Internal Medicine EOR: Hematology (Smarty PANCE)

What are the types of acute leukemia and their age distributions?

Acute Lymphoblastic Leukemia (ALL): most common in children <15 years; Acute Myeloid Leukemia (AML): most common in adults >65 years

What are the classic symptoms of acute leukemia? Use mnemonic FABING

Fatigue/weakness, Anemia symptoms, Bleeding/petechiae, Infection/fever, Neutropenia complications, Gingival hyperplasia (AML-M5)

What laboratory findings suggest acute leukemia?

Peripheral blood: blasts >20%, anemia, thrombocytopenia; Bone marrow: >20% blasts (diagnostic); elevated LDH, uric acid

What are Auer rods and their significance?

Needle-like cytoplasmic inclusions seen in myeloblasts - pathognomonic for AML (never seen in ALL)

What is the difference between chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL)?

CML: Philadelphia chromosome (BCR-ABL), younger patients (40-60), splenomegaly; CLL: older patients (>60), lymphocytosis, smudge cells

What is the Philadelphia chromosome?

t(9;22) translocation creating BCR-ABL fusion gene - present in 95% of CML cases, treated with tyrosine kinase inhibitors (imatinib)

What are smudge cells and their significance?

Fragile lymphocytes that rupture during blood smear preparation - characteristic of CLL

What is the most common leukemia in adults overall?

Chronic Lymphocytic Leukemia (CLL) - typically indolent course in elderly patients

What is tumor lysis syndrome and when does it occur?

Life-threatening complication of chemotherapy causing hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, acute kidney injury

What is anemia of chronic disease (ACD)?

Anemia due to chronic inflammation causing decreased iron availability, blunted EPO response, and shortened RBC survival

What are the classic laboratory findings in anemia of chronic disease?

Low iron, low TIBC, normal or elevated ferritin, normal or low MCV, elevated ESR/CRP

How is anemia of chronic disease differentiated from iron deficiency anemia?

ACD: low iron, low TIBC, normal/high ferritin; IDA: low iron, high TIBC, low ferritin

What chronic conditions commonly cause anemia of chronic disease?

Chronic infections (TB, endocarditis), autoimmune diseases (RA, SLE), malignancy, chronic kidney disease

What is the mechanism of anemia in chronic disease?

Increased hepcidin (from inflammation) blocks iron release from stores and absorption - functional iron deficiency

What is the treatment for anemia of chronic disease?

Treat underlying condition (primary treatment), erythropoietin-stimulating agents if EPO deficient, iron supplementation only if truly deficient

What is hemophilia A vs hemophilia B?

Hemophilia A: Factor VIII deficiency (most common, 85%); Hemophilia B (Christmas disease): Factor IX deficiency

What is the inheritance pattern of hemophilia?

X-linked recessive - affects males, carried by females (daughters of affected males are obligate carriers)

What are the classic laboratory findings in hemophilia?

Prolonged PTT, normal PT, normal platelet count, normal bleeding time, decreased specific factor level

What is the treatment for hemophilia?

Factor replacement therapy: recombinant Factor VIII (hemophilia A) or Factor IX (hemophilia B), desmopressin (DDAVP) for mild hemophilia A

What is von Willebrand disease (vWD)?

Most common inherited bleeding disorder - deficiency or dysfunction of von Willebrand factor (platelet adhesion and Factor VIII carrier)

What are the laboratory findings in von Willebrand disease?

Prolonged bleeding time, prolonged or normal PTT, decreased vWF antigen, decreased ristocetin cofactor activity

What is the treatment for von Willebrand disease?

Desmopressin (DDAVP) for Type 1 vWD, vWF/Factor VIII concentrates for Types 2 and 3

What is G6PD deficiency?

X-linked recessive enzyme deficiency causing hemolytic anemia when exposed to oxidative stress

What are common triggers for hemolysis in G6PD deficiency? Use mnemonic FAVA

Fava beans, Antimalarials (primaquine, chloroquine), Sulfonamides, Aspirin (high dose), Infection/illness

What are the classic laboratory findings in G6PD deficiency during hemolysis?

