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Clin Chem > Hemostasis 1 > Flashcards

Hemostasis 1 Flashcards

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
Q

Triggers of DIC

A 
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
Q

Hemophilia A & B

A

↑ 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
Q

Endothelial cells vs subendothelium

A

Endothelium
• Anticoagulant properties –> inhibit platelet aggregation
• Activation –> pro-coagulant

Subendothelium
• always thrombogenic

28
Q

von Willebrand factor

A

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
Q

How is initial vasoconstriction maintained?

A

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
Q

Pathogenesis of Platelet plug

A 
1 - Rolling
2- Adhesion & contraction
3- Granule content secretion
4- Aggregation
--> platelet plug formation
31
Q

Why does anemia ↑ bleeding risk?

A

normal Hct –> maintains platelet rolling

• ↓ Hct –> ↓ marginating/rolling –> ↑ risk of bleeding

32
Q

How does platelet adhesion work?

A

Platelet membrane receptor = gp1B/9a
Binds vWF on collagen

vWF –> platelet adhesion to sub endothelium

  • -> platelet changes shape
  • -> expose membrane receptors
  • -> content expulsion
33
Q

Alpha granules

A

1 - Adhesion proteins
• vWF, Fibrinogen, thrombocytopenia

2- Growth modulator
• Stimulate healing
• PF-4, TGF-B, thrombospondin

3- Coagulation factors
• 5, 11, HMWK, fibrinogen

34
Q

Dense granules

A 
Energy & signaling
• ATP / ADP
• Ca++ (factor 4)
• Serotonin
• Histamine
35
Q

Platelet aggregation

A

Platelet to platelet binding
• VWF – gp1B / IXa (receptor)
- platelet to subendothelium

• Fibrinogen –gp2B / 3a (receptor)
- platelets to each other

36
Q

4 Mechanisms to consider w/ 1° hemostasis disorders

A

1 - Thrombocytopenia (platelet number)

2- Vasculopathy (vessels)

3- von Willebrand dz (linking)

4- Thrombopathy (defective fxn)
Thrombasthenia (weak adhesion)

37
Q

Features of DIC

A 
1 - Thrombocytopenia
2- Schistocytes
3- Prolonged APTT
4- Prolong PT
5- ↑ FDP or D-dimers (fibrinolysis evidence)
6- ↓ Antithrombin 3
38
Q

Normal life span of platelets

A

Dog
• 5-7 days

Cats
• 1.5 days

39
Q

1° vs 2° Immune Mediated Thrombocytopenia (ITP)

A 
1° 
• Poodles
• Old English sheepdogs
• Cocker spaniel 
• Females
• < 20,000/uL = very low

2°
• infectious agents
• drugs
• neoplasia

40
Q

Sources of vWF

A
  • endothelial cells
  • megakaryocytes
  • platelets
41
Q

Type 1 von Willebrand Dz

A

All multimer size present - ↓ total numbers
• Mild bleeding tendency
- only if challenged
• Doberman Pinscher (GSD, Corgi, Retrievers)

42
Q

Type 2 von Willebrand Dz

A

↓ numbers, esp Lg’er multimers
• ~12-20% of normal vWF
• German Shorthaired pointer

43
Q

Type3 von Willebrand Dz

A

No/small ant of vWF
• Lethal - severe bleeding tendency
• Scotties, Chesapeake Bay retrievers

44
Q

Testing for vWD

A

Qualitative
• Buccal mucosa bleeding time
• APTT
- needs to have vWF severely ↓ to compromise Factor8

Quantitative
• Ab based assay
• <20% = abnormal hemorrhage likely

45
Q

Congenital Thrombapathy dz’s

A 
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
Q

Acquired thrombapathies

A

Drugs

  • Anesthetics
  • Abx
  • Anti-histamines
  • Asprin - Prevents TxA2
  • NSAIDs

Systemic Dz

  • Uremia
  • Pancreatitis
  • Liver Dz
  • neoplasia
  • IMHA
47
Q

Blood smear platelet estimates

A

8-10/ Oil obj field = > 100, 000
6-7/OIF = ~100,000

< 3-4/OIF = <50,000
- would explain prolonged hemorrhage

48
Q

BMBT

A
  • 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
Q

Erroneous hemostasis values come from?

A

Improper blood collection

  • Patient excitement
  • vessel probing
  • from existing catheter
      • heprin
      • dilution
50
Q

Proper blood citrate ratio in Sodium Citrate tube (blue top)

51
Q

What does PT measure?

A

Extrinsic ( Factor 3 & 5 ) & Common

52
Q

What factors are assoc’d w/ common pathway

A

10, 5, Thrombin, fibrinogen

53
Q

Describe PT test

A
  • Thromboplastin (tissue factor) + Ca added
  • Prolonged = < 30% of normal quantity
  • May not show bleeding
54
Q

Describe APTT test

A
  • Phospholipid + calcium + negatively charged surface (to activate Hagman factor)
  • Prolonged = < 30% of normal quantity
55
Q

Describe ACT test (Activated Clotting Time)

A
  • Platelets > 10,000 = provide phospholipids

* <5% of normal quantity

56
Q

What is Russell viper venom test

A
  • Tests common

* activates clotting factors 5 & 10

57
Q

Describe TT (Thrombin Time)

A
  • Thrombin added

* tests Fibrinogen only

58
Q

Anti-coagulation

A

• 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
Q

Testing for fibrinolytic activity

A
  • FDP - fragments of fibrin
  • D-dimer - fragments of x-linked fibrin in a clot
  • must use these + other markers when Dx DIC
60
Q

What is vitamin K required for?

A

Synth of
• pro-coagulants - 2, 7, 9, 10
• Anti-coagulants - Protein C & S

61
Q

Which would ↑ first with DIC?

• PT or APTT

A

APTT ↑ first

- no good reason why

62
Q

Lab findings that can be assoc’d w/ DIC

A 
• Thrombocytopenia (1°)
• Schistocytes
• ↑ APTT --> ↑ PT
• ↓ fibrinogen
          - except horse (normal to ↑)
• ↑ FDP & d-dimers
• ↓ AT3

Clin Chem (12 decks)

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