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Clinical Pathology > Platelets > Flashcards

Platelets Flashcards

1
Q

Platelets

A

initial hemostatic plug

Temporary

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2
Q

Coagulation proteins

A

reinforce the platelets framework

Definitive hemostatic plug

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3
Q
A

Dog Platelet

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4
Q
A

cat platelet

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5
Q
A

horse platelet

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6
Q
A

cow platelet

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7
Q
A

Bird Platelet

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8
Q

Platelet Regulation by Thrombopoietin

A
  • Major effect on every step of platelet production
  • Produced predominantly by the liver at a constant rate
  • Most TPO is removed by circulating platelets
    • bound
    • internalized
    • degraded
  • When platelet mass decreases, TPO concentrations increase
  • Result is increased platelet production
  • Inflammatory cytokines increased production
    • reactive thrombocytosis
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9
Q

Thrombocytopenia

A

decreased platelet concentration

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10
Q

Thrombocytosis

A

increased platelet cocnentration

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11
Q

Thrombopathia

A

a qualitative disorder of platelets

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12
Q

Extrinsic Platelet Disorder

A

Platelets are normal

Von Willebrand factor missing or reduced

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13
Q

Intrinsic Platelet Disorder

A

Platelets are abnormal

Defective granules, membrane receoptors, signaling molecures, platelet formation protiens

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14
Q

Platelet disorder categories

A
  1. Congenital causes for abnormal concentration
  2. Acquired causes for abnormal concentration
  3. Congenital functional defects
  4. Acquired functional defects
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15
Q

Platelet-Type Bleeding

A
  • Bleeding from mucosal surfaces, including:
    • epistaxis
    • Gingival bleeding
    • Urinary tract hemorrhage
    • GI bleeding
  • Petechial and/or ecchymotic hemorrhage on any skin or mucosal surface
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16
Q

Normal Platelet Range

A

Roughly for most species:

100,000 to 500,000/uL

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17
Q

At what point might there be risk of spontaneous bleeding due to low platelet concentration?

A

<50,000 platelets/uL

Always evaluate a blood smear to confirm low platelet concentration

In platelet-type bleeding is occuring with platelet numbers at or above 50,000/uL, consider additional underlying problems:

Von Willebrand disease

Platelet inhibitory medications

Intrinsic platelet disorder

FelV induced platelet disorder

Hyperproteinemia

Neoplastic platelet disorder

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18
Q

Platelet Assessment

A
  • Platelet concentration
    • manual vs. automated counting
    • Blood smear evaluation
  • Mean platelet Volume (MPV)
    • from automated
  • Bleeding time
  • Clot refraction
  • Platelet Aggregation
  • Molecular Assays
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19
Q

Automated Counting

A

Platelet clumping is probably the most common reason for erroneous platelet data

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20
Q

Manual Counts - hemocytometer

A

It is a common misconception that if there are clumps in the sample a manual platelet count will be more accurate than an automated count

NO NO NO

clumps affect the automated and manual count

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21
Q

Platelet Estimation from a bood film

A

VERY helpful

/ 1000x field for 10 fields

Some use Each platelet per 1000x field = 15,000 platelet/uL

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22
Q

Mean Platelet Volume (MPV)

A

An indication of the average size of circulating platelts

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23
Q

High MPV - with thrombocytopenia

A

Megakaryocytes are attempting to respond to the low platelet number by releasing larger platelets into the circulation

This is a favorable sign

But larger platelets are NOT younger platelets

24
Q

Low MPV - with thrombocytopenia

A

may indicate insufficient numbers of megakaryocytes present or that they are failing to respond

25
Q

Tests for Platelet Function

A

Buccal Mucosal Bleeding TIme (BMBT)

Clot Retraction - Test platelet function

Platelet Aggregometry - GOLD Standard

26
Q

Buccal Mucosal Bleeding Time (BMBT)

A
  • Indicator of primary hemostasis or platelet status
  • Spring-loaded cassette delivers percise cut
  • Avoids the hair and thick skin
  • May require anesthesia
  • Test reserved for patients adequate platelet concentrations but platelet function is questioned
  • BMBT especially useful in doberman pinschers
  • BMBT cannot be used to detect coagulopathies
    • hemophiliacs have normal buccal mucosa bleeding times
    • Dog: 1.5-4 mins
    • Cat: 1-2.5 mins
27
Q

Clot retraction - Tests platelet function

A
  • Draw 0.5mls blood directly into plastic syringe contianing 4.5mls of cold saline
  • Mix gently
  • Dispense 2 mls of the mixture inot each of 2 glass tubes containing 0.1ml to 10 units/ml thrombin
  • Cap and mix the tubes. Place the tubes in a refrigerator for 30 minutes
  • Transfer tubes to a 37C water bath
  • Record the degree of clot retraction at 1 and 2 hours as 1+ to 4+
28
Q

Platelet Aggregometry

A

GOLD STANDARD

the definitive means for evaluating platelet function

Highly specialized and not readily available

Testing must be completed within 4 hours of collection

Platelets are stirred in front of a light source in a siliconized glass cuvette.

