TICS: Thalassemia, Iron deficiency, Chronic disease (can be normo- or microcytic), Sideroblastic. Lead poisoning too.
Split by retic: high → hemolysis or acute blood loss; low → anemia of chronic disease, CKD (↓EPO), aplastic anemia, early iron deficiency.
Megaloblastic (B12/folate, hypersegmented neutrophils) vs non-megaloblastic (alcohol, liver disease, hypothyroidism, MDS, reticulocytosis).
Reticulocytes are immature RBCs. A proper bone-marrow response to anemia raises the retic (corrected/retic index >2%). High retic anemia = blood loss or hemolysis (marrow working). Low retic anemia = production problem (nutrient deficiency, marrow failure, ↓EPO, chronic disease).
| Finding | Think |
|---|---|
| Target cells | Thalassemia, liver disease, HbC, asplenia |
| Schistocytes (helmet cells) | Microangiopathic hemolysis — DIC, TTP/HUS, mechanical valve |
| Spherocytes | Hereditary spherocytosis, warm autoimmune hemolysis |
| Bite cells / Heinz bodies | G6PD deficiency (oxidative stress) |
| Sickle cells / Howell-Jolly bodies | Sickle cell disease (Howell-Jolly = asplenia) |
| Hypersegmented neutrophils | B12 / folate deficiency (megaloblastic) |
| Teardrop cells | Myelofibrosis, marrow infiltration |
| Rouleaux | Multiple myeloma (↑protein) |
| Basophilic stippling | Lead poisoning, sideroblastic, thalassemia |
| Smudge cells | CLL |
| Auer rods | AML (esp. APL) |
| Condition | Serum iron | Ferritin | TIBC | Transferrin sat |
|---|---|---|---|---|
| Iron deficiency | ↓ | ↓↓ | ↑ | ↓ |
| Anemia of chronic disease | ↓ | ↑ (or normal) | ↓ | normal/↓ |
| Thalassemia | normal | normal/↑ | normal | normal |
| Sideroblastic | ↑ | ↑ | normal/↓ | ↑ |
Causes: chronic blood loss (menstrual, GI — think malignancy in older adults), poor intake, malabsorption (celiac), pregnancy. Sx: fatigue, pica, koilonychia (spoon nails), glossitis, restless legs. Smear: microcytic, hypochromic. ↓ferritin, ↑TIBC/RDW. Tx: oral ferrous sulfate (take with vitamin C, avoid with food/PPI); find the source.
Inflammation → hepcidin traps iron in macrophages. Usually normocytic, sometimes mildly microcytic. ↑ferritin, ↓TIBC. Seen with chronic infection, autoimmune disease, malignancy, CKD. Tx: treat the underlying disease.
Defective globin chains; Mediterranean/Asian/African ancestry. Normal iron studies with microcytosis out of proportion to anemia and a normal/low RDW. β-thal: ↑HbA2 on electrophoresis; α-thal: normal electrophoresis (gene deletions). Mentzer index <13 favors thalassemia over IDA. Don't give iron blindly.
Defective heme synthesis → iron-loaded mitochondria ring the nucleus (ringed sideroblasts). Causes: alcohol, lead, isoniazid (B6 deficiency), copper deficiency, MDS, congenital. ↑iron, ↑ferritin. Lead poisoning: basophilic stippling, ± neuro/abdominal symptoms.
| Vitamin B12 (cobalamin) | Folate | |
|---|---|---|
| Neuro symptoms | YES — subacute combined degeneration (dorsal columns: ↓vibration/proprioception), peripheral neuropathy, dementia | NO neuro findings |
| Causes | Pernicious anemia (anti-IF Ab), gastrectomy, terminal ileum disease (Crohn), vegan diet, Diphyllobothrium, metformin/PPI | Poor diet/alcohol, pregnancy, methotrexate, phenytoin, hemolysis |
| Labs | ↓B12, ↑methylmalonic acid & ↑homocysteine | ↓folate, normal MMA, ↑homocysteine |
Impaired DNA synthesis → big RBCs and hypersegmented neutrophils (>5 lobes). Can cause mild pancytopenia and ↑LDH/indirect bilirubin (intramedullary hemolysis). MMA and homocysteine help distinguish B12 from folate.
