Emergency Medicine EOR: Hematology (Smarty PANCE)

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

Acute Lymphoblastic Leukemia (ALL): most common in children < 15 years; Acute Myeloid Leukemia (AML): most common in adults >60 years

What peripheral blood finding is pathognomonic for AML and never seen in ALL?

Auer rods — needle-like cytoplasmic inclusions in myeloblasts; pathognomonic for AML (especially M3 subtype/APL)

What blast percentage on bone marrow biopsy is required to diagnose acute leukemia?

≥20% blasts on bone marrow biopsy (or peripheral smear) is diagnostic of acute leukemia

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

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

What lab findings are seen in acute leukemia?

Peripheral blasts >20%, anemia, thrombocytopenia, elevated LDH and uric acid; WBC can be high, normal, or low

What is the most feared complication of AML-M3 (APL) and its emergency treatment?

DIC — treat emergently with All-Trans Retinoic Acid (ATRA) before genetic confirmation

What chromosomal translocation is associated with CML and its classic presentation?

Philadelphia chromosome t(9;22) BCR-ABL; presents with massive splenomegaly, leukocytosis, basophilia; treated with imatinib

What are the classic lab findings in iron deficiency anemia (IDA)?

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

What is the best single test to diagnose iron deficiency anemia?

Serum ferritin < 30 ng/mL — most sensitive and specific; elevated in inflammation so pair with CRP if infection suspected

What type of anemia is seen in chronic kidney disease and why?

Normocytic normochromic anemia due to decreased erythropoietin (EPO) production; treat with EPO analogs and iron

What are the MCV-based categories of anemia and their key causes?

Microcytic (MCV < 80): IDA, thalassemia, sideroblastic, ACD; Normocytic (MCV 80-100): blood loss, ACD, hemolysis, aplastic; Macrocytic (MCV >100): B12/folate deficiency, alcohol, hypothyroidism

What smear finding differentiates B12 deficiency from folate deficiency anemia?

Both cause macrocytic anemia with hypersegmented neutrophils (≥5 lobes); B12 deficiency additionally causes subacute combined degeneration (posterior/lateral columns); folate does not

What is anemia of chronic disease (ACD) and its key differentiating lab from IDA?

ACD: normocytic or microcytic anemia with low serum iron AND low TIBC (vs IDA with high TIBC); ferritin is normal or elevated in ACD

What is the classic triad of aplastic anemia?

Pancytopenia (anemia + leukopenia + thrombocytopenia) with a hypocellular bone marrow (fat replacement >70%)

What are the most common causes of aplastic anemia?

Idiopathic (most common, autoimmune T-cell destruction); drugs (chloramphenicol, NSAIDs, gold, carbamazepine); viral (EBV, hepatitis, parvovirus B19); radiation

What is the gold standard diagnostic test for aplastic anemia?

Bone marrow biopsy showing hypocellularity with >70% fat replacement

What is the definitive treatment for severe aplastic anemia in patients

Allogeneic bone marrow (stem cell) transplantation from an HLA-matched sibling; older patients or no donor: antithymocyte globulin (ATG) + cyclosporine

What peripheral blood finding is characteristic of aplastic anemia on smear?

Normocytic normochromic anemia; notable absence of reticulocytes (reticulocytopenia) — hypoproliferative pattern

What clotting factor is deficient in Hemophilia A and how does it present?

Factor VIII deficiency; X-linked recessive (males affected); presents with hemarthroses, deep muscle hematomas, prolonged PTT with normal PT and normal bleeding time

What clotting factor is deficient in Hemophilia B (Christmas disease)?

Factor IX deficiency; X-linked recessive; identical clinical presentation to Hemophilia A; distinguished only by specific factor assay

What is von Willebrand Disease (vWD) and its classic lab pattern?

Most common inherited bleeding disorder; vWF deficiency or dysfunction; presents with mucocutaneous bleeding; prolonged bleeding time + prolonged PTT; normal PT; treat with DDAVP (type 1)

What is the key lab difference between hemophilia and von Willebrand disease?

