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PLT D/O Flashcards

1
Q

PLT hematopoiesis derives from what stem line?

A

Myeloids > megakaryocyte that splinters to 2-3k fragments =PLTs

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2
Q

PLT fx?

A

Help stop blood loss by forming PLT plug

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3
Q

PLT granules contain?

A

Clot promoting chemicals (PLT activators/aggregation)

  • ADP
  • Thromboxane A2
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4
Q

PLT life span?

A

5-9D

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5
Q

PLT formation is regulated by?

A

Thrombopoietin

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6
Q

Thrombopoietin is produced where? MOA?

A

Liver, Stimulates Stem cells to produce Megakaryocytes

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7
Q

1st general consideration why PLTs may be ABNL is?

A

Quan vs Qual

And R/O pseudothrombocytopenia

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8
Q

How to R/O pseudothrombocytopenia?

A

RPT PLT count w/ Non-EDTA blood tube like Sodium Citrate.

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9
Q

Thrombocytopenia QUAN issue reducing SURVIVAL

A

Immune Thrombocytopenia
HIT
Thrombotic Thrombocytopenic Purpura (TTP)/HUS
Hypersplenism

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10
Q

Thrombocytopenia QUAN issue reducing PRODUCTION

A

BM D/O
Infections
Rx

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11
Q

Which issue is more likely to be overlooked?

A

Qualitative issues (until significant bleeding occurs)

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12
Q

Thrombocytopenia QUAL issues?

A

VWF Dz
Acquired D/O (Uremia, Rx, ETOH)
Congenital

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13
Q

Immune Thrombocytopenia is?

A

Antibodies bind to PLTs > increased clearance

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14
Q

Immune Thrombocytopenia forms?

A

Primary vs Secondary

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15
Q

MC immune thrombocytopenia?

A

Primary immune Thrombocytopenia

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16
Q

Primary immune Thrombocytopenia is

A

Idiopathic thrombocytopenic purpura (ITP)

Dx of exclusion (req to R/O secondary causes 1st)

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17
Q

Secondary immune Thrombocytopenia is due to or ass/w?

A
  1. Dz - SLE, lymphoprolif D/O (CLL), Conn tiss D/O
  2. Infection - HIV, Hep C, or other viral infections
  3. Drug induced
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18
Q

Acute versus chronic immune Thrombocytopenia timeframe?

A

Acute <6mo

Chronic >6mo

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19
Q

Acute ITP is MC seen in what pop?

A

PEDs 2-10yo

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20
Q

Chronic ITP is MC seen in what pop?

A

Adults ass/w Autoimmune Dz - SLE, HIV, Antiphospholipid syndrome (APS) or Rx induced

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21
Q

ITP clinical features?

A

Mild mucosal bld - epitaxis, gingival bld, Easy bruise
Splenomegaly - uncommon
Isolated thrombocytopenia <50k
Severe - older patients w/ comorbids

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22
Q

ITP order of bleeding w/ PLT count reduction progression?

A

1st - Skin
2nd - MM
3rd - Viscera

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23
Q

ITP w/ no Cutaneous petechiae indicates?

A

LOW likelihood of intracranial hemorrhage = less severe form of ITP

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24
Q

ITP Dx

A 
Dx of exclusion (R/O Hep B/C, HIV)
CBC- Isolated thrombocytopenia (bld = +- anemia)
Hx - No rx, ETOH, Food/herbal causes
--Quinine, Sulfonamide, Heparin
BM Bx - R/O MDS in older pts >50yo
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25
Q

If severe thrombocytopenia and mucocutaneous bleeding w/in 7-14d post initiating new Rx suspect?

A

Rx induced ITP

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26
Q

When splenectomy is considered for ITP pt what should be done before surgery?

A

BM Bx

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27
Q

ITP TXT goal?