Alcohol (most common), liver disease, hypothyroidism, MDS, and reticulocytosis (large young RBCs after hemolysis/bleeding). No hypersegmented neutrophils.
X-linked; episodic hemolysis after oxidative stress — infections, fava beans, dapsone, sulfa, antimalarials, nitrofurantoin. Smear: bite cells & Heinz bodies. Test when NOT acutely hemolyzing (young cells have enzyme). Tx: avoid triggers.
Membrane (spectrin/ankyrin) defect; spherocytes, ↑MCHC, +osmotic fragility/EMA binding. Splenomegaly, pigmented gallstones, aplastic crisis with parvovirus B19. Tx: folate; splenectomy for severe disease (Coombs negative — distinguishes from AIHA).
HbS (valine for glutamate). Vaso-occlusive pain crises, acute chest syndrome, splenic sequestration/autosplenectomy (Howell-Jolly bodies → encapsulated-organism infection risk), dactylitis, aplastic crisis (parvovirus B19), priapism, stroke. Tx: hydration, analgesia, O2; hydroxyurea (↑HbF) reduces crises; vaccinate; penicillin prophylaxis in kids.
Warm (IgG): spherocytes, extravascular (spleen); SLE, CLL, drugs. Tx: steroids. Cold (IgM): agglutination, acrocyanosis; Mycoplasma, mono (EBV). Tx: avoid cold. Both Coombs positive.
Schistocytes from RBCs sheared in small vessels: TTP, HUS, DIC, mechanical valves, malignant hypertension, HELLP. Coombs negative.
Pancytopenia with a hypocellular marrow (fatty). Causes: idiopathic/autoimmune, drugs (chloramphenicol, carbamazepine, chemo), radiation, viral (hepatitis, parvovirus, EBV), benzene. Tx: remove cause, immunosuppression, transplant.
Autosomal recessive HFE (C282Y) → excess iron absorption/overload. Classic: cirrhosis, diabetes ("bronze diabetes"), skin hyperpigmentation, plus cardiomyopathy, arthropathy (2nd/3rd MCP), hypogonadism. Labs: ↑transferrin saturation (>45%) and ↑ferritin; confirm with HFE genetic testing ± liver biopsy/MRI. Tx: therapeutic phlebotomy; avoid iron/vitamin C/alcohol. ↑risk hepatocellular carcinoma.
Acquired clonal PIGA mutation → loss of GPI-anchored complement regulators CD55/CD59 → complement-mediated intravascular hemolysis. Triad: hemolytic anemia, thrombosis (unusual sites — hepatic vein/Budd-Chiari), and marrow failure/pancytopenia. Dark morning urine (hemoglobinuria). Dx: flow cytometry (↓CD55/CD59). Tx: eculizumab (anti-C5), supportive; transplant for marrow failure.
| Platelet / vascular (primary) | Coagulation factor (secondary) | |
|---|---|---|
| Bleeding type | Mucocutaneous — petechiae, epistaxis, gum/GI bleeding, menorrhagia | Deep — hemarthrosis, muscle hematoma, delayed bleeding |
| Onset after injury | Immediate | Delayed |
| Key test | Platelet count, vWF; (bleeding time) | PT / aPTT |
| Test | Pathway / factors | Prolonged in |
|---|---|---|
| PT/INR | Extrinsic (VII) + common | Warfarin, vitamin K deficiency, liver disease, factor VII |
| aPTT | Intrinsic (XII, XI, IX, VIII) + common | Heparin, hemophilia A (VIII) / B (IX), vWD, antiphospholipid |
| Both | Common pathway (X, V, II, fibrinogen) | DIC, liver failure, severe vitamin K deficiency, DOACs |
Most common inherited bleeding disorder (autosomal dominant). Mucocutaneous bleeding; ↑aPTT possible (vWF carries VIII), abnormal ristocetin cofactor. Tx: desmopressin (DDAVP) releases vWF; vWF concentrate for severe.
