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121 Cards in this Set
- Front
- Back
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platelet survival time
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7-10 days
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alpha granules
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large proteins
alpha thromboglobulin, pdgf, thrombospodin, pf4, vWF, platelet fibrinogen, p-selectin |
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delta granules
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small molecules, dense granules
atp, adp, calcium ions, serotonin |
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platelet antigens
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ABO, I, i P, Le, Class I MHC,
GPIa/V/IX (vWF), GPIIB/IIIa (fibrinogen), GpIa/IIa(collagen) |
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Adhesion
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GPIa/V/IX binding to vWF (subendothelial & circulating) & GpIa/IIa collagen, plts change shape
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Aggregation
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GPIIb/IIIa binds fibrinogen, so platelets bind to each other
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Degranulation
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TXA2, plt agonists
epi, adp, collagen, paf, thrombin, TxA2 |
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Intrinsic pathway
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Historically named because blood + negatively charged glass. XII, XI, IX, VIII, measure with PTT, deficiency increased PTT, HMWK, prekallikrien, not in vivo:
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Extrinsic pathway
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TF (III) and VII bind to platelets surface and autocatalyze F7, follow with PTT
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Common pathway
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X,II, I, V
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What does thrombin activate
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fibrinogen to fibrin, XI, IX, V, F13, XIII
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What does tissue factor pathway inhibitor bind
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TF-F7A-F10a
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What does F13 do>
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It crosslinks fibrin
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Normal Hemostatsis
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Vasoconstriction
Primary platelet plug (adhesion/aggregation) Secondary (Coag to fibrin) Tertiary (crosslink fibrin & fibronolysis) |
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10ase
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calcium, platlet surface, F9a + F8a
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prothrombinase complex
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f10a + f5a anhored by PS & PI
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fibrinogen
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a-a, B-b, gamma. a= fpa; b=fpb
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PF3
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Lipid only exposed after platelet activated
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Vit K dependent factors
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II, VII, IX, X, C, S
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What does Vit K do
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carboxylation of gamma carbons in glutamic acid
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What does Thrombin activate
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1-1a
v-va viii-viiia Xi-xia Xiii-Xiiia |
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Tissue factor pathway inhibitor
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Blocks extrinsic activation of clotting cascade - however Thrombin acitivates XI-XIa which causes more fibrin
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2 phases of platelet aggregations
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1 - 1st phase of aggregation (ADP)
2nd phase of aggregation (more TXA2 & ADP) |
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Ristocetin cofactor study
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Aggregation is dependent on
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Bernard Soulier
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Defect in GPIb Recepetor
defective Ristocetin study anemia, large platelets Normal response to epi, collagen, adp |
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PT
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measures extrinsic & common pathways - add phopholipid &
tF - enlongated by liver disease, Vit K deficiency, fsp (dic) |
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PTT
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heparin (Binds to antithrombin III - factor Xa & IIa), fibrin (fdP) & LA
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Thrombin Time
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Decreased functional fibrinogen
Congenital fibrinogen (afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia) Acquired hypofibrogenemia, dysfibrinogenemia |
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Vascular causes of bleeding
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hereditary hemorrhagic telegantectasia
Elhers Danlos syndrome Scurvy |
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Disorders of primary hemostasis
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menorrhagia, trauma, surgery
purupura, mucosa, petechiea |
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Glanzmann's thromboesthenia
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Problem with GpIIb/IIIa
Normal Ristocetin Abnormal epi, adp, collagen Same pattern as afibriongenemia |
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Storage pool deficiencies
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Gray platelet syndrome
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Problems with secondary hemostasis
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Delayed bleeding, joint bleeding
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Plasmin
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Dissolves fibrin
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TPA...
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cleaves plasminogen to plasmin
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Alpha-2 antiplasmin inhibits...
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plasmin
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PAI inhibits
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plasminogen
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TAFI (Thrombin activatable fibrinolysis inhibitor) inhibits....
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binding of plasminogen & TPA to fibrin
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Protein C...
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Thrombomodulin binds to thrombin to activate protein C - binds to Protein S. APC inhibits FV & FVIII
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Antithrombin...
