2 Hematology Flashcards
1
Q
What are the initial steps of primary hemostasis?
A
Subendothelial collagen exposure –> Platelet adhesion–> shape change –> granulation release (ADP, TXA2) –> Recruitment –> hemostatic plug (Aggregation)
2
Q
What are the three initial responses to vascular injury?
A
Vascular vasoconstriction
Platelet adhesion
Thrombin generation
3
Q
What initiates the intrinsic pathway?
A
Exposed collagen
Prekallikrein
HMW kininogen
Factor XII
4
Q
What are the steps in the intrinsic pathway?
A
Exposed collagen/prekallikrein/HMW kininogen/factor XII
- -> activates XI
- -> activate IX, then add VIII
- -> activate X, then add V
- -> convert prothrombin (Factor II) to thrombin
- -> thrombin then converts fibrinogen to fibrin
5
Q
What initiates the extrinsic pathway?
A
Cellular injury –> release of tissue factor
Factor VII
6
Q
What are the steps in the extrinsic pathway?
A
Cellular injury leads to release of tissue factor - reacts with VII
- -> Activates X, then add V
- -> convert prothrombin to thrombin
- -> thrombin then converts fibrinogen to fibrin
7
Q
What are the steps in the common pathway?
A
Prothrombin (Factor II) is converted to thrombin
–> Thrombin then converts fibrinogen to fibrin
8
Q
What is the prothrombin complex?
A
X, V, Ca, platelet factor 3 and prothrombin
Forms on platelets
Catalyzes the formation of thrombin
9
Q
What is the convergence point for both coagulation pathways?
A
Factor X
Needed for conversion of prothrombin to thrombin
10
Q
Function of Tissue factor pathway inhibitor?
A
Inhibits factor X
11
Q
Function of Fibrin
A
Links platelets together
Binds GpIIb/IIIa molecule
Forms a platelet plug - hemostasis
12
Q
Role of XIII
A
Helps crosslink fibrin
13
Q
Functions of thrombin
A
Key to coagulation
Converts fibrinogen to fibrin and fibrin split products
Activates factors V and VIII
Activates platelets
14
Q
Function of Antithrombin III
A
Key to anticoagulation
Binds and inhibits thrombin
Inhibits factors IX, X and XI
Heparin activates AT-III (up to 1000x normal activity)
15
Q
Function of Protein C
A
Vitamin K-dependent
Degrades factors V and VIII
Degrades fibrinogen
16
Q
Function of Protein S
A
Vitamin K-dependent
Protein C cofactor
17
Q
What enzymes regulate fibrinolysis?
A
Tissue plasminoagen activator
Plasmin
Alpha-2 antiplasmin
18
Q
Function of Tissue plasminogen activator
A
Released from endothelium
Converts plasminogen to plasmin
19
Q
Function of Plasmin
A
Degrades factors V and VIII, fibrinogen and fibrin
Causes degradation of platelet plug
20
Q
Function of Alpha-2 antiplasmin
A
Natural inhibitor of plasmin
Releases from endothelium
21
Q
Which factor has the shortest half-life?
A
Factor VII
22
Q
Which factors are liable - activity is lost in stored blood, but not lost in FFP?
A
Factors V and VIII
23
Q
Which factors is NOT synthesized in the liver? Where is is synthesized?
A
Factor VIII
Synthesized in endothelium
24
Q
Which factors are vitamin K-dependent?
A
II, VII, IX, X
Proteins C & S
25
How long does it take for Vitamin K to be effective?
6 hours
26
How long does it take for FFP to be effective? How long does it last?
Immediate
| Lasts 6 hours
27
Which factor is prothrombin?
Factor II
28
What is the normal half life of RBCs?
120 days
29
What is the normal half life of platelets?
7 days
30
What is the normal half life of PMNs?
