Hematology

Question 1

vit K def

Answer 1

• rare, vit K usually comes from liver, green leafy veg, broccoli, peas, green beans, soybeans
• occurs from deficient intake of vitK, malabsorption, or decreased intestinal production by bacteria (from chemotherapy or abx)
• vit K plays role in activity of coag factors II, VII, IX, and X
• sxs: soft tissue ecchymosis, hematomas, mucosal bleeding
• dx: PT prolonged, clotting factors low
• tx: vitK via IV or PO

Question 2

polycythemia vera

Answer 2

• inc production of basophils and mast cells → itching after hot shower from hist release
• onset 50-70yo, clonal stem disorder w/ excessive proliferation of erythroid, myeloid, and mekakaryocytic progenitor cells
• spent phase: extramedullary hematopoiesis in liver and spleen w/ normocytic anemia
• sxs: elevate Hgb/Hct, full body itching w/ warm water, HTN, HA, fullness of face/head, dizziness, impaired vision, CP, claudication
• signs: splenomegaly, hepatomegaly, plethora or ruddy complexion
• dx: CBC (hyperviscosity, high RBC count, red cell mass increased, thrombosis, leukocytosis, low serum EPO, elevated B12, hyperuicemia, bone marrow bx
• tx: phlebotomy (goal = hct <45%), low dose ASA, hydroxyurea, median survival = 9-14y

Question 3

iron deficiency anemia

Answer 3

• significant def in mass of circ RBCs (O2 carrying capacity = low
• dec cell mass or Hgb conc; microcytic (MCV <80), hypochromic w/ low H/H
• sxs: fatigue, palps, SOB, weakness, HA, tinnitus
• signs: tachycardia, tachypnea on exert, pallor, glossitis, angular chelitis, pica, koilonychia, jaundice and splenomegaly
• dx: CBC (retic low, RDW = high), dec iron, ferritin, and transferrin, inc TIBC, ferritin <15 (diagnostic), check hgb and hct, periph smear → poikilocytes (pencil or cigar shaped)
• tx: oral iron TID (6wk to correct anemia, 6mo to replete iron) → Ferrous sulfate 3mg/kg once or twice daily, give between meals with juice, not milk

Question 4

sickle cell anemia

Answer 4

• mutation in B-globin gene that changes the 6th amino acid form glutamic acid to valine
• sxs: acute pain (hrs to 2wk); RF → infxn, fever, excess exercise, anxiety, abrupt change in temp, hypoxia, hypertonic dyes
• signs: TTP, fever, tachycardia, anxiety
• complications: pulm HTN, ESRD, hand foot syndrome, priapism (permanent impotence)
• dx: hemolytic anemia, reticulocytosis, granulocytosis, periph smear → elongated and crescent RBCs, target cells, nucleated RBC, Hgb electro, mass spec, sickling tests (confirms)
• tx: crisis → vigorous hydration, aggressive pain meds (morphine), nasal O2; severe sxs → hydroxyurea, pts 3+ crises/year or repeated ACS → increases production of Hgb F (cant sickle), BMT

Question 5

acute chest syndrome

Answer 5

• in situ sickling w/in lung, producing pain and temporary pulm dysfn
• sxs: CP, fever, cough
• signs: tachypnea
• dx: arterial O2 desat
• tx: monitor hydration for pulm edema, O2 tx, transfuse to Hct >30
• complicaitons: pulm HTN, cor pulmonale

Question 6

B thalassemia

Answer 6

• only 2 Bglobin genes on chrom 11, but 4 alpha genes on chrom 16 → disrupts ratio between alpha and beta chains → changes stability of Hb and causes hemolysis
• sxs: asx, mild anemia
• signs: HSM, jaundice
• dx: Hgb electrophoresis, CBC (microcytic hypochromic anemia), iron NL to increased (serum iron, ferritin, transferrin sat, normal TIBC), peripheral smear → target cells, basophilic stippling, elliptocytes
• tx: transfusion, PO iron repletion and B12 only if concomittant iron def anemia, allogenic bone marrow transp, folic acid, deferoxamine (iron chelator), splenectomy