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Binds to heparin (inactivates IIa, Xa)
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Protein C &S
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Vitamin K dependent (effected by Coumadin)
PositiveAcute Phase Reactants (falsely normal (in deficiency) with illness |
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aPTT
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phospholipid + patient plt poor plasma & calcium
meaures intrinsic & common doesn't measure F7 & F13 |
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PT
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Tissue factor, phospholipids, pt plt poor plasma + calcium chloride
Measures extrinsic & common |
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INR formula
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Pt PT/Normal mean PT to ISI power
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Normal PT, PTT, Plts
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mild vWD
Uremia Surgery Inherited plt d/o Vascular d/o Fibrinolytic d/o F13 deficiency dysfibrinogenemia Mild factor deficiency (F8,F9, F11) |
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inc PT, nml PTT, nml Plts
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F7 deficiency or inhibitor
Coumadin Liver disease Vit K deficiency Dysfibrinogenemia |
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nml PT, inc PTT, nml plts
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heparin
vWD F8, F9 , F11 deficiency inhibitor Lupus anticoagulant |
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inc PT, inc PTT, nml plts
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Coumadin
Heparin Liver Vit K DIC Dysfibrinogenemia Primary fibrinolysis |
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inc PT, inc PTT, dec plts
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DIC
liver disease Heparin with TCP |
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nml PT, nml PTT, dec Plts
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destruction
sequestration decreased production Bernard Soulier |
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nml PT, nml PTT, inc Plts
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myeloproliferative d/o
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Thrombin Time
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exogenous thrombin
pt platelet poor plasma measure - common pathway (fibrinogen) -paraprotein, amyloid, heparin, dysfibrinogemia - increased |
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Reptilase Time
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Bothrops atrox venom
Pt plt poor plasma Reptilase mesures fibrinogen to fibrin insensitive to heparin Ex. TT prolonged with heparin, normal TT with Reptilase Normal TT with heparin & protamine Inc Reptilase - dysfibrinogenemia |
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Mixing study
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immediate & two hour
with correction - deficiency w/o correction - inhibitor (Lupus anticoag) Weak inhibitor try 4(pt):1(nml) mix Time dependent prolongation - F8 inhibitor will correct then prolong dysfibrongen inhibitor paritally correct hypofibrinogenemia corrects |
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Platelet aggregation studies
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Pt platelet rich plasma + aggregating agent (ristocetin, adp, collagen, epi, arachidonic acid)
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Platelet aggregation studies...first phase
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ADP release
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Platelet aggregation studies...second phase
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more ADP release & TXA2 release
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Platelet aggregation studies...ADP & EPi
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Biphasic
No secondary phase w/ epi & ADP in storage pool defects & ASA |
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Bernard Soulier
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Failure of plts to aggregate with ristocetin in normal plasma
Defect GPIb/V/IX receptor - can't bind vWF Giant plts, TCP, Adhesion problem Nml PT, PTT, increased bleeding time impaired Ristocetin (flat) Normal Epi, Collagen, ADP Same aggregation as vWD AR, consanguinity, hemorrhage Absent CD42 on flow |
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Glanzmann's thrombasthenia
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Doesn't aggregate with ADP, epi, collagen
Abnormal GP IIb/IIIa Nml plts with normal morphology Normal ristocetin Clot retraction test - clot no retract in test tube DDX: afibrinogenemia (inc PT & PTT) Severe bleeding, AR Deficient CD41/61 on flow |
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May Hegglin Anomaly
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Mutated Myosin Heavy Chain 9
Dohle Body (RER) + Giant plt Little bleeding - Autosomal Dominant |
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Giant Platelets
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ITP, May Heglin, Gray Platelet syndrome, Bernard Soulier, Montreal plt syndrome
Mediterranean macrothormbocytosis Sebastian, fechner, epstein, alport;s syndromes |
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Storage Pool deficiency
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decreased plt aggregation
dec alpha or delta or both granules normal morphology, no granules (EM) No 2nd wave - ADP, Epi, impaired collagen, AA Normal ristocetin Increased ATP:ADP ratio |
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Gray plt deficiency
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No alpha granules
large gray platelets Cardiopulmonary bypass Plt aggregation blunted except ADP/epu |
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Quebec plt d/o
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no alpha granules
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Wiskott Aldrich syndrome
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X-linked
No delta granules on EM Small granulated plts, like FeDa TCP, infection, eczema increased malignancy |
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Chediak Higashi
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No delta granules on EM
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Hermansky-Pudiak syndrome
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No delta granules on EM
inc pigmented reticuloendothelial cells swiss cheese plts increase AK, nevi, tumors, pulmonary fibrosis Puerto Ricans/Swiss Increase vW |
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Thrombocytopenia with absent radii
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seee pg 13
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Acquired Disorders of plt dysfunction
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Drugs, Uremia, myeloproliferative, cardiopulmonary bypass (transient plt activiation, decreased granules)
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ASA/NSAIDS
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decreased plt funciton (acetylate plt cyclooxygenase which leads to decreased TXA2 formation)
Plt aggregation studies - |
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Osler-Weber-Rendu
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Hereditary telegectasia (Oral telegectasia, FeDA)
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Ehlers-Danlos, type 4
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Connect tissue d/o - plts can't stick, brusing, purpura, loose skin
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Hemoch-Schonlein
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vasculitis, purpura, thrombocytopenia
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arteriovenous malformation
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decreased plts
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Scurvy
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decreased vitamin C, bad teeth, perifollicular petechiae
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Marfan's osteogenesis imperfecta
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Collagen d/o
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Amyloidosis
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Decreased F10, plts don't stick, endothelium coatd, lambda light chains
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von Willibrand disease
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binds to F8
