Coagulation Flashcards

1
Q

What molecule attaches to naked endothelium, platelts attach with?

Then what happens?

Two types of granules in plts?

A

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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2
Q

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

Glanzmann’s is from issue with?

Bernard-Soulier disease is an issue with?

A

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

GpIIb/IIIa complex

GpIb

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3
Q

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?

A

vWF (made in endothelial cells)

–ve charged glass

Tissue factor

No, elevated PTT

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4
Q

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

What factor is involved in tertiary hemostatsis?

What breaks down fibrin?

A

Probably not! Most likely outside of the cascade

Factor XIII–>XIIIa briding thrombin

Plasmin!

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5
Q

Three inhibotors of plamin pathway?

Fibrin broken down into?

A

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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6
Q

What proteins inhibit FV and FVIII?

Antithrombin made where, and bind to?

A

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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7
Q

How does plt count work?

Bleeding time was a test for; better test?

A

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

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

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8
Q

PTT test method; what factors not measured?

PT, method, and pathways?

A

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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9
Q

What is INR?

What is Thrombin time, measures what pathway?

Increased in?

A

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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10
Q

What is Reptilase time?

Increased in?
If patient is on heparine?

If on heparine what is thrombin time and Reptilase time?

A

Take Bothrops atrox venon, add PPP, measure clot time

Increased in dysfibrinogenemia

Thrombin time increased; reptilase normal

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11
Q

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?

A

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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12
Q

What does a platelet aggregation nstudy do?

A

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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13
Q

Bernard-Soulier

Defect?
Size of plts?

Increase or decrease in Plts?

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

Flow results?

A

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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14
Q

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

PT; PTT (and differs from afibrinogenemia)?

A

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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15
Q

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

A

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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16
Q

Common causes of acquired disorders of platelet function?

A

Drugs

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

Myeloproliferative disorders

Cardiopulmonary bypass; plt activation, decreased granules

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17
Q

Mechanism of action of Aspirin/NSAIDS?

Aggregation study results?

A

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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18
Q

vWF binds to?

Multimers cleaved by?

Where is it made?

Decreased vWF seen in what type of stored blood?

A

F8 and subeptiehial collagen and GPib

ADAMTS-13

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

Type O

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19
Q

Difference between VWF antigen and Risoceten Cofactor tests?

RIPA test?

A

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

20
Q

Tyep I VWF?

IIA?

IIB; mutation?

III?

A

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

21
Q

vWF Type 2M; suspect when labs show?

2N; patient population?

A

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

22
Q

What is Pseudo VWF-platelt type?

Gene mutation?

Gel for vWF shows?

Lab studies?

A

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

23
Q

Hemophilia A factor?

B faactor?

A

A: Decreased F8

B: Decreased F9

24
Q

Hemophillia A inheritence pattern; who rarely gets disease?

Chromosome issue?

Labs?

A

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

25
Q

Hemophilia B (other name), inheritence pattern?

Do inhibitors correct in mixing studies?

Bethesda activity?

A

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%

26
Q

Factor 11 deficiency casues?

Labs?

Facotr 13 deficiency labs?

A

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

27
Q

Does mixing study correcta figrinogenemia?

What about reptilase adn thrombin times?

A

Yes; but nto dysfibrinogenemia only partially corrects

Both cause increased reptilase and thrombin times

28
Q

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?

A

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

29
Q

What causes pseudtothrombocytopenia?

Use what type of tube?

What is platelet satellitism?

A

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

30
Q
A
31
Q

DIC lab findings?

Peripheral smear shows?

A

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

Schistocytes

32
Q

TTP/HUS clinical picture?

TTP vs HUS vWF findings?

Tx?

A

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

33
Q

What is activated Prot C resistance?

Mutation in what factor?

What other mutation makes this worse?

A

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

34
Q

How to screen for Factor V Leiden/Protein C inactivation issues?

Protein C deficiency (Hetero vs homo)?
If they take Warfarin?

A

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

35
Q

Protein S deficiency casues?

Labs?

Drugs that make this worse?

A

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)

36
Q

ATIII deficiency?

Lab results show?

A

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

37
Q

What is Prothrombin (F2) G20210A?

What is antiphospholid syndrome?

Plts and thrombosis risk?

A

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

38
Q

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?

A

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

39
Q

HITT has issue with?

Time frame?
Labs?

Can you give more plts?

A

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

40
Q
A
41
Q

T or F Homocystinemia can cause clotting?

What is the folate level?

A

True!: Auto Recessive

Decreased

42
Q

What factors increase in pregnancy?

Decrease?

Liver disease, what factors are best indicator?

A

7, 8, 9, 10 , fibrinogen

Decreased S; C and ATIII stay the same!

F7 falls first, FV and 7 are most sensitive

43
Q

Heparine affects PT or PTT?

Test to monitor LMWH?

A

PTT; Adequeate when PTT is 2x mean normal

anti-factor Xa

44
Q

Does TEG correlate with Coag (PT and aPTT)?

Is it sensitive to vWF deficency?

A

No!!!

No!

45
Q

Plt problem on TEG shows?

TEG with coag problem shows?

A

Decreased max amplitude; normal R and LY30; TX plts

Coag: Longer R (inital time to clot)

46
Q

Coagulation factors with shortest half-lives?

Longest half-life?

“Gold standard” for Neonatal alloimmune thrombocytopenia?

A

F7 (~5 hrs); F8 (~8 hours)

F1

Washed maternal antibodies