Hemophilia: prolonged PTT, normal PT, normal bleeding time; vWD: prolonged PTT, normal PT, prolonged bleeding time (platelet-dependent)

What coagulation tests are prolonged in DIC and what is the treatment?

Prolonged PT, PTT, TT; elevated D-dimer; low fibrinogen; low platelets; schistocytes on smear; treat underlying cause + FFP, platelets, cryoprecipitate

What factor deficiency causes Hemophilia A and what is its acute treatment in the ED?

Factor VIII deficiency; treat acute bleeds with Factor VIII concentrate; DDAVP for mild cases; avoid aspirin/NSAIDs

How do you differentiate platelet-type bleeding from coagulation factor bleeding on exam?

Platelet disorders: mucocutaneous bleeding (petechiae, purpura, gingival, epistaxis); Coagulation factor disorders: deep bleeds (hemarthroses, muscle hematomas, post-op hemorrhage)

What are the most common causes of easy bruising to consider in the ED?

Thrombocytopenia, vWD, medications (aspirin, NSAIDs, anticoagulants, steroids), liver disease, scurvy (vitamin C deficiency), senile purpura, elder abuse

What distinguishes petechiae from purpura and ecchymosis?

Petechiae: < 3mm, non-blanching (thrombocytopenia, vasculitis); Purpura: 3–10mm, non-blanching; Ecchymosis: >10mm (bruising); all are non-blanching (vs blanching erythema)

What lab workup should be ordered for a patient with easy bruising in the ED?

CBC with differential (platelet count), PT/INR, PTT, bleeding time, peripheral smear, LFTs, LDH; consider vWF antigen if platelets and coagulation normal

What is Henoch-Schönlein Purpura (HSP/IgA vasculitis) and its classic tetrad?

IgA-mediated small vessel vasculitis; classic tetrad: palpable purpura (lower extremities/buttocks), arthritis, abdominal pain, renal involvement (hematuria)

What medication-induced cause of easy bruising is most commonly seen in elderly patients?

Corticosteroids — cause dermal atrophy and capillary fragility leading to senile/steroid purpura; skin is thin and tears easily

What are the most common causes of fatigue presenting to the ED to consider?

Anemia, hypothyroidism, depression, chronic infection, malignancy, heart failure, diabetes, sleep apnea, adrenal insufficiency, medications

What thyroid finding causes fatigue and what confirms the diagnosis?

Hypothyroidism — elevated TSH (most sensitive screen), low free T4; symptoms: fatigue, cold intolerance, weight gain, constipation, dry skin, bradycardia

What lab abnormalities suggest adrenal insufficiency as a cause of fatigue in the ED?

Hyponatremia, hyperkalemia, hypoglycemia, eosinophilia; confirm with AM cortisol

What cardiac cause of fatigue must be ruled out in the ED and how?

Heart failure — BNP >100 pg/mL (sensitive), CXR (cardiomegaly, pulmonary edema), echo (EF

What infectious cause of fatigue in a young patient presents with splenomegaly and atypical lymphocytes?

Infectious mononucleosis (EBV); monospot test (heterophile antibodies); avoid contact sports (spleen rupture risk); treat supportively

What is the mechanism of hemolytic anemia and key lab findings?

Premature RBC destruction (< 120 days); elevated indirect bilirubin, elevated LDH, decreased haptoglobin, reticulocytosis, and peripheral smear findings

What peripheral smear finding is pathognomonic for microangiopathic hemolytic anemia (MAHA)?

Schistocytes (fragmented RBCs); seen in TTP, HUS, DIC, malignant hypertension, mechanical heart valves

What is the classic pentad of TTP and its emergency treatment?

Thrombocytopenia, MAHA (schistocytes), Fever, Renal failure, Neurological changes (FAT RN); treat with emergent plasma exchange (plasmapheresis) — do NOT give platelets

What is the Coombs test and when is it used?