Question 7

megaloblastic anemia

Answer 7

• MCV >100, inhib of DNA synth during RBC produciton
• dx: CBC, iron studies (NL to inc serum iron, ferritin, transferrin sat; NL to DEC TIBC), periph smear shows macrocytic megaloblastic cells

Question 8

Vit B12 deficiency

Answer 8

• vit B12 = cobalamin
• autoimmune destruciton of gastric parietal cells → atrophic gastritis → lack of intrinsic factor produciton; cofactor for 2 enzymatic rxns required for DNA synth, brain/nervous system fn, formation of RBC
• RF: chronic alc, vegetarian, celiac and crohn dz, gastric bypass surg, parasites
• MCC: pernicious anemia (lack of IF)
• sxs: anemia, sore tongue, periph neruopathy, balance probs, depression, dementia, glossitis
• signs: loss of vib touch
• dx: B12 dec, homocysteine inc, methylmalonic acid inc, hyperseg neutrophils
• tx: lifelong IM B12 → cyanocobalamin daily x1wk, weekly x1m, monthly for life

Question 9

folic acid def

Answer 9

• cofactor for DNA synth, alcs and malnourished have smaller stores, dec intake, inc requirement, sickle cell, thalassemia, sprue, crohn, drugs
• sxs: less neuro sxs, neural tube defects (spina bifida)
• dx: homocysteine inc, serum folic acid low, RBC folic acid <150 (dxic), macroovalocytes and hyperseg PMNs (pathognomonic)
• tx: po folic acid 1-5mg, avoid ETOH, green leafy veggies, yeast, legumes, fruits, animal proteins, prophylactic folic acid for preg/lactating and sickle cell

Question 10

hemolytic anemias

Answer 10

• sxs of acute/chronic anemia, dark urine, back pain
• signs: jaundice
• dx: CBC (high retic), inc iron, ferritin, transferrin sat, dec TIBC, total (indirect) bili inc, haptoglobin dec, periph smear → microcytic, normochromic anemia, spherocytes, bone marrow bx

Question 11

glucose-6 phosphate dehydrogenase def

Answer 11

• oxidant sensitive hemolytic dz (heinz bodies + bite cells → RBC destruction)
• MC seen in tropical areas prevalent for malaria (Africa, China, Mediterranean)
• hx: hemolysis only with infxn, met acidosis, and certain meds, chronic hemolytic anemia, jaundice, sx of hemolysis
• dx: periph smear: bite cells, heinz bodies
• tx: avoid potentially harmful drugs, monitor infxn, acute → blood transfusion

Question 12

hereditary spherocytosis

Answer 12

• congenital hemolytic jaundice, familial hemolytic anemia
• inherited dysfn or deficiency in one of the erythrocyte membrane proteins (spectrin, ankyrin, band 3 protein, or protein 4.2) → spherocytic erythrocytes are sequestered and destroyed in spleen; autosomal dom
• sxs: mild jaundice, mild-mod anemia, malaise, abd pain in LUQ
• signs: splenomeg
• dx: CBC, MCV dec; retic count, LDH, indirect bili, stool urobili → elevated; hgb low, EDW elevated, spherocytes on periph smear, osmotic fragility inc, coombs test neg
• tx: splenectomy, cholecystectomy if gallstones present
• complications: hypoplastic crises (follow acute viral illness → profound anemia, HA, N, abd pain, pancytopenia, hypoactive marrow, pigmented gallstones

Question 13

aplastic anemia

Answer 13

• maybe autoimmune, 50% idiopathic, radiation, infeciton, toxins, drugs, inherited . = fanconi syndrome
• sxs: weakness, fatigue, palps, DOE, tinnitus, bleeding and bruising, infxns
• dx: CBC (normocytic anemia, neutropenia, thrombocytopenia), peripheral smear shows peripheral pancytopenia with marrow hypocellularity, bone marrow bx to r/o BDS
• tx: transfusion dependent with growth factors, immunosuppression (ATG stops Tcell response, cyclosporin), cure is allogenic stem cell transplant

