Chapter 2: Hematology Flashcards
1
Q
Three initial responses to vascular injury
A
Vascular vasoconstriction, platelet adhesion, thrombin generation
2
Q
Intrinsic coagulation cascade
A
Exposed collagen + prekallikrein + HMW kiniogen + Factor 12 -> activate factor 11 -> activate 9, then 8 -> activate 10, then add 5 -> Convert prothrombin (factor II) to thrombin -> thrombin then converts fibrinogen to fibrin
3
Q
Extrinsic coagulation cascade
A
Tissue factor (injured cells) + factor 7 -> activate 10, then add 5 -> convert prothrombin to thrombin -> thrombin then converts fibrinogen to fibrin
4
Q
Prothrombin complex (for intrinsic and extrinsic pathways)
A
- 10, 5, Ca, platelet factor 3, prothrombin.
- Forms on platelets
- Catalyzes the formation of thrombin
5
Q
Convergence point for intrinsic and extrinsic pathway
A
Factor 10
6
Q
Inhibits factor 10
A
Tissue factor pathway inhibitor
7
Q
Links platelets together (binds GpIIb /IIIa molecules) to form platelet plug -> hemostasis
A
Fibrin
8
Q
Helps crosslink fibrin
A
XIII
9
Q
- Key to coagulation
- Converts fibrinogen to fibrin and fibrin split products
- Activates factors 5 and 13
- Activates platelets
A
Thrombin
10
Q
- Key to anticoagulation
- Binds and inhibits thrombin
- Inhibits factors 9, 10, and 11
- Heparin activates AT-III (up to 1000x normal activity)
A
Antithrombin III (AT-III)
11
Q
Vitamin-K dependent; degrades factors 5 and 8; degrades fibrinogen
A
Protein C
12
Q
Vitamin K dependent, protein C cofactor
A
Protein S
13
Q
Released from endothelium and converts plasminogen to plasmin
A
Tissue plasminogen activator
14
Q
Degrades factors 5 and 9, fibrinogen, and fibrin -> lost platelet plug
A
Plasmin
15
Q
Natural inhibitor of plasmin, released from endothelium
A
Alpha-2 antiplasmin
16
Q
Components of fibrinolysis
A
Tissue plasminogen activator, plasmin, alpha-2 antiplasmin
17
Q
Factor: shortest half life
A
Factor 7
18
Q
Factors: labile factors, activity lost in stored blood; activity not lost in FFP
A
Factors 5 and 8
19
Q
Factors: only factor not synthesized in the liver (synthesized in the endothelium)
A
Factor 8
20
Q
Factors: 2, 7, 9, 10, protein C and protein S
A
Vitamin-K dependent factors
21
Q
Takes 6 hours to have effect
A
Vitamin K
22
Q
Effect is immediate and lasts 6 hours
A
FFP
23
Q
Prothrombin
A
Factor II
24
Q
Half life: RBCs
A
120 days
25
Half-life: platelets
7 days
26
Half life: PMNs
1-2 days
27
- From endothelium
| - Decreases platelet aggregation and promotes vasodilation (antagonistic to TXA2)
Prostacyclin (PGI2)
28
- From platelets
- Increases platelet aggregation and promotes vasoconstriction
- Triggers release of calcium in platelets -> exposes Gp2b/3a receptor and causes platelet-to-platelet binding; platelet-to-collagen binding also occurs (Gp1b receptor)
Thromboxane (TXA2)
29
Contains highest concentration of vWF-VIII; used in von Willebrand's disease and hemophilia A (factor 8 deficiency), also has high levels of fibrinogen
Cryoprecipitate
30
Has high levels of all coagulation factors, protein C, protein S, and AT-III
FFP
31
Causes release of VIII and vWF from endothelium
DDAVP and conjugated estrogens
32
Measures 2, 5, 7, and 10; fibrinogen; best for liver synthetic function
PT
33
Measures most factors except 7 and 13 (thus does not pick up factor 7 deficiency); also measures fibrinogen
PTT
34
What do you want PTT for routine anticoagulation?
60 - 90 sec
35
ACT
activated clotting time
36
What do you want ACT (activated clotting time) for routine anticoagulation?
Want ACT 150 - 200 sec for routine anticoagulation, > 460 sec for cardiopulmonary bypass
37
INR: relative contraindication to performing routine procedures
INR > 1.5
38
INR: relative contraindication to central line placement, percutaneous needle biopsies, and eye surgery
INR > 1.3
39
Most common cause of surgical bleeding
Incomplete hemostasis
40
Most common congenital bleeding disorder
Von Willebrand's disease
41
- Reduced quantity of vWF
| Tx: recombinant VIII:vWF, DDAVP, cryoprecipitate
Type 1 von Willebrand's disease
42
- Defect in vWF molecule itself, vWF does not work well
| Tx: recombinant VIII:vWF, cryoprecipitate
Type 2 von Willebrand's disease
43
- Complete vWF deficiency (rare)
| Tx: recombinant VIII:vWF, cryoprecipitate; (DDAVP will not work)
Type 3 von Willebrand's disease
44
Lab findings of von Willebrand's disease
PT normal; PTT can be normal or abnormal. Prolonged bleeding time (ristocetin test).