Large multimers cleaved by ADAMTS-13 most common genetic plt type bleeding disorder Ch 12 AD Less in type O, old blood |
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Secondary vWD
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Wilms' tumor, congenital heart disease, hypothyroid
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vWD Diagnostic Testing
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Plts decreased
FVIII Co vWFAg vWF:RCo RIPA plt aggregation studies vWF multimers Mixing study |
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Type 1 vWD
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all polymeric forms, intensity decreased
Asymptomatic or mild forms - 40-60% Tx with DDAVP |
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Type 2a vWD
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No intermediate or high molecular weight multimers
Factor VIII decreased or normal disporportionately low vWF:RCo (quality) relative to vWFAg (quantity) |
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Type 2b vWD
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Highest molecular weight multimers missing
Do not respond to DDAVP Enhance responsiveness to of platelet rich plasma to lower than normal concentrations of ristocetin (inc affinity for GP1b) Inc RIPA low ristocetin DDX: pseduo vWD |
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Type 2M vWD
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Defect in GP1b binding
decreased interaction of vWF with plts similar profile to type 2A vWD, but normal multimer analysis vwf:RCof<vwf Ag |
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Type 2N vWD
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Decreased binding of factor VIII to vWF
Multimer analysis normal Low factor VIII levels women with low F8 levels |
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Type 3 vWD
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Severe bleeding disorder like Hemophilia A
Low F8, no vWF, low ristocetin co factor activity AR, most AD no DDAVP |
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Acquired vWD
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Autoantibody, SLE, autoimmune, lymphoma, myeloma,
Plts - myeloproliferative d/o, PV, |
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vWF:RCo
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decrease in vWF parameters w/ history of bleeding - diagnostic
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Laurell rocket electrophoresis
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height of the rocket is proportional to the concentration of vWF
<40% consistent with vWF |
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pseudo vWD
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plt problem - bind large vWF multimers
abn RIPA Needs more ristocetin than 2B Plt aggregate w/ cryo Increased affinity plt gpIb for plasma vWF receptor |
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Factor Deficiencies
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Inc PT/PTT or both
Nml Bleeding time XLR-females carriers, males affected |
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Factor deficiency : mixing studies
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PTT corrects immediately and at 1 hr
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F8 deficiency carriers
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Woman (dad hemophiliac)
50% dtrs carriers 50% sons affected Mild F8 - possible w LYon hypothesis Chr Xq28 50% intron 22 conversion |
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Hemophilia B
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XLR
less than common hemophiliac A |
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Inhibitor
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1 Bethesda unit - 50% activity
2 Bethesda unit - 25% activity 3 BEthesda unit -12.5% activity |
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F11 deficiency
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AR, hemophilia C, can't activate TAFI
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F13 deficiency
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nl PT, PTT can't crosslink fibrin
Can't stop 5M urea from dissolving clot |
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Afibrinogenemia
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Quantiative, AR,
Corrects w/ mixing study |
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Dysfibriongenemia
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AD, thrombophilic, qualitative
Partially corrects, inhibitor |
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Fibrinogen
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Positive acute phase reactant
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Vit K deficiency
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gamma carboxylation of glutamic acid on F2, &7, 9, 10
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Liver disease
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low factors, low K (dec bile),
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alpha2antiplasmin
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dec euglobulin lysis time - measures time to dissolve a clot
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pseudothrombocytopenia
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edta clumping
antibodies gpIIb/IIIa |
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APC resistance
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#1 thrombophilia
point mutation factor 5 (prevents inactivatiob by protein C) |
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factor 5 gene mutation
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arg for gln position 506 factor v leiden
arg for thr 306 factor v cambridge |
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APC resistance - functional assay
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add Prot C - increase PTT >2:1 - normal
add prot C - increase PTT<2:1 APC (less prolonged) |
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Protein C deficiency
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Heterozygous - type I reduced protein
Homozygous type II defective protein Coumadin - skin necrosis |
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Protein S deficiency
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Type I - low total and free protein S
Type II normal total & free, decreased activity Type iii - normal total, decreased free negative acute phase reactant |
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Antithrombin III
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binds to heparin to inhibit II & X
deficiency - decreased response to heparin |
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Prothrombin G20210A
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Point mutation - increased prothrombin levels
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Antiphospholipid syndrome
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antibodies to B2 glycoprotein
anticardiolipin lupus anticoagulant |
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Antiphospholipid syndrome tests
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Inc PTT
Dilute RVVT - RVV +FV+phospholipid+ca = activates FX - prolongs PTT |
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Lupus anticoagulant antibodies
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Inc PTT - fails to correct with mixing study - partial correction with phospholipid
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anticardiolipin
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NO increase in PTT, ELISA
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B2glycoprotein I antibodies
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immunoassay
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Plt neutralization procedure
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PTT fails to correct with mixing study, PTT corrects w/ hexagonal phase...
Kaolin clotting time |
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HIT
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IgG ab to PF4 in alpha granules
decrease plts 5-8 days Serotonin release assay PF4 elisa - measure abs TX: no heparin, plts, warfarin Give thrombin inhibitors |
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Homocysteine
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forms methionine &cystationine
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Homocystenemia
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AR, lens dislocation, MR, peripheral neuropathy, folate decreased
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