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Clinical Pathology > Platelets and Primary Hemostasis > Flashcards

Platelets and Primary Hemostasis Flashcards

1
Q

What is hemostasis? What factors are important?

A

stoppage of blood without obstruction of blood flow

  • prothrombin
  • Factor VII
  • Factor IX
  • Factor X
  • Factor XI
  • Factor XII
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2
Q

What balances hemostasis?

A

concentrations of procoagulants (coagulation factors) vs anticoagulants (natural anticoagulants)

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3
Q

What are the 2 things that imbalances of hemostasis can lead to?

A
  1. THROMBUS leading to obstructed blood flow and hypoxia - increased procoagulant activity or decreased fibrinolysis (pulmonary thromboembolism)
  2. HEMORRHAGE - decreased procoagulant activity, decreased platelet numbers or loss of function, fibrinolysis (immune-mediated thrombocytopenia)
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4
Q

What is required for primary hemostasis? Secondary hemostasis?

A

formation of platelet plug - platelets and endothelium

coagulation - clotting factors

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5
Q

What is the morphology of platelets like?

A
  • anucleated
  • blue cytoplasm with reddish cytoplasmic granules
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6
Q

What 2 cytoplasmic granules are present in platelets?

A
  1. ALPHA GRANULES - seen on blood smear and contains coagulation factors and proteins (fibrinogen, Factor V, vWF, thrombospondin, PDFG)
  2. DENSE GRANULES
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7
Q

What are equivalent to platelets in non-mammalian species? How does their morphology compare?

A

thrombocytes

  • rounder and denser nucleus
  • clear cytoplasm in a smaller amount
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8
Q

What is thrombopoiesis?

A

platelet production from megakaryocytes in bone marrow

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9
Q

Where are megakaryocytes found? How do they multiply?

A

bone marrow sinus

replicate DNA without cell division (endomitosis)

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10
Q

How do megakaryocytes produce platelets? What is their maturation time?

A

proplatelets (cytoplasm) processes extend into sinus lumen and break off into individual platelets

4-5 days

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11
Q

What regulates thrombopoiesis? Where is it produced?

A

thrombopoietin regulates production and differentiation

liver, kidney, muscle

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12
Q

What is the circulating lifespan of platelets? Where are most circulating platelets found?

A

5-9 days

spleen

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13
Q

What is primary hemostasis? What 4 things do platelets do?

A

vasoconstriction and platelet plug formation

  1. adhesion
  2. activation
  3. aggregation
  4. granule secretion
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14
Q

Primary and secondary hemostasis happen simultaneously and are mechanistically intertwined. What are imbalances in these processes due to?

A
  • too much clotting = thrombosis
  • bleeding = not enough clotting
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15
Q

What 3 steps cause the formation of the primary hemostatic plug?

A
  1. platelets adhere to endothelium
  2. platelets undergo activation
  3. platelets aggregate to form the plug
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16
Q

What 5 things are required for platelet adhesion?

A
  1. von Willebrand Factor (vWF)
  2. calcium
  3. ADP
  4. thromboxane A2 (TXA2)
  5. thrombin
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17
Q

What does von WIllebrand Factor do?

A

binds to GP1b on platelet surface and creates a bridge between platelet and exposed collagen from injury on endothelium

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18
Q

What 2 things are required for platelet activation?

A
  1. platelet shape change
  2. secretion of granule products to activate more platelets
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19
Q

How do platelets change shape when activated? What causes this?

A

shift from smooth discs into spheres with many filopodia to increase surface area

collagen exposure and release of thrombin (FII)

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20
Q

What 4 things does platelet activation lead to?

A
  1. recruitment of more platelets
  2. further platelet activation
  3. facilitated coagulation
  4. vessel repair
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21
Q

What 4 things are secreted by platelets to cause aggregation?

A
  1. thromboxane A2 - irreversible platelet aggregation
  2. thrombin - product of secondary hemostasis
  3. ADP
  4. calcium
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22
Q

What causes clot retraction? What does this facilitate?

A

actinomyosin filaments

wound closure and vessel patency

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23
Q

What is the correct order of platelet plug formation?

A

adhesion —> activation —> aggregation

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24
Q

What are samples collected in to evaluate platelet concentration? What are 2 methods of evaluation?

A

EDTA purple top tubes

  1. evaluation on a blood smear
  2. hematology analyzer (part of routine CBC)
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25
Q

Why is venipuncture technique especially important for platelet evaluation?

A

rough handling can activate platelets and cause coagulation

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26
Q

How do you manually count platelet concentration by blood smear?

A
  • count platelets in 10 HPT at 100x under immersion oil
  • calculate the average
  • multiply average by 20,000 to approximate platelet concentration/uL
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27
Q

In what 2 species is it common to find physiologic platelet clumps?

