Heme

inc ptt, activates antithrombin iii and affects intrinsic pathway

• inc pt, inhibits vit k, 2, 7, 10, 9, c, s
• extrinsic pathway

• 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

Hemophilia!

Because warfarin inhibits protein C and S before other vitamin K dependent factors leading to transient period of hyper coagulability

• 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

• 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

• 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

• 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!

• 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

neutrophil, eosinophil, basophil

Iron def, thalassemia, chronic disease, sideroblastic

• microcytic, fail to make completely formed heme molecules so deposit iron in mito-ring around nucleus
• MAT: prussian blue staining for ringed sideroblasts

• 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

loss of gastric parietal cells which secrete intrinsic factor needed to absorb B12

• 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)

• 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

• 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

• osteo: MCC S. aureus but also prone to salmonella
• inc risk for AVNecrosis of the hip

treat cholelithiasis with cholecystectomy, chronic folate supp, pneumococcal vacc and when <5, penicillin BID

• 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

• 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

• 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

• 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

• APL, has auer rod, give trans retinoic acid to rx
• increased risk of DIC and chromosome translocation 15;17

• chemo, before thereapy hydrate
• if high WBC start allopurinal to prevent hyperuricemia
• Leukostasis syndrome: rx with hydroxyurea

• ALL: age <1 or >10, WBC>50000, phil chrom 9;22, CNS at dx
• AML: >60, elevated LDH

• 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

• 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

• ALL: <13
• AML: 13-40
• CML: 40-60
• CLL: >60

• 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

• 85% B cell origin, 5x MC than HL
• Age >50
• Dx: excisional lymph node biopsy, stage based on number of nodes and bilat

• 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

• 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)

• 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

• AL: light chains: MM and waldenstroms macro
• AA: Amyloid A- Acute phase reactant, chronic inflamm z: RA, inf/neoplasms
• Dialysis related: B2 micro globulin

ANC <1500, ANC= WBC count * (%bands+%seg neutrophils)