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Boards: Coag Transfusion > Hemostatic disorders > Flashcards

Hemostatic disorders Flashcards

1
Q

What are inherited forms of hypercoagulability in animals?

A

None reported in vet med

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2
Q

What are the components of the Virchow’s triad?

A
  • endothelial damage
  • hypercoagulability
  • blood stasis/altered blood flow
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3
Q

List how the glycocalyx prevents excessive thrombosis

A
  • heparan sulfate makes up most of the proteoglycans of the glycocalyx - binding site for antithrombin
  • binds heparin cofactor 2 and thrombomodulin
  • binds TFPI
  • senses shear stress –> releases NO from endothelial cells –> vasodilation, PLT inhibition

NOTE inflammation => decreases glycosaminoglycan production => integrity of glycocalyx compromised => cannot bind anticoagulants as well

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4
Q

List 5 substances that can activate endothelial cells to release ultralarge multimers of vWF => platelet adhesion and tethering

A
  • TNF-alpha
  • histamine
  • thrombin
  • bradykinin
  • vascular endothelial growth factor
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5
Q

What cleaves ultra large multimers of vWF?

A

ADAMTS13

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6
Q

How does TF induce inflammation?

A

induces NFkB –> TNF alpha production

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7
Q

Do dogs and cats have vWF in their platelet alpha granules?

A

only cats

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8
Q

What are the contents of NETS

A

DNA
histones
myeloperoxidase
neutrophil elastase

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9
Q

Describe how antithrombin can be reduced in systemic inflammation

A
  • consumption (from thrombin generation)
  • decreased production (negative acute phase protein)
  • degradation by neutrophil extracellular traps
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10
Q

Protein S increases APC’s inhibition of FVa and FVIII xxxxx-fold

A

nearly 20-fold

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11
Q

How are Protein C and S affected in inflammation?

A
  • negative acute phase proteins - produced less
  • APC needs TM-thrombin complex for activation - TNF-alpha downregulates TM, endotoxin-activated neutrophils release elastases which cleaves TM
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12
Q

How does inflammation affect fibrinolysis?

A

TNF-alpah and IL-1 => lead to delayed but profound PAI-1 release - more than tPa => fibrinolysis decreased

NETs integrate into clots and delay fibrinolysis

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13
Q

List changes contributing to a hypercoagulable state in systemic inflammation or sepsis

A
  • TF expression (tissue damage, microparticle circulatin etc.)
  • EC activation (TF expression, ultra large multimers of vWF expression, etc.)
  • disruption of the glycocalyx (unable to bind and present important anticoagulants)
  • decreased Protein S and C
  • fibrinolysis inhibition (high PAI-1 levels, NETs inhibiting fibrinlysis)
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14
Q

Can you use Antithrombin activity to predict risk of thrombosis in PLN?

A

No, has failed to uniformly predict risk of thrombosis in people

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15
Q

List the procoagulant mechanism in IMHA

A
  • excessive TF expression
  • cell free heme => decreases NO bioavailability + upregulates endothelial cell adhesion molecules
  • NET formation (inflammation, hypoxia, exposure to free heme)
  • augmented thrombin generation from hemolysis (increased microparticles and procoagulant erythrocyte membrane)
  • PLT activation showed conflicting results in studies
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16
Q

What are the 3 most common neoplasias to cause DIC in dogs

A

hemagiosarcoma
mammary carcinoma
adenocarcinoma of the lung

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17
Q

What coag panel changes should raise concern for a consumptive coagulopathy in patients with systemic inflammaiton?

A
  • PLT count drop
    OR
  • PT prolongation by 20% or more
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18
Q

In cats with spontaneous echocontrast, how common was coagulopathy?

A

in 50% in one study

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19
Q

How commonly are both pelvic limbs affected in FATE?

A

75%

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20
Q

How common is an underlying cardiomyopathy in FATE. How commonly has this cardiomyopathy been previously known of?

A
  • 90%
  • < 10%
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21
Q

What is the 5P rule of FATE?

A
  • Pallor (purple or pale toes)
  • Polar (cold extremeties)
  • pulselessness
  • paralysis
  • pain
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22
Q

List diagnostic tools to differentiate for FATE

A
  • 5Ps
  • toe nail cut to the quick and not bleeding
  • absence of doppler flow
  • visualization of the thrombus on US
  • thermal imaging
  • angiography
  • glucose/lactate difference of peripheral limb versus central blood
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23
Q

What was assessed in the BLASST study?

A

thrombolytic therapy with tPA compared to placebo in FATE

showed discharge rates of 45 versus 30%

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24
Q

What are positive and negative prognostic indicators in FATE?

