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Senior - Heme-Onc > Lecture 7 - Platelet Disorders > Flashcards

Lecture 7 - Platelet Disorders Flashcards

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1
Q

Describe platelet hematopoiesis

A

Myeloid stem cells —> megakaryocyte

Megakaryocytes splinter into 2-3k fragments

Fragments get enclosed in plasma membrane

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2
Q

Describe a platelet

A

Disc-shaped with many vesicles

No nucleus

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3
Q

How do platelets stem bleeding?

A

They form a platelet plug

Their granules contain blood clot promoting chemicals

  • ADP
  • Thromboxane A2
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4
Q

Life span of platelets?

A

5-9 days

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5
Q

What controls platelet formation?

A

Thrombopoietin

Produced in the liver and stimulates megakaryocytes

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6
Q

You see a platelet abnormality on CBC, now what?

A

Ask yourself if its quantitive or qualitative

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7
Q

Fancy medical word for platelet clumping?

How do i r/o this with a platelet abnormality?

A

Pseudothrombocytopenia

R/o by repeating plt ct in non-EDTA containing tube
- sodium citrate tube

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8
Q

Youve narrowed it down to a quantative problem, what are some things that can cause this?

A

Reduced survival

Reduced production

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9
Q

What causes reduced survival of plt?

A
  • Immune thrombocytopenia
  • HIT
  • TTP
  • HUS
  • Hypersplenism
  • key
    HIT (heparin induced thrombocytopenia)
    TTP (thrombotic thrombocytopenic purpura
    HUS (hemolytic uremic syndrome
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10
Q

What will cause reduced production of plt?

A
  • Bone marrow disorder
  • infection
  • drugs
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11
Q

When are you more likely to notice qualitative plt disorders?

A

When clinically significant bleeding occurs

  • Von Willebrand’s disease
  • acquired disorders (uremia, drugs, ETOH)
  • congenital causes
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12
Q

What is immune thrombocytopenia?

A

Autoimmune condition - antibodies bind PLTs, results in accelerated PLT clearance

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13
Q

Primary vs secondary immune thrombocytopenia?

A

Primary: idiopathic thrombocytopic purpura (ITP)
- MC

Secondary: disease/drugs

  • autoimmune (SLE)
  • lymphoproliferative d/o (chronic lymphocytic leukemia)
  • connective tissue d/o
  • HIV/Hep C
  • drugs
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14
Q

Acute vs chronic immune thrombocytopenia?

A

Acute < 6mo

Chronic > 6 mo

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15
Q

Which populations are prone to acute vs chronic ITP?

A

Acute - kids
Chronic - adults
- secondary is also more likely to be chronic

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16
Q

Clinical features of ITP?

A
  • Mild mucosal bleeding
  • sever bleeding (old and sick pts)
  • splenomegaly (uncommon)
  • low plts (<50,000) if sever isolated form
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17
Q

Bleeding location follows the platelet count. As it descends what order does bleeding occur?

A

Skin

Mucous membrane

Viscera

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18
Q

If a ITP pt has no cutaneous petachie they have a low likelihood of?

A

Intracranial hemorrhage

I.e. they have a less sever form of ITP

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19
Q

How is ITP diagnosed?

A

Diagnosis of exclusion
- R/O Hep B, C, HIV

CBC - isolated thrombocytopenia

HX - must lack drug, etoh, food and herbal causes

Bone marrow bx

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20
Q

How long after starting a new drug will the pt get sever thrombocytopenia and mucotaneous bleeding if it is drug induced?

A

W/in 7-14 days

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21
Q

Who needs a bone marrow bx?

A

Older pts - r/o myelodysplastic syndrome

Unexplained cytopenias

Fail initial therapy

Prior to splenectomy

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22
Q

What is the goal of treatment with ITP?

A

To reduce risk of clinically important bleeding

- not to normalize plt count

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23
Q

Treatment for ITP?

A

Corticorsteroids =/- IVIG or anti-D
- mainstay of tx <30,000

PLT transfusion as needed

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24
Q

Tx for refractory cases of ITP?