45
- VIII deficiency
- Sex linked recessive
- Prolonged PTT, normal PT
Hemophilia A
46
Why may hemophilia A newborns not bleed at circumcision?
Factor 8 crosses the placenta
47
Treatment for hemophiliac joint bleeding
- Do not aspirate
- Ice, keep joint mobile with ROM exercises
- Factor 8 concentrate or cryoprecipitate
48
Treatment for hemophiliac epistaxis, intracerebral hemorrhage, or hematuria
Recombinant factor 8 or cryoprecipitate
49
Goals for hemophilia A pre and post op
Need levels 100% pre-op, keep at 80-100% for 10-14 days after surgery
50
- Sex-linked recessive
- Prolonged PTT and normal PT
Tx: Recombinant factor 9 or FFP
Hemophilia B - Factor 9 deficiency - Christmas Disease
51
Goals for Hemophilia B pre and post op
Need levels 100% pre-op, keep at 30-40% for 2-3 days after surgery
52
Prolonged PT.
Normal PTT.
Bleeding tendency.
Tx: Recombinant factor 7 concentrate or FFP
Factor 7 deficiency.
53
Causes bruising, epistaxis, mucosal bleeding, petechiae, purpura.
Platelet disorders
54
Platelet disorder: caused by H2 blockers, heparin
Acquired thrombocytopenia
55
Platelet disorder: Gp2b/3a receptor deficiency on platelets (cannot bind to each other).
- Fibrin normally links the Gp1b/3a receptors together.
Tx: ?
Glanzmann's thrombocytopenia
| Tx: Platelets
56
Gp1b receptor deficiency on platelets (cannot bind to collagen)
- vWF normally links Gp1b collagen.
Tx: ?
Bernard Soulier
| Tx: Platelets
57
How does uremia affect platelets?
Uremia inhibits platelet function.
| Tx: hemodialysis (1st), DDAVP, platelets
58
Thrombocytopenia due to antiplatlet antibodies (IgG PF4 antibody) results in platelet destruction.
- Can also cause platelet aggregation and thrombosis.
- Forms a white clot.
- Can occur with low doses of heparin.
Heparin-induced thrombocytopenia (HIT)
59
Treatment for heparin-induced thrombocytopenia (HIT)
Stop heparin, start argatroban (direct thrombin inhibitor) to anticoagulate
60
- Decreased platelets, low fibrinogen, high fibrin split products, and high d-dimer
- Prolonged PT and prolonged PTT
- Often initiated by tissue factor
Tx: need to treat the underlying cause
Disseminated intravascular coagulation (DIC)
61
Inhibits cyclooxygenase in platelets and decreases TXA2
Aspirin
62
Aspirin pre-op recommendations
Stop 7 days before surgery; patients will have prolonged bleeding time
63
Plavix pre-op recommendations
Stop 7 days before surgery; ADP receptor antagonist.
| Tx: platelets
64
Coumadin pre-op recommendations
Stop 7 days before surgery; consider starting heparin while Coumadin wears off
65
Platelet pre-op recommendations
Want them > 50,000 before surgery, > 20,000 after surgery
66
Surgery: can release urokinase, activates plasminogen -> thrombolysis.
Tx: e-aminocapropic acid (Amicar)
Prostate surgery
67
Best way to predict bleeding risk
H & P
68
Does normal circumcision rule out bleeding disorders?
No, they can still have clotting factors from the mother
69
Picks up 99% of patients with bleeding disorder
Abnormal bleeding with tooth extraction or tonsillectomy
70
Common with vWF deficiency and platelet disorders
Epistaxis
71
Common with bleeding disorders
Menorrhagia
72
Present as venous or arterial thrombosis / emboli (e.g., DVT, PE, stroke)
Hypercoaguability Disorders
73
- 30% of spontaneous venous thromboses
- MC congenital hypercoaguability disorder.
- Causes resistance to activated protein C; the defect is on factor 5.
Tx: heparin, warfarin
Factor V Leiden mutation
74
Treatment for hyperhomocysteinemia
Folic Acid.
| B12
75
Tx: prothrombin gene defect G20210A
Heparin, warfarin
76
Tx: protein C or S deficiency
Heparin, warfarin
77
- Heparin does not work in these patients
- Can develop after previous heparin exposure
Tx: recombinant AT-III concentrate or FFP (highest concentration of AT-III) followed by heparin, then warfarin
Antithrombin H1 deficiency
78
Tx: dysfibrinogenemia, dysplasminogenemia
Heparin, warfarin
79
- Defect in platelet function; can get thrombosis
| - Keep Hct
Polycythemia vera
80
Causes of polycythemia vera
Primary: JAK2 mutation
Secondary: low oxygen tension (e.g.: living at high altitudes, smoking, carbon monoxide exposure)
81
- Procoagulant (get prolonged PTT, but are hyper coagulable)
| - Caused by antibodies to cardiolipin and lupus anticoagulant (phospholipids)
Anti-phospholipid antibody syndrome)
82
```
Prolonged PTT (not corrected with FFP).