A

unilateral limb paralysis (70% survival to discharge versus 25% if both limbs affected)

negative:
* lower rectal temp (most consistent across studies)
* CHF present
* lower HR
* higher P cc
* absence of motor function
* higher affected limb lactate at admission

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25
Q

List the complications of thrombolytic therapy in FATE

A
  • AKI
  • hyperkalemia
  • clinical bleeding
  • coagulation abnormalities
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26
Q

What was assessed in the REVEAL study on FATE?

A

the cummulative risk for fate in cats with HCM or HOCM
1 year 3.5%
5 years 9.5%
10 years 11.3%

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27
Q

What did the FATCAT study assess in FATE?

A

clopidogrel versus aspirin in cats with previous FATE

recurrence rate 75% in aspirin group and 49% in clopidogrel group

time to recurrence of FATE or cardiac death 11.5 months for clopidogrel, 4.3 months for aspirin

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28
Q

What clinical sign has been associated with increased transfusion requiredments and mortality in ITP?

A

melena at time of hospital admission

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29
Q

What is the DOGiBAT score

A

score assessing bleeding - grades for 9 different anatomic sites

correlated with transfusion requirements and inversely correlated with platelet count

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30
Q

Where do autoantibodies bind on PLTs in ITP?

A

fibrinogen receptor (GPIIIbIIIa, integrin alphaIIb-beta3)
vWF receptor (GPIbIX)

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31
Q

Which Pattern Recognition Receptor is expressed on platelets?

A

TLR-4

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32
Q

In uremia-associated platelet dysfunction is aggregation, activation, or adhesion affected? What laboratory finding is this supported by?

A

adhesion

diminished vWF binding ability despite normal vWF concentration

will clinically resemble vWF disease

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33
Q

List classes of drugs that can affect platelet function

A
  • antiplatelet drugs (clopidogrel, aspirin)
  • NSAIDs (conflicting data)
  • PDE inhibitors (Sildenafil, Pimobendan)
  • NO donors (nitroprusside, nitroglycerin)
  • antithrombotics (heparin, factor X inhibitors)
  • fibrinolytic drugs
  • antimicrobials (beta-lactams, cephalosporins)
  • serotonin reuptake inhibitors
  • synthetic colloids
  • Vitamin E
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34
Q

How are synthetic colloids suspected to affect platelet function?

A
  • binding of colloidal molecules to GPIIbIIIa (integrin alphaIIbbeta3) and GP1b
  • interfers with vWF/FVII complex formation => eliminated faster
  • interfers with intracellular signaling function
35
Q

List the 3 Types of vWD

A

Type 1 - reduced quantities of all vWF multimers - Dobermans common
* bleeding following procedures

Type 2 - reduced quality of vWF, reduced high molecular weight vWF
* more severe bleeding diatheses, spontaneous mucocutaneous bleeding

Type 3 - complete absence of vWF
* spontaneous vWF, life-threatening hemorrhage after trauma or procedures, spontaneous mucosal bleeding

36
Q

List 5 types of congenital thrombocytopathies

A

Glanzman Thrombasthenia
* absent or reduced GPIIbIIIa

Bernard-soulier Syndrome
* GBIb-IX-V abnormalities
* macrothrombocytopenia

P2Y12 and P2Y2 abnormalities
* greater swiss mountain dogs

Chediak-Higashi syndrome
* persian cats
* intrinsic platelet storage pool defect - cannot store dense granules

Canine Scott Syndrome
* impairment of platelet-dependent thrombin formation
* cannot perform scrambling of platelet phospholipids - cannot externalize phosphatidylserine

37
Q

What are Tier 1, 2, and 3 diagnostics to evlauate for platelet disorders?

A

Tier 1:
* PLT count
* PLT size/morphology
* clotting times
* vWF concentration
* vWF binding assay

Tier 2:
* BMBT
* Platelet function analyzer
* Clot retraction
* Platelet aggregometry

Tier 3:
* Flow cytomety
* Western blot analysis
* Molecular testing
* Whole-genome sequencing

38
Q

What is the recommendation for patients requiring invasive procedures but getting anitplatelet drugs?

A

discontinue at least 5-7 days before procedure

39
Q

What is assessed by BMBT?

A

Platelet function

40
Q

What are normal values for BMBT?
What could affect the results besides platelet function?

A

< 3 min dog
< 2 min cat

blood viscosity, hematocrit

41
Q

List methodologies for platelet function analysis?

A
  • BMBT
  • bench-top platelet function analyzer (PFA-100)
  • aggregometry
  • flow cytometry
  • Platelet mapping viscoelastic testing - insensitive
42
Q

What is added to blood to measure aPTT?