1-2 days
31
Function and source of Prostacyclin (PGI2)
From endothelium
Decreases platelet aggregation, promotes vasodilation
Antagonistic to TXA2
32
Function and source of Thromboxane (TXA2)
From platelets
Increases platelet aggregation and vasoconstriction
Triggers release of calcium in platelets - exposes GpIIb/IIIa receptors and causes platelet-to-platelet binding
Platelet-to-collagen binding also occurs (GpIb receptors)
33
Contents of cryoprecipitate
Highest concentration of vWF-VIII
Used in von Willibrand's disease, Hemophillia A (Factor VIII deficiency)
Has high levels of fibrinogen
34
Contents of fresh frozen plasma
High levels of all coagulation factors, protein C, protein S, and AT-III
35
Function of DDAVP and conjugated estrogens
Causes release of VIII and vWF from endothelium
36
What does PT assess?
Measures II, V, VII, X, fibrinogen
| Best for liver synthetic function
37
What does PTT assess?
Measures all factors, except VII and XIII, fibrinogen
| Goal PTT 60-90sec
38
Goal Activated Clotting Time?
Routine anticoagulation ACT 150-200sec
| For pardiopulmonary bypass >460sec
39
INR level that is a relative CI for surgical proceedures
INR > 1.5
40
INR level that is a relative CI for central line placement, percutaneous needle biopsies or eye surgery
INR > 1.3
41
What is the most common cause of surgical bleeding?
Incomplete hemostasis
42
What is the most common congenital bleeding disorder?
Von Willebrand's disease
43
Inheritance patterns for vW disease
Type I/II - AD
| Type III - AR
44
Function of vWF
GpIb receptor on platelets to collagen
45
Coagulation test results in vWF disease
PT normal
PTT can be normal or abnormal
Prolonged bleeding time (ristocetin test)
46
Which form of vWF disease is the most common? Symptoms?
Type I
| Mild symptoms
47
Which form of vWF disease has the most severe bleeding?
Type III
48
What is the defect in Type I vWF disease? Treatment?
Reduced quantity of vWF
| Tx: recombinant VIII:vWF, DDAVP (increased release of vWF), cryoprecipitate
49
What is the defect in Type II vWF disease? Treatment?
Defect in vWF molecule itself, doesn't work well
| Tx: Recombinant VIII:vWF, cryoprecipitate
50
What is the defect in Type III vWF disease? Treatment?
Complete deficiency of vWF
| Ts: Recombinant VIII:vWF, cryoprecipitate
51
Why do you not give DDAVP in type II/III vWF disease?
Because they have crappy vWF (type II) or no vWF (type III), trying to increase the release of vWF will have no effect
52
Hemophilia A
VIII deficiency
Sex-linked recessive
Prolonged PTT, normal PT
Sx: joint bleeding, epistaxis, ICH, hematuria
53
What are goals of VIII in Hemophilia A for surgery?
Need levels 100% pre-op
| Keep >80% post-op for 10-14 days
54
How do you treat Hemophilia A with joint bleeding?
Do NOT aspirate
Ice, keep joint mobile with ROM exercises
Give factor VIII concentrate or cryoprecipitate
55
How do you treat Hemophilia A with epistaxis, ICH or hematuria?
Recombinant factor VIII or cryoprecipitate
56
Why do Hemophilia A patients not bleed at circumcision?