Various agents are added to the cuvette and the ability of the platelets to respond is recorded on a strip chart recorder

29
Q

Cats and their Platelets

A
  • ~10 times more reactive than other species
  • Highly variable in size
  • Giant platelets are a common finding
  • Impedance hematology analyzers do not give accurate platelet concentrations
  • Cats with thrombocytopenia and bleeding usually have another underlying problem
  • Cats with FeLV infection may have any combination of platelet concentration and clinical signs
30
Q

Congenital Thrombocytopenia:

Inherited Macrothrombocytopenia

A
  • Affects >90% of Cavalier King Charles Spaniels in US
    • carrier of affected
    • Affected do NOT have clinical bleeding
    • Platelets between 30,000 and 100,000/uL
    • Heterozygotes have platelets concentrations between homozygote and unaffected
    • Mutation is the gene encoding beta 1-Tubulin
  • Identical or similar mutaions identified in other breeds
    • English toy spaniels, Shih tzu, matlese, jack russel terrier, havanese, toy poodles, boxer, cocker spaniels, bichon frise, miniature schnauzer, komondor, chihuahua, labrador retriever, norfolk and cairn terriers, and several crossbreed dogs
  • Misdiagnosis can lead ot inappropriate treatment with steroids and or antibiotics
31
Q

Acquired Thrombocytopenia: Causes

A
  • Immune-mediated
  • Drug-induced
  • Enhanced consumption
  • Virus-induced
  • Decreased production
  • Sequestration
32
Q

Immune-mediated Thrombocytopenia

A

Circulating platelts and/or megakaryocytes are destroyed by immune-mediated mechanisms:

Platelets concentration is usually very low

Confirmed by blood smear evaluation

33
Q

Immune-mediated Thrombocytopenia:

Causes

A
  • Primary or autoimmune
  • Secondary to immune-complex absorption or neoantigen expression
  • Incompatible transfusion
34
Q

Rickettsial-Induced Thrombocytopenia

A
  • Ehrlichia Canis
  • Anaplasma platys
  • Anaplasma Phagocytophilum
  • Rickettsia rickettsia (Rocky mountain spotted fever)

Immune mediated clearance

Decreased life-span

Vasculitis-induced consumption

35
Q

Drug induced thrombocytopenia:

Primary

A

circulating platelets are destroyed by drug interaction

36
Q

Drug Induced thrombocytopenia:

Secondary

A

Drug-Dependent vs. Independent

37
Q

Drug induced thrombocytopenia:

Secondary (Bone marrow suppression)

A

Estrogen; antifungals; anticancer drugs; antibiotics; antivirals; and anti-inflammatory drugs

38
Q

Disseminated Intravascular Coagulation (DIC)

A

Pathological process characterized by the widespread activation of the clotting cascade that results in the formation of blood clots throughout the body

Can occur secondary to any event that causes massive tissue damage:

Septicemia

Neoplasia

Parasites

Vasculitis

Viruses

39
Q

Destruction or crowding of the marrow cavity resulting in generalized marrow hypoplasia

A

Myelophthsis/myelofibrosis

Myeloproliferative disease

Inflammatory disease

40
Q

Congenital Extrinsic Platelet Function DIsorders:

Von Willebrand Disease

A
  • most common inherited bleeding disorder in dogs, rare in cats, cattle, rabbits, pigs, and horses. Pigs are a common disease model
    • An extrinsic platelet function disorder
      • persentation is like taht of thrombocytopenia, however, platelet concentration is normal
    • Von Willebrand Factor is markedly reduced
      • decreased platelet adhesion
    • Diagnosed using ELISA to determin antigen levels
      • ALWAYS USE PLASMA< NOT SERUM
    • DNA-based testing available for some breeds
    • Clot retraction test is normal
    • APTT is normal
41
Q

Von Willebrand Disease

Type 1

A

Quantitative disorder

Von Willebrand Factor is detectable but low

Most common form of Von Willebrand Disease in Dogs

Very common in Doberman Pinschers

42
Q

Von Willebrand Disease:

Type 2

A

Qualitative disorder

Von Willebrand Factor multimers are altered

Less common in domestic species

43
Q

Von Willebrand Disease:

