Platelets and Hemostasis Flashcards

1
Q

Thrombocytosis:

Def

Causes

A

Def: increased platelets

Causes:

  1. inflammation (IL-6, TNF-alpha, IL-1) => cause inc thrombopoietin production
  2. Iron deficiency anemia
  3. Cushing’s disease 4. Steroid therapy
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2
Q

What doesn’t cause a thrombocytopenia (usually)

A

hemorrhage bleeding

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3
Q

Platelets

A

Have calcium in them (most clotting rxns need Ca2+)

Use purple top tube with K/EDTA

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4
Q

Purple top tube

A

Has K/EDTA EDTA => chelates Ca2+ and inhibits clotting

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5
Q

Calcium in clotting

A

Positively charged

Mediates binding of coagulation factor enzyme complexes via their negatively charged residues to negatively charged phospholipid surfaces of platelets

Ca is a bridge of positivity, allows platelets to act as scaffolds for clotting reactions

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6
Q

Alpha granules in platelets

A

Adhesion proteins (like Von Willebrands factor)

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7
Q

Common breed for Von Willebrand’s factor deficiency

A

Dobermans

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8
Q

Cat Platelets

A

Larger with a higher mean platelet volume (MPV) Especially sensitive to activation during blood sample collection

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9
Q

Snakes

A

Have thrombocytes Their platelets are very large and are an actual cell type

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10
Q

How to do a platelet estimate

A
  1. Count number of platelets in 10-100X oil immersion fields and average. 2. For dogs average count in 10 fields x 15,000/microLiter 3. For cats average count in 10 fields x 20,000/microLiter
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11
Q

Hemostasis

A

The arrest of bleeding.

Requires integrated response from blood vessels:

  1. endothelial cells
  2. collagen
  3. smooth muscle cells
  4. fibroblasts…..

and platelets, circulating clotting factors, and fibrinogen becoming fibrin.

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12
Q

Primary Hemostasis

A

Peripheral vasoconstriction occurs

Blood starts flowing again after momentary stoppage

Platelets start degranulating and releasing Ca2+ to form a platelet plug

(Endothelial defect exposes subendothelial collagen)

End result = platelet plug

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13
Q

Secondary Hemostasis

A

Stimulation of the coagulation system

Thrombin (Factor 2a) converts fibrinogen (Factor 1) to the active fibrin (Factor 1a)

Fibrin is incorporated into the clot and clot is stabilized

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14
Q

Coagulopathy

A

Excessive bleeding due to abnormal function/lack of presence of a coagulation factor.

Defect in secondary hemostasis usually leading to more severe bleeding than a platelet or primary hemostasis problem.

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15
Q

Coagulopathies lead to

A

Hemoabdomens, hemothoraxes, hemarthrosis, hematuria, and of course petechiae and purpura.

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16
Q

If there is a clot in the blood tube….

A

Don’t trust values from a hematology analyzer.

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17
Q

Automated platelet counts in cats….

A

Are NOT reliable.

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18
Q

Platelet counts

A

Lower in King Charles Spaniels and greyhounds.

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19
Q

King Charles Spaniels have a high prevalnce of

A

inherited asymptomatic thrombocytopenia with macrocytic platelets:

60-80,000 platelets can be normal

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20
Q

MPV

A

Large platelets are often young platelets

Platelet clumps will falsely decrease a plately count and falsely increase the MPV

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21
Q

Increased MPV

A

Seen in enhanced thrombopoiesis in response to thrombocytopenia

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22
Q

Thrombocytopenia often leads to

A

Petechiae, purpura, or ecchymoses.

-usually when less than 50,000/microLiter or less than that

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23
Q

Facial petechiae around the eyes

A

May be caused by a tight leash or a rabies pole.

Do a blood smear to look for platelets.

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24
Q

In a thrombocytopenic animal…

A

Do not use the jugular vein for blood, too close to the heart.

Do not poke organs, they may not stop bleeding.

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25
Q

Hall mark of tick-borne disease

A

Thrombocytopenia

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26
Q

Evan’s syndrome

A

Immune mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (ITP) simultaneously.

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27
Q

Thrombocytopenia differentials

A

1. Decreased platelet production.

2. Increased platelet consumption.

3. Increased platelet destruction (most common cause)

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28
Q

Decreased platelet production

A

To assess do a bone marrow aspirate to look for sufficient platelet precursors, megakaryocytes.

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29
Q

Not enough megakaryocytes

A

Myelopthisis: space occupying lesion of bone marrow

Myeloproliferative diseases: Aplastic anemia, bone marrow not making anything ie: estrogen knocks out bone marrow in ferrets and dogs

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30
Q

Increased platelet consumption

A

DIC and thrombosis, vasculitis, hemangiosarcoma in dogs.

These animals will likely show changes in PT/PTT since platelets used up for clotting.

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31
Q

Increased platelet destruction

A

Most common cause of thrombocytopenia

Primary immune thrombocytopenia (ITP)

Secondary immune-mediated thrombocytopenias (drugs, infectious agents, neoplasia, SLE)

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32
Q

Vitamin K dependant clotting factors

A

2, 7, 9, 10

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33
Q

Vitamin K works by

A

inhibiting the enzyme, vitamin K epoxide reductase in the liver

-makes these factors hypofunctional

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34
Q

Which clotting test is prolonged first?

A

PT expected to be prolonged before PTT due to the short half-life of Factor 7.

Prolongation of PTT first is possible as well, depending on the species involved.

For the test think PT!!!!

