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Hematology 2 > Lecture 22 Platelet Disorders > Flashcards

Lecture 22 Platelet Disorders Flashcards

1
Q

What are the 4 main components platelets are made from?

A

Platelet made up of 4 main components:
1) Plasma membrane
2) Submembranous filaments
3) Peripheral Microtubules
4) Organelles most importantly the α and dense granules

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2
Q

Describe what the platelet plasma membrane is made up of?

A

Plasma Membrane: contains glycoproteins which are important to adhesion and aggregation. Also contain PF3 (phospholipids) which provide a surface for coagulations factors of the intrinsic and extrinsic pathways. Open canalicular system (OCS) provides large area of absorption of plasma factors.

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3
Q

What are responsible for platelets discoid shape, pseudopod formation and clot retraction? What is another function they do?

A

Microtubules and microfilaments are responsible for the discoid shape, pseudopod formation, and clot retraction. This area also responsible for movement of organelles toward surface of platelet

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4
Q

What are microtubules made of and how is it arranged? What do they do?

A

Microtubules:
1. Composed of subunits of tubulin parallel the platelet cell membrane and maintain the platelet discoid shape
2. Move inward on platelet activation to release α-granule contents and reassemble during platelet shape change to provide rigidity to pseudopods

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5
Q

What do microfilaments, microtubules and intermediate filaments do in platelets?

A

Microtubules, actin microfilaments and intermediate filaments control platelet shape change, extension of pseudopods, and secretion of granule contents

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6
Q

What organelles are in platelet cytoplasm?

A

Organelles: are the major portion of platelet cytoplasm. The structures include, mitochondria, dense bodies (granules), α (alpha) granules.

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7
Q

What are the 3 categories of platelet bleeding disorders?

A
  1. Decreased production
  2. Increased destruction.
  3. Defective function.
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8
Q

What acquired conditions result in decreased platelet production?

A

Viral Infections
Drug toxicity
Chemicals
Alcohol
Uremia
Bone marrow failure

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9
Q

What hereditary conditions result in thrombocytopenia?

A

Hereditary Thrombocytopenia
1. May-Hegglin
2. Wiskott-Aldrich
3. Bernard Soulier

Above conditions also have structural and functional defects.

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10
Q

Name some immune condition causes of platelet destruction?

A

Immune
1. Immune & idiopathic thrombocytopenic purpura (ITP)
2. Alloantibodies; neonatal and post transfusion
3. Autoantibodies (ie from Lupus and CLL)
4. Heparin induced thrombocytopenia (HIT)
5. Drugs

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11
Q

List the microangiopathic hemolytic anemias that result in platelet destruction.

A

Microangiopathic hemolytic anemias
- DIC
- TTP
- HUS
- HELLP

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12
Q

What impact can surgery have on platelets?

A

Consumption due to surgery.

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13
Q

What are two types of platelet function disorders?

A

Hereditary and
Acquired

See slide 13 for an overview list.

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14
Q

List conditions (4) that have platelet defects of adhesion.

A

Bernard-Soulier
Uremia
DIC
Paraproteinemias

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14
Q

List conditions (4) that have platelet defects of adhesion.

A

Bernard-Soulier
Uremia
DIC
Paraproteinemias

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15
Q

What type of defect do these two conditions have Glanzmann thrombasthenia and Afibrinogenemia
?

A

Defects of Primary Aggregation

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16
Q

What defect of platelets is related to aspirin and ethanol?

A

Defects of Release

See slide 14 for other conditions (long list).

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17
Q

What do the platelets lack in individuals with Bernard-Soulier disorder?

A

Bernard-Soulier platelets syndrome lacks GpIb/V/IX (necessary for proper platelet adhesion) which leads to lack of adhesion and bleeding conditions.

Inherited Disorder

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18
Q

Compare those with homozygous Bernard-Soulier disorder to heterozygous?*

A
  1. Heterozygotes have normal to near normal function
  2. Homozygotes have giant platelets, thrombocytopenia, usually decreased platelet survival. Moderate to severe bleeding disorder. Platelet counts 40 to near normal.
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19
Q

What is the coagulation problem caused by uremia?

A

Uremia: Increased urea can cause decreased adhesion, aggregation and defective platelet granule release.

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20
Q

How does DIC impact platelet function?

A

DIC: Fibrin degradation products known to inhibit adhesion and aggregation.

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21
Q

How do paraproteinemias like Multiple Myeloma and Waldenstroms Macroglobulinemia afect platelet function?

A

Paraproteinemias: protein coats platelet and can inhibit all platelet functions: aggregation, secretion, clot retraction and procoagulant activity.

22
Q

What is the cause and effect of Glanzmann Thrombasthenia? What is normal in it?

