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Fiser Chaper 2. HEMATOLOGY Flashcards

1
Q

Intrinisic pathway

A

-Exposed collagen, prekallikrein, HMW kininogen, factor 7

–> activate 11

–> activate 9, then add 8

-> activate X, then add V

–> contvert prohrombin (2) to thrombin

-> thrombin converts fibrinogen to fibrin

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2
Q

Extrinisic pathway

A

Injured cells: tissue factor + 7

  • > convert prothrombin to thrombin
  • > thrombin converts fibrinogen to fibrin
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3
Q

Prothrombin complex

A

10, 5, calcium, platelet facotr 3, prothrombin

Forms on platelets

Catalyzes the formation of thrombin

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4
Q

What is the convergent point for intrinsic and extrinsic pathways

A

X

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5
Q

Tissue factor pathway inhibitor does what?

A

Inhibits factor 10

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6
Q

Factor13 does what?

A

Helps crosslink fibrin

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7
Q

Fibrin dose what?

A

Binds GpIIb/IIIa molecule to link platelets together and form platelet plug

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8
Q

Thrombin does what?

A

Key to coagulation

COnverts fibrinogen to fibrin and fibrin split products

Activates 5 and 13, and platelets

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9
Q

Key to normal AC?

A

Antithrombin III

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10
Q

What does AT-III do?

A

Key to anticoagulation

Binds and inhibits Thrombin

Also inhibits 9, 10, 11

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11
Q

How does heparin work?

A

Activates AT-III (up to 1000x normal activity)

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12
Q

Protein C and S

A

Both vitamin K dependent

C: decreades 5and 8 and fibrinogen

S: protein Ccofactor

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13
Q

Fibrinolysis needs what?

A

Tissue plasminogen activator: released from endothelium and converts plasminogen to plasmin

–> Plasmin degrades factors 5, 8, fibrinogen, fibron

–> lose platelet plug

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14
Q

Alpha-2 antiplasmin

A

Natural inhibitor of plasmin, released from endothelium

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15
Q

Shortest half life factor?

A

7

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16
Q

Only factor not synthesized in liver?

A

8 (endothelium)

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17
Q

Vit K dependent factors

A

2, 7, 9, 10, C and S

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18
Q

How long does vit k take?

A

6 hours to have effect

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19
Q

How long does FFP take?

A

Immediate, lasts 6 hours

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20
Q

Half life of RBCs, platelets, PMNs

A

RBCs: 120 days

Platelets: 7 days

PMNs: 1-2 days

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21
Q

PGI2

A

prostacyclin

from endothelium

decreases platelet aggregation and promotes vasodilation

antagonist to TXA2

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22
Q

TXA2

A

Thromboxane

From platelets

Increases platelets aggregation and vasoconstriction

Triggers release of calciumin platelets –> exposes GpIIb/IIIa receptor and causes platelet-to0platelet binding; platelet-to-collagen binding also occurs (Gp1b receptor)