A

kaolin and phospholipids

43
Q

With synthetic colloid administration is PT or aPTT typically prolonged?

A

aPTT

44
Q

What is the suspected cause for hypercoagulable TEG tracings in anemic patients?

A

recent ex vivo model showed hypercoagulable tracing in impacted by plasma proteins and available fibrinogen as opposed to packed cell volumes

45
Q

What are typical coag panel changes in DIC?

A
  • prolonged PT, aPTT
  • hypofibrinogenemia
  • elevated D-dimers
  • reduced antithrombin activity
46
Q

List 4 differentials for hyperfibrinolysis in dogs

A
  • Greyhound dogs
  • Trauma-induced coagulopathy
  • Hemoperitoneum
  • Liver disease
47
Q

List drawbacks of BMBT

A
  • operator dependent variability
  • insensitive for mild defects of platelet function
  • has shown unreliable in predicting surgical bleeding
48
Q

What percentage decrease of clotting factors is necessary for prolongation of PT, aPTT, or ACT?

A

60-70% for PT aPTT
90% of ACT

49
Q

Which clotting time can be affected by PLT counts?

A

ACT - PLT < 10k can prolong ACT

50
Q

How long should hypotensive resuscitation be applied for?
What is a contraindication for it?

A

No longer than 90 min (MAP of 60 mm Hg)

ICH - want MAP of 90 mm Hg

51
Q

What are the 2 effects of Desmopressin?

A
  • release of vWF from endothelial weibel palade bodies
  • enhances density of platelet surface glycoproteins - enhances adhesion
52
Q

List interventions that can bed used to stop epistaxis

A
  • benign neglect - often stop on their own
  • ice-packing
  • sedation
  • phenylephrine infusion into nasal cavity (diluted in saline or lidocaine)
  • nasal packing - risk of penetration into the cranial vault!
  • yunnan baiyao orally or topical - anecdotal
  • antifibrinolytic agents
  • foley catheter insertion and inflation
  • carotid artery ligation
53
Q

How is platelet production regulated?

A

By the hormone thrombopoietin

up or downregulated by circulating PLT numbers, PLTs bind to thrombopoietin therefore if less PLTs circulating less is bound and more active –> stimulating megakaryocytes

54
Q

List platelet’s trophogens and what is their function?

A
  • platelet-derived growth factor
  • vascular endothelial growth factor
  • fibroblast growth factor
  • stem cell factor
  • sphingosine-1-phosphate

keep endothelial tight-junctions tight - if PLT counts < 20-25k -> not enough trophogens and RBC extravasation

only happens with thrombocytopenia, not PLT dysfunction

55
Q

Why is bleeding into the brain rare with thrombocytopenia?

A

endothelial tight junctions there do not rely on trophogens

56
Q

How do the clinical signs of thrombocytopenia and thrombocytopathia differ

A

Both PLT dysfunction and thrombocytopenia can cause ecchymoses (bruising) but petechiation is only caused by thrombocytopenia (note: trophogens!)

57
Q

List causes of PLT sequestration.

A
  • splenomegaly
  • neoplasia
  • severe hypothermia

usually only causes mild thrombocytopenia

58
Q

How does vincristine improve platelet counts?

A
  • induces platelet release from megakaryocytes
  • reduces phagocytosis of opsonized platelets
59
Q

Where are tPA and uPA produced?

A

tPA - endothelium
uPA - mesothelial cells, fibroblasts, epithelia, monocytes, endothelium

60
Q

What triggers tPA release?

A
  • bradykinin
  • histamine
  • alpha-adrenergic agonists
  • PAF
  • acetylcholine
61
Q

What are the half-lives of uPA and tPA?

A

uPA 8 min
tPA 1-4 min

62
Q

Name 2 plasma proteins that inhibit plasmin directly

A
  • alpha-2-antiplasmin
  • alpha-2-macroglobulin
63
Q

Name 2 inhibitors of tPA and uPA

A
  • PAI-1
  • protease nexin
64
Q

What endogenous antifibrinolytic has been shown to be upregulated in dogs with sepsis?

A

TAFI
PAI-1

65
Q

Describe the role of thrombomodulin in acute coagulopathy of trauma

A
  • endothelial damage + catecholamine surgery => thrombomodulin release
  • binds thrombin => TM-T complex activates APC
  • APC inhibits not just FVa and FVIII but also PAI-1
  • low PAI-1 levels while endothelium releases excessive PA => hyperfibrinolysis
66
Q

Which snake types cause hyperfibrinolysis and does it happen?

