Fiser ABSITE Review UAMS COPY > Chapter 2 - Hematology > Flashcards

Chapter 2 - Hematology Flashcards

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1
Q

What are the three initial responses to vascular injury

A
  1. vasoconstriction
  2. platelet adhesion
  3. thrombin generation
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2
Q

Intrinsic Pathway starts with?

A

exposed collagen, prekallikrein, HMW kininogen, factor XII

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3
Q

Intrinsic pathway steps?

A
  • collagen, prekallikrein, HMW kininogen + XII
  • activate XI
  • activate IX, then add VIII
  • activate X, then add V
  • convert prothrombin (factor II) to thrombin
  • thrombin converts fibrinogen to fibrin
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4
Q

Extrinsic pathway starts with?

A

Tissue factor from incured cells + factor VII

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5
Q

Steps of extrinsic?

A
  • tissue factor + factor VII
  • activate X then add V
  • convert prothrombin to thrombin
  • thrombin then converts fibrinogen to fibrin
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6
Q

What is the prothrombin complex and what does it do?

A

X, V, Ca, PF-3, Prothrombin

forms on platelets

catalyzes the formation of thrombin

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7
Q

What is the convergence point for both intrinsic and extrinsic paths?

A

Factor X

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8
Q

What does the Tissue factor pathway inhibitor do?

A

Inhibits factor X

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9
Q

What does Fibrin do?

A

combines with platelets (GpIIb/IIIa) to form the platelet plug to create hemostasis

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10
Q

What does factor XIII do?

A

helps crosslink Fibrin

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11
Q

Why is thrombin the key to coagulation? What does it activate?

A

Thrombin

  • converts Fibrinogen to Fibrin and Fibrin split products
  • activates factors V and VIII
  • activates platelets
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12
Q

What is Protein C, what does it do?

A
  • Vitamin K-dependent anticoagulation factor
  • degrades factors V and VIII
  • degrades fibrinogen
  • Deficiency can lead to DVTs and Warfarin skin necrosis
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13
Q

What is protein S, what does it do?

A
  • Vitamin K dependent anticoagulation factor
  • cofactor of Protein C
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14
Q

TPA is released from where and does what?

A
  • released from endothelium
  • converts plasminogen to plasmin
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15
Q

Plasmin does what?

A
  • degrades factor V and VIII, fibrinogen, and fibrin
  • destruction of platelet plug
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16
Q

What is Alpha-2 antiplasmin?

A
  • natural inhibitor of plasmin
  • released from endothelium
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17
Q

What factor has the shortest half life?

A

VII

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18
Q

What factors’ activity is lost in stored blood but not FFP?

A

V and VIII

labile factors

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19
Q

What factor is not synthesized in the liver? where is it synthesized?

A

VIII

synthesized in the endothelium (with vWF)

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20
Q

What are the vitamin K dependent factors?

A

II, VII, IX, X, C and S

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21
Q

How long does it take for Vitamin K to take effect?

A

12 hours

Not adequate alone for emergency bleeding - need FFP too

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22
Q

How long does it take FFP to work and how long does it last?

A

immediately

lasts 6 hours

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23
Q

What is factor II?

A

Prothrombin

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24
Q

What is the normal half life of RBCs? Platelets? PMNs?