Hemolytic anemia, elevated reticulocytes, bite cells, Heinz bodies, elevated indirect bilirubin, decreased haptoglobin

What ethnic groups have highest prevalence of G6PD deficiency?

African, Mediterranean, Middle Eastern, Southeast Asian descent - provides malaria resistance

What is the treatment for G6PD deficiency?

Avoid oxidative triggers, supportive care during hemolytic episodes, transfusion if severe anemia, monitor for jaundice

What is Virchow's triad for hypercoagulable states?

Stasis (immobility), Endothelial injury (surgery, trauma), Hypercoagulability (genetic or acquired factors)

What are the most common inherited hypercoagulable disorders?

Factor V Leiden (most common), Prothrombin G20210A mutation, Protein C/S deficiency, Antithrombin deficiency

What are acquired hypercoagulable states?

Malignancy, pregnancy/postpartum, oral contraceptives, antiphospholipid syndrome, prolonged immobility, surgery

What is Factor V Leiden?

Most common inherited thrombophilia - resistance to activated Protein C causing increased clotting risk (5-10x)

What is antiphospholipid syndrome?

Acquired hypercoagulable state with arterial/venous thrombosis, recurrent pregnancy loss, prolonged PTT paradoxically

What laboratory findings suggest antiphospholipid syndrome?

Prolonged PTT (lupus anticoagulant), positive anticardiolipin antibodies, positive anti-β2 glycoprotein I antibodies

When should hypercoagulable workup be performed?

Unprovoked VTE, recurrent VTE, VTE at young age (<50), unusual thrombosis sites, family history of VTE

What is idiopathic thrombocytopenic purpura (ITP)?

Autoimmune disorder causing isolated thrombocytopenia due to antiplatelet antibodies destroying platelets in spleen

What are the classic presenting features of ITP?

Petechiae, purpura, mucosal bleeding, platelet count <100,000 (often <30,000), otherwise normal CBC and smear

How is ITP diagnosed?

Diagnosis of exclusion: isolated thrombocytopenia, normal hemoglobin/WBC, large platelets on smear, no splenomegaly

What is the difference between acute and chronic ITP?

Acute ITP: children, follows viral infection, self-limited (<6 months); Chronic ITP: adults, insidious onset, lasts >12 months

What is the treatment for ITP based on platelet count?

>30,000: observation; 20,000-30,000: corticosteroids; <20,000 or bleeding: corticosteroids + IVIG or anti-D immunoglobulin

What is the first-line treatment for symptomatic ITP?

Corticosteroids (prednisone 1mg/kg/day or dexamethasone pulse therapy)

When is splenectomy considered in ITP?

Refractory to medical therapy, chronic symptomatic ITP, platelet count <30,000 despite treatment

What is iron deficiency anemia?

Most common cause of anemia worldwide - microcytic hypochromic anemia due to inadequate iron for hemoglobin synthesis

What are the most common causes of iron deficiency anemia?

Blood loss (GI bleeding, menstruation most common), inadequate dietary intake, malabsorption (celiac disease), increased demand (pregnancy)

What are the classic laboratory findings in iron deficiency anemia?

Microcytic anemia (MCV <80), low ferritin (<30 ng/mL), low iron, elevated TIBC (>450), low transferrin saturation (<20%)

What is the best single test to diagnose iron deficiency?

Serum ferritin <30 ng/mL - most sensitive and specific marker for iron deficiency

What are the classic symptoms of iron deficiency?

Fatigue, pallor, pica (ice/clay craving), koilonychia (spoon nails), glossitis, angular cheilitis

What is the treatment for iron deficiency anemia?

Oral ferrous sulfate 325mg TID (65mg elemental iron per tablet), taken with vitamin C, on empty stomach

When should parenteral iron be used?

Intolerance to oral iron, malabsorption, chronic kidney disease on dialysis, severe anemia requiring rapid correction

What is Plummer-Vinson syndrome?

Triad of iron deficiency anemia, esophageal webs, and dysphagia - increased risk of esophageal cancer

What is the difference between Hodgkin and Non-Hodgkin lymphoma?

