Heme

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Heme
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2013-07-11 10:10:00
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Heme
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  1. Heparin
    inc ptt, activates antithrombin iii and affects intrinsic pathway
  2. Warfarin
    • inc pt, inhibits vit k, 2, 7, 10, 9, c, s
    • extrinsic pathway
  3. Hemophilia A and B
    • Hemophilia A: dec of factor viii
    • B: def IX
    • Inc bleeding, presents with spontaneous hemorrhage into tissue and joints can lead to arthropathy and joint destruction
    • PT normal, PTT prolonged
    • Mixing study: BIT, should correct
    • Rx: transfuse clotting factors, mild can be rx with ddavp
  4. Boy from russia with hemarthroses following minimal trauma?
    Hemophilia!
  5. Why heparin bridge?
    Because warfarin inhibits protein C and S before other vitamin K dependent factors leading to transient period of hyper coagulability
  6. VWD
    • AD, deficient or defective vWF with low levels of VIII which is carried by vWF.  
    • Muscosal bleeding, easy bruising, worsens with aspirin
    • Dx: PT nml, PTT prolonged, bleeding time prolonged
    • Ristocetin cofactor assay measures capacity of vWF to agglutinate
    • Rx: DDAVP(releases VIII), OCPS
  7. Hypercoag states
    • MC Factor V leiden: polymorph in factor 5 leaving it resistant to inactivation by protein C
    • recurrent clots
    • Other causes: antithrombin iii def, antiphospholipid syndrome, nephrotic syn
    • rx: treat dvt/pe with heparin then 3-6 m warfarin for rist event, 6-12 m for 2nd and lifelong for recurrent
    • If CI to warfarin- IVC filter
  8. DIC
    • deposition of fibrin in small vessels leading to thrombosis and end organ damage, depletion of clotting factors and platelets
    • Disorders assoc: ob comp, infection, neoplasm, PML, pancreatitis, drugs, ards
    • Acute: bleed from venipuncture sites
    • Chromic: brusing, mucosal bleed, renal dysfunction.  Dx: dec clotting factors, inc pt and ptt, dec plt, inc FDP/fibrin, dec fibrinogen
    • Rx: rbc transfusion, platelets
  9. TTP
    • platelet microthrombi that block small vessels, RBC fragmented->hemolysis
    • Causes: infectious, drugs, AI
    • 5 signs/sx: Low plt, Microangiopathic hemolytic anemia, neuro changes(seizure), impaired renal fxn, fever (VS HUS: low plt/MAHA/Renal)
    • Rx: steroids dec microthrombus formation, severe cases:plasmapheresis
    • PLATELET TRANS=CONTRAINDICATED!
  10. ITP
    • IgG formed against platelets, bone marrow prod increases- inc megakaryocytes
    • Sx: minor bleeding
    • Causes: lymphoma, leukemia, sle, hiv, hcv
    • Acute: kids after virus, hemorhaggic (2-6 yo)
    • Chronic: insidious onset unrelated to infection, 20-40 yo
    • Dx of exclusion
    • Rx: recover spontaneously, transfusions useless-will destroy
    • Rx: CST, IVIG, splenectomy
  11. Myeloblasts
    neutrophil, eosinophil, basophil
  12. Microcytic anemia causes
    Iron def, thalassemia, chronic disease, sideroblastic
  13. Sideroblastic anemia
    • microcytic, fail to make completely formed heme molecules so deposit iron in mito-ring around nucleus
    • MAT: prussian blue staining for ringed sideroblasts
  14. Thalassemia
    • microcytic anemia, dec or absent globin
    • MAT: hemo electrophoesis
    • Beta major: 0/2 beta, severe, chronic transfusions
    • Beta minor: asyx but hypochrom/micro cells
    • Alpha:
    • Hyrdops-all 4, H: 1/4 retic count elevates 
    •  Trait: 2/4
    • Silent 3/4
  15. Pernicious anemia
    loss of gastric parietal cells which secrete intrinsic factor needed to absorb B12
  16. B12 def
    • PErnicious anemia(no intrinsic factor) panc insufficiency: need panc enzymes to bind intrinsic factor and absorb B12 (CF needs replacement), crohns, celiacs
    • B12 def takes years to develop but demyelinating subacute combined degen: loss of position and vibration, ataxia
    • Hyperseg neutro
    • Elevated MMA and homocysteine (VS folate: nml MMA, elevated homocyst)
  17. Hemolytic anemias
    • normocytic
    • ex: G6PD def: XR
    • Paroxysmal nocturnal hemoglovinuria: abnormal CD 55 and 59, DAF, abnormal compliment act- thrombotic events
    • Hered spherocytosis
    • Sickle cell
    • Microangiopathic hemo anemia: ttp, hus, dic