A
  • RBCs 120 days
  • platelets 7 days
  • PMNs 1-2 days
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25
Where is Prostacyclin (PGI2) released from and what does it do?
* Endothelium * Decreases platelet aggregation and causes vasodilitation (antagonistic to TXA2) * Increases cAMP in platelets
26
Thromboxane (TXA2) - where is it released from, what does it do?
* Platelets * Increases plt aggregation and promotes vasoconstriction * Triggers the release of Ca2+ in platelets → exposes GpIIb/IIIa recepter → platelet-platelet binding * platelet to collagen binding (GpIb) * activates PIP system to further release calcium The opposite of PGI2 (prostacyclin from endothel, vasodilates, stops aggregation)
27
What is in high concentration in cryoprecipitate and what is it used for?
* high concentrations of vWf, VIII * use in von Willebrands disease and hemophilia A (VIII def) * contains fibrinogen
28
What is in FFP?
High levels of all factors including V and VIII, C, S, AT-III
29
Why are DDAVP and conjugated estrogens used in the setting of coagulopathy? *remember estrogen exposure increases DVT risk
Cause release of VIII and vWF from endothelium
30
What factors does PT measure?
II, V, VII, X, fibrinogen best for liver synthetic function
31
What does PTT measure?
All but VII and VIII - Does not pick up VII deficiency routine anticoag: measure q6h, keep at 60-90 sec
32
What is an ACT?
Activated clotting time 150-200 for routine anticoagulation 480 for Cardiopulmonary bypass
33
What level INR is a relative contraindication for surgical procedures?
\>1.5
34
What level INR is a relative contraindication for central line, PCT biopsies, and eye surgery?
\>1.3
35
What is the most common cause of surgical bleeding?
Incomplete hemostasis
36
What is the most common congenital bleeding disorder?
_von Willebrands_ MC Psx: epistaxis
37
What is the inheritance of von willebrand's disease?
I and II are AD. III is AR.
38
what does vWf do?
links GpIb receptor on platelets to collagen
39
In von willebrand's, what is the PT and PTT? Bleeding time?
* PT normal * PTT normal or abnormal (VIII can be affected) * bleeding time long (ristocetin test)
40
In these types of von willebrand's disease there is a problem in vWf quantity. How do you treat?
* I - reduced quantity of vWF, MC * III - complete deficiency, most severe bleeding * Tx: recombinant VIII, vWf, cryoprecipitate * DDAVP, conjugated estrogens works for I but not III (nothing to release)
41
This type of Von willebrand's disease has a problem in the quality of vWf
Type II Tx: recombinant VIII:vWF, cryoprecipitate, DDAVP
42
What is Hemophilia A and what is its inheritance? MC symptom?
* Factor VIII deficiency * Sex linked recessive * MC Sx: hemarthrosis
43
Does factor VIII cross the placenta?
Yes. Circumcision may not cause bleeding in hemophila A pts.
44
What is Hemophilia B and what is its inheritance?
Factor IX deficiency - Christmas disease. Sex linked recessive.
45
What can cause an acquired thrombocytopenia?
H2 blockers, heparin
46
What is Glanzmann's thrombocytopenia?
* GpIIb/IIIa receptor def - platelets cannot bind to each other * Fibrin normally links them together at this site * Tx: platelets * Like abciximab - GpIIb/IIIa inhibitor used in PCI
47
What is Bernard Soulier?
* GpIb receptor deficiency on platelets * Can't bind vWF to collagen * Tx: platelets
48
What does Uremia do to platelets and what is the treatment?
* Inhibits platelet function by inhibiting vWF release * Labs: BUN \>60-80 * Tx: hemodialysis first, DDAVP for acute reversal, cryo for moderate/severe bleeding
49
What does Ticlopidine do to platelets?
* decreases ADP on platelet surface (fibrinogen can't bind) * prevents exposure of GpIIb/IIIa (Glanzman like) * Tx: platelets
50
What does Dipyridamole do to platelets?
* inhibits cAMP phosphodiesterase, increases cAMP * decreases ADP induced platelet aggregation * Tx: platelets
51
What does Pentoxifylline do to platelets?
* inhibits platelet aggregation * Tx: platelets
52
What does Clopidogrel do?
* irreversibly inhibits P2Y12 receptor (ADP receptor) * Tx: platelets * Similar mechanism to prasugrel and ticagrelor
53
PCN/cephalosporins do what to platelets?
* bind platelets * can increase bleeding time
54
HIT is caused by what antibody?
* IgG heparin-PF4 ab (anti-heparin ab) - causes platelet destruction
55
What type of clot does HIT cause?
White clot
56
How do you diagnose and manage HIT?
* Suspect w/ heparin exposure \>5 days (previous hospitalization) * \>50% platelet drop, necrotic lesions at injection sites, thrombus, or anaphylaxis 1. Stop all heparin 2. Start direct thrombin inhibitor - argatroban, hirudin, ancrod, or dextran 3. Send serotonin release assay (confirmatory test, ELISA for hep-ab) 4. Avoid platelet transfusion (risk of thrombosis) 5. If wanting to start warfarin, wait for platelets to recover (\>150K), then bridge
57
What are the lab findings in DIC?
* decreased platelets (often initiated by tissue factor) * prolonged PT and PTT * low fibrinogen * high fibrin splits/high D-Dimer * Tx: underlying cause (eg sepsis)
58
How many days before surgery should ASA be stopped?
7 days * inhibits COX in platelets * decreases TXA2 (vasoconstriction, platelet aggregation) * b/c platelets lack DNA, they can't resynth COX
59
How many days before surgery should coumadin be stopped?
7 days * consider starting heparin anticoag while warfarin wears off * if bleeding - give vit K and FFP
60
What should platelets be at before surgery? after surgery?
50k; 20k
61
Prostate surgery has what effect bleeding?
can relase urokinase, activates plasminogen = thrombolysis Treat with e-Aminocaproic acid (Amicar, inh fibrinolysis)
62
Tooth extraction or tonsillectomy will pick up what percentage of Pt's with a bleeding disorder?