A

Eastern and western diamondback rattlesnakes
tPA-like substance in venom

67
Q

Explain how hypofibrinolysis occurs in sepsis

A

TNF-alpha, lipopolysaccharides, TGF-beta, IL-1
=> induce endothelial PAI-1 synthesis

68
Q

Describe the euglobulin clot lysis time

A

test to assess speed of clot lysis

cold acetic acid causes precipitation of euglobulin fraction (plasminogen, tPA, fibrinogen) => clots with thrombin and then the time until dissolution is monitored

largely replaced by viscoelastic testing

69
Q

List tests of fibrinolysis

A
  • ECLT (euglobulin clot lysis time)
  • tPA assays
  • plasminogen assays
  • PAI-1 assays
  • TAFI assays
  • alpha-2-antiplasmin assays
  • Viscoelastic testing
70
Q

What is aproptin?

A

serine protease inhibitor (i.e., plasmin) - inhibits fibrinolysis

used in human coronary artery bypass grafting - anecdotally in dogs - no published reports though

71
Q

What are the main findings of the CRASH-2 trial?

A

in human patients with hemorrhagic shock TXA administration within 3 hours improved mortality without increasing risk of thrombotic events

72
Q

Are antifibrinolytic drugs safe in cats?

A

unknown at this time
experimental studies showed sezireus and myocardial injuries from TXA - but administration was not consistent with what would be done clinically

no studies showing safety at this time

73
Q

What are available recombinant tPA products?

A

alteplase
reteplase
tenecteplase

74
Q

Why doesn’t the Hageman trait typically lead to clinical signs of bleeding?

A

FXII deficiency - contact pathway not necessary for cell-based model of coagulation - more so activated in systemic inflammation and other disorders

will show up as elevated aPTT but not cause bleeding in otherwise healthy patient

75
Q

What is the onset of action time and duration of action of Desmopressin?

A

onset of action 30 min
duration of action 2 hours

76
Q

What is HASHTI?

A

6 step measure protocol for anticoagulant-associated coagulopathy

H: Hold further doses
A: Antidote if available
S: Stabilize and Support
H: Hemostatic measures
T: Transfusion
I: Investigate for bleeding source

77
Q

What is the antidote for heparin overdose?

A

Protamine
* works fast for UFH - within 5-10 min, effect monitored with aPTT or ACT
* not as efffective for LMWH - cannot fully reverse it, effect difficult to monitor without anti-factor Xa assays

side effect: histamine release and anaphylaxis

78
Q

What are the 2 fibrinolysis phenotypes of DIC and what conditions have each been reported?

A

Suppressed fibrinolytic type DIC
* most common in sepsis
* increased PAI-1
* causes microthrombosis and increased risk of MODS and death

Enhanced fibrinolytic type DIC
* augmented fibrinolytic activity and hemorrhage
* seen with different cancers in people
* reported with hemangiosarcoma in a dog

79
Q

List diagnostic criteria supporting diagnosis of DIC

A
  • underlying disorder known to cause DIC
  • thrmbocytopenia
  • prolonged PT APTT (>25-50%)
  • decreased fibrinogen cc
  • red cell fragmentation (schistocytes, acanthocytes)
  • increased FDP and d-dimer cc
80
Q

List the causes of coagulopathy in liver disease

A
  • cholestasis/biliary duct obstruction - decreased Vit K absorption - decreased carboxylation of clotting factor II VII IX X Protein C and S
  • thrombocytopenia from decreased synthesis of thrombopoietin, consumption with DIC, splenic-platelet sequestration due to portal hypertension
  • platelet dysfunction from signaling dysfunction
  • dysfibrinogenemia from failure of liver removing sialic acid from fibrinogen
  • hyperfibrinolysis - decreased clearance of tPA, decreased PAI-1, TAFI, alpha-2-antiplalsmin
81
Q

What are risk factors for bleeding complications after percutaneous ultrasound-guided biopsy of the liver

A
  • dogs PT > 1.4
  • cats aPTT > 1.4
  • PLT count < 86k
82
Q

What is the difference between TAC and ACOTS and RAC?

A

TAC - trauma-associated coagulopathy => includes both the early endogenous causes of coagulopathy and resuscitation-induced coagulopathy

ACOTS - endogenous coagulopathy from trauma and shock

RAC - resuscitation-associated coagulopathy

83
Q

Name 3 potential causes of acidosis in TAC.

A

hyperlactatemia from tissue hypoxia and catecholamine release
chloride-rich fluid administration
citrate administration with blood products

84
Q

How are platelets activated in ACOTS?

A

suspected:
wide-spread ADP release - prematurily activates and consumes platelets

Boards: Coag Transfusion (13 decks)

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