Coagulation Flashcards by Ben Saylor

What molecule attaches to naked endothelium, platelts attach with?

Then what happens?

Two types of granules in plts?

vWF; the platelets attachs by glycoprotein Ib/V/XI

Plt’s release granules

Alpha : thromboglobulin, P-selectin-PDGF, PF4, platelet fibrinogin, VWF, thrombospondin

Dense: ADP (causes vaso constriction), ATP, serotonin, Ca2+

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What happens after plt’s change shape; what is exposed?

Glanzmann’s is from issue with?

Bernard-Soulier disease is an issue with?

Fibrinogin and GPIIb/IIIa and platelets bind to this; causes primary plug

GpIIb/IIIa complex

GpIb

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What coag factors are not made in liver?

Intrinsic pathway is activated by?

Extrinsic pathway activated by?

Patients with low kallikrein and pre-kallirein do they have bleeding?

vWF (made in endothelial cells)

–ve charged glass

Tissue factor

No, elevated PTT

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If PT and PTT normal is there an issue with the cascade?

What factor is involved in tertiary hemostatsis?

What breaks down fibrin?

Probably not! Most likely outside of the cascade

Factor XIII–>XIIIa briding thrombin

Plasmin!

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Three inhibotors of plamin pathway?

Fibrin broken down into?

Alpha two antiplasmin inhibits plasmin

PAI inhibits plasminogen

TAFI (thrombin activatable fribrinolysis inhibitor) inhbitis plasminogen to TPA/Fibrin

Breaks down into D Dimers awnd Fragment E

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What proteins inhibit FV and FVIII?

Antithrombin made where, and bind to?

Activated factor C carried by protein S inhibits FV and FVIII

Liver, bind Heparin and inhibits II to IIa and inhibits Xa

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How does plt count work?

Bleeding time was a test for; better test?

Count things less than <13fL (no functional information)

Bleeding time: Plt activity; worthless; use platelet function analysizer

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PTT test method; what factors not measured?

PT, method, and pathways?

Negatively charged surface phospholipid and PPP and CaCl added; <40 seconds; intrinsic and common; ALL BUT 7 and 13

PT: Take tissue factor and phospholipids; add citrated PPP and CaCL; <15 seconds; extrinsic andn common

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What is INR?

What is Thrombin time, measures what pathway?

Increased in?

Standardized reactivity of tissue factor INR= (patient PT/Normal mean PT) raised to ISI

Thrombin time: Take xogenous thrombin, add PTT, measure clot time; common pathway; No Ca or phospholiped needed

Increased in: increased paraprotein, amyloid, heparin, dysfibrinogenemia

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What is Reptilase time?

Increased in?
If patient is on heparine?

If on heparine what is thrombin time and Reptilase time?

Take Bothrops atrox venon, add PPP, measure clot time

Increased in dysfibrinogenemia

Thrombin time increased; reptilase normal

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What is a mixing study?

If PTT corrects, think?

If PTT doesn’t correct, think?

Which inhibitor corrects and then prolongs after 1-2 hours?

Will dysfibrinogenemia correct?

Take patient plasma and mix with pooled normal

Measure PT and PTT and at 1 hr interval
If PTT correct= factor deficency

If PTT doesn’t correct=inhibitor

F8!!

Partially; hypofibrinogenemia will completely correct

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What does a platelet aggregation nstudy do?

Take patient’s platelet rich plasma and add ristocetin (causes aggregation); looka t light transmission and look for decreased turbidity and increase in transmission

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Bernard-Soulier

Defect?
Size of plts?

Increase or decrease in Plts?

PT, PTT, Bleeding time?
Ristocetin aggreation results, mixing?

Flow results?

GPIb/V/IX (CD42); plts cannot bind to vWF

Large plts with pseduonucleolus

Decrease/thrombocytopenia

PT, PTT normal; Bleeding time increased (plts don’t work correctly)
Impaired ristocetein aggregation–corrects if mixed with normal plts

Flow shows decreased CD42a, b, d

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Glansman thrombocytopenia problem?
Abnormal protein complex?
Risocetin test results?
Flow?

PT; PTT (and differs from afibrinogenemia)?

GPIib-IIIa cannot bind fibrin (so adhesion but not aggregation); Normal plt count

Decressed aggrecation ADP, collagen, and EPI but NORMAL risocetin

Decreased CD41 (GPIIb) and CD61 (GPIIIa)

Normal in Glansman (afibrinogenemia increased PT and PTT–no fibrin!)

