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Heparin
inc ptt, activates antithrombin iii and affects intrinsic pathway
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Warfarin
- inc pt, inhibits vit k, 2, 7, 10, 9, c, s
- extrinsic pathway
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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
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Boy from russia with hemarthroses following minimal trauma?
Hemophilia!
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Why heparin bridge?
Because warfarin inhibits protein C and S before other vitamin K dependent factors leading to transient period of hyper coagulability
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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
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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
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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
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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!
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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
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Myeloblasts
neutrophil, eosinophil, basophil
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Microcytic anemia causes
Iron def, thalassemia, chronic disease, sideroblastic
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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
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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
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Pernicious anemia
loss of gastric parietal cells which secrete intrinsic factor needed to absorb B12
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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)
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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
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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
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Sickle Cell: osteo and AVN
- osteo: MCC S. aureus but also prone to salmonella
- inc risk for AVNecrosis of the hip
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Health maintenance of sickle cell
treat cholelithiasis with cholecystectomy, chronic folate supp, pneumococcal vacc and when <5, penicillin BID
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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
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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
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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
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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
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AML M3
- APL, has auer rod, give trans retinoic acid to rx
- increased risk of DIC and chromosome translocation 15;17
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Rx ALL/AML
- chemo, before thereapy hydrate
- if high WBC start allopurinal to prevent hyperuricemia
- Leukostasis syndrome: rx with hydroxyurea
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Bad prognostic factors AML/ALL
- ALL: age <1 or >10, WBC>50000, phil chrom 9;22, CNS at dx
- AML: >60, elevated LDH
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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
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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
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Age: ALL, AML, CLL, CML
- ALL: <13
- AML: 13-40
- CML: 40-60
- CLL: >60
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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
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NHL
- 85% B cell origin, 5x MC than HL
- Age >50
- Dx: excisional lymph node biopsy, stage based on number of nodes and bilat
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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
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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)
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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
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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
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Neutropenia
ANC <1500, ANC= WBC count * (%bands+%seg neutrophils)
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