Hemostasis 1 Flashcards

(62 cards)

1
Q

Hemostasis

A
  • arrest of bleeding

- can be 1° / 2° hemostasis

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2
Q

Coagulation

A
  • sequential processes in for formation of a fibrin clot

- 2° hemostasis

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3
Q

1° hemostasis purpose

• 3 major components

A
  • Form a temporary platelet plug (occludes bleeding)

1 - Vessels
2- vWF
3- Platelets (fxn/number)

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4
Q

2° hemostasis purpose

• 3 major pathways

A
  • cross-link fibrin –> stabilizes & contacts plug

- Thrombin generation

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5
Q

3° hemostasis

A

aka fibrinolysis

- prevents exuberant thrombosis & restricts clot size

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6
Q

3° hemostasis purpose

• 3 main components

A
FIbrinolysis
• F12a (hagmen factor) 
& tPA (from endothelial cell, need fibrin to act)
--> plasminogen binds fibrin
--> plasmin 
--> fibrinolysis 
--> FDP, d-dimer 
--> inhibit hemostasis
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7
Q

Clinical signs assoc’d w/ 1° hemostasis disorder

A
  1. Petechiation (not w/ vWD)
  2. Ecchymoses
  3. Cutaneous bruising
  4. Mucosal bleeding
    • Epistaxis , GI , Hematuria
  5. Prolonged wound bleeding
    • after tooth extractions or venipuncture

Hx
• Outdoor activities (wood/tick)
• Drugs (platelet fxn/marrow tox)

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8
Q

Clinical signs assoc’d w/ 2° hemostasis disorder

A
  • Lg SQ hemorrhage
  • Lg hematomas
  • Hemarthrosis
  • Deep muscles
  • Cavitary hemorrhage
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9
Q

Collection tube used for Platelet count

A

-

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10
Q

Collection tube used for PT

A
  • Na Citrate
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11
Q

Collection tube used for ACT

A
  • ACT tube
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12
Q

Collection tube used for APTT

A
  • Na Citrate
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13
Q

Collection tube used for Clinical chemistry profile

A

vWF - …
fibrinogen - …
gp ib - …

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14
Q

Tests used to ID 1° bleeding disorders
• when would you request them?
• limitations?

A
  • Platelet numbers
  • BMBT
  • vWF : Ag
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15
Q

4 main categories of thrombocytopenia ddx

A

SPUD

Sequestration
     1 - ↑ organ capacity
     2- hypothermia 
     3- endotoxemia
     --> hepato- / splenomegaly / lungs

Production

 1. Megakaryocyte aplasia
 2. Aplastic anemia / myelodysplasia
 3. Myelopthistic dz (neoplasia/ myelofibrosis)
 4. Drug/toxin
 5. Rickettsial dz

Utilization

 1. DIC
 2. Blood loss

Destruction
1. Immune - mediated–> ↓ life span

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16
Q

3 fxn of vWF that can be compromised in von Willebrand Dz

A

1 - platelet adherence to vessel wall
2 - platelet aggregation
3 - Stabilization of Factor 8

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17
Q

how are FDPs & D-dimers formed?

A
  • evidence for fibrinolysis
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18
Q

What is the significance of FDP & D-dimers?

A
  • fibrinolysis

• ↑ w/ DIC or inflammation

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19
Q

von Willebrand dz

A
  • Defective platelet plug
  • prolonged APTT

3 Types
• Type 1 - mildest
• Type 2- more severe
• Type 3- Lethal

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20
Q

Vitamin K deficiency/antagonist

A

Warfarin / pindone = 1st generation
Bromadiolone / brodifacoum = 2nd generation
Coccidiostat - Sulfaquinoxaline

  • Factor 7 = short 1/2 life –> extrinsic affected before intrinsic

Early: PT first
Later: APTT, PT

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21
Q

Hageman factor (12) deficiency

A

Relatively common in cats
• Thrombosis due to lack of fibrinolysis
• ↑ APTT (if cat, R/O hemophilia)

