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PLT D/O Flashcards

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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
If severe thrombocytopenia and mucocutaneous bleeding w/in 7-14d post initiating new Rx suspect?
Rx induced ITP
26
When splenectomy is considered for ITP pt what should be done before surgery?
BM Bx
27
ITP TXT goal?
Reduce risk of bleeding and not to normalize PLT count
28
ITP mainstay TXT
Sig BLD + PLT <30k = CCS +- IVIG or Anti D(WinRHo) Add PLT Transfusion PRN for severe Bleed (GI, Head) Response w/in 3-5Ds
29
ITP refrac TXT
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)
30
ITP asymptomatic pts + PLT >30K TXT?
Observe w/ serial PLT counts F/Us req to watch for bleeding Educate severe bleeding S/S (melena, severe HA)
31
HIT is?
Life threatening acquired complication of Heparin therapy (LMWH - Unfractionated Heparin) occuring 5-10d post exposure,
32
Is HIT dose related?
NO
33
Can HIT occur w/ hep-locks, line flushes, heparin coated caths?
YES
34
HIT pathophys?
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
Forms of HIT?
Type I (mild) vs Type II (Severe)
36
Type I HIT attributes?
``` No clinical consequence Modest thrombocytopenia (100k) w/in 1-2d of heparin therapy and returns to NL usually ```
37
Type I HIT mechanism causes?
Direct effect of heparin on PLT activation > | non-immune PLT aggregation
38
Type I HIT TXT?
Continue heparin and observe
39
Type II HIT attributes?
Occurs 5-10D post exposure Immune mediated - formed AB against Heparin PF4 > enhances thrombin formation > Paradoxical thrombosis + thrombocytopenia
40
Type II HIT pts are at risk for?
DVT/PE (venous) -AND Arterial thrombosis
41
Thrombotic risk (hypercoaguable state) of HIT lasts how long?
Persists for weeks-months after heparin D/C
42
HIT Dx?
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
Confirmation of HIT dx?
Positive PF4-heparin ELISA Fx assays - higher specificity (2nd to ELISA) -- 1. - Positive Serotonin release assay -- 2. - Heparin-induced PLT aggregation (HIPA)
44
What is the 4 T's score of HIT?
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
HIT TXT
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
HIT TXT and warfarin? OK?
Yes and No - CI as initial TXT due to potential transiently worsening hypercoagulability. Transition only when PLTs recover to >150k
47
HIT prognosis
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
Thrombotic Microangiopathy (TMA) is
Acute complex syndromes w/ vascular endothelial injury that leads to widespread thrombi formation in microvasculature
49
Examples of TMA?
Thrombotic thrombocytopenic Purpura (TTP) | Hemolytic Uremic Syndrome (HUS)
50
Primay features of both TTP/HUS are?
1. MAHA - shearing of RBCs > schistocytes | 2. Thrombocytopenia - used during thombi formations
51
TTP MC related to?
Acquired inhibitor of vWF-cleaving protease (ADAMTS 13)
52
ADAMTS 13 is?
Plasma enzyme that attaches to endothelial cells and cleaves LRG vWF multimers
53
TTP is due to?
Idiopathic - autoantibodies from against ADAMTS 13 leading to increase of LRG vWF multimers causing PLT aggregation and thrombosis.
54
TTP may also be 2/2?
Rx, Chemo, Cancer
55
TTP presents w/?
``` FAT RN F- Fever A- Anemia - microangiopathic hemolytic anemia T- Thrombocytopenia R- Renal Dz N- Neuro complications (AMS) ```
56
HUS is defined as?
Simultaneous occurence of 1. microangippathic hemolytic anemia 2. thrombocytopenia 3. Acute kideny injury
57
What is a main cause of acute kidney injury in children?
HUS
58
PEDs pts w/ HUS all present w/?
Classic triad 1. microangippathic hemolytic anemia 2. thrombocytopenia 3. Acute kideny injury
59
Other HUS S/S?
Petechial rash HTN Renal failure
60
HUS may be preceded by?
Gastroenteritis | -MC in PEDs w/ E Coli 0157:H7 shiga toxin (STEC)
61
Other atypical causes of HUS?
Rx - Cyclosporine/Chemo) Autoimmune Infection
62
HUS is MC in what pop?
Children
63
TTP/HUS clinical features
FAT RN, however, | Dx - made w/ MAHA and thrombocytopenia alone
64
What findings are mC w/ TTP vs HUS?
TTP - Neurologic - scattered thrombi w/in brain or bld HUS - Renal - thrombi + hemolysis = hemoglobinuria and renal failure
65
TTP/HUS labs
``` CBC w/ Diff -thrombocytopenia -Schistocytes Hemolytic labs - (^LDH, ^indirect bili, v-haptoglobin) NEG Direct Coombs DAT ^ creatinine POS stool Cx (HUS only) ```
66
TTP TXT
Plasma exchange - remove Antibodies to ADAMTS 13 -Continue exchange until PLT NL x2d 2nd line - immunosupression (refrac to exchange) -CCS -Rituximab -Cyclosporine
67
HUS TXT PEDs
Supportive -(MC self limits) - Resolved infection | CI -antimotility or ABX Rx (INC shiga-like toxin release)
68
Other QUAN Platelet D/O of reduced SURVIVAL (hypersplenism) management and pathophys?
Splenomegaly causes increased PLT sequestration | TXT UC of hypersplenism
69
Other QUAN Platelet D/O of reduced PRODUCTION
BM D/O (AA, MDS) Infections Drugs
70
Inherited QUAL PLT D/O attributes?
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
Acquired QUAL PLT D/O attributes?
Uremia- - Severe renal failure - Impaired QUAL PLT fx related to circulating toxin - Anticipate w/ severe renal dysfx and Dialysis
72
Myeloproliferative QUAL PLT D/O attributes?
Paradoxical bleeding risk w/ essential INC PLTs/RBCs - Thrombocythemia - Polycythemia Vera Pathogenesis - NL PLT count - ABNL Fx due to ABNL cloncal proliferation.
73
Rx QUAL PLT D/O attributes?
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

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