Question 14

acute lymphoblastic leukemia

Answer 14

• neoplasm of early lymphocyte precursors, MC in young children <15, MC childhood cancer, peak 2-5y
• RF: initial WBC and age at dx, rate of response, cytogenetics
• sxs: anemia, neutropenia (inc risk of bact infxn), thrombocytopenia (abnl mucosal or cutaneous bleeding, splenomegaly, hepatomegaly, LAD, bone and jnt pain, CNS involvement (meningitis, seizures), testicular involvement (ALL), anterior mediastinal mass (T-cell ALL)
• dx: innunofluorescence assay (TdT +), histology shows lymphoblasts, bone marrow bx required for dx and shows myeloblasts
  
  • labs: WBC count variable with large number of blasts (hyperleukocytosis), anemia, thrombocytopenia, granulocytopenia, electrolytes (hyperuricemia, hyperkalemia, hyperphosphatemia
• tx: most responsive to chemo, 75% achieve full remission, relapses occur but respond well, with aggressive tx, survival rates can be up to 15y or longer
• poor prognostic factors = age <2 or >9, WBC >100000 and CNS involvement

Question 15

burkitt lymphoma

Answer 15

• African and american versions
  
  • African linked to EBV, involves facial bone and jaw
  • American rapidly expanding abdominal mass, GI sx, marrow or CNS dz
  • starry sky appearance, grave prognosis unless txed aggressively with chemo, treatment cures 50-60%

Question 16

Disseminated intravascular coag

Answer 16

• generalized activation of coag cascade → widespread fibrin formation → consumption of platelets and clotting factors → microthrombosis → increased fibrinolysis
• causes: infxn, mech tissue injury, malig, preg, consumptive coagulopathy (consumption of clotting factors 5 and 8, protein C, and low platelets), hereditary and acquired factors tip balance in favor of clotting → thrombophilic v. hypercoaguable state
• sxs: generalized hemorrhage (petechiae and ecchymoses → GI bleed, GU bleed, surg wound, mucocutaneous or venupuncture site bleed), mental status change, focal ischemia or gangrene, oliguria, renal cortical necrosis, ARDS
• dx: thrombocytopenia, FDP/D-dimer increased, fibrinogen decreased, PTT/PT prolonged, protein C decreased
• tx: supportive care, replete platelets or clotting factors if going into surg, FFP to replace coagulation factors, anticoag only if DIC shifted toward hypercoag (heparin)
• complications: thrombosis, organ fail, purpura fulminans, sepsis, bacteremia

Question 17

Von Willebrand factor deficiency or dz

Answer 17

• platelet dysfn, impairment in synth or fn, clots take longer to form or do not form properly, bleeding takes longer to stop, autosomal dominant (type 1 most common), F=M, + Fhx, surg bleed, MC congenital bleeding disorder
• sxs: recurrent epistaxis, gingival bleeding, unusual bleeding, GI bleed, menorrhagia (hemarthrosis not typical unless severe)
• dx: PTT prolonged (corrects with mixing), PT NORMAL, + PFA-100 prolonged, vWF antigen (ELISA) low to nl with low activity, ristocetin cofactor assay, vWF multimer assay
• tx: DDAVP - releases vWF and factor 8 from storage, vWF concentrate (Humate P), avoid antiplatelet meds (ASA< NSAID, heparin), VWF protects factor 8 from degredation

Question 18

Hemophilia A (factor 8), hemophilia B (factor 9)

Answer 18

• x-linked recessive, mostly males, generally presents in infancy or early childhood
• sxs
  
  • neonates: ICH, prolonged hemorrhage from cicumcision or heel puncture
  • infancy: SQ nodular hematoma
  • toddler: hemarthrosis (painful swelling aorund joint), oral mucosa bleeding, ICH (any child that sustains severe head bump or has persistent HA, lethargy, V, seizures)
• complications: retroperitoneal bleed
• dx: prolonged PTT, quant assay for individual factors, normal PT, thrombin time, and INR; CT scan URGENTLY if signs of ICH
• tx: give factor concentrates, antifibrinolytics
  
  • hemophilia A: DDAVP SQ or intranasal (potentiates vWF and factor 8 release), gene tx for factor 8