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22
Q

↓ hepatic fxn’l mass

A
  • Liver synthesis most coagulation factors & inhibitors

- -> ↓ Vit K absorption

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23
Q

Evan’s syndrome

A
  • 1° immune mediated thrombocytopena + IMHA
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24
Q

Rickettsial dz

A
  • vasculitis
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25
Triggers of DIC
``` 1 - Tissue factor activation • Severe trauma • Inflamm --> Macrophage activation --> TF release --> initiates common & intrinsic = amplification! 2- Endothelial damage • (Endo)Toxins • Hypoxia • Acidosis --> Intrinsic pathway & Platelet recruitment / activation ``` (3- direct activation of cascade) • Simultaneous activation of COAGULATION + FIBRINOLYSIS + PLATELET CONSUMPTION
26
Hemophilia A & B
↑ APTT alone Hemophilia A = ↓ Factor 8 • German shepherds (& cats) -- X-linked recessive • bleeding w/ minor injury ``` Hemophilia B = ↓ Factor 9 • less common • x-linked • epistaxis, hemarthrosis, subQ hemorrhage ```
27
Endothelial cells vs subendothelium
Endothelium • Anticoagulant properties --> inhibit platelet aggregation • Activation --> pro-coagulant Subendothelium • always thrombogenic
28
von Willebrand factor
Cross-linking agent - Endothelium - Megakaryocytes - Platelet Alpha-granules Fxn: • X-link PLATELETS & SUBENDOTHELIUM • X-link ACTIVATED PLATELETS • Circulates as a complex w/ FACTOR 8 (stabilizes)
29
How is initial vasoconstriction maintained?
1 - TxA2 from activated platelets • also a potent platelet aggregator • Asprin = irreversibly blocks TxA2 • PGI2 (prostacyclin) = opposes TxA2 2- Tissue Factor • Released by damaged tissue 3- Coagulation by-products
30
Pathogenesis of Platelet plug
``` 1 - Rolling 2- Adhesion & contraction 3- Granule content secretion 4- Aggregation --> platelet plug formation ```
31
Why does anemia ↑ bleeding risk?
normal Hct --> maintains platelet rolling • ↓ Hct --> ↓ marginating/rolling --> ↑ risk of bleeding
32
How does platelet adhesion work?
Platelet membrane receptor = gp1B/9a Binds vWF on collagen vWF --> platelet adhesion to sub endothelium - -> platelet changes shape - -> expose membrane receptors - -> content expulsion
33
Alpha granules
1 - Adhesion proteins • vWF, Fibrinogen, thrombocytopenia 2- Growth modulator • Stimulate healing • PF-4, TGF-B, thrombospondin 3- Coagulation factors • 5, 11, HMWK, fibrinogen
34
Dense granules
``` Energy & signaling • ATP / ADP • Ca++ (factor 4) • Serotonin • Histamine ```
35
Platelet aggregation
Platelet to platelet binding • VWF -- gp1B / IXa (receptor) - platelet to subendothelium • Fibrinogen --gp2B / 3a (receptor) - platelets to each other
36
4 Mechanisms to consider w/ 1° hemostasis disorders
1 - Thrombocytopenia (platelet number) 2- Vasculopathy (vessels) 3- von Willebrand dz (linking) 4- Thrombopathy (defective fxn) Thrombasthenia (weak adhesion)
37
Features of DIC
``` 1 - Thrombocytopenia 2- Schistocytes 3- Prolonged APTT 4- Prolong PT 5- ↑ FDP or D-dimers (fibrinolysis evidence) 6- ↓ Antithrombin 3 ```
38
Normal life span of platelets
Dog • 5-7 days Cats • 1.5 days
39
1° vs 2° Immune Mediated Thrombocytopenia (ITP)
