2ry Hemostasis

Prekallikrein and High molecular weight kininogen (HMWK) are aka _

Fletcher factor

contact activation cofactor, Fitzgerald, Flaujeac Williams factor

factor I is aka

fibrinogen (Ia = fibrin)

factor II is aka

prothrombin → (IIa = thrombin)

factor III is aka

tissue factor (TF)

factor IV is aka

Ca2+

factor V is aka

proaccelerin, labile factor, accelerator (Ac-) globulin

factor VI (Va) is aka

accelerin

factor VII is aka

proconvertin, serum prothrombin conversion accelerator (SPCA), cothromboplastin

factor VIII is aka

antihemophiliac factor A, antihemophilic globulin (AHG)

*hemophilia A = defic of f-VIII

factor IX is aka

Christmas factor, antihemophiliac B, plasma thromboplastin componenet (PTC)

*Hemophilia B = defic in f-IX

get Hemophilia B for Christmas if Bad Boy

factor X is aka

Stuart-Prower factor

factor XI is aka

plasma thromboplastin antecedent (PTA)

factor XII is aka

Hageman factor

(rhymes w/Asian for XII defic, no bleeding, inc risk thrombosis)

factor XIII is aka

protransglutaminase, fibrin stabilizing factor (FSF), fibrinoligase

extrinsic factors are

VII, III (TF)

intrinsic factors are

XII, XI, IX, VIII

common factors are

X, V, II, I

contact factors are (do not require Ca2+)

XII, XI, prekallikrein, HMWK

coag testing specimen requires

WB:anticoag must be 9:1

anticoag = 3.2% sodium citrate, loosely binds Ca2+

• need plt count of <10,000/mm3

• stable at RT for 4 hr

• Hct>55% → must adjust

• no grossly hemolyzed samples

• lipemic or icteric → ACL top read at 671 nm to eliminate interference

prothrombin time (PT)

measures extrinsic & common pw

uses: thromboplastin (TF) + calcium + phospholipid

what value is used to monitor Coumadin/Warfarin therapy?

PT/INR

• correction factor assigned to PT rgt/equipment system, based on WHO standard

patients INR = (patient PT/PT geo mean)^ISI

ISI: lower, more sensitive the reagent

Coumadin/Warfarin dec ___?

vit K-dependent factors: II, X , IX, VII (2, 7, 9, 10)

also protein C and S production

takes ~3 days for effect

prolonged use of Abx → kill bacteria that produce majority of vit K → same effect

aPTT (PTT, activated partial thromboplastin time)

measures intrinsic & common pw

uses: contact activator (micronized silica) + calcium + phospholipid (cephalin)

PTT vs aPTT?

mechanical vs optical clot detection

basis of PT, PTT, fibrinogen assays

mechanical: measures based on resistance to mvmt (viscoelasticity)

optical: light transmission through a sample

heparin

• what is it?

• how does it work

  • types?

anticoagulant that enhances antithrombin III (ATIII) → ATIII inhibits Xa → inhibits IIa (AT3=8 → 2+8=10)

neutralizes activated serine proteases: XII, XI, IX, X, II (12, 11, 9, 10, 2)

immediately acting

types:

• unfractionated: oligos chains of varying lengths

• low molecular weight (Lovenox): more predictable response, shorter chains, less bleeding

  • can’t monitor w aPTT

normal vs abnormal clot curves

clot curves

• which peak = PT?

• which peak = PTT?

1st order rxn = 1st derivative = PT

2nd order rxn = 2nd derivative = PTT

chromogenic heparin assay

CHA measures heparin inhibiting factor Xa

• requires pt’s own AT3

• low heparin activity: less color change bc heparin concentration is low → less Xa inhibited

• high heparin activity: more color change → more Xa inhibited

why would PT/aPTT be prolonged? 3 categories:

anticoag therapy

• Hep/Warf or new anticoag (Rivoraxiban, etc)

inhibitors

• Heparin

• Lupus inhibitor (anti-phospholipid Ab against rgt phospholipid)

• factor inhibitor (Ab against a factor)

factor deficiency

• acquired: usually liver dz, vit K defic, or Warf

• congenital: usually single factor (m/c = VIII, IX vWF)

how to differentiate an inhibitor from a factor deficiency?