99% H&P best way to predict bleeding risk
63
What is the most common cause of congenital hypercoagulability?
_defect of factor V Leiden_ * resistance to activated protein C * Tx: heparin, warfarin
64
What is the treatment of hyperhomocysteinemia
folic acid and B12 (10% of spontaneous DVT's)
65
What is the treatment for G20210 prothrombin gene defect?
heparin, warfarin (5% of spontaneous DVT's)
66
How does Antithrombin III deficiency develop and how is it treated?
* can develop after previous heparin exposure * heparin will not anticoagulate these patients * Tx: recombinant AT-III or FFP THEN heparin/warfarin
67
What antibody is the lupus anticoagulant, what does it do to PTT and to coagulation? How is it diagnosed? How is it treated?
* Antiphospholipid antibodies - cardiolipin, lupus anticoagulant * Causes a procoagulant state - thrombi, loss of pregnancy * Not all have SLE * Labs: PTT prolonged (but hypercoag), not corrected by FFP * Dx: by positive russell viper venom time, false + RPR * Tx: heparin, warfarin
68
What are some causes of acquired hypercoagulability?
Tobacco (#1), malignancy, inflammatory state, Inflammatory Bowel disease, oral contraceptives, pregnancy, rheumatoied, postop, myeloproliferative
69
How does cardiopulmonary bypass cause hypercoagulable state and what is the prevention?
Causes factor XII activation. Prevent with heparin.
70
What is the pathogenesis of warfarin skin necrosis?
* Pts who don't get heparin bridge * Protein C and S have short half life * Transient hypercoaculable state * Protein C deficiency especially susceptible * Tx: heparin
71
What is Virchow's Triad?
Stasis, Endothelial injury, hypercoagulable state Leads to venous thromboses
72
What is the key element in the development of an arterial thrombus?
endothelial injury
73
How long must a pt be on warfarin for their 1st, 2nd, or 3rd DVT?
* 1 = 6 months * 2 = 1 year * 3 or significant PE= lifetime
74
What are the indications for a greenfield IVC filter?
* contraindications to anticoagulation * documented **PE** on anticoagulation * _free floating_ ileofemoral, IVC, or femoral DVT * pts _s/p pulmonary embolectomy_
75
Patient has pulmonary embolism and is in shock despite massive ionotropes, what do you do?
* OR - open embolectomy vs angiography w/ suction catheter * If not in shock, give heparin * thrombolytics not proven to increase survival * MC from ileofemoral region
76
What percentage of positive V/Q scans have negative duplexes?
33%
77
How does warfarin work?
prevents vitamin K-dependent decarboxylation of glutamic resudues on vitamin K-dependent factors (II, VII, IX, X) protein C and S also affected
78
How does Dextran work?
Inhibits platelets and coagulation factors - antiplatelet and anticoagulant
79
How do SCD's work?
improve venous return but also induce fibrinolysis with compression (TPA)
80
How does Heparin work?
potentiates antithrombin III
81
How is heparin reversed?
Protamine (1-1.5 protamine/100U heparin) follow PTT's
82
What is the half life of heparin and how is it cleared?
60-90 minutes Cleared by retuculoendothelial system (spleen, macrophages)
83
What are the long term side effects of heparin? Does it cross placenta?
osteoporosis, alopecia no - okay for pregnancy, unlilke warfarin
84
What are the problems/reactions of protamine?
* cross reacts with NPH insulin or previous heparin exposure * 4-5% of patients get reaction - hypotension, bradycardia, decreased cardiac fxn
85
How dies Hirudin work? is it reversible?
* From leeches * Irreversible direct thrombin inhibitor (most potent) * Want PTT 60-90 * High risk of bleeding
86
How does **Argatroban** work? Where is it metabolized? What is the half life? What is it often used for?
* direct thrombin inhibitor * metabolized in liver * T1/2 50 mins * use for HITT
87
How does Bivalirudin work? where is it metabolized? half life?
* _reversible_ direct thrombin inhibitor * metabolized by proteinase enzymes in the blood * half life 25-30 mins
88
How does Ancrod work? where does it come from?
* Malaysian pit viper venom * stimulates tPA release
89
How does Amicar (e-aminocaproic acid) work?
* _Inhibiting plasmin_ → inhibits fibrinolysis (preserves clot) * Uses: DIC, persistent bleeding after cardiopulmonary bypass, **thrombolytic overdose**
90
What are common thrombolytics? Which one has high antigenicity?
* urokinase, tPA, streptokinase * streptokinase has high antigenicity
91
What is required for thrombolytics to work?
Guidewire must get past obstruction
92
What are acceptable Fibrinogen levels when using thrombolytics?
* \>100 * \<100 associated with increased risk/severity of bleeding.
93
What are absolute contraindication to using thrombolytics?
* active internal bleeding * recent CVA or NSGY (\<3 months) * intracranial pathology * recent GI bleed
94
Major (not absolute) contraindications to thrombolytics?
* recent surgery (\<10 days) * organ biopsy * left heart thrombus * active peptic ulcer * major trauma * uncontrolled HTN
95
What is the key to anticoagulation? What does it do?
_Antithrombin III_ * binds and inhibits thrombin * inhibits factors IX, X, and XI * Heparin upregulates ATIII up to 1000x normal activity
96
How do you manage Hemophilia A peri-operatively?
* needs levels 100% preop * keep 80-100% for 10-14 days after surgery * follow PTT q8h postop (psx w/ prolong PTT and nl PT) * Psx: epistaxis, ICH, hematuria * Tx: recombinant FVIII, cryo * Psx: hemarthrosis (MC psx) * Tx: don't aspirate, ice, RoM exercise, FVIII, cryo
97
How do you manage Hemophilia B peri-operatively?
* need levels 100% pre-op * keep 30-40% 2-3 days postop * labs: PTT prolong, normal PT (like Hemophilia A) * Tx: recombinant IX, FFP
98
How do platelet disorders present?
epistaxis, bruising, petechiae, purpura
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