Type 3

A

Quantitative Disorder

Von willebrand factor is not detectable

Rare in dogs

Scotties, Shelties,, Chesapeake Bay Retriever

44
Q

Von Willebrand Disease

Manifestations

A

Prolonged bleeding at tail docking, ear cropping, or dew claw removal, spay/neuter are common

+/- mucosal bleeding primarily manifested by gingival bleeding, epistaxis, and hematuria

Many dogs that carry this disease in thier genetic makeup go undetected until a minor surgery or small, superficial injury results in significant blood loss

45
Q

Testing for Von Willebrands Disease

A
  • vWF antigen:
    • EDTA or cirtrated Plasma
    • do NOT let the sample clot
    • Clotting will result in vWF incorporated into clot
  • DNA test
46
Q

Congenital Intrinsic Platelet Function Disorders:

A
  • Glanzmazz thrombasthenia
  • CALDAG-GEFI thrombopathias
    • basset hound thrombopathia
    • Spitz thrombopathia
    • Landseer-ECT thrombopathia
    • Bovine Thrombopathia
  • P2Y12 ADP receptor defect
  • LAD-III syndrome
  • Cycline Hematopoiesis
  • CHediak-Higashi syndrome
  • Dense Granule Defect
  • Scott syndrome
47
Q

Glanzmann thromboasthenia

A

Inherited disorder described in otterhounds, Great pyrenees, and horses

Clot retraction is absent

Clinical Signs:

Platelets type bleeding

Chronic epistaxis, gingival bleeding

48
Q

CalDAG-GEFI thrombopathia

A

Mutations in the gene encoding calcium diacylglycerol regulated quanine nucleotide exchange factor 1 resulting in signal transduction abnormalitity

DNA testing available at Auburn University

  • Clinical Signs:
    • epistaxis, gingival bleeding, petechiation, hematuria, excessive bleeding with minor procedures
  • Platelet, vWF, coagulation screening assays – normal
  • Defect of signal transduction resulting in decreased binding of platelets to fibrinogen
  • Thrombin-induced aggregation – extent normal, but rare impaired. Clot retraction – normal
49
Q

Inherited Platelet Function Defects:

Chediak-Higashi Syndrome

A

autosomal recessive

Abnormal leukocyte, melanocyte, and platelet granulation

Platelets do not form tight aggregates in response to ADP

Prolonged bleeding at incision sites, and the development of hematomas following venipuncture

50
Q

Inherited Platelet Function Defects:

Cyclic Hematopoiesis

A

Autosomal recessive grey collies

Cyclic fluctuations in neutrophils, reticulocytes, and platelets

Neutropenic episodes occurring approximately every 12 days

Mortality is high, most puppies die prior to 6 months of age due to fulminating infections

Platelet numbers usually do not decline below the normal range and fluctuate between 300,000 and 700,000/uL

Platelet reactivity is defective

Platelet dense granules are absent

Clot retraction and platelet adhesiveness are impaired

51
Q

P2Y12 mutation

A

~60% of the dogs tested are wither Carriers or Affected for the mutation

The gene pool is small, prevalence is likely high, be careful

Carriers have been reported to have clinical signs

Clinical signs of bleeding in affected or carrier dogs are not recognized unless they are challenged with significant trauma or surgery

Most common reports have described severe bleeding following routine spays/castrations; many die

52
Q

Scott syndrome

A

When platelets become activated they express a negatively charged surface due to the flip-flop of negatively charged phosphatidyl serine

Negatie surface required for assembly of coagulation factors

A platelet disorder wiht clinical signs more typical of a coagulopathy

German Shepherd Dogs

Rare

53
Q

Summary:

Extrinsic Disorders

A

Platelets are normal.

A protein necessary for platelet function is either absent, reduced, or dysfunctional.

54
Q

Summary:

Intrinsic Disorders

A

Platelets are abnormal

Abnormalities may be related to granules, membrane glycoproteins, signal transduction proteins

55
Q

Summary:

Inherited Thrombocytopenia

A

Seen in cavalier king charles spaniels and other breeds

Does not result in clinical bleeding

NO TREATMENT NECESSARY

56
Q

Acquired Qualitative Platelet Function DIsorders

Feline Leukemia Virus

A

Viral accumulation in cytoplasm of megakaryocytes resutls in infection of platelets

Thrombocytopenia, thrombocytosis or function defects may result

57
Q

Acquired Qualitative Platelet Function Disorder

Drug Induced

A

Drugs can impair platelet funciton by inhibiting receptor binding agonists, by inhibiting transduction of messages or by inhibitinng response

Drug-induced impairment is usually not clinically significant unless coupled with another underlying disorder or the patient requires surgery

Clinical Pathology (20 decks)

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