A

GpIIb-IIIa lacking in Glanzmann thrombasthenia results in decreased aggregation. Associated bleeding is severe and disabling.

Normal platelet count and normal morphology

Inherited Disorder
GpIIb-IIIa necessary for fibrinogen binding and proper platelet aggregation

23
Q

What is storage pool disease?

A

Storage Pool Disease
Defective or decreased α-granules, dense granules or both

24
Q

What can granule fibrinogen deficiency lead to?

A

Conditions of granule fibrinogen deficiency will also lead to decreased aggregation
Affects platelet functions such as aggregation, vasoconstriction, adhesion, smooth muscle repair

25
Q

What is the cause of Gray platelet syndrome?

A

Gray platelet syndrome
- α granule deficiency
- Dense tubular system; storage site
of calcium and cyclooxygenase
are also abnormal.
-Granule release and platelet aggregation findings are variable.

26
Q

What is the morphology of platelets describe as in Gray platelet syndrome?

A

-Platelet morphology is larger and
gray to blue-gray in color.

27
Q

What is the clinical result of Gray platelet syndrome on the patient?

A

Lifelong history of mild bleeding, easy bruising, moderate thrombcytopenia.

28
Q

Describe the cause and clinical/lab findings of Wiskott-Aldrich Syndrome (WAS)?

A

Wiskott-Aldrich Syndrome (WAS)
- lacking in storage pool nucleotides
- α-granule deficiency and decrease in mitochrondria also reported.
- Abnormal platelets removed by spleen.
- is an immunodeficiency disorder characterized by small platelets with thrombocytopenia, recurrent infections and eczema.

29
Q

What condition has a striking lack of dense granules? What are the distinct clinical/lab findings?

A

Hermasky-Pudlach Syndrome
1. Striking lack of dense granules
2. α-granules are normal

This disorder characterized by albinism, ceroid-like pigment in macrophages and bleeding.

30
Q

What condition has a abnormal granule fusion deficiency that also occurs in WBCs as well as platelets?

A

Chediak-Higashi Anomaly
1. Characterized by albinism, recurrent infections, hemorrhagic tendencies
2. Thrombocytopenia
3. Dense granule deficiency
4. Platelet aggregation tests are abnormal.

31
Q

What does Cyclooxygenase Deficiency result in decreased production of?

A

Cyclooxygenase deficiency leads to decreased production of Thromboxane A2 and decreased platelet aggregation.

Note: Thomboxane A2 is a strong platelet aggregating agent.

32
Q

What affect does aspirin have on cyclooxygenase and platelet function?

A

Aspirin acetylates cyclooxygenase irreversibly. Aspirin permanently blocks the action of cyclooxygenase-1 and TxA_2 synthesis, impairing platelet function.

Decreased Thomboxane A2 production leads to decreased aggregation.

33
Q

What are two types of immunologically mediated Immune Thrombocytopenia Purpura (ITP)?

A

Immune Thrombocytopenia Purpura (ITP)
1. Acute
2. Chronic
Both types are immunologically mediated, caused by autoimmune antibodies which destroy the platelets

34
Q

Describe the features and symptoms of Acute ITP (Immune Thrombocytopenia Purpura)?

A

Acute ITP
1. Primary feature is thrombocytopenia frequently occurring 1-3 weeks after an infection
2. Infection most often upper respiratory tract or gastrointestinal tract viral infection
3. May also occur following vaccination for rubella, rubeola, chickenpox

Symptoms:
1. Abrupt onset of bruising, petechiae, mucosal bleeding such as epistaxis (nosebleeds)

Primarily disorder of children, occ’l in adults

35
Q

What is the cause thought to be of Acute ITP?

A

Because found following illness, cause thought to be antibodies or immune complexes formed against viral antigens react with platelets causing thrombocytopenia

Note:
Incidence is 4 in 100,000
Peak age between 2 – 5 years
No sex preference

36
Q

If Acute ITP lasts for longer than 6 months what is it called?

A

10 – 15% persists for 6 mos or longer reclassified as Chronic ITP

37
Q

When is a bone marrow not required to be performed to rule out malignancy on suspected Acute ITP?

A

Bone marrow examination to rule out malignancy (ie leukemia) may not be required if other CBC findings normal, no previous episodes or no family history of bleeding

38
Q

Are there specific tests for diagnosis of acute or chronic ITP?

A

At present no specific test for diagnosis of acute or chronic ITP

39
Q

What symptoms do people with Acute ITP have?

A

Most cases of Acute ITP develop extensive petechiae, some ecchymoses (soft tissue bruising) and may have hematuria or epistaxis or both

Note: Approx 3 – 4% of cases considered severe. Generalized purpura often with GI bleeding, hematuria, mucous membrane bleeding, retinal hemorrhage.