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Storage pool deficiency shows:
What agregation changes?
What morphology; EM changes?
Plt agg studies results?
What ATP:ADP ratio?

decreased agg due to alpha/dense granule issues

Normal morphology; no granules EM
Plt agg: NO 2nd way-ADP or EPI; decreased collagen +AA, normal ristocetin

Increased ATP:ADP

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Common causes of acquired disorders of platelet function?

Drugs

Uremia: Abnormal adhesion, abnormal aggregation (ADP, Epi, Collagen)

Myeloproliferative disorders

Cardiopulmonary bypass; plt activation, decreased granules

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Mechanism of action of Aspirin/NSAIDS?

Aggregation study results?

Block acetylation of platelet cyclooxygenase–> decrease th romboxane formation

Decreased 2nd wave to ADP, EPI, no response to collagen or arachadonic acid

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vWF binds to?

Multimers cleaved by?

Where is it made?

Decreased vWF seen in what type of stored blood?

F8 and subeptiehial collagen and GPib

ADAMTS-13

Megakaryocytes (alpha granules and endothelial cells Weibel-Palade bodies)

Type O

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Difference between VWF antigen and Risoceten Cofactor tests?

RIPA test?

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VWF Ag: measures vWF quantiy in blood add F8–>measure vWF activity

vWF Risto: Measures vWF activity; Pt plasma + normal plts + ristocetin then measure aggregation; SPECIFIC and SENSITIVE; can get % activity

RIPA: Ristocetin induced platet aggregation; pts plasma + pt plts+ low does ristocetin: all or nothing aggregation

Tyep I VWF?

IIA?

IIB; mutation?

III?

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I: All cleaved products but at lower quantities: Most common: Tx DDAVP

IIA: Missing intermediate to high molecular weight multimers: low vWF:RCo and vWF Ag

IIB: Missing very high molecular weight: mutaiton; exon 28 vWF gene; increased affinity VWF for GP1ba; Elevated RIPA

III: Missing all multimers: Most severe; auto recessive; low vWF and F8

vWF Type 2M; suspect when labs show?

2N; patient population?

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GP1b binding defect, no loss HMW; vWF made but doesn’t work (low vWFRco); Suspect: vWF:Rcof<vwf></vwf>

2N: Defect binding vWWF to FVIII; Hemophilia like (AR); Women low F8

Tests: Decreased F8 and vWFAg:C levels

Normal: RIPA, ml multimlers, nl ristocetein

NORMAL F8 gene

What is Pseudo VWF-platelt type?

Gene mutation?

Gel for vWF shows?

Lab studies?

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Mutation in GP1ba protein; increased GPIba binding ot HMW VWF

Abnormality on plts!!

Decreased HMW

Aggregation with cryoprecipitate; platlet agg studies show low does ristocetin aggregation; Abn RIPA studies

Hemophilia A factor?

B faactor?

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A: Decreased F8

B: Decreased F9

Hemophillia A inheritence pattern; who rarely gets disease?

Chromosome issue?

Labs?

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X- linked recessive; 30% spontaneous: Rare females (mostly XO, skewed lyonization, homozygosity of mother and affected father); rule out vWF 2N and 3

Inversion intron 22 Chromosome X

Elevated PTT and normal PT; decreased F8 level; mixing corrects immediatly and at 2 hrs

Hemophilia B (other name), inheritence pattern? Do inhibitors correct in mixing studies? Bethesda activity?

Christmas disease; **less common than A; X-linke drecessive;** less severe than Hemophilia A No; **F8I will correct then prolong** 1 unit: 50%, 2 units: 25%; 3 units: 12.5%

Factor 11 deficiency casues? Labs? Facotr 13 deficiency labs?

Mild bleeding; **Jews; auto recessive** **Decreased prekallikrine** and decreased HMWF vWF Increased PTT but no bleeding **Decreased F12-Hageman, increased PTT but thrombosis** F13 def: nl PT, and PTT; cannot crosslink Fibrin; 5M urea disolves clots \<24 hr

Does mixing study correcta figrinogenemia? What about reptilase adn thrombin times?

Yes; but nto dysfibrinogenemia only partially corrects Both cause increased reptilase and thrombin times

Vitamin K affects what Factors? Liver disease has what factor at normal levels? Alpha 2 antiplasmin deficiency had bleeding but what PT and PTT levels? Labs?