Factor VIII crosses the placenta
57
Hemophilia B
IX deficiency (Christmas disease)
Sex-linked recessive
Prolonged PTT, normal PT
Tx: Recombinant factor IX or FFP
58
Factor VII deficiency
Prolonged PT and normal PTT
Bleeding tendency
Tx: recombinant factor VII concentrate or FFP
59
Symptoms of platelet disorders
Bruising, epistaxis, mucosal bleeding, petechiae, purpura
60
Causes of acquired thrombocytopenia
H2 blockers
| Heparin
61
Glanzmann's thrombocytopenia
GpIIb/IIIa receptor deficiency on platelets - they cannot bind to each other
Fibrin normally links the receptors
Tx: Platelets
62
Bernard Soulier thrombocytopenia
GpIb receptor deficiency on platelets - they cannot bind to collagen
vWF normally links GpIb to collagen
Tx: Platelets
63
Uremia platelet dysfunction
Inhibits platelet function
| Tx: hemodialysis, DDAVP, platelets
64
Heparin-induced thrombocytopenia - Type I
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Self limited
Onset 2-3 days
Platelets ~100,000
Occurs in 10-20% patients
No antibodies
Tx: Monitor patient - do not need to stop Heparin
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65
Heparin-induced thrombocytopenia - Type II
```
Severe
Onset 5-10 days
Platelets 10-20,000
Antiplatelet antibodies (IgG PF4)
Can also cause platelet aggregation/thrombosis
White clot
Test: Platelet factor 4(PFE4) antibody; seretonin assay
Tx: Stop heparin, start argatroban
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66
What is argatroban?
Direct thrombin inhibitor
67
Disseminated intravascular coagulation (DIC)
Decreased platelets, low fibrinogen, high fibrin split products, high D-dimer
Prolonged PT/PTT
Initiated by tissue factor
Tx: treat underlying cause (i.e. sepsis)
68
Anticoagulation effect of ASA
Inhibits cyclooxygenase in platelets and decreases TXA2
Platelets lack DNA - cannot re-synthesize COX, need to wait for new platelets to form
Stop 7 days before surgery - prolonged bleeding time
Reversal - platelets
69
Anticoagulation effect of Clopidogrel (Plavix)
ADP receptor antagonist
Stop 7 days before surgery
Reversal - platelets
70
Anticoagulation effect of Coumadin
Inhibits Vitamin K decarboxylation of clotting factors
| Stop 7 days before surgery - bridge with Heparin
71
Operative platelet goals for surgery?
Pre-op >50,000
| Post-op >20,000
72
Thrombolytic problems in prostate surgery?
Cane release urokinase, activates plasminogen, which causes thrombolysis
Tx: g-aminocaproic acid (Amicar)
73
How do hypercoagulability disorders present?
Venous or arterial thrombosis
Emobli
DVT, PE, stroke
74
Factor V Leiden mutation
Most common congenital hypercoagulability disorder
Factor V is resistance to activated protein C
Tx: heparin, warfarin
75
Hyperhomocysteinemia
Hypercoagulability
Tx: Folic acid B12
(This is why they assess it in stroke patients)
76
Prothrombin gene defect G20210 A
Hypercoagulabiltiy
| Tx: Heparin, warfarin
77
Protein C or S deficiency
Hypercoagulability
| Tx: Heparin, warfarin
78
Antithrombin III deficiency
Hypercoagulability
Can develop after previous heparin exposure (development of antibodies)
NOTE: Heparin will no longer work for them
Tx: recombinant AT-III concentrate or FFP, followed by Heparin, then warfarin
79
Dysfibinogenemia, dysplasminogenemia
Hypercoagulability
| Tx: heparin, warfarin
80
Polycythemia vera
Defect in platelet function and extra RBCs, causes thrombosis
Keep Hct <48, platelets <400 before surgery
Tx: Phlebotomy, ASA
81
Anti-phospholipid antibody syndrome
Not always associated with SLE
Procoagulant
Prolonged PTT but hypercoagulable
Caused by antibodies to cardiolipin and lupus anticoagulant (phospholipids)
Dx: prolonged PTT (not corrected with FFP), positive Russell viper venom time, false-positive RPR test for syphillis
Tx: Heparin, warfarin
82
Causes of acquired hypercoagulability
```
Tobacco*
Malignancy
Inflammatory states
Inflammatory bowel disease
Infections
Oral contraceptives
Pregnancy
Rheumatoid arthritis
Post-op status
Myeloproliferative disorders
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83
Cardiopulmonary bypass effect on hypercoagulability
Activates factor XII (Hageman factor)
| Tx: Heparin to prevent
84
Warfarin-induced skin necrosis
Occurs when starting coumadin without bridging with heparin
Due to short half-life of protein C/S; procoagulant factors outlive them
Patients with relative protein C deficiency are especially susceptible
Tx: Heparin if occurs
85
Key elements in the development of venous thromboses
Virchow's triad
| Stasis, endothelial injury, hypercoagulability
86
Key elements in the development of arterial thromboses
Endothelial injury
87
Risk factors for DVT
Stasis, venous injury and hypercoagulability
88
Post-operative treatment of DVT
1st - Warfarin for 6 months
2nd - Warfarin for 1 year
3rd or significant PE - Warfarin for lifetime
89
Indications for IVC filters?