A

Reduce risk of bleeding and not to normalize PLT count

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28
Q

ITP mainstay TXT

A

Sig BLD + PLT <30k = CCS +- IVIG or Anti D(WinRHo)
Add PLT Transfusion PRN for severe Bleed (GI, Head)
Response w/in 3-5Ds

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29
Q

ITP refrac TXT

A

2nd Line TXT protocol

  • Monoclonal Antibodies- Rituximab (AB to CD20 B-cell)
  • Splenectomy- (no response, relapse, high doses CCS)
  • TPO-R ag stim PLT synth (Eltrombopag/Romiplostim)
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30
Q

ITP asymptomatic pts + PLT >30K TXT?

A

Observe w/ serial PLT counts
F/Us req to watch for bleeding
Educate severe bleeding S/S (melena, severe HA)

31
Q

HIT is?

A

Life threatening acquired complication of Heparin therapy (LMWH - Unfractionated Heparin) occuring 5-10d post exposure,

32
Q

Is HIT dose related?

33
Q

Can HIT occur w/ hep-locks, line flushes, heparin coated caths?

34
Q

HIT pathophys?

A

Formation of IgG AB to Heparin/PLT factor 4 complex

  • IgG + hep-PF4 complex bind/activate PLTs > prothrombotic state
  • Coated PLTs removed by MACs via RES of spleen > thrombocytopenia
35
Q

Forms of HIT?

A

Type I (mild) vs Type II (Severe)

36
Q

Type I HIT attributes?

A 
No clinical consequence
Modest thrombocytopenia (100k) w/in 1-2d of heparin therapy and returns to NL usually
37
Q

Type I HIT mechanism causes?

A

Direct effect of heparin on PLT activation >

non-immune PLT aggregation

38
Q

Type I HIT TXT?

A

Continue heparin and observe

39
Q

Type II HIT attributes?

A

Occurs 5-10D post exposure
Immune mediated - formed AB against Heparin PF4 >
enhances thrombin formation >
Paradoxical thrombosis + thrombocytopenia

40
Q

Type II HIT pts are at risk for?

A

DVT/PE (venous)
-AND
Arterial thrombosis

41
Q

Thrombotic risk (hypercoaguable state) of HIT lasts how long?

A

Persists for weeks-months after heparin D/C

42
Q

HIT Dx?

A

Clinical - Suspect if -
Post heparin use and Pt has S/S of w/in 5-10d?
– unexplained thrombocytopenia
– Venous/arterial thrombosis ass/w thrombocytopenia
– PLT count dropped >50% pts baseline
– Necrotic Skin lesions at Heparin injection sites

43
Q

Confirmation of HIT dx?

A

Positive PF4-heparin ELISA
Fx assays - higher specificity (2nd to ELISA)
– 1. - Positive Serotonin release assay
– 2. - Heparin-induced PLT aggregation (HIPA)

44
Q

What is the 4 T’s score of HIT?

A

Objective measure - HIT Dx vs other etiologies

  1. thrombocytopenia
  2. timing of PLT count fall (5-10d ex)
  3. Thrombosis or other sequelae
  4. Other possible cause of thrombocytopenia
45
Q

HIT TXT

A

Stop heparin (including other heparin devices)
Non-heparin anti-coagulation Rx for 3mo
-Argatroban - Synth direct thrombin inhibitor (DTI)
-Bivalirudin - Thrombin inhibitor
-Fonaparinux - F10a inhibitor

46
Q

HIT TXT and warfarin? OK?

A

Yes and No - CI as initial TXT due to potential transiently worsening hypercoagulability.
Transition only when PLTs recover to >150k

47
Q

HIT prognosis

A

IgG antibodies to Heparin-PF4 complex do not persist therefore NL w/in 100d or later
Recurrent Risk before 100d is high
Pts w/ HIT Hx should avoid Heparin all together unless absolutely req (life saving cardiac surgery)

48
Q

Thrombotic Microangiopathy (TMA) is

A

Acute complex syndromes w/ vascular endothelial injury that leads to widespread thrombi formation in microvasculature

49
Q

Examples of TMA?

A

Thrombotic thrombocytopenic Purpura (TTP)

Hemolytic Uremic Syndrome (HUS)

50
Q

Primay features of both TTP/HUS are?

A
  1. MAHA - shearing of RBCs > schistocytes

2. Thrombocytopenia - used during thombi formations

51
Q

TTP MC related to?