2, 7, 9, and X F8 Alpha2 antiplasmin deficiency: **normal PT and PTT** Decreased euglobulin lysis time (\<2 hours); decreased fibrinogen, DIC, and increased tPA

What causes pseudtothrombocytopenia? Use what type of tube? What is platelet satellitism?

Plts clump from **EDTA; antibodies to GPiib/IIIa cause clumping** Sodium citrate anticoagulatin tubes usually normal Plts invitro bind to leukocytes in EDTA anticoagulated blood

DIC lab findings? Peripheral smear shows?

Increased PT, PTT, TT, decreased Plt count, Fibrinogen, ATIII, plasminogen, Protein C and S, increased D-Dimer (most specific) Schistocytes

TTP/HUS clinical picture? TTP vs HUS vWF findings? Tx?

Hemolytic anemia **w schistos,** decreased plts, fever, kidney/brain issues, ab pain TTP: Big vWF multimers, shear RBCs HUS: **Normal vWF products; E. Coli O157:h7 shigella/salmonella** TTP: FFP, IviG, aphoresis; **don't give plts** HUS: Supportive+ antibiotic

What is activated Prot C resistance? Mutation in what factor? What other mutation makes this worse?

**Mutaiton in FV prevents inactivation by C leading ot thrombosis** FV mutaiton: Arg for Gln on 506 (Factor V Leiden) or Arg for Thr on 306 **F2 and Methylene tetrahodyrofolate reductase**

How to screen for Factor V Leiden/Protein C inactivation issues? Protein C deficiency (Hetero vs homo)? If they take Warfarin?

Protein blood and add ProtC; if PTT\>2:1 normal; if activated protein C resistance: PTT goes up \<2:1 PCD: Hetero live; homo die infancy Skin necrosis

Protein S deficiency casues? Labs? Drugs that make this worse?

60% S binds to C4b and only 40% is free functional Labs: C4b is increased and protein S is decreased **Autodominant; want to measure activity** Oral contraceptives and estrogen and pregnancy decrease Protein C (lead to thrombosis risk)

ATIII deficiency? **Lab results show?**

Binds heparin to inhibit Factors II and X In deficiency Hep cannot bind Lab: Thrombosis and tx with heparine but **PT DOES NOT RISE sufficiently**

What is Prothrombin (F2) G20210A? What is antiphospholid syndrome? Plts and thrombosis risk?

High prothrombin levels; guanidine to adenine on 3' untranslated region of Chr 11 APLS: **Autoantibiodies to different phospholipid (B-2 glycoprotin; anticardiolipin and lupus anticoagulant) LOW PLTS AND THROMBOSIS**

What is the PTT in pts with Antiphospholipid antibody tests? What is the dilute Russell viper venom test? What do mixing studies show; Plt neutralization procedure? What tests are give false positives with this syndrome?

Increased PTT **Viper venon - F V, Phospholipid and calcium activate FX, if plasmsa has Lupus antibodies the PTT is increased** Mixing shows inhibitor activity with partial correction with phopholipids; **PTT corrects when you add hexagonal phase phosphatidyl ethanolamine** **VDRL/RPR**

HITT has issue with? Time frame? Labs? Can you give more plts?

IGG Ab to Heparin **PF4 complex; 8% in unfractioned heparin** **5-8 days post heparin** Serotonin release is negative in HITT; **PF4 ELISA is best test to measure antibodies, OFTEN FALSE +** Do not give more plts; they will just be activated

T or F Homocystinemia can cause clotting? What is the folate level?

True!: **Auto Recessive** Decreased

What factors increase in pregnancy? Decrease? Liver disease, what factors are best indicator?

7, 8, 9, 10 , fibrinogen Decreased S; C and ATIII stay the same! **F7 falls first, FV and 7 are most sensitive**

Heparine affects PT or PTT? Test to monitor LMWH?

PTT; Adequeate when PTT is 2x mean normal anti-factor Xa

Does TEG correlate with Coag (PT and aPTT)? Is it sensitive to vWF deficency?

No!!! No!

Plt problem on TEG shows? TEG with coag problem shows?

Decreased max amplitude; normal R and LY30; **TX plts** ## Footnote **Coag: Longer R (inital time to clot)**

Coagulation factors with shortest half-lives? Longest half-life? "Gold standard" for Neonatal alloimmune thrombocytopenia?

F7 (~5 hrs); F8 (~8 hours) F1 **Washed maternal antibodies**

Coagulation Flashcards

(46 cards)