Positive Russell viper venom time, false-positive RPR test for syphillis.
Tx: heparin, warfarin
```
Anti-phospholipid antibody syndrome
83
MC factor causing acquired hypercoagulability
Tobacco
84
Causes of acquired hyper coagulability
Tobacco. Malignancy. Inflammatory states. IBD. Infections. OCPs. Pregnancy. Rheumatoid arthritis. Post-op patients. Myeloproliferative disorders.
85
How does cardiopulmonary bypass result in hyper coagulability?
Activates Factor 12 (Hageman factor). Tx: heparin to prevent.
86
Why does warfarin-induced skin necrosis occur?
Short half-life of proteins C and S, which are first to decrease in levels compared with the pro coagulation factors; results in relative hyperthrombotic state.
- Occurs when placed on coumadin without being heparinized first.
87
Who is at risk for warfarin-induced skin necrosis?
Patients with relative protein C deficiency are especially susceptible.
88
Key elements in the development of venous thromboses
Virchow's triad (stasis, endothelial injury, hyper coagulability)
89
Key element in the development of arterial thrombosis
Endothelial injury
90
Risk factors for DVT
Stasis. Venous injury. Hypercoaguability.
91
Post-op DVT Tx:
1st:
2nd:
3rd:
1st: Warfarin for 6 mo.
2nd: Warfarin for 1 yr.
3rd or significant PE: Warfarin for life.
92
Indications for Greenfield filter
- Contraindications to anticoagulation
- Documented PE while on anticoagulation
- Free-floating IVC, ilio-femoral, or deep femoral DVT
- Recent pulmonary embolectomy
93
When are temporary IVC filters indicated?
Can be inserted in patients at high risk for DVT (e.g. head injury patients on prolonged bed rest)
94
Most common origin of PE
Ilio-femoral region
95
Tx pulmonary embolism
Shock (despite massive interpose, pressors) -> OR.
| No shock -> Heparin (thrombolytics have not shown an improvement in survival) or suction catheter-based intervention.
96
- Inhibits fibrinolysis by inhibiting plasmin
| - Used in DIC, persistent bleeding following cardiopulmonary bypass, thrombolytic overdoses
Aminocaproic acid (Amicar)
97
Prevents vitamin-K dependent decarboxylation of glutamic residues on vitamin K dependent factors
Warfarin
98
Improve venous return but also induce fibrinolysis with compression (release of tPA (tissue plasminogen activator) from endothelium.
SCDs.
99
- Binds and activates anti-thrombin III
- Reverse with protamine
- Cleared by the reticuloendotehlial system
- Does not cross placental barrier
Heparin
100
Risks of long-term heparin
Osteoporsis. Alopecia.
101
Half-life / goal PTT of heparin
Half-life: 60-90 minutes.
| Goal PTT: 60-90 seconds
102
Cross reacts with NPH insulin or previous protamine exposure; 1% get protamine reaction (hypotension, bradycardia, and decreased heart function).
Protamine
103
- Lower risk of HIT compared to unfractionated heparin
- Binds and activates antithrombin III but increases neutralization of just 10a and thrombin
- Not reversed with protamine
Low molecular weight heparin (ex, enoxaparin, fondaparinux)
104
- Reversible direct thrombin inhibitor
- Metabolized in the liver
- Half life: 50 minutes
- Often used in patients with HITT
Argatroban
105
- Reversible direct thrombin inhibitor
- Metabolized by proteinase enzymes in the blood
- Half life: 25 minutes
Bivalirudin (Angiomax)
106
- Irreversible direct thrombin inhibitor
- Most potent direct inhibitor or thrombin
- High risk for bleeding complications
Hirudin (Hirulog; form leeches)
107
Malayan pit viper venom; stimulates tPA release
Ancrod
108
- Activate plasminogen
| - Need to follow fibrinogen levels: fibrinogen
Thrombolytics: Streptokinase, urokinase, tPA
109
Treatment for thrombolytic overdose
e-aminocaproic acid (Amicar)
110
Absolute contraindications to TPA
Active internal bleeding. Recent CVA or neurosurgery (
111
Major contraindications to TPA.
Recent (
112
Minor contraindications to TPA.
Minor surgery. Recent CPR. A fib with MV disease. Bacterial endocarditis. Hemostatic defects (i.e. renal or liver disease). Diabetic hemorrhage retinopathy. Pregnancy.