Direct Coombs (DAT): detects antibodies/complement on RBCs — positive in autoimmune hemolytic anemia (AIHA), hemolytic transfusion reactions; Indirect Coombs: detects antibodies in serum (pre-transfusion screen)

What RBC enzyme deficiency causes hemolytic anemia triggered by oxidative stress (infections, drugs)?

G6PD deficiency — X-linked; Heinz bodies (denatured Hgb) and bite cells on smear; triggers: dapsone, primaquine, nitrofurantoin, sulfonamides, fava beans

What is the most common hereditary hemolytic anemia in Northern European populations?

Hereditary spherocytosis — spectrin defect; spherocytes on smear, negative Coombs, elevated MCHC; osmotic fragility test positive; treat severe cases with splenectomy

What are the most common inherited hypercoagulable states?

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

What is Antiphospholipid Syndrome (APS) and its classic lab findings?

Autoimmune hypercoagulable state causing arterial AND venous clots + recurrent pregnancy loss; positive lupus anticoagulant, anticardiolipin Ab, anti-β2-glycoprotein I Ab; paradoxically prolongs PTT in vitro

What is the initial anticoagulation treatment for acute DVT/PE in the ED?

Heparin (IV unfractionated or LMWH) bridging to warfarin; DOACs (rivaroxaban, apixaban) now preferred for most non-cancer patients — no bridging needed

What clinical decision tool is used to risk-stratify DVT and PE in the ED?

Wells Criteria: DVT Wells score (clinical features); PE Wells score; combined with D-dimer — if low probability + negative D-dimer, VTE excluded without imaging

What thrombophilia workup caveat must be remembered in the ED?

Do NOT draw hypercoagulable labs during acute clot or while on anticoagulation — falsely abnormal results; defer to outpatient hematology follow-up

What is the most common type of Hodgkin Lymphoma and its pathognomonic cell?

Nodular Sclerosis Hodgkin Lymphoma (most common in young adults); Reed-Sternberg cells (owl-eye nuclei, CD15+/CD30+) are pathognomonic

What are classic B symptoms of lymphoma and their significance?

Fever >38°C, drenching night sweats, weight loss >10% in 6 months — indicate systemic disease (upstages prognosis, Stage B)

What is the Ann Arbor staging system for lymphoma?

Stage I: single node region; Stage II: ≥2 regions same side of diaphragm; Stage III: both sides of diaphragm; Stage IV: disseminated/extranodal; A=no B symptoms, B=B symptoms

What distinguishes Hodgkin from Non-Hodgkin Lymphoma clinically?

Hodgkin: younger patients, contiguous node spread, mediastinal involvement, Reed-Sternberg cells, B symptoms common; NHL: older patients, non-contiguous spread, more extranodal

What lymphoma is most common in AIDS/HIV patients and is an AIDS-defining illness?

Primary CNS Lymphoma (PCNS-L) and Burkitt lymphoma; Burkitt: "starry sky" pattern, c-Myc translocation t(8;14), associated with EBV

What is the most common non-Hodgkin lymphoma in adults?

Diffuse Large B-Cell Lymphoma (DLBCL) — aggressive, CD20+; treat with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

What are the two types of polycythemia and how are they differentiated?

Primary (Polycythemia Vera/PV): JAK2 mutation, low EPO; Secondary: elevated EPO due to chronic hypoxia (COPD, OSA, high altitude) or EPO-secreting tumors

What mutation is diagnostic of Polycythemia Vera (PV)?

JAK2 V617F mutation in >95% of cases; EPO level is LOW (distinguishes from secondary polycythemia where EPO is elevated)

What are the classic symptoms of polycythemia and the pathognomonic symptom of PV?

Headache, plethora, hypertension, thrombosis, pruritus after hot shower (aquagenic pruritus — pathognomonic for PV), splenomegaly

What are the diagnostic criteria thresholds for polycythemia?

