antifibrinolytics (tranexamic acid)

OTHER COAGULATION DISORDERS

🔍 Bleeding Disorders:

Factor XI Deficiency: Mild bleeding, common in Ashkenazi Jews. Prolonged PTT
Vitamin K Deficiency: ↓Factors II, VII, IX, X. Prolonged PT and PTT. Causes: malabsorption, antibiotics, warfarin
Liver Disease: Decreased synthesis of all clotting factors. Prolonged PT/PTT, low platelets
DIC: Consumption of clotting factors and platelets. ↓Fibrinogen, ↑PT/PTT, ↑D-dimer, schistocytes

🔍 Thrombotic Disorders:

Factor V Leiden: Most common inherited thrombophilia. Resistance to activated protein C
Prothrombin G20210A Mutation: Elevated prothrombin levels
Protein C/S Deficiency: Autosomal dominant. Warfarin-induced skin necrosis risk
Antithrombin Deficiency: Most severe thrombophilia. Heparin resistance
Antiphospholipid Syndrome: Lupus anticoagulant, anticardiolipin antibodies. Paradoxical thrombosis with prolonged PTT

🟢 Other Hematologic Disorders

Lymphomas, Plasma Cell disorders, and other conditions

LYMPHOMAS

🔍 Hodgkin Lymphoma:

Classic Hodgkin: Reed-Sternberg cells required. B symptoms common (fever, night sweats, weight loss)
Subtypes: Nodular sclerosis (most common, young females), Mixed cellularity, Lymphocyte-rich, Lymphocyte-depleted
Staging: Ann Arbor staging system. Favorable prognosis with ABVD chemotherapy ± radiation

🔍 Non-Hodgkin Lymphoma:

Diffuse Large B-Cell Lymphoma (DLBCL): Most common NHL. Aggressive, rapidly growing mass. R-CHOP chemotherapy
Follicular Lymphoma: Indolent, t(14;18) BCL2 translocation. Watch and wait vs treatment
Mantle Cell Lymphoma: t(11;14) Cyclin D1. Intermediate prognosis
Marginal Zone Lymphoma: MALT lymphoma. Associated with H. pylori (gastric)
Burkitt Lymphoma: Highly aggressive, "starry sky" appearance, c-myc translocation, associated with EBV
Peripheral T-Cell Lymphomas: Heterogeneous group, generally poor prognosis

📊 Diagnosis:

Lymph node biopsy with immunohistochemistry and flow cytometry, PET/CT for staging

PLASMA CELL DISORDERS

🔍 Multiple Myeloma:

Definition: Clonal plasma cell proliferation >10% in bone marrow with end-organ damage
CRAB Criteria: Calcium elevated, Renal insufficiency, Anemia, Bone lesions
Labs: Monoclonal protein (M-spike) on SPEP/UPEP, elevated free light chains, Bence Jones proteinuria
Imaging: Lytic bone lesions on skeletal survey or whole-body CT
Treatment: Induction therapy (bortezomib, lenalidomide, dexamethasone) ± autologous stem cell transplant

🔍 MGUS:

Monoclonal gammopathy of undetermined significance. M-protein <3 g/dL, <10% plasma cells, no end-organ damage. 1% annual risk of progression to myeloma

🔍 Waldenström Macroglobulinemia:

Lymphoplasmacytic lymphoma with IgM monoclonal protein. Hyperviscosity syndrome possible. MYD88 L265P mutation

🔍 Amyloidosis (AL):

Clonal plasma cells produce light chains that deposit as amyloid. Affects heart, kidneys, nerves. Congo red stain shows apple-green birefringence

MISCELLANEOUS DISORDERS

🔍 Hemochromatosis:

Iron overload disorder. HFE gene (C282Y). Bronze diabetes: skin hyperpigmentation, diabetes, hepatomegaly, cardiomyopathy. High ferritin, high transferrin saturation. Treatment: phlebotomy

🔍 Porphyrias:

Heme synthesis defects. Acute intermittent porphyria: abdominal pain, neuropsychiatric symptoms. Porphyria cutanea tarda: photosensitivity, blistering

🔍 Methemoglobinemia:

Oxidized hemoglobin (Fe³⁺) cannot carry oxygen. Cyanosis with normal PaO₂. Chocolate-colored blood. Causes: dapsone, nitrates, benzocaine. Treatment: methylene blue

🔍 Hemoglobinopathies:

Sickle Cell Disease: HbSS, vaso-occlusive crises, splenic sequestration, acute chest syndrome
Hemoglobin C Disease: Mild hemolytic anemia, target cells
Hemoglobin E: Common in Southeast Asia, mild microcytic anemia

🩸 Hematology Unveiled

🔴 Red Blood Cell Disorders

MICROCYTIC ANEMIAS MCV < 80 fL

NORMOCYTIC ANEMIAS MCV 80-100 fL

MACROCYTIC ANEMIAS MCV > 100 fL

⚪ White Blood Cell Disorders

ACUTE LEUKEMIAS

CHRONIC LEUKEMIAS

MYELOPROLIFERATIVE NEOPLASMS (MPN)

MYELODYSPLASTIC SYNDROMES (MDS)

🟡 Platelet Disorders

THROMBOCYTOPENIA (Low Platelets <150,000/μL)

THROMBOCYTOSIS (High Platelets >450,000/μL)

PLATELET FUNCTION DISORDERS

🟣 Coagulation Disorders

HEMOPHILIA

VON WILLEBRAND DISEASE (VWD)

OTHER COAGULATION DISORDERS

🟢 Other Hematologic Disorders

LYMPHOMAS

PLASMA CELL DISORDERS

MISCELLANEOUS DISORDERS