X-linked recessive (boys). A = factor VIII (more common), B = factor IX. ↑aPTT, normal PT/platelets; hemarthrosis, deep muscle bleeds. Tx: factor replacement; DDAVP for mild A.
Isolated low platelets, otherwise normal counts/smear; anti-platelet antibodies. Kids: post-viral, self-limited. Adults: chronic. Dx of exclusion. Tx (if bleeding or very low): steroids, IVIG; splenectomy/TPO agonists later.
TTP pentad: MAHA + thrombocytopenia + neuro + renal + fever (ADAMTS13 deficiency). Tx: plasma exchange (NOT platelets). HUS: MAHA + thrombocytopenia + AKI, often after Shiga-toxin E. coli O157:H7 in kids; supportive care.
Systemic activation of clotting (sepsis, OB emergencies, malignancy, trauma) → consumes factors/platelets → bleeding + thrombosis. Labs: ↑PT & aPTT, ↓platelets, ↓fibrinogen, ↑D-dimer, schistocytes. Tx: treat the cause; replace products if bleeding.
Affects factors II, VII, IX, X (+ protein C/S). PT rises first (factor VII shortest half-life). Newborns, malabsorption, antibiotics, warfarin. Reverse: vitamin K; 4-factor PCC (or FFP) for serious bleeding.
Factor V Leiden (most common; activated protein C resistance), prothrombin G20210A mutation, protein C/S deficiency, antithrombin III deficiency. Suspect with unprovoked/recurrent VTE, young age, unusual sites, or family history.
Antiphospholipid syndrome (paradoxically ↑aPTT, arterial+venous clots, miscarriages; lupus anticoagulant/anti-cardiolipin) — treat with warfarin. Also malignancy, pregnancy, estrogen, nephrotic syndrome, immobility, surgery.
| Drug | Mechanism / monitor | Reversal |
|---|---|---|
| Unfractionated heparin | Activates antithrombin (↓IIa,Xa); monitor aPTT | Protamine sulfate |
| LMWH (enoxaparin) | ↓Xa > IIa; usually no monitoring (anti-Xa if needed); preferred in pregnancy/cancer | Protamine (partial) |
| Warfarin | ↓Vitamin K factors II,VII,IX,X; monitor INR | Vitamin K, 4-factor PCC, FFP |
| DOAC — Xa (apixaban, rivaroxaban) | Direct factor Xa inhibitor | Andexanet alfa (or PCC) |
| DOAC — dabigatran | Direct thrombin (IIa) inhibitor | Idarucizumab |
| Leukemia | Who | Hallmarks |
|---|---|---|
| ALL | Children (most common childhood cancer) | TdT+, CNS/testicular spread, t(12;21) good / Ph+ poorer; responds well to chemo; tumor lysis risk |
| AML | Adults (older) | Auer rods; APL = t(15;17) → DIC, treat with ATRA; myeloperoxidase+ |
| CLL | Older adults (>60), most common adult leukemia | Smudge cells, mature lymphocytosis; often asymptomatic; can cause warm AIHA; Richter transformation |
| CML | Adults 40–60 | Philadelphia chromosome t(9;22) BCR-ABL; ↑↑WBC with all granulocyte stages, low LAP; blast crisis. Tx: imatinib (TKI) |
Rapid onset from blasts crowding marrow → pancytopenia: anemia (fatigue), neutropenia (infection), thrombocytopenia (bleeding). >20% blasts in marrow. Medical urgency; watch tumor lysis syndrome.
Insidious; mature-appearing cells. Often found incidentally (lymphocytosis or leukocytosis). CLL = B cells/smudge cells; CML = granulocytes/Ph chromosome.
| Hodgkin lymphoma | Non-Hodgkin lymphoma | |
|---|---|---|
| Cell | Reed-Sternberg ("owl eyes," CD15+/CD30+) | B (most) or T cell; many subtypes |
| Spread | Contiguous, localized; bimodal age (young adults & elderly) | Non-contiguous, often widespread/extranodal |
| Clues | Painless cervical nodes, B symptoms (fever, night sweats, weight loss), pain with alcohol, EBV-associated | Older adults; HIV/EBV/H. pylori (MALT), autoimmune links; Burkitt = "starry sky," t(8;14) |
Malignant plasma cells. CRAB: hyperCalcemia, Renal failure, Anemia, Bone lesions (lytic "punched-out," pain, fractures). M-spike on SPEP, Bence Jones protein in urine, rouleaux, ↑plasma cells in marrow. Infection risk. Not usually a cause of hot/blastic bone scan (lytic).