40
Q

What % of patients with Acute ITP are at risk of intracranial hemorrhage?

A

25% - 50% considered be at risk for intracranial hemorrhage which is responsible for the 1% - 2% mortality rate of Acute ITP

Most patients with life threatening hemorraghic episodes have very low platelet counts < 4 x 10^9/L

41
Q

Can patients recover with Acute ITP? If so, how long does it take?

A

Recovery with or without treatment usually seen in about 3 weeks, some cases take up 6 months.

42
Q

What is the treatment for Acute ITP? How do the treatments work?

A
  1. Most cases of do not require treatment
  2. In severe cases steroids such as prednisone, IVIG, platelet transfusions, splenectomy or combination of these may be required.

Note: Steroids (prednisone) suppress the immune system thereby decreasing amount of antibodies produced. Intravenous immunoglobulin (IVIG) thought to slow or shut down immune system thereby reducing amount of antibodies produces against the platelets. Platelet transfusions offer only temporary relief as transfused platelets will bind to antibodies and be removed by the spleen. Splenectomy will help as it is the spleen which removes the platelets which have immune complexes attached.

43
Q

How does Chronic ITP begin and at what age range and gender is most at risk?

A

Most cases between ages of 20 – 50 yrs
Females outnumber males 2:1 to 3:1
Highest incidence in women 20 – 40 yrs of age
Begins insidiously with platelet counts variably decreased and sometimes normal for periods of time

44
Q

How are the platelets destroyed in Chronic ITP?

A
  1. Platelet destruction result due to auto antibodies attaching to platelets
  2. Reticuloendothelial cells, primarily spleen remove platelets from circulation
  3. Normal life span of platelet (7 -10) days shortened to a few days
  4. 50 – 60 % patients demonstrate autoantibodies with current testing methods
45
Q

What are the symptoms of chronic ITP?

A

Symptoms include mucocutaneous bleeding with menorrhagia, recurrent epistaxis and easy bruising (ecchymoses)

46
Q

What would have if plasma from a patient with ITP was given to a normal recipient?

A

Plasma from a patient with ITP infused to normal recipient will develop thrombocytopenia

47
Q

What the typical lab findings in someone with chronic ITP?

A
  1. Only CBC abnormalities related to platelets
  2. Platelet counts typically 30 – 80 x 10^9\L
    Periods of near normal to decreased typical in Chronic ITP
  3. Morphologically normal, although larger in size reflected by increased MPV due to early release from bone marrow
  4. Platelet associated IgG levels increased in most patients

No method is currently specific or sensitive for ITP platelet antibodies

48
Q

What is the treatment for chronic ITP?

A
  1. Counts > 30 x 10^9\L usually need no treatments unless other risk factors such as age, surgery, trauma, coagulation defects
  2. When urgent treatment needed IVIG treatment of choice
  3. If not urgent treatment usually steroids (prednisone) with 70% to 90% response rate
  4. In some non-responsive cases splenectomy may be required with an 88% response rate
  5. Platelets given only in severe bleeding cases as they offer only temporary benefit
49
Q

What are some of the biggest differences between Acute ITP and Chronic ITP?

A

Age of onset (2-5 yrs for acute, but 20-50 yrs for chronic).
Prior infection is common in acute but unusual for chronic.

See slide 42 for more details.

50
Q

What conditions are associated with Reactive Thrombocytosis and are generally not at risk of thrombosis or bleeding

A

Reactive Thrombocytosis not usually associated with thrombosis or hemorrhage

  1. Blood loss and surgery
  2. Postsplenectomy
  3. Iron deficiency anemia
  4. Reactive thrombocytosis (such as infection or infection plus surgery)
  5. Stress (including trauma and postoperative)
  6. Rebound after myelosuppressive chemotherapy.
51
Q

What type of thrombocytosis patients are at risk of thrombotic/bleeding episodes?

A

Patients with quantitative and qualitative defects such as that seen in Myeloproliferative Disorders do pose a significant risk of thrombotic/bleeding episodes.

Note: Patients with Chronic Myeloproliferative Disorders can present with a variety of platelet associated conditions. Thrombosis can occur due to large numbers of platelets and qualitative defects which contribute to thrombosis. Bleeding typically is a result of platelet qualitative (functional) defects. Thrombohemorrhagic events with thrombosis occurring first following by bleeding is also known to occur.

See slide 43 for more details.

52
Q

Which of the Chronic Myeloproliferative Disorders has the greatest risk of risk of thrombosis and/or bleeding?

A

Essential Thrombocythemia demonstrates greatest risk due to the greatest elevation of platelet count and greater number of qualitative defects.

Hematology 2 (23 decks)

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