A
  1. cats*
  2. cattle
28
Q

What species have high variation in platelet size?

A

cats

29
Q

How does the morphology of platelets compare in horses?

A

pale staining

30
Q

What are macroplatelets? What does an increased number indicate?

A

large platelets the same size or larger than RBCs

active production of platelets - regeneration

31
Q

How do hematology analyzers count platelets? How can this give incorrect counts?

A

categorized by size

macroplatelets and platelet clumps will not be counted, making platelet counts seem decreased

32
Q

How do hematology analyzers calculate mean platelet volume? What does it mean if it is increased?

A

sized, counted, and calculated the average size of all those counted

increased thrombopoiesis, a sign of platelet regeneration

33
Q

When are platelet production tests done? How is it evaluated?

A

in cases of thrombocytopenia

bone marrow aspirate (BMA) counts megakaryocytes and analyzes morphology

34
Q

How should platelet concentration be interpreted?

A

THROMBOCYTOPENIA = lower PLT count below RI
- mild = 80,000/ul
- moderate = 30,000-80,000/ul
- severe = <30,000/ul

THROMBOCYTOSIS - higher PLT count above RI

35
Q

When are patients at risk for spontaneous hemorrhage?

A

when platelet counts are below 30,000/uL

36
Q

What are 4 clinical signs of thrombocytopenia?

A
  1. platelet-associated bleeding patters from mucosal membranes (epistaxis, gingival bleeding, GI bleeding, hematuria)
  2. petechia or ecchymosis
  3. prolonged bleeding post wound or surgery
  4. excessive cutaneous bleeding
37
Q

What are 5 causes of thrombocytopenia?

A
  1. decreased production by bone marrow
  2. increased destruction
  3. sequestration
  4. increased consumption/use
  5. pseudothrombocytopenia
38
Q

What is a condition in dogs that causes thrombocytopenia due to decreased production?

A

pure megakaryocytic hypoplasia

39
Q

What is bone marrow panhypoplasia commonly present with? What 3 external sources can cause this?

A

leukopenia (before the thrombocytopenia)

  1. drugs: estrogen, chemotherapy
  2. toxins: mycotoxins
  3. radiation
40
Q

What is myelophthisis? What are 5 causes?

A

decreased production of platelets due to replacement of thrombopoietic tissue

  1. disseminated inflammation
  2. primary neoplasia: leukemia
  3. secondary neoplasia: mast cell tumor, histiocytic sarcoma
  4. myelofibrosis/necrosis
  5. infection agents: FeLV, FIV, EIA, BVD
41
Q

What are the 2 types of immune-mediated thrombocytopenia?

A
  1. PRIMARY: antibodies against platelet antigens (GPIIb/ IIIa)
  2. SECONDARY: antibodies secondary to another underlying condition, like systemic lupus erythematosus, neoplasia, drugs, vaccines
42
Q

What 3 vaccines have the possibility of causing immune-mediated thrombocytopenia?

A
  1. Distemper
  2. Parvovirus
  3. Panleukopenia
43
Q

What are the expected results on CBC, coagulation tests, bone marrow aspirate, and serum biochemistry in patients with immune-mediated thrombocytopenia?

A
  • severe thrombocytopenia +/- acute hemorrhagic anemia (regenerative, hypoproteinemia) and leukocytosis
  • normal
  • increased megakaryocytes
  • normal
44
Q

What clinical signs are seen with immune-mediated thrombocytopenia?

A

platelet-assoicated bleeding patterns:

  • epistaxis
  • gingival bleeding
  • GI bleeding
  • hematuria
45
Q

Where are platelets typically sequestered? In what 4 situations is this seen?

A

large vascular beds

  1. splenomegaly, splenic torsion
  2. hepatomegaly, portal hypertension
  3. vasodilation in endotoxic shock
  4. severe hypothermia
46
Q

What are 2 common causes of increased platelet consumption? When will hemorrhage occur?

A
  1. disseminated intravascular coagulation
  2. vasculitis (Rickettsial disease, FIP)

coagulation defects or leakage of blood from vessels

47
Q

What is pseudothrombocytopenia?

A

hematology analyzer does not measure present platelets because they are too big or clumped

48
Q

In what dog is macrothrombocytopenia commonly seen? What causes this?

A

Cavalier King Charles Spaniel

mutation in B1-tubulin gene that alters megakaryocyte proplatelet formation and release

49
Q

Do Cavalier King Charles Spaniels present clinically for macrocytopenia? How does it appear on CBC?

A

no bleeding tendencies - platelets function normally

  • total platelet mass (plateletcrit) is normal
  • giant platelets (high MPV) with low platelet count
50
Q

What bleeding test is done to test platelet function? What does it test? What are the 2 possibilities that cause abnormal (prolonged) times?