MGUS: M-protein but no end-organ damage; premalignant, ~1%/yr → myeloma; monitor. Waldenström macroglobulinemia: IgM → hyperviscosity (vision, neuro, bleeding); treat with plasmapheresis for symptoms.
| Disorder | Hallmark |
|---|---|
| Polycythemia vera | JAK2 mutation; ↑RBC (and often WBC/plt); aquagenic pruritus (itch after warm shower), facial plethora, ruddy cyanosis, thrombosis, ↓EPO. Tx: phlebotomy + aspirin ± hydroxyurea |
| Essential thrombocythemia | ↑↑Platelets (>450k); JAK2/CALR; thrombosis & bleeding; aspirin ± cytoreduction |
| Primary myelofibrosis | Marrow fibrosis → teardrop cells, leukoerythroblastic smear, massive splenomegaly, "dry tap" |
| CML | BCR-ABL (Philadelphia) — see Leukemias tab |
Primary (PV): JAK2+, low EPO. Secondary: high EPO from hypoxia (COPD, OSA, high altitude, smoking) or EPO-secreting tumor (RCC). Relative polycythemia = dehydration (normal RBC mass).
Clonal marrow failure in older adults → cytopenias with dysplasia and a hypercellular marrow; ringed sideroblasts, <20% blasts. Risk of transformation to AML. Supportive care, hypomethylating agents.
pRBCs raise Hgb (~1 g/dL per unit). Platelets for thrombocytopenic bleeding. FFP for multiple factor deficiencies/warfarin reversal when PCC unavailable. Cryoprecipitate for fibrinogen (also VIII, vWF, XIII) — DIC, hypofibrinogenemia.
Hypocalcemia (citrate), hyperkalemia, hypothermia, dilutional coagulopathy. Use balanced ratios in trauma.
| Reaction | Timing / cause | Features & action |
|---|---|---|
| Acute hemolytic | Minutes; ABO mismatch (clerical error), IgM | Fever, flank pain, hypotension, hemoglobinuria, DIC — STOP, IV fluids, support |
| Febrile non-hemolytic | Most common; cytokines/WBC antibodies | Fever/chills, no hemolysis — stop, antipyretics; leukoreduce future |
| Allergic / urticarial | Plasma proteins | Hives — antihistamine, can resume slowly |
| Anaphylactic | IgA-deficient recipient | Shock — stop, epinephrine; washed products |
| TRALI | <6 h; donor anti-leukocyte antibodies | Non-cardiogenic pulmonary edema/hypoxia — supportive |
| TACO | Volume overload | Dyspnea, ↑BP, JVD — diurese, slow rate |
| Delayed hemolytic | Days; anamnestic minor antigen (Rh, Kidd) | Falling Hgb, ↑bili — usually mild |
Hemodynamics before diagnosis. Airway/Breathing → control bleeding source → Circulation: 2 large-bore IVs, crystalloid, prepare blood. O-negative for life-threatening bleeding (especially women of childbearing age); O+ acceptable for males/postmenopausal when type unknown. Red flags: spontaneous intracranial bleed, GI bleed + hypotension, diffuse IV-site oozing, large spontaneous hematomas. Labs: PT/INR, aPTT, CBC + smear, fibrinogen, lactate/base deficit, LFTs.
Balanced 1:1:1 plasma : platelets : RBCs (≈6 pRBC + 6 FFP + 1 apheresis platelet) plus TXA and calcium (citrate chelates Ca). Massive transfusion = ≥10 units RBC/24 h (or ≥3 units/hr). Activate for ABC score ≥2, persistent instability, or ongoing bleeding needing OR/angio. Recheck labs q30–60 min.