Question 19

factor 5 leiden

Answer 19

• point mutation - resistant to proteolysis by protein C, leads to overabundant conversion of prothrombin to thrombin, autosomal dominant
• sxs: DVT, PE
• complications: pre-eclampsia, placental abruption, IUGR, stillbirth
• dx: DNA test, APC-resistance assay
• tx: anticoag to prevent propagation of clot, dissolution of local clot, prevent recurrent VTE

Question 20

Idiopathic thrombocytopenic purpura etiology, RF, and sxs

Answer 20

• acquired autoimmune disorder, circulating antiplatelet IgG autoantibody (produced in spleen) directed against a membrane protein which is the fibrinogen receptor (glycoprotein IIb/IIIa) → clears complexes via macrophages, destroyed in spleen → reduces life span of platelet
• reduction in number of platelets, abundant megakaryocytes in bone marrow, shortened platelet life span, MC indication for splenectomy
• sxs: acute (children <8yo) → 1-3wks after viral URI get bleeding gums, vaginal bleed, GI bleed, hematuria, epistaxis, easy bruising, petechiae, ecchymoses, NO SPLENOMEG, CNS bleed
  
  • chronic (any age, F) → insidious, long hx of easy bruising and menorrhagia, petechiae over pressure areas, cyclic remissions and exacerbations

Question 21

idiopathic thrombocytopenic purpura

Answer 21

• dx: no single dx test, dx of exclusion → bleeding time prolonged, thrombocytopenia, CBC shows IDA, assess bone marrow (inc large megakaryocytes without platelet budding), cap fragility increased, PT/PTT NORMAL
• tx: mild-mod → obs, avoid contact sports, elective surg, and unnecessary meds
  
  • first line: children → IVIG; adults → high dose steroids
  • second line: rituximab → clears active B-cells making abs
  • splenectomy: for persistently low platelet counts despite steroid tx, requires PCV vaccine, most effective tx
• better prognosis: young age, short duration of dz

Question 22

heparin-induced thrommbocytopenia (HIT)

Answer 22

• in 3% of pts trigger immune response between platelet factor 4 and heparin - forms abs that cross-react with platelets (ab-induced process), MC thormbocytopenia in postop period (occurs 4-7 after initation of heparin prophylaxis or tx)
• sxs: occurs 4-7d after initiation of heparin prophylaxis or tx
  
  • thrombocytopenia + 50% drop in platelets from baseline (not below 30,000 - bleeding is not common)
  • venous or arterial thrombosis (activated platelets render pt hypercoag)
• dx: PT/PTT normal; check ELISA for PF4-hep - associated IgG; doppler LE to ro DVT; CBC shows thrombocytopenia
• tx: discontinue hep and heparin-coated products (avoid platelet transfusion, anticoagulate (use lepirudin or argotraban), long-term anticoag on warf, higher incidence with UFH than enoxaparin sodium (lovenox), 50% reduction in total platelet volume, surgical pts (orthopedic/cardiac) at inc risk

Question 23

thrombotic thrombocytopenic purpura

Answer 23

• MC: adults, F 30-35yo
• RF: preg, infxn, inflamm, med, HIV/AIDS, innappropriate platelet plug -> thrombi -> impede flow and cause ischemia -> multiorgan failure and death
  
  • lack of ADAMTS13 acquired dt inhib Ab blocking enzyme activity
• cause: unknown
• sxs: classic pentad = thrombocytopenia, fever, anemia, renal insuff (AKI), mental status/neuro changes (HA, szs, hemiparesis, disorientation)
• signs: nonpalpable petechial purpura, sz, stroke, focal neuro deficit, coma
• dx: microangiopathic hemolytic anemia, high LDH, indirect bili, and retics, low haptoglobin, peripheral smear - helmet cells and megakaryocytes, schistocytes, PT/PTT normal (distinguishes from DIC), ADAMTS13 test
• tx: plasma exchange and FFP, refractory - IVIG, vincristine, cyclophosphamide, splenectomy, rituximab, avoid PLT transfusion unless ICH or life-threatening bleed, avoid ASA
• prognosis: high mortality rate (>90%)

Question 24

hodgkin lymphoma

Answer 24

• malig proliferation of lymphoid cells from lymph nodes, thymus, spleen
• MC type: nodular sclerosis; bimodal, associated with epsterin-barr virus, typically have a hx of autoimmune disorders
• RF: same sex siblings, identical siblings
• sxs: MC = painless LAD (supraclav, cervical, axillary, mediastinal; spreads from one node to another)
  