PTT or PT inhibitor screen/Mixing Studies (50/50 mix)

• mix 1:1 pt plasma & normal pool plasma → incubate 5 min 37C → retest

• incubate 2 hr 37C → retest

if return to normal PT/PTT value → pt has factor defic

if still prolonged value → factor specific inhibitor or Lupus anticoagulant or heparin

inhibitors in mixing studies

heparin: thrombin time is v long

Lupus anticoagulant (LA): anti-PL → confirm w/ anti-PL panel: DRVVT (dilute russell viper venom time), hexagonal phase, anti-cardiolipin

factor inhibitor (Ab)

fibrinogen assay

• does this measure amount of fibrinogen?

• what dz may this test indicate?

pt clotting time is compared to reference curve

= functional assay (does NOT directly measure fibrinogen)

may indicate fibrinogen DO

• afibrinogenemia - lack of

• hypofibrinogenemia - low fxnal

• defic

• dysfibrinogenemia - qualitative

thrombin (thrombin = factor IIa) time (TT) vs reptilase time (RT)

TT = time for fibrinogen → fibrin (I → Ia)

• pt plasma + dilute thrombin rgt → fibrin clot

• SUPER sensitive to heparin (inhibits Xa & IIa)

RT

• reptilase sub’d for thrombin (converts I → Ia)

• insensitive to heparin, use when heparin is suspected

inc TT and normal RT → heparin present

if inc TT/RT → problem w fibrinogen → eg dysfibrinogenemia

factor VIII:C assay (C = coagulant)

key in dx Hemophilia A (defic in factor VIII) and vWD

measures activity of VIII

1. make 1:1 dilution w normal pool plasma that has depleted factor VIII

2. pt clotting time is compared to reference curve

??

factor XIII

• is this factor tested in PT/PTT? if not, what test can be used for XIII defic?

XIII stabilizes fibrin clot via covalent bonds b/t fibrin strands

• activated by thrombin

• XIII defic → unstable blood clots

• NOT part of PT/PTT test system

qualitative test: clot stabilizing factor urea clot lysis screen

• create clot + 5M urea → incubate 24 h

• clot dissolved → <10% factor XIII → 13 defic

• stable clot → normal

also indirectly test XIII activity on TEG/ROTEM/Quantra

Hemophilia A

• congenital defic of VIIIC (m/c defic)

• sex-linked to X chromosome

• → joint bleeds, deep muscle bleeds, intracranial hemorrhage)

recall vWF is the carrier of VIII → vWD type 2N: dec binding → mimics Hemophilia A

• also recall common name of VIII

Hemophilia B

• congenital defic of factor IX (2nd m/c)

  • aka Christmas factor; if Bad → get Hem B for gift

• sex-linked to X chromosome

• → joint bleed, deep muscle bleeds, intracranial hemorrhage (same as Hem A)

• recall common name of factor IX

Hemophilia C

• autosomal recessive, defic in factor XI

• rare, except in European Jewish subpopn

  • mostly asympto, but → mild mucus membrane or post-surgery bleeds

defic in factor XII (Hageman factor)

• autosomal recessive

• rare, but prevalent in Asians

• doesn’t bleed, but may have inc thrombosis, since XII is activator for clot lysis system

acquired coag disorders

liver disease

• all factors made in liver, except vWF and VIII

vit K defic

• majority prod by gut bacteria → Abx, chronically ill, or Warfarin → vit K defic → dec factor II, VII, IX, X

DIC

• consumes factors, plt, esp fibrinogen

Disseminated intravascular coagulation (DIC)

• what does it do?

• what are the various causes?

• consumes coag factors & plts → produces fibrin clot → bleeding and/or thrombosis

• due to exposure of TF in underlying tissue layers which occurs via:

  • bacterial sepsis (triggered by GNR’s LPS)

  • blood parasites

  • pregnancy: dead fetus, amniotic fluid emobolus

  • surgery complications

  • brain/lung trauma

  • burns

  • snake venoms: direct factor activators

DIC is tested via

PT, aPTT

fibrinogen

plt count

FDP (fibrinogen degradation product, 1ry & 2ry fibrinolysis)

D-dimer (2ry fibrinolysis)

IIa (thrombin) acts on which coag cascade factors?

VIII

V

I

XIII

XI

(1, 5, 8, 11, 13)

13-11 = (2)

13=8+5

just remember 1