CI to anti-coagulation
Documented PE while on anti-coagulation
Free-floating IVC, ilio-femoral, or deep femoral DVT
Recent pulmonary embolectomy
90
Treatment of pulmonary embolism
Shock, despite massive inotropes/pressors --> go to OR
| Stable - Heparin (thrombolytics not shown to have an improvement in survival) or suction catherter-based intervention
91
Most common source of PE
Ilio-femoral region
92
g-Aminocaproic acid (Amicar)
Anti-fibrinolytic
Inhibits plasmin
Uses: DIC, persistent bleeding following cardiopulmonary bypass, thrombolytic overdose
93
Warfarin (Coumadin)
Prevents vitamin K-dependent decarboxylation of glutamic residues on vitamin K-dependent factors
94
Sequential compression devices
Improves venous return
| Induces fibrinolysis - release of tPA (tissue plasminogen activator) from endothelium
95
Heparin
Binds and activates anti-thrombin III (1000x more activity)
Reversed with protamine (binds heparin)
Half-life 60-90min
Cleared by reticuloendothelial system
Safe in pregnancy (does not cross placenta)
96
Side effects of long-term use of Heparin
Osteoporosis, alopecia
97
Protamine
Reverses Heparin by binding to it
Cross reacts with NPH insulin or previous protamine exposure
1% get protamine reaction
98
Symptoms of protamine reaction
Hypotension
Bradycardia
Decreased heart function
99
Low molecular weight heparin
| enoxaparin, fondaparinux
Binds and activates antithrombin II, but increases neutralization of just Xa, Thrombin
Not reversed with protamine
Lower risk of HIT compared to unfractionated heparin
100
Argatroban
Reversible direct thrombin inhibitor
Metabolized in lifer
Half-life is 50 min
Used in patients with HITT
101
Bivalirudin (angiomax)
Reversible direct thrombin inhibitor
Metabolized by protinase enzymes in the blood
Half-life of 25 minutes
102
Hirudin (Hirulog)
From leeches
Irreversible direct thrombin inhibitor
Most potent direct inhibitor of thrombin
High risk for beleding complications
103
Ancrod
Malayan pit viper venom
| Stimulates tPA release
104
Thrombolytic medications
Streptokinase (high antigenicity)
Urokinase
tPA
105
MOA thrombolytic medications
Activate plasminogen
Need for follow fibrinogen levels (<100 associated with increased risk/severity of bleeding
Tx for thrombolytic overdose: g-aminocaproic acid (Amicar)
106
Contraindications to thrombolytic use
```
Absolute:
- Active internal bleeding
- <3mo CVA/neurosurgery
- intracranial pathology
- recent GI bleed
Major:
- <10d surgery, organ biopsy, delivery
- Left heart thrombus
- Active peptic ulcer
- Recent major trauma
- Uncontrolled HTN
- Recent eye surgery
Minor:
- Minor surgery
- Rcent CPR
- Afib with mitral valve disease
- Bacterial endocarditis
- Hemostatic defects (renal or liver disease)
- Diabetic hemorrhagic retinopathy
- Pregnancy
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