Hgb >16.5 g/dL in men or >16 g/dL in women (or Hct >49% men, >48% women); confirm with JAK2 mutation and bone marrow biopsy

What is the treatment of Polycythemia Vera and the key immediate intervention?

Phlebotomy (target Hct < 45%) is first-line; aspirin 81mg daily for thrombosis prevention; hydroxyurea for high-risk patients; treat symptoms

What is the most common cause of death in polycythemia vera?

Thrombosis (arterial > venous) — including stroke, MI, DVT/PE; secondary risk of AML transformation (~10% at 20 years)

What are the 4 types of sickle cell crisis and their ED presentations?

Vaso-occlusive (pain crisis) — most common; Aplastic crisis (parvovirus B19); Sequestration crisis (spleen/liver trapping); Hemolytic crisis (accelerated hemolysis)

What is the first-line ED management of sickle cell vaso-occlusive pain crisis?

IV hydration (NS or LR), aggressive IV opioid analgesia (morphine/hydromorphone), NSAIDs adjunct, oxygen if hypoxic, incentive spirometry

What is acute chest syndrome (ACS) in sickle cell disease and its treatment?

New pulmonary infiltrate + fever/respiratory symptoms in SCD; most common cause of death; treat with simple or exchange transfusion, antibiotics (covers atypicals), O2, incentive spirometry

What triggers should patients with sickle cell avoid and be counseled about?

Dehydration, hypoxia, cold temperatures, high altitude, infection, acidosis, stress — all precipitate sickling

What preventive medications are prescribed for sickle cell disease and their mechanisms?

Hydroxyurea: increases HbF (fetal hemoglobin), reducing sickling — reduces pain crises and ACS by 50%; Penicillin VK prophylaxis in children

What is the splenic complication unique to sickle cell adults vs children?

Children: splenic sequestration crisis (acute splenomegaly, sudden Hgb drop) — requires transfusion; Adults: autosplenectomy (functional asplenia from repeated infarcts) — risk of encapsulated organisms (Strep pneumo, H. flu, Neisseria)

What vaccines are mandatory in asplenic/functionally asplenic sickle cell patients?

Pneumococcal (PCV13 + PPSV23), Meningococcal (MenACWY + MenB), Haemophilus influenzae type b (Hib) — protect against encapsulated organisms

What is Immune Thrombocytopenic Purpura (ITP) and its classic presentation?

Autoimmune platelet destruction by anti-GPIIb/IIIa antibodies; isolated thrombocytopenia (< 100K), normal PT/PTT, no splenomegaly; children: post-viral; adults: chronic, females

What is the treatment of ITP in the ED for active bleeding or platelets

Corticosteroids (prednisone 1mg/kg) first-line; IVIG for rapid platelet rise; Rh(D) immunoglobulin in Rh+ non-splenectomized; platelet transfusion only for life-threatening bleed

What is Thrombotic Thrombocytopenic Purpura (TTP) and how does it differ from HUS?

TTP: ADAMTS13 deficiency, predominantly neurological; HUS: Shiga toxin (E. coli O157:H7), predominantly renal failure, children; both have MAHA + thrombocytopenia

What platelet count threshold is used for prophylactic transfusion in a non-bleeding patient?

Platelets < 10,000/μL (or <20,000 if febrile/septic) — prophylactic transfusion; <50,000 for invasive procedures; <100,000 for neurosurgery/ocular surgery

What drug class is the most common cause of drug-induced thrombocytopenia in the ED?

Heparin (HIT — Heparin-Induced Thrombocytopenia); also: quinine, quinidine, sulfonamides, vancomycin, linezolid; HIT: platelet drop >50% on days 5-10 of heparin, paradoxically thrombotic

What is the 4T score and its use in HIT?

4T score assesses: Thrombocytopenia magnitude, Timing of drop (days 5-10), Thrombosis or other sequelae, oTher causes excluded; score ≥4 = intermediate/high probability; stop heparin immediately, switch to argatroban or fondaparinux