  • B sxs: fever, night sweats, unintentional wt loss, itching, cough
• signs: mediastinal mass, abd mass
• dx: reed-sternberg cells (neoplastic large cell with 2+ nuclei - “owl’s eyes”, usually B-cell phenotype, nonspecific, presence of inflamm cell infiltrates (distinguishes hodgkin from NHL), CXR and CT, bone marrow bx, leukocytosis, eosinophilia, ESR, node histology
• tx: radiation (stage 1, 2, 3a), chemo with ABVD (adriamycin, bleomycin, vinblastine, decarbazine; stages 3b, 4)
• 70% cure rates

Question 25

non-hodgkin lymphoma (B-cell)

Answer 25

• MC type: diffuse large B-cell, starts in lymph nodes and spreads to blood and bone marrow, sometimes GI tract, group of solid tumors occuring with the malignant transformation and growth of B or T cell lymphocytes or their precursors in the lymphatic system
• RF: HIV/AIDS, immunosuppression, hx of EBV, hx of H. pylori gastritis, autoimmune dz
• sxs: nontender LAD (supraclavicular, cervical, axillary - painless, firm, mobile, rapid enlargement), B-sxs less than Hodgkin lymphoma, HSM, abd pain or fullness, recurrent infxn, anemia or thrombocytopenia, SVC obst, resp involvement, bone pain, skin lesions, “virchow’s node LAD”
• dx: lymph node bx (starry sky appearance), CXR reveals hilar or mediastinal LAD, CT scan, bone marrow bx, LDH, alk phos elevated, LFTs or bilirubin elevated
• tx: rituximab, CHOP tx (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone)
• prognosis; indolent forms, not curable, 5-7y 75% survival rate

Question 26

acute myeloid leukemia

Answer 26

• neoplasm of myelogenous progenitor cells, mostly adults (80% of adult leuks) 40-60yo
• RF: exposure to radiation, myeloprolif syndromes, down syndrome, chemo
• sxs: anemia, neutropenia (inc risk bacterial infxn), thrombocytopenia (abnl mucosal or cut bleeding), splenomegaly, hepatomegaly, lymphadenopathy, bone and jnt pain, CNS involvement (meningitis, szs), skin nodules
• dx: auer rods - leads to DIC, bone marrow bx - inc myeloblasts
• tx: transretinoic acid (vit A), if recurrent or refractory - bone marrow transplant (best chance remission/cure)

Question 27

chronic myelogenous leukemia

Answer 27

• MC >40, neoplastic, clonal prolif of myeloid stem cells, + philadelphia chromosomes t(9,22) - mutation of BRC-ABL gene
• sxs: prolonged indolent course before transforms to acute leuk (blast crisis), most present in chronic phase (asxatic, discovered incidentally), constitutional sxs, recurrent infxns, easy bruising and bleeding, anemia, splenomegaly, hepatomegaly, lymphadenopathy
• dx: leukocytosis, small # blasts and promyelocytes, eosinophilia, dec leukocyte alkaline phophatase activity, thombocytosis, BMB = leukemic cells
• tx: imatinib (oral tyrosine kinase inhib), people with PC have shorter survival times and respond poorly to tx

Question 28

chronic lymphocytic leukemia

Answer 28

• mostly adults >65, unkown cause, monoclonal prolif of lymphocytes that are morphologically mature, but fnally defective, least aggressive type of leukemia
• sxs: generalized painless LAD, splenomegaly, frequent resp or skin infxns, constitutional sx in advanced dz, fatigue, wt loss, pallor, skin rash, easy bruising, bone tenderness, abd pain
• dx: discovered on routine CBC with lymphocytosis, anemia, thrombocytopenia, neutropenia, peripheral blood smear = dxic (absolute lymphocytosis - most wbc are small and mature, smudge cells = fragile leukemic cells that are broken when placed on slide), flow cytometry, bone marrow bx, CXR normal
• tx: chemo - little effect on survival, but given for sxatic relief and reduction in infxns