A

Monoclonial antibodies
- rituximab

Splenectomy
- for failed tx or high dose steroids

Eltrombopag/romiplostim
- TPO-R agonist to stimulate plt production

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25
Tx for asymptomatic pts or pts with plt count > 30,000-40,000?
There is only a 15% chance of sever thrombyctopenia requiring tx - serial PLT counts - watch for bleeding - counsel pts on s/s of bleeds
26
What is HIT?
heparin induced thrombocytopenia Lifethreatening complication of heparin (LMWH or unfractionated heparin) - 5-10 days post heparin - not dose related (even hep-locks) - seen in 5% of pts w heparin
27
Pathophysiology of HIT?
Body forms IgG antibodies to heparin-platelet factor 4 (PF4) complexes - leads to prothrombotic state - macrophages eat the platelets —> thrombocytopenia
28
Types of HIT?
Mild - type I - can continue heparin Severe - type II - hypercoagulatable state lasts for months
29
Describe type I HIT
Not immune mediated - no clinical consequence - modest thrombocytopenia (100,000) - begins 1-2 days after therapy
30
What causes type I HIT?
We’re not sure but we think: | Direct effect of heparin on platelet activation (causing a non-immune platelet aggregation)
31
Describe type II HIT
- 5-10 days after tx - immune mediated ab against Heparin PF4 - enhanced thrombin formation - paradoxical thrombosis - thrombocytopenia - risk of DVT/PE/thrombosis - hypercoagluatable state lasts weeks-months
32
When to suspect HIT?
Any of the following w/in 5-10 days of heparin - unexplained thrombocytopenia - venous/arterial thrombosis from thrombocytopenia - PLT count drops 50% or more - necrotic skin lesions at inj site
33
How is HIT usually diagnosed?
Clinically The lab can confirm but it is slow - ELISA test - Serotonin release assay - heparin-induced platelet aggregation
34
What is the 4Ts score for HIT?
Objective measure to determine if thrombocytopenia is HIT or something else 1. Thormbocytopenia 2. Timing of platelet count fall 3. Thrombosis/sequelae 4. Thrombocytopenia (Other causes)
35
Tx for HIT?
STOP HEPARIN Switch to - agratroban - bivalirudin - fondaparinux After 3 months or when plt count reaches 150,000 pt can have warfarin
36
HIT pts also cannot have?
Warfarin - may worsen hypercoagulability Until their platelet count is >/= 150,000
37
Prognosis?
Usually can use heparin again 100 days later (IgG ab dont last) - < 100 days recurrence is high But since other meds are available its best to just give them the other drugs
38
What is TMA?
Thrombotic microangiopathy Acute complex syndrome w 1. VASCULAR ENDOTHELIAL INJURY leading to WIDESPREAD THROMBI FORMATION in the microvasculature 2. TTP AND HUS
39
Primary feature of vascular endothelai injury, TTP, and HUS that are required to be present for a diagnosis of TMA to be made?
MAHA - microangiopathic hemolytic anemia - shearing of RBC (schitocytes) Thrombocytopenia
40
Therapy for TMA?
Plasma exchange - removal of pt plasma and replacement with donar plasma
41
Most cases of TTP (thrombotic thrombocytopenic purpura) involve?
Acquired inhibitor of von Willebrand factor-cleaving protease - ADAMTS 13
42
What is ADAMTS 13?
ADAMTS 13 attaches to endothelial cells and cleaves large vWF multimers
43
What happens with ADAMTS 13 when you get TTP?
Idiopathic: Autoantibodies form against ADAMTS 13 leading to large accumulation of large vWF multimers that cause plt aggregation and thrombosis - can also be 2/2 drugs, chemo, cancer
44
TTP presentation: FAT RN
F: fever A: microangiopathic hemolytic ANEMIA T: thrombocytopenia R: renal disease (AKI) N: neurologic complications (altered/confused)
45
What is HUS?
Hemolytic uremic syndrome Simultaneous occurence of - Microangiopathic hemolytic anemia - Thrombocytopenia - Acute kidney injury
46
Common cause of kidney injury in kids?
Hemolytic uremic syndrome Kids always exhibit the classic triad
47
HUS s/s?
Petechial rash HTN Renal failure Preceded by Gastroenteritis
48
If your HUS is not preceded by 0157:H7 or STEC it is considered?
Atypical Usually medication, autoimmune, or some other type of infection
49
Therapy for HUS?
Supportive
50
FAT RN is the classic pentatd for TTP and HUS the presence of ___ and ___ should increases your suspicions
MAHA (microangiopathic hemolytic anemia) and thrombyctopenia
51
What findings common with TTP?
Neurologic | - Scattered thrombi formation in brain and subsequent impaired blood flow and O2 delivery
52
What findings are more common in HUS?
Renal findings | - microvascular thrombus formation and hemoglobinuria from intravascular hemolysis causing renal failure
53
Labs for TTP and HUS?
- thrombocytopenia - fragmented cells on PBS - hemolytic labs — H LDH — L haptoglobin — H indirect bilirubin - NEG DAT (coombs) - POS stool cx (HUS)
54
TTP tx?
Plasma exchange - removes antibodies to ADAMTS 13 - performed daily x 2 days 2nd line/refractory - immunosuppresion - corticosteroids - rituximab - cyclosporine
55
quantitive platelet disorder causing reduced survival?
Hypersplenism - splenomegaly —> increased plt sequestration
56
quantitive platelet disorders causing decreased production?
Bone marrow disorder Infection Drugs
57
qualitative platelet disorder inherited?
vWF - coagulation problem Platelet count is otherwise normal
58
Qualitative platelet disorder that is acquired?
Uremia | - renal failure from circulating toxins
59
Qualitative platelet disorder that are myeloproliferative?
Myleoproliferative disorders - paradoxical bleeding risk - essential thrombocythemia and polycythemia vera Normal numbers of platelets but they have abnormal function
60
Drugs that cause platelet disorders?
Aspirin - reduced aggregation GP IIB/IIIA inhibitors - abciximab - eptifibantide - tirofiban Adenosine diphosphate inhibitors - clopidogrel - ticlodipine
61
You mama so FAT
When Dracula sucked her blood her got diabetes

Senior - Heme-Onc (6 decks)

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