A

Acquired inhibitor of vWF-cleaving protease (ADAMTS 13)

52
Q

ADAMTS 13 is?

A

Plasma enzyme that attaches to endothelial cells and cleaves LRG vWF multimers

53
Q

TTP is due to?

A

Idiopathic - autoantibodies from against ADAMTS 13 leading to increase of LRG vWF multimers causing PLT aggregation and thrombosis.

54
Q

TTP may also be 2/2?

A

Rx, Chemo, Cancer

55
Q

TTP presents w/?

A 
FAT RN
F- Fever
A- Anemia - microangiopathic hemolytic anemia
T- Thrombocytopenia
R- Renal Dz
N- Neuro complications (AMS)
56
Q

HUS is defined as?

A

Simultaneous occurence of

  1. microangippathic hemolytic anemia
  2. thrombocytopenia
  3. Acute kideny injury
57
Q

What is a main cause of acute kidney injury in children?

58
Q

PEDs pts w/ HUS all present w/?

A

Classic triad

  1. microangippathic hemolytic anemia
  2. thrombocytopenia
  3. Acute kideny injury
59
Q

Other HUS S/S?

A

Petechial rash
HTN
Renal failure

60
Q

HUS may be preceded by?

A

Gastroenteritis

-MC in PEDs w/ E Coli 0157:H7 shiga toxin (STEC)

61
Q

Other atypical causes of HUS?

A

Rx - Cyclosporine/Chemo)
Autoimmune
Infection

62
Q

HUS is MC in what pop?

63
Q

TTP/HUS clinical features

A

FAT RN, however,

Dx - made w/ MAHA and thrombocytopenia alone

64
Q

What findings are mC w/ TTP vs HUS?

A

TTP - Neurologic - scattered thrombi w/in brain or bld

HUS - Renal - thrombi + hemolysis = hemoglobinuria and renal failure

65
Q

TTP/HUS labs

A 
CBC w/ Diff
-thrombocytopenia
-Schistocytes
Hemolytic labs - (^LDH, ^indirect bili, v-haptoglobin)
NEG Direct Coombs DAT
^ creatinine
POS stool Cx (HUS only)
66
Q

TTP TXT

A

Plasma exchange - remove Antibodies to ADAMTS 13
-Continue exchange until PLT NL x2d
2nd line - immunosupression (refrac to exchange)
-CCS
-Rituximab
-Cyclosporine

67
Q

HUS TXT PEDs

A

Supportive -(MC self limits) - Resolved infection

CI -antimotility or ABX Rx (INC shiga-like toxin release)

68
Q

Other QUAN Platelet D/O of reduced SURVIVAL (hypersplenism) management and pathophys?

A

Splenomegaly causes increased PLT sequestration

TXT UC of hypersplenism

69
Q

Other QUAN Platelet D/O of reduced PRODUCTION

A

BM D/O (AA, MDS)
Infections
Drugs

70
Q

Inherited QUAL PLT D/O attributes?

A

Von Willebrand Dz - variable deficits of vWF
Appears like coag issue due inability F8 stabilization
Cause QUAL PLT defect due to PLT agg inability
Otherwise PLT count is NL (QUAN good)

71
Q

Acquired QUAL PLT D/O attributes?

A

Uremia-

  • Severe renal failure
  • Impaired QUAL PLT fx related to circulating toxin
  • Anticipate w/ severe renal dysfx and Dialysis
72
Q

Myeloproliferative QUAL PLT D/O attributes?

A

Paradoxical bleeding risk w/ essential INC PLTs/RBCs

  • Thrombocythemia
  • Polycythemia Vera

Pathogenesis - NL PLT count - ABNL Fx due to ABNL cloncal proliferation.

73
Q

Rx QUAL PLT D/O attributes?

A

ASA - Irrev binds COX-1 leading to reduced PG and reduced PLT agg

GP IIb/IIIa inhibitors

  • -ABCiximab
  • -eptifibatide
  • -tirofiban

Adenosine Diphosphate inhibitors

  • -Clopidogrel
  • -Ticlodipine

Heme (8 decks)

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