Hodgkin: Reed-Sternberg cells present, bimodal age (20s and >55), better prognosis; Non-Hodgkin: no Reed-Sternberg cells, older age

What are Reed-Sternberg cells?

Owl's eye appearance - large binucleated cells pathognomonic for Hodgkin lymphoma

What are the classic B symptoms of lymphoma?

Fever >38°C, night sweats (drenching), unintentional weight loss >10% body weight in 6 months

What is the most common presentation of Hodgkin lymphoma?

Painless cervical or supraclavicular lymphadenopathy in young adults (20-30s), may have mediastinal mass

What is the most common type of Non-Hodgkin lymphoma?

Diffuse large B-cell lymphoma (DLBCL) - aggressive but potentially curable

How is lymphoma diagnosed?

Excisional lymph node biopsy (not FNA) - requires tissue architecture for classification

What imaging is used for lymphoma staging?

PET-CT scan - most accurate for staging and treatment response assessment

What is the Ann Arbor staging system for lymphoma?

Stage I: single lymph node region; II: ≥2 regions same side of diaphragm; III: both sides of diaphragm; IV: extranodal involvement

What is multiple myeloma?

Malignant plasma cell disorder causing bone destruction, hypercalcemia, renal failure, and anemia - peak age 65-70 years

What are the classic features of multiple myeloma? Use mnemonic CRAB

Calcium elevated (hypercalcemia), Renal failure, Anemia, Bone lesions (lytic lesions)

What laboratory findings are diagnostic for multiple myeloma?

Monoclonal protein (M-spike) on SPEP/UPEP, >10% plasma cells in bone marrow, elevated free light chains

What is Bence Jones protein?

Monoclonal light chains (kappa or lambda) in urine - seen in 75% of multiple myeloma cases

What imaging findings are characteristic of multiple myeloma?

"Punched-out" lytic bone lesions on X-ray, especially in skull (salt and pepper appearance), vertebrae, ribs

What are the major complications of multiple myeloma?

Pathologic fractures, spinal cord compression, hyperviscosity syndrome, infections (encapsulated organisms), renal failure

What is rouleaux formation?

RBCs stacked like coins on blood smear - caused by increased serum proteins in multiple myeloma

What is the treatment for multiple myeloma?

Chemotherapy combinations (bortezomib, lenalidomide, dexamethasone), autologous stem cell transplant for eligible patients

What is sickle cell anemia?

Autosomal recessive disorder - hemoglobin S (HbSS) causing RBC sickling under hypoxic conditions

What are the classic complications of sickle cell disease? Use mnemonic SICKLE

Stroke, Infections (encapsulated organisms), Crisis (vaso-occlusive), Kidney disease, Lung (acute chest syndrome), Eye (retinopathy)

What is a vaso-occlusive crisis in sickle cell disease?

Most common crisis - severe pain from vascular occlusion, triggered by dehydration, infection, cold, hypoxia

What is acute chest syndrome?

Life-threatening complication - new pulmonary infiltrate with fever, chest pain, hypoxia - leading cause of death in sickle cell

What laboratory findings are seen in sickle cell disease?

Hemolytic anemia (Hgb 6-9), reticulocytosis, sickled cells on smear, positive sickle cell prep, hemoglobin electrophoresis (HbSS)

What is the treatment for vaso-occlusive crisis?

Aggressive hydration (IV fluids), pain control (opioids), oxygen if hypoxic, identify/treat triggers

What preventive measures are essential in sickle cell disease?

Hydroxyurea (increases HbF), penicillin prophylaxis (until age 5), vaccinations (pneumococcal, H. flu, meningococcal), folic acid

What is the mechanism of hydroxyurea in sickle cell disease?

Increases fetal hemoglobin (HbF) production, decreases sickling, reduces vaso-occlusive crises by 50%

What is thalassemia?

Hereditary disorder causing decreased or absent globin chain synthesis - alpha or beta chains

What is the difference between alpha and beta thalassemia?