(1) Bleeding? (2) RBCs being destroyed? (3) Marrow not producing? (4) Unstable? Labs: CBC + indices, reticulocyte count, smear, LDH, haptoglobin, LFTs, type & crossmatch. Symptomatic + hemodynamic compromise → transfuse pRBCs; give iron only after stabilization — never delay a critical transfusion for iron.
Sickled cells block small vessels → ischemic pain (chest, back, limbs). If SpO₂ <95% → oxygen. Otherwise first priority is early, aggressive IV opioids within 30 min + adjuncts (heat). IV fluids if dehydrated (avoid overload). Work up complications (CBC/retic, CMP, CXR if chest symptoms, cultures if febrile).
ACS: new pulmonary infiltrate + respiratory symptoms ± fever → O₂ first, then CXR to confirm; incentive spirometry, antibiotics, pain control, transfusion/exchange if severe. Splenic sequestration (kids): sudden anemia + splenomegaly + shock → urgent transfusion. Aplastic crisis (parvovirus B19): low retic → transfuse. Stroke → exchange transfusion. Priapism → urologic emergency.
ANC <500 + fever ≥38.3 °C. Within 1 hour: rapid assessment + source exam (skin, lungs, oral, perirectal, lines), 2 blood cultures BEFORE antibiotics, then empiric broad-spectrum IV — piperacillin-tazobactam or a carbapenem. Fever in a neutropenic patient is always an emergency.
WBC >100,000 (usually leukemia) → blasts clog microcirculation (resp failure, AMS). ICU, heme consult, leukapheresis + hydroxyurea, hyperhydration (1.5–2× fluids). Avoid RBC transfusion (worsens viscosity).
After chemo of high-burden leukemia/lymphoma: ↑K, ↑phosphate, ↑uric acid → AKI, ↓Ca (binds phosphate). Arrhythmia/seizure risk. Tx: ICU, aggressive IV fluids, allopurinol (or rasburicase), correct electrolytes.
SVC obstruction (malignancy ~70%: lung > lymphoma; also lines/pacemakers). Facial/neck swelling, distended neck veins, bilateral arm edema, dyspnea, cough. Dx: contrast chest CT (mass/widened mediastinum). Tx: elevate head, protect airway, O₂, then chemo/radiation/stent ± anticoagulation; ICU if airway threat.
Always biopsy persistent lymphadenopathy — painless node >2–4 wks + B symptoms → excisional biopsy. B symptoms = worse prognosis. PET/CT for staging. Hodgkin = contiguous spread + Reed-Sternberg; NHL = non-contiguous, extranodal.
ADAMTS13 deficiency → large vWF multimers → microthrombi consume platelets, shear RBCs. FAT RN: Fever, Anemia (hemolytic), Thrombocytopenia, Renal failure, Neuro. Labs: ↓platelets, ↑LDH/indirect bili, ↓haptoglobin, ↑retic, normal PT/aPTT, schistocytes. Tx: plasma exchange + steroids (rituximab if refractory). Never give platelets — fuels thrombosis.
DIC (sepsis, trauma, malignancy, OB): oozing + thrombosis; ↓platelets, ↑PT/aPTT, ↓fibrinogen, ↑D-dimer. Treat the cause; replace products if bleeding. HIT: platelets fall days 5–10 of heparin, thrombosis > bleeding (4Ts score) → stop all heparin, start argatroban; never give platelets.
CO has ~200× the affinity of O₂ for hemoglobin → carboxyhemoglobin. Headache (most common), nausea, AMS, dyspnea, angina; cherry-red is late/unreliable. Dx: co-oximetry COHb level (pulse ox is falsely normal). Tx: 100% O₂ non-rebreather (hyperbaric for severe); goal COHb <10% (half-life 250 min RA → ~75 min on high-flow O₂).
Inhibits vitamin K factors (II, VII, IX, X) → GI bleed, ecchymosis, elevated INR. Reverse per severity: hold ± oral vitamin K; serious bleeding → 4-factor PCC (or FFP) + IV vitamin K.