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35
Q

Anticoaculation proteins

A

Anti-thrombin

Alpha 2 macroglobulin

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36
Q

Anti-thrombin

A

Stops thrombin from acting.

Thrombin converts fibrinogen to fibrin

Heparin keeps thrombin and anti-thrombin together

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37
Q

PLE

A

Protein losing enteropathy:

Low albumin and low globulin

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38
Q

PLN

A

Protein losing nephropathy.

Low albumin only.

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39
Q

Low antithrombin

A

Hypercoagulable state

DIC

PLN

PLE

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40
Q

Phase of clotting

A
  1. Vascular phase:

Exposure of subendothelial matrix and exposure of tissue factor (TF)

  1. Platelet phase:

Adhesion, activation, shape change, secretion (degranulation), aggregation

=> Platelet adhesion: Von Willebrands factor is how platelets adhere to each other and the vasculature (deficiency in dobermans)

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41
Q

Desmopressin

A

Stimulates transient release of von Willebrand factor from the endothelial cells.

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42
Q

von Willebrand factor

A

synthesized and released from endothelial cells and platelets

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43
Q

Major platelet agonists

A

PAF (Platelet activating factor)-made by cells of immune system, this is one way that inflammation and coagulatio are linked.

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44
Q

Intrinsic clotting cascade

A

12, 11, 9, 8 (PTT test) + common pathway

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45
Q

Extrinic clotting cascade

A

VII and TF (PT test) + common pathway

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46
Q

Common pathway

A

10, 5, 2, 1

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47
Q

How do you evaluate platelet function?

A

BMBT (buccal mucosal bleeding test)

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48
Q

Which clotting factor has the shortest half life?

A

Factor VIIa

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49
Q

Which clotting factor test would be prolonged if an animal got into a vitamin K rodenticide?

A

The animal will have a prolonged PT.

VIIa is an extrinsic pathway factor so use PT.

2, 7, 8, 10 all need vitamin K

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50
Q

Prolonged PT and PTT

A

Common clotting pathway is the problem

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51
Q

Platelet function disorder

A

von WIllebrand factor deficiency

52
Q

Blood tube to test PT/PTT

A

Blue top=citrated plasma

53
Q

Function of factor XIIIa

A

Cross links fibrin

54
Q

Causes of fibrinolysis

A

Occurs from crotalase in Eastern Diamondback rattlesnake venom

55
Q

Cryoprecipitate contains

A

Von Willebrand factor

Fibrinogen

Factor 8

Factor 13

56
Q

Cats and platelets…

A

Cats have largest and most activated platelets of any species.

57
Q

Thrombocytosis

A

Increased platelets.

Most common cause: Inflammation

IL-6 leads to increased thrombopoietin

58
Q

Iron deficiency anemia

A
  1. Seen with cushings (inc adrenal secretion of cortisol) or prednisone

=>cortisol is immunosuppressive and prevents macs from phagocytosing old platelets

  1. Rebout response to thrombocytopenia.
  2. Withing one week following a splenectomy
59
Q

Hyper coagulable state

A

More likely to have a clot

Initial reactions that lead to thrombosis and DIC

Anti-thrombin deficiency

60
Q

Mast cells in circulation in a dog

A

IMHA, inflammation, or Parvo virus

Likely not from a mast cell tumor

61
Q

Mast cells in circulation in cats

A

Likely has a mast cell tumor in spleen, liver, or intestines (visceral organs)

62
Q

Snake venoms

A

Degrade fibrinogen

=>increase FDPs, not increased D-dimers

=>sperocytes may be seen in blood film

63
Q

Increased FDPs

A

Snake bite

Breakdown of fibrin monomers by plasmin before they’ve been crosslinked, before Facto13a has crosslinked the fibrin.

=> these usually removed from circulation by the liver.

Doesn’t necessarily mean activation of clotting cascade with active lysis of cross-linked fibrin clot.

64
Q

Presense of D-dimers

Increased D-Dimers

A

Means the active breakdown of covalently, crosslinked (via Factor 13a) fibrin

Active coagulation and breakdown of clots

65
Q

D-dimers specific for

A

Thrombus formation because it only occurs when soluble fibrin has been crosslinked by Factor 13a and plasmin has cleaved this stable fibrin to form this unique D-dimers

66
Q

Fibrinogen

A

Acute phase protein.

Increases with inflammation.

May be the only early sign of inflammation in large animals.

Inflamed animals without elevated fibrinogen

=> liver not making fibrinogen (liver failure)

=> or fibrinigen getting converted to fibrin (look for other signs of DIC

67
Q

Other signs of DIC

A

Low fibrinogen

Increased D-dimers AND increased FDPs

Fragmentation morphologies

=> acanthocytes

=> schistocytes

=> keratocytes

Consumption of platelets (thrombocytopenia)

68
Q

DIC treatment

A

PLASMA NOW

Then find underlying cause of DIC

69
Q

Hemophilia A

A

Factor 8 deficiency

70
Q

Hemophilia B

A

Factor 9 deficiency

71
Q

Factor 12 and testing

A

Abscense doesn’t cause bleeding disorders

=> Not necessary for secondary hemostatis in vivo

=> Missing in some cats and other species

=> Will cause an increase in PTT b/c test is in a plastic tube, and assess for 12, 11, 9, 8, 10, 5, 2, and 1

72
Q

If PT/PTT are both prolonged

A

Think common pathway

Factors 10, 5, 2 (pro-thrombin to thrombin) and 1 (fibrinogen to fibrin)

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