Alpha: decreased alpha chains (chromosome 16), 4 genes; Beta: decreased beta chains (chromosome 11), 2 genes

What are the types of beta thalassemia?

Thalassemia minor (trait): 1 gene, mild microcytic anemia; Thalassemia major (Cooley's): 2 genes, severe transfusion-dependent anemia

What are the classic laboratory findings in thalassemia?

Microcytic anemia (MCV <80), normal or elevated RBC count, normal ferritin, target cells, elevated RDW in beta thalassemia

How is thalassemia differentiated from iron deficiency?

Mentzer index: MCV/RBC count - <13 suggests thalassemia, >13 suggests iron deficiency

What is the hemoglobin electrophoresis pattern in beta thalassemia major?

Elevated HbF (fetal hemoglobin) and HbA2, absent or minimal HbA

What are the complications of beta thalassemia major?

Severe anemia requiring transfusions, iron overload, cardiomyopathy, hepatosplenomegaly, skeletal abnormalities (chipmunk facies)

What is the treatment for beta thalassemia major?

Regular blood transfusions (maintain Hgb >9-10), iron chelation therapy (deferoxamine, deferasirox), allogeneic stem cell transplant (curative)

What is thrombotic thrombocytopenic purpura (TTP)?

Life-threatening thrombotic microangiopathy - deficiency of ADAMTS13 enzyme causing platelet microthrombi

What is the classic pentad of TTP?

Thrombocytopenia, Microangiopathic hemolytic anemia, Renal failure, Fever, Neurologic changes (only 40% have all five)

What laboratory findings are diagnostic for TTP?

Severe thrombocytopenia (<20,000), schistocytes on smear, elevated LDH, low haptoglobin, negative Coombs, ADAMTS13 <10%

How is TTP differentiated from HUS (hemolytic uremic syndrome)?

TTP: primarily neurologic symptoms, ADAMTS13 deficiency; HUS: primarily renal failure, often follows E. coli O157:H7 infection in children

What is the mechanism of TTP?

Deficiency of ADAMTS13 (vWF-cleaving protease) causes large vWF multimers that aggregate platelets forming microthrombi

What is the treatment for TTP?

Plasma exchange (plasmapheresis) - must start immediately, life-saving; corticosteroids, rituximab for refractory cases

What is the prognosis of untreated vs treated TTP?

Untreated: 90% mortality; With plasma exchange: >85% survival

What is vitamin B12 deficiency anemia?

Macrocytic megaloblastic anemia due to inadequate B12 for DNA synthesis - causes neurologic complications

What are the most common causes of B12 deficiency?

Pernicious anemia (anti-intrinsic factor antibodies), dietary deficiency (vegans), malabsorption (Crohn's, gastrectomy, ileal resection)

What are the classic symptoms of B12 deficiency?

Anemia symptoms PLUS neurologic: paresthesias, ataxia, decreased proprioception/vibration, dementia, subacute combined degeneration

What is subacute combined degeneration?

Demyelination of dorsal columns and lateral corticospinal tracts from B12 deficiency - causes ataxia and spastic paresis

What are the laboratory findings in B12 deficiency?

Macrocytic anemia (MCV >100), hypersegmented neutrophils (>5 lobes), elevated methylmalonic acid and homocysteine, low B12 (<200)

What is pernicious anemia?

Autoimmune destruction of gastric parietal cells causing decreased intrinsic factor and B12 malabsorption

How is folate deficiency differentiated from B12 deficiency?

Both cause macrocytic anemia with hypersegmented neutrophils; Only B12 causes neurologic symptoms and elevated methylmalonic acid

What is the treatment for B12 deficiency?

Intramuscular B12 (1000 mcg) daily x 1 week, then weekly x 4 weeks, then monthly for life; oral high-dose B12 alternative if not pernicious anemia

What medications can cause folate deficiency?

Methotrexate, trimethoprim, phenytoin, sulfasalazine, alcohol

What is the treatment for folate deficiency?

Oral folic acid 1mg daily; ALWAYS check B12 first - treating folate alone can worsen B12 neurologic symptoms