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23
Q

Cryoprecipitate

A

highest conc of vWF-8; also has fibrinogen

used in vWF disease and hemophilia A

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24
Q

FFP

A

all coag factors, C, S, AT-III

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25
DDAVP and conjugated estrogens
Cause release of 8 and vWF from endothelium
26
PT
measures 2, 5, 7, 10, fibrinogen; best for liver synthetic function
27
PTT
measures most factors except 7 and 13 (so does NOT pick up factor 7 def)
28
ACT goals
Activated clotting time 150-200 sec for AC >460 for cardioplum bypass
29
MCC surgical bleeding
Incomplete hemostasis
30
MCC congenital bleeding disorder
vWF disease Types 1 (MCC) and 2 are AD, 3 (severe) is autosomal recessive
31
vWF
Links Gp1b receptor on platelets to collagen
32
vWF disease labs
INR/PT normal PTT normal or abnormal Prolonged bleeding time (ristocetin test)
33
vWF disease types
1. MCC, reduced vWF quantity, tx recombinant 8:vWF, DDAVP, cryo 2. defect, vWF molecule not working well, tx recombinant 8:vWF, cryo 3. absent (rare), tx recombinant 8:vWF, cryo; DDAVP WILL NOT WORK
34
Hemophilia A
8 deficiency sex-linked recessive need levels 100% preop 80-100% for 10-14 days after surgery prolonged PTT, normal PT factor 8 crosses placenta so newborns may not bleed at circumcision Join bleed: DO NOT ASPIRATE: tc ice, ROM exercises, factor 8 concentrate or cryo Epistatxis or ICH or hematuria: tx recombinant factor 8 or cryo
35
Hemophilia B
9 deficiency sex-linked recessive need level 100% preop 30-40% for 2-3 days after surgery prolonged PTT, normal PT Tx recombinant factor 9 or FFP
36
Factor 7 deficiency
Prolonged PT/INR, normal PTT Tx: recombinant factor 7 or FFP
37
Bruising, epistaxis, mucosal bleeding, petechiae, purpura
Platelet disorder (acquired thrombocytopenia, Glanzmann's thrombocytpoenia, Bernard Soulier thrombocytopenia, Uremia)
38
Acquired thrombocytopenia causes
H2 blockers | Heparin
39
Glanzmann's thrombocytopeniais a deficiency in what?
GIIIb/IIa receptor (so platelets cannot bind to each other) Fibrin normally links the GpIIb/IIIa receptors together Tx: platelets
40
Bernard-soulier thrombocytopenia is a deficiency in what?
Gp1b receptor (platelets cannot bind to collagen) vWF normally bind Gp1b to collagen Tx: Platelets
41
Uremia causes what?
Inhibits platelet function Tx: HD first, DDAVP, platelets
42
HIT is due to what?
Antiplatelet antibodies (IgG PF4 ab) Causing platelet destruction (can also cause aggregation and thrombosis) White clot LMWhas a decreased risk of causin HIT Tx: Stop heparin, start argatroban (DTI)
43
DIC
Decreased platelets and fibrinogen; high fibrin split products and D-dimer; prolonged PT and PTT
44
DIC often initiated by waht factor?
Tissue factor
45
How long before surgery do patients need to stop asa? plavix? warfarin?
7 days
46
Aspirin MoA
Inhibits COX in platelets and decreases TXA2 Irreversible because platelets lack dNA so cannot resynthesize COX
47
Clopidegril MoA
ADP receptor antagonist Tx: platelets
48
Prostate surgery effects on coag?
Can release urokinase, which activate plasminogen causing thrombolysis Tx: E-aminocaproic acid (amicar)
49
Does normal circumcision rule of bleeding disorder?
No
50
Tooth extraction or tonsillectomy in history good way to tell bleeding risk?
Yes picks up 99% of patients with bleeding disorder
51
Epistaxis is common in what coag disorder?
vWF and platelet disorders
52
MCC congenital hypercoag disorder
Factor V LEiden: resistanceto activated proctein C, defect is on factor V Tx: Heparin and warfarin
53
Hyperhomocysteinemia tx
B12 and folic acid
54
Prothrombin gene defect G20210A tx
Heparin and warfarin
55
Protein C or S def treatment
Heparin and warfarin
56
AT-III deficiency tx
Heparin does NOT work (heparin activates AT-III) Can develop after prvious heparin exposure Tx: Recombinant AT-III concentrate or FFP (highest conc of AT-III), followed by heparin and warfarin
57
Dysfibrinogenemia, dysplasminogenemia tx
Heparin and warfarin
58
PV
