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90 Cards in this Set
- Front
- Back
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Platelet hematopoiesis
1st recognizable cell? Stim by? regulation? |
Megakaryoblast
TPO, GM-CSF, IL-11 Constant basal rate; incr consumption -> incr production |
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Approach - 4 parts
Bleeding d/o? 5 Inherited or acquired? 3 Affect plt/vessel wall or coag? 5 Nature and extent? 3 |
Onset
Rx Hx: bleeding, menorrhagia, Sx in combo? Age of onset, duration, FHx plt ct, bleeding time, fibrinogen, APTT, PT Specific factors, plt fxn test, coag inh & Ab |
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HHT = hereditary hemorrhagic telangiectasisa
Assoc syndromes? 2 Patho? Sx? Locale? |
Osler-Weber-Rendu: vessel wall degeneration
Ehlers-Danlos: SQ collagen OWR: Violaceous non-pulsatile telangiectasisas on mucous membrane ED: pseudoxanthoma elasticum |
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Plt/wall d/o Sx v. Coag d/o Sx
Type? Bruises? Onset s/p surg? |
P/W: skin, mucosal
Coag: IM, deep P/W: petechiae, bruises Coag: hemarthroses P/W: immediate Coag: delayed |
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Bleeding tests
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Plt ct: 150-450,000
Bleeding time: 2-7 min Plt fxn/aggregation Plt secretion |
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Coag tests 4 - which pathway?
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PT extrinsic
APTT intrinsic TT fibrinogen EDTA for clumping from Ab -> r/o pseudothrombocytopenia |
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Coag cascade!!! DON'T BE DAUNTED
Intrinsic: 3 Extrinsic:main way 1 Common: 4 |
12 -> 12a via PK, HMWK
11 -> 11a via 12a 9 -> 9a via 11a 7 -> 7a via PL, TF 10 -> 10a via 9a, 7a, PL Prothrombin -> thrombin via 10a, 5, PL, Ca Fibrinogen -> fibrin via thrombin Fibrin -> polymerization via 13a (req for strong clot) |
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Coag factors:
Vit K dependent Unnecessary [13] needed 1/2 lives: 5 8 2, 5, 9, 11, 12 Fibrinogen, 13 |
Vit K: 2, 7, 9, 10
PK, HMWK, 12 1% 5 hr (1st to form) 12 hr 1-3d 4-5d |
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Mixing study:
Purpose? Procedure? Results? |
See if factor def
Mix pt + norm + 2 hr incubation + APTT APTT corrects -> factor def APTT not correct -> inhibitor |
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Basic plt info:
Circ 1/2 life? Dense granules? 5 alpha granules? 10 Enzymes? 2 |
7-10d
ATP, ADP, Ca, 5HT, Mg Alb, fibrinogen, vWF, 5, 7, HMWK, beta-tg, PF4, PDGF, thrombin Lysozyme, acid hydrolases |
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Glycoprotein fxn:
vWF plt aggregation tissue collagen tissue fibronectin |
Gp 1b, 5, 9
GP 2b/3a GP 5, 6, 1a/2a alpha-5-beta-1 |
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Responses:
Agonists: 2 Shape change: 1 Aggregation: 1 Secretion: 4 |
TXA2, ADP/5HT
discoid -> sphere fibrinogen -> GP 2b/3a Collagen -> TK -> Ca -> MLC -> MLC-P -> secretion ADP, thrombin, TXA, PAF -> Gq -> PLC -> IP3 -> Ca -> PLA2 -> AA -> COX -> PGG2/PGH2 -> TS -> TXA DG -> PKC -> pleckstrin-P -> secretion |
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Etio dec production
Marrow failure 1 Congenital 4 Marrow invasion 3 Marrow injury 9 |
aplastic anemia
Congenital amegakaryocytic thrombocytopenia: Fanconi anemia May-Hegglin anomaly Wiskott-Aldrich syndrome Carcinoma Fibrosis Leukemia CA chemo, gold, chloramphenicol, sulfonamides, EtOH, benzene Radiation HIV, hepatitis |
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Congenital amegakaryocytic thromobycytopenia
Genetics? Defect? Sx? |
Auto R
MPL defect very low plt ct |
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May-Hegglin anomaly
Genetics? Defect? Smear triad? Sx? 2 |
Auto dom; MYH9
large plt, WBC Dohle bodies, thrombocytopenia Renal F, hearing loss |
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Wiskott Aldrich syndrome
Genetics? Sx? 3 |
X-linked
Small plt, severe immunodef, eczema |
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Etio incr destruction
Purpuras 3 Rx 3 Reactive thrombocytosis 5 Autonomous thrombocytosis 3 Adhesion d/o 2 Aggregation d/o 2 Secretion d/o 3 Pro-coag d/o 1 |
ITP, TTP, post-transfusional
Heparin, vancomycin, GP2b/3a antag Fe def, infl, malig, splenectomy, rebound MPS, PV, ET von Willebrand dz (lack vWF), Bernard Soulier syndrome (lack GP 1b, 5, 9) Congenital afibrinogenemia, Glanzmann thrombasthenia (missing 2b/3a) Gray plt syndrome (a granule def) Hermansky-Pudlak syndrome (dense granule def) Defect TXA synth Scott syndrome (membrane defect) |
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ITP
Dx? Epi adults 3 v. children 3 Test? 3 Patho? 1st line Tx? 5 2nd line Tx? 7 |
Dx of exclusion
Adults: insidious, chronic, F > M Children: acute, 66% spont recovery, usu after viral inf Dec plt, incr megakaryocyte in marrow, incr plt-assoc IgG Ab-mediated incr destruction plt Prednisone, dexamethasone, methylprenisolone IV IgG IV anti-D Splenectomy, TPO, rituximab, cyclosporine, CTX, azathioprine, vinicristine |
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HIT
Onset? Patho? Tx? 3 Req? |
5-10d after Tx
PF4 bind plt surface -> hep/GAG-PF4 complex -> IgG -> Fc-R -> pro-coag rich microparticles D/c heparin, Leupirudin, argatroban L req good kidney; A req good liver |
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TTP
Sx? 5 Patho? Tx? 3 |
dec plt, MAHA, acute renal F, fluctuating neuro Sx, fever
Dec ADAMTS13 -> large vWF -> incr plt binding Plasma infusion, plasmapheresis, steroids |
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vWD v. Hemophilia
Chr Activity test Ag test 8 coag vWF Ag vWF Ristocentin activity Ristocetin aggregation Bleeding time |
H: 12, 8:C, 8:Ag, dec, dec, dec, dec, inc
V: X, Ristocetin cofactor, vWF:Ag, dec, no, no, no, no |
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% bleeding Sx:
50-100 25-50 5-25 1-5 0-1 |
none
major trauma bleeding severe bleeding at surg, minor trauma bleeding spont hemorrhage bleeding in muscle/joint spont |
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Hemophilia defects:
Type A? Type B? Other? 3 Occurs where? |
A: factor 8