A

buccal mucosal bleeding time (BMBT) - tests the ability of platelets to form a platelet plug (NOT fibrin plug)

  1. decreased platelet function
  2. decreased platelet numbers
51
Q

How is the buccal mucosa bleeding time test done? What 2 things cause bleeding times to vary?

A
  • make a standard incision
  • blot blood gently
  • measure time for bleeding to cease
  1. species
  2. lancet used
52
Q

What are the normal bleeding times on buccal mucosal bleeding time tests on cats, dogs, and horses/cattle? What does a time over 4 minutes indicate?

A
  • CATS = 1-3 mins
  • DOGS = 2-4 mins
  • HORSES/CATTLE = 8-10 mins

vWB deficiency or thrombocytopathy

53
Q

When is the buccal mucosa bleeding time test done? In what patients is it not needed?

A

patients with normal platelet counts with concurrent clinical signs of primary hemostasis disorder —> must rule out possible coagulopathy (secondary hemostasis)

thrombocytopenic patients —-> does not add information

54
Q

What are 2 mechanisms of thrombocytosis? How do patients usually present?

A
  1. increased production
  2. increased distribution in plasma

asymptomatic

55
Q

When is thrombocytopenia typically physiologic?

A

epinephrine-induced splenic contractions due to excitement or fright

(mild or transient)

56
Q

What causes reactive (inflammatory) thrombocytopenia?

A

inflammatory IL-6 stimulated TPO release, which causes increased platelet production

57
Q

In what situation is thrombocytosis common after recovery from previous thrombocytopenia?

A

rebound response of increased bone marrow megakaryocyte production

58
Q

What causes thrombocytosis post-splenectomy?

A

increased thrombopoiesis and TPO production

59
Q

Essential thrombocythemia and megakaryocytic leukemia is extremely rare. How must they be diagnosed?

A

evaluate bone marrow (BMA) and rule out other causes first

60
Q

In what dogs is inherited von Willebrand disease most common? How can it be acquired?

A

Doberman Pinscher**, German Shorthair Pointer, Chesapeake Bay Retriever, Scottish Terrier

excessively high shear stress conditions, like aortic stenosis or cardiovascular disease

61
Q

What is the main clinical feature of von Willebrand disease? When do signs typically decrease?

A

mild to severe bleeding exacerbated by surgery or trauma

with age and successive pregnancies

62
Q

What platelet count, BMBT, and PTT/ACT is expected with von WIllebrand disease? What must be done for diagnosis?

A
  • normal
  • prolonged
  • usually normal, but can be prolonged if Factor VIII deficiency is pronounced

analyze plasma for vWF concentration

63
Q

What is the most common way to test for von Willebrand disease? What other 2 tests can be done?

A

ELISA

  • immunoelectrophoresis determines relative amount of different vWF multimers
  • collagen-binding activity assay detects only vWF that can bind to collagen
64
Q

What is Glanzmann thrombasthenia? In what species is this common?

A

deficiency of GPIIb-IIa making platelets unable to bind to fibrinogen, causing no platelet aggregation or clot formation

  • Otterhounds
  • Great Pyrenees
  • Quarterhorses
  • Thoroughbreds
  • Peruvian Paso
65
Q

What is the clot retraction test? When is it indicated? What patients show abnormal retraction times?

A

measures the amount of time it takes for a clot to retract from a test tube after thrombin is added

animals with normal platelet count, but questionable platelet function

dogs and horses with Glanzmann thrombasthenia

66
Q

CASE: 1 y/o Pointer has been treated for neck and back pain with corticosteroids by a referring veterinarian. The dog was thought to have GI parasites due to occult blood in feces and was treated with anthelmintics. The dog returned a month later with a PCV of 15% and MCV of 40fL. At the time the dog has an abdominal effusion.
- Upon physical exam, the dog seems to have a painful abdomen and pale mucous membranes.
- Hematology shows numerous keratocytes, few schistocytes, and some RBCs appear hypochromic.

A

ERYTHROGRAM:
- PCV, Hgb are both decreased - ANEMIA
- RBC is WNL, suggesting small erythrocytes
- MCV is decreased - ALWAYS caused by iron deficiency , which is indicative of chronic external blood loss in adults (also aligns with small RBCs)
- reticulocytes NOT increased - NON-REGENERATIVE ANEMIA
- morphology alights with IRON DEF. ANEMIA

LEUKOGRAM:
- neutrophilia and increased bands - INFLAMMATORY
- compatible with the presence of inflammation in the peritoneal cavity

PLATELETS:
- thrombocytosis - HALF OF ALL animals with iron def. anemia will have increased platelets, likely due to cytokines and growth factors

NON-REGENERATIVE IRON DEF. ANEMIA
- usually regenerative, but inflammation can exacerbate

Clinical Pathology (33 decks)

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