Defect in platelet function, can get thrombosis Keep Hct<48, platelets <400 before surgery Tx: phlebotomy and asa
59
Anti-phospholipid antibody syndrome
Not all have SLE Get high PTT but hypercoagulable Caused by cardiolipin and lupus anticoagulant abs
60
High PTT but hypercoagulable
Anti-phospholipid ab syndrome
61
Dx of antiphospholipid ab syndrome
Prolonged PTT, not corrected with FFP Positive Russell vipor venom time False-positive RPR test for syphilis
62
Antiphospholipid ab syndrome tx
Heparin and warfarin
63
MCC acquired hypercoagulability
Tobacco Other: malignancy, inflammatory states, IBD, infection, OCP, pregnancy, RA, postop patients, myeloproliferative disorders
64
Hypercoagulability from cardiopulmonary bypass is due to what?
Hageman factor (Factor 12) activation Tx: Heparin to prevent
65
Who is especially susceptible to warfarin induced skin necrosis?
Protein C deficiency Protein C and S have shortest half life, so these anticoag factors first decrease before the coag factors decrease Tx: Heparin
66
Virchow's triad
Stasis, endothelial injury, hypercoagulability
67
Key element in development of arterial thrombosis
Endothelial injury
68
Postop DVT tx for 1st,2md and 3rd postop DVT
1st: 6 months warfarin 2nd: 1 yr warfarin 3rd or significant PE: lifelong warfarin
69
Who with a DVT gets a Greenfield filter?
Patients with contraindication to AC Documented PE while on AC Free-floating DVT in IVF, iliofemoral, or deep femoral Recent pulmonary embolectomy
70
Treatment of PE
Heparin (thrombolytics no improvement in survival) or suction catheter-based intervention If patient in shock despite massive inotropes and pressors, go to OR
71
Most common source of PE
iliofemoral
72
Procoagulant agents (anti-fibrinolytics)
E-aminocaproic acid (amicar): inhibits plasmin (which inhibits fibrinolysis), used in DIC, persistent bleeding after cardiopulm bypas, thrombolytic overdose, prostate surgery
73
Anticoagulation agents
Warfarin SCDs Heparin LMWH Argatroban Bivalirudin Hirudin Ancrod
74
Warfarin MoA
Inhibits vit-K dep DECARBOXYLATION of glutamin acid residues on vit-K dep factors
75
SCD MoA
Improves venous return but also induced fibrinolysis with compression (releast of tPA fromendothelium)
76
Heparin MoA
Binds and activates AT-III (1000x more activity)
77
What can you use to reverse heparin?
Protamine (binds heparin) Cross-reacts with NPH insulin or previous protamine exposure 1% get protamine reaction (hypotension, bradycardia, decreased heart function)
78
Heparin halft life
60-90 min
79
How is heparin cleared?
Reticuloendothelial system
80
Side effects of longterm heparin
Osteoporosis, alopecia
81
What AC to use in preg?
Heparin (does not cross placental barrier, while warfarin does)
82
LMWH
Enoxaparin, fondaparinux Lower risk of HIT Binds and activates AT-III but increases neutralization of just Xa and thrombin NOT reversed with protamine
83
Argatroban MoA
Reversible DTI Metabolized by liver Half life 50 min Used in HIT
84
Bivalirudin (Angiomax) MoA
Reversible DTI Metabolized by proteinase enzymes in blood Half life 25 min
85
Hirudin (Hirulog; from leeches)
Irreversible DTI MOST POTENT DIRECT INHIBITOR OF THROMBIN High risk for bleeding complications
86
Ancrod
Malayan pit viper venom StimulatestPA release
87
Thrombolytics
Streptokinase Urokinase tPA
88
Thrmbolytic MoA
Activate plasminogen Need to follor fibrinogen levels: <100 associated with increased risk and severity of bleeding
89
Tx for thrombolytic OD
E-aminocaproic acid (amicar)
90
CI to thrombolytics (tPA, urokinase, streptokinase)
Absolute: active internal bleeding, recent CVA or neurosurgery <3 mo, intracranial pathology, recent GIB Major: recent surgery/organ bx/obstetric delivery <10 days ago, left heart thrombus, active peptic ulcer, recent major trauma, uncontrolled HTN, recent eye surgery Minor: Minor surgery, recept CPR, A fib with mitral valve disease, bacterial endocarditis, hemostatic defects (renal or liver disease), diabetic hemorrhagic retinopathy, pregnancy

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