``` 1° • Poodles • Old English sheepdogs • Cocker spaniel • Females • < 20,000/uL = very low ``` 2° • infectious agents • drugs • neoplasia
40
Sources of vWF
* endothelial cells * megakaryocytes * platelets
41
Type 1 von Willebrand Dz
All multimer size present - ↓ total numbers • Mild bleeding tendency - only if challenged • Doberman Pinscher (GSD, Corgi, Retrievers)
42
Type 2 von Willebrand Dz
↓ numbers, esp Lg'er multimers • ~12-20% of normal vWF • German Shorthaired pointer
43
Type3 von Willebrand Dz
No/small ant of vWF • Lethal - severe bleeding tendency • Scotties, Chesapeake Bay retrievers
44
Testing for vWD
Qualitative • Buccal mucosa bleeding time • APTT - needs to have vWF severely ↓ to compromise Factor8 Quantitative • Ab based assay • <20% = abnormal hemorrhage likely
45
Congenital Thrombapathy dz's
``` 1 - Chediak-Higashi syndrome • Persian cats • Aleutian mink - Lack Dense Granules - Abnormal granules in many cells (neuts) 2- Glanzmann Thrombasthenia • aggregation disorder • gp2b/3a missing ```
46
Acquired thrombapathies
Drugs - Anesthetics - Abx - Anti-histamines - Asprin - Prevents TxA2 - NSAIDs Systemic Dz - Uremia - Pancreatitis - Liver Dz - neoplasia - IMHA
47
Blood smear platelet estimates
8-10/ Oil obj field = > 100, 000 6-7/OIF = ~100,000 < 3-4/OIF = <50,000 - would explain prolonged hemorrhage
48
BMBT
- in vivo test - evaluate 1° hemostasis - superficial cut -- too superficial to need fibrin * Dog = < 4 mins * Cat = <3.3 mins * platelets, vessel wall defects & vWF
49
Erroneous hemostasis values come from?
Improper blood collection - Patient excitement - vessel probing - from existing catheter - - heprin - - dilution
50
Proper blood citrate ratio in Sodium Citrate tube (blue top)
1 : 9
51
What does PT measure?
Extrinsic ( Factor 3 & 5 ) & Common
52
What factors are assoc'd w/ common pathway
10, 5, Thrombin, fibrinogen
53
Describe PT test
* Thromboplastin (tissue factor) + Ca added * Prolonged = < 30% of normal quantity * May not show bleeding
54
Describe APTT test
* Phospholipid + calcium + negatively charged surface (to activate Hagman factor) * Prolonged = < 30% of normal quantity
55
Describe ACT test (Activated Clotting Time)
* Platelets > 10,000 = provide phospholipids | * <5% of normal quantity
56
What is Russell viper venom test
* Tests common | * activates clotting factors 5 & 10
57
Describe TT (Thrombin Time)
* Thrombin added | * tests Fibrinogen only
58
Anti-coagulation
• Anti-thrombin 3 + heparin - Inhibit Thrombin & Xa - heparin potentiates AT3 • Thrombomodulin + thrombin - Activate Protein C - -> ↓ 5a & 8a --> inhibits coagulation - Reduces thrombin avail for coagulation • Endothelial secretion - PGI2 --> vasodilates / platelet aggregation - NO --> vessel relax - ADPase --> inhibits platelet aggregation
59
Testing for fibrinolytic activity
* FDP - fragments of fibrin * D-dimer - fragments of x-linked fibrin in a clot - must use these + other markers when Dx DIC
60
What is vitamin K required for?
Synth of • pro-coagulants - 2, 7, 9, 10 • Anti-coagulants - Protein C & S
61
Which would ↑ first with DIC? | • PT or APTT
APTT ↑ first | - no good reason why
62
Lab findings that can be assoc'd w/ DIC
``` • Thrombocytopenia (1°) • Schistocytes • ↑ APTT --> ↑ PT • ↓ fibrinogen - except horse (normal to ↑) • ↑ FDP & d-dimers • ↓ AT3 ```