B: factor 9 11a, 9, 7 occurs on PL w/ Ca |
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DDx of:
Incr TT: 4 PTT abnormal even with plasma inh: 5 PTT abnorm, norm PT/other w/o bleeding: 3 w/ bleeding: 4 PT abnorm, norm PTT/other: 5 Abnorm PTT & PT, other norm: 4 |
heparin, hypofibrinogenemia, dysfibrinogenemia, fibrin degradation products
Ab to coag protein (8 most common): hemophiliacs, postpartum, SLE, elderly, Rx Lupus anticoag Defect intrinsic pathway 12 def, PK def, HMWK def 8 def, 9 def, vWD, 11 def Defect extrinsic pathway: 7 def (rare), vit K def, coumadin, liver dz, multi-factor Common path defect: rare 2, 5, 10 def; usu multiple |
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Liver dz fx on factors:
Fibrinogen, 5 7 8 C, S, AT3 |
dec only in liver failure
First factor to dec May inc with dz Dec in dz |
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DIC
Patho? 2 Conditions? 4 Lab? 4 Cardinal Sx? 5 Tx? 2 |
Thrombin generation, plasmin generation
Sepsis, malig, obstetric complications, massive trauma, shock Inc PT, Inc PTT, Inc D-dimer, Dec Fibrinogen Single site bleeding, purpura/petechiae, multiple sites, acral cyanosis, thrombosis Replacement, heparin |
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Inhibitors in coag cascade:
AT3? 5 Plasmin? 1 TFPI? 2 APC? 2 |
12, 11, 9, 10a, thrombin
fibrin 8a + TF 5a, 8a (req protein S) |
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Sx inherited thromobphilia: 7
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>90% VTE - DVT, PE
rarely mesenteric, cerebral superficial thrombophlebitis FHx 1st thrombosis < 40 neonatal purpura fulminas recurrent fetal loss |
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AT def
Genetics? Plasma level? Consequence? RF VTE? |
Auto dom
40-60% May have heparin resistance 25x |
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Protein C def
Genetics? If homozygous? Presentation? 4 Contraindication? 1 RF VTE |
Auto dom; purpura fulminas
~ 20 y/o, DVT, iliofemoral, mesenteric Warfarin-induced skin necrosis 10x |
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Protein S def
Patho? Presentation? Acquired from? RF VTE |
complex to C4b-binding protein
DVT, sup TP, PE, warfarin-induced skin necrosis Preg, OCP, liver dz, DIC, acute VTE 4-5x |
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Factor V leiden
Genetics? Associations? 3 Prevalence? RF VTE? |
Arg -> Gln; very common
Not assoc w/ MI, CVA; Assoc w/ VTE 2-10% pop heterozygous: 5x; homozygous 50x |
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Prothrombin variant G20210A
Consequence RF for VTE? Prevalence? |
Incr prothrombin
Incr 2.8x 2% pop |
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Hyperhomocysteinemia
Patho? Independent RF for? 3 Fx? 8 RF for VTE? |
B6 def
CVA, MI, PAD Endo desquamation, SM proliferation, intimal thickening, induction TF activity, inh TPA, impaired NO/PGI2 generation, interfered APC, suppress heparin 3x |
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Preg & hypercoag:
Incr risk VTE? When highest? Assoc? 2 |
5-6x
Postpartum highest Incr preg loss, complications |
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APS = antiphospholipid syndrome
Labs? 2 Consequence? 3 |
Incr PTT
Anticardiolipin immunoassay VTE Preg mobidity Thrombocytopenia sometimes |
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Classification of Thrombosis Tx
High-indefinite: 8 Moderate:6 |
2+ thrombosis, 1 life-threatening thrombosis, 1 episode + genetic defect/ AT def/ protein C def/ protein S def/ APS/ malig
asymptomatic carrier, APS, MPD, malig, PNH, 1 episode w/ provocative stimulus |
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DVT
Suggestive: 9 Nonsuggestive: 7 Labs: 1 DVT 2 PE 3 |
Paralysis, paresis, bedridden > 3d, localized tenderness, entire leg swelling, pitting edema > other leg, prior DVT, CA w/in last 6m, collaterol non-varicose sup veins
Baker cyst, cellulitis, muscle damage, SVT, post-phlebitis syndrome, inguinal LAD, external venous compression DVT: Duplex doppler US, venogram PE: Spiral CT, V/Q scan, pulm angiogram D-dimer |
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Pt risk, prophylaxis: risk, Tx
Minor surg, mobile pt GU surg Hip/knee arthroplasty, HFS, major trauma, SCl, High VTE risk |
<10%; no spec prophylaxis; agressive ambulation
10-40%; LWMH, LDUH, fondaparinux 40-80%: LMWH, fondaparinux, coumadin, mech prophylaxis |
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ET
Dx? Criteria? 3 Sx? 3 Tx? 4 |
Dx of exclusion
Sustained pl > 450,000 Megakaryocyte proliferation Not meet PV, PMF, CML Splenomegaly, microvasc thrombotic events, hemorrhages hydroxyurea, aspirin, platelet-pheresis pre-op, IFN-alpha |
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mech of heparin
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enhance ATIII activity
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3 ways OCP make prothrombotic
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dec ATIII, inc 5/8, inc fibrinogen
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ATIII works on 5
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12, 11, 10, 7, prothrombin, thrombin
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What activates plasminogen to release plasmin
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tPA
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what is vWF
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plt adhesion molecule
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other fxn
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prevents 8c degradation
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tissue thromobplastin activates
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Factor 7
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plt receptor that binds vWF
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Gp1b
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plt receptors for fibrinogen
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Gp2b-3a
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Which drugs interfere with this
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clopidogrel, abciximab, ticlopidine