    Rx: usually steroids, iron supp, may need splenectomy
  18. Aplastic anemia
    • failure of blood cell production due to destruction of bone marrow cells
    • Fanconis: hereditary: cafe au lait, short, radial/thumb hypoplasia
    • Auto immune, viral: HIV, parvo
    • Toxins, radiation
    • Sx: pancytopenia
    • Bone marrow: hypocellularity and fat
    • Rx: transfusion and stem cell transplant
  19. Sickle Cell: osteo and AVN
    • osteo: MCC S. aureus but also prone to salmonella
    • inc risk for AVNecrosis of the hip
  20. Health maintenance of sickle cell
    treat cholelithiasis with cholecystectomy, chronic folate supp, pneumococcal vacc and when <5, penicillin BID
  21. Polycythemia
    • erythrocytosis can be primary: inc rbc production or secondary: dec plasma volume/hemocont
    • Sc: inc hct, inc cardiac work, hyperviscosity
    • Cann see plethora, pruritus after hot bath, chf, blurred vision, hepatomegaly
    • Primary: hypoxia, neoplasia or polycythemia vera (JAK2 mutation causing prolif of marrow, elderly)
    • Use EPO level to distinguish pcv(EPO is low) vs other causes when EPO is elevated
    • Rx: phlebotomy
    • PCV: rx with cytoreductive drugs: hydroxyurea/inf, asa
  22. Porphyria
    • sign=PINK urine after college student consumes etoh and barbituates at a party, next day abdom pain/brown urine
    • Gen: photodermatitis, neuropsych, visceral complaints-colicky abd pain and seizures
    • erythema, blisters, tachy
    • Triggers: alcohol, barbs, ocps
    • Rx: avoid triggers, high doses glucose can dec heme synth during attacks
  23. Transfusion reactions
    • 1. nonhemo febrile rxn: cytokine formation during storage of blood, fever/chills 1-6 hr after transfusion.  Rx: stop trans, acetaminophen
    • 2. Minor allergic rx: Ab form against donor proteins usually after getting plasma product, sx: urticaria, rx: antihis
    • 3. Hemolytic transfusion rx: ABO incomp/ minor Ag mismarch, chill/feber/burning at IV/tachy/hypotension Rx: STOP! IV fluid
  24. Acute leukemia
    • lots of blasts
    • ALL MC in child
    • Sx: anemia, thrombocytopenia, bone pain, HSM
    • Dx: BIT: blood smear showing blasts
    • MAT: flow cytometry
    • Examine bone marrow, if >20-30% blasts=leukemia
    • AML: myeloblasts(neuro/baso/eoino)
    • ALL: lymphoblasts
    • WBCs usually elevated but dysfunctional, freq infection
  25. AML M3
    • APL, has auer rod, give trans retinoic acid to rx
    • increased risk of DIC and chromosome translocation 15;17
  26. Rx ALL/AML
    • chemo, before thereapy hydrate
    • if high WBC start allopurinal to prevent hyperuricemia
    • Leukostasis syndrome: rx with hydroxyurea
  27. Bad prognostic factors AML/ALL
    • ALL: age <1 or >10, WBC>50000, phil chrom 9;22, CNS at dx
    • AML: >60, elevated LDH
  28. CLL
    • older adults, median age 65
    • Dx: flow cytometry with CD5 with CD20 and 21
    • lymphocytosis with small lymph and smudge cells 
    • Rx: palliative, chemo
    • ~5% convert to lymphoma, PCP proph. needed
  29. CML
    • excess granulocytes/basophils, BCR ABL translocation (Phil chrom: 9;22)
    • Middle aged patients
    • splenomegaly
    • Chronic->
    • Accelerated: inc periph and bone marrow counts, abrupt inc basophils and thrombocytopenia
    • Blast crisis: resembles acute leukemia, die 6 m
    • MAT phil. chrom, Very high WBC
    • LAP low, LDH/B12 high
    • Rx: imatinib, BMT
  30. Age: ALL, AML, CLL, CML
    • ALL: <13
    • AML: 13-40
    • CML: 40-60
    • CLL: >60
  31. Hairy cell leukemia
    • d/o of well diff B cell, rare, older male, pancytopenia, splenomegaly
    • weak/fatirue/ inf with weird bad(MAC), abd pain
    • Dx: hairy cells, TRAP stain positive, leukopenia
    • Rx: cladribine
  32. NHL
    • 85% B cell origin, 5x MC than HL
    • Age >50
    • Dx: excisional lymph node biopsy, stage based on number of nodes and bilat
  33. Hodgkins lymphoma
    • B cell malignancy, bimodal age 30s: nodular sclerosing and 60s lymphocyte depleted type
    • USually presents above diaph as cervical adenopathy B sx, pruritis, HSM
    • DxX: excisional lymph node biopsy-reed sternberg cells, bilob eosinophilic nuclei
    • Rx: Best is lympho predcominant, worst=depleted
  34. Multiple myeloma
    • Anemia/renal failure/bone pain=think mm
    • Clonal prolif of malig plasma cells, excessive IgA/IgG or light chain production, peak around 70
    • Anemia, plasmacytosis, lytic bone lesions, hypercalc, renal abnormality, elevvated M protein(M spike)
    • BIT: Xray
    • MAT: BM biopsy with 10% plasma + bone lytic lesions or 30% plasma on biopsy
    • Rx: melphalan, prednisone
    • Periph smear shows stacks of IgG-Rbcs (rouleaux)
  35. Waldenstroms macroglobinemia
    • Clonal disorder of B cells, elevated IgM leading to hypervisc, cold agglutinin dz, chronic, indolent dz of elderly
    • Labs: elevated ESR, alk phos
    • BMP to dx: see dutcher bodies-PAS+ IGM deposits around nucleus
    • Rx: plasmapheresis, prednisone
  36. Amyloidosis types
    • AL: light chains: MM and waldenstroms macro
    • AA: Amyloid A- Acute phase reactant, chronic inflamm z: RA, inf/neoplasms
    • Dialysis related: B2 micro globulin
  37. Neutropenia
    ANC <1500, ANC= WBC count * (%bands+%seg neutrophils)

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