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Most important factor of extrinsic system
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Factor 7
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factors of intrinsic sys
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factors 12, 11, 9, 8
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what activates kininogen system?
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8a
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final common pathway?
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10, 5, 2 (pro/thrombin), 1 (fibrin/ogen)
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what crosslinks insoluble fibrin monomers
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factor 8
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vit K dependent factors: 6
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2, 7, 9, 10, C, S
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role of Ca in formation?
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binds g-carboxylated vitamin K-dependent factors
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factors consumed in clot
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1, 2, 5, 8
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what Rx inh plasminogen?
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aminocaproic acid
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D-dimers signify
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cross-linked fibrin monomers
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TXA2 works by
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enhancing fibrinogen attachment to Gp2b-3a
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Purpose of fibrinogen activation?
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fibrinogen makes temporary plug; fibrin stabilizes
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Best test of plt fxn up to temporary plug stage
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Bleeding time
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best test of vWF fxn
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Ristocetin cofactor assay
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PT evaluates factors
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7, 10, 5, 2, 1
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PTT evaluates factors
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12, 11, 9, 8, 5, 2, 1
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what standardizes PT for warfarin therapy
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INR
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Bernard-Soulier is a defect in
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plt adhesion (absent gp1b for vWF)
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Glanzmann's dz is a defect in
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plt aggregation (absent gp2b-3a)
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renal failure causes a defect in
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plt aggregation
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scurvy causes a defect in
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plt adhesion
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Best test for DIC
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D-dimer
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clinical findings of plt d/o 4
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epistaxis, petechiae, ecchymoses, superficial scratches bleed
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clinical findings of coag d/o 2
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late rebleeding, hemarthroses
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senile purpura is due to
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vessel instability
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genetics of hemophilia
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XR
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Defect in hemophilia A
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factor 8c def
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defect in hemophilia B
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factor 9 def
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genetics of vWD
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AD
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associated w/? 3
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MVP, Marfans, angiodysplasia
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vWD is a defect in
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plt adhesion (lack vWF AND 8c)
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Tx for vWD
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desmopression or OCP
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Mixing study does not correct with?
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Circ anticoagulant
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With cirrhosis, is PT corrected with vit K shot?
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NO b/c dec synth of factors
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most common cause DIC
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sepsis
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Lab findings of DIC: 5
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inc PT, PTT, BT, D-dimers; dec plt
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2 main anti-phospholipid Ab
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lupus anticoag, anticardiolipin
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patho of factor 5 leiden
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cant be degraded by C or S
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no prolongation of PTT after heparin injection
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ATIII def
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complication of warfarin given to protein C def pt
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hemorrhagic skin necrosis
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