Coagulation and Transfusion Flashcards
1
Q
Regulators of Hemostasis
A
- vascular extracelular matrix and endothelial reactivity
- platelets
- coagulation proteins
- inhibitors of coagulation
- fibrinolysis
2
Q
Clot Formation
A
- coagulation cascade!*
- tissue factor release
- factor VIIa generation
- plt activation
- cellular and humoral activation pathways
3
Q
Clot Prevention
A
- PGI2 (prostacyclin) tPA, heparin sulfate, antithrombin III, protein C, endothelium derived relaxing factor (EDRF)
- these are expressed to inhibit plt activation, fibrin formation, and provide for vascular patency
4
Q
Platelet Activation
A
- receptors on platelets bind to damaged blood vessel wall
- form bridges w VWF to initiate platelet adhesion
- once adhered, platelet surface receptor changes and causes platelet aggregation
- upon aggregation, they expose surface factors that ativate coagulation cascade forming a hemostatic plug
- issues: abnormalities in platelet number or function
5
Q
How does aspirin work?
A
- inhibits the synthesis of platelet thromboxaneA2 (factor that causes platelets to aggregate) by irreversible acetylation (inactivation) of cyclooxygenase
6
Q
How does ibuprofen work?
A
- block both prostaglandin and thromboxane formation by reversibly inhibiting COX activity
7
Q
Aspirin, Ibuprofen MOA (visual)
A
8
Q
Coagulation Cascade Visual
A
9
Q
Inherited (Genetic) Hypercoagulability Risk Factors
A
- inherited antithrombin deficieny
- prothrombin G20210A mutation
- Factor V Leiden
- Dysfibrinogememia
10
Q
Prothrombin G20210A Mutation
A
- these pts have higher prothrombin levels (precursor for thrombin)
- 2% population
- heterozygous = 3x risk of thrombus
- homozygous = very rare
11
Q
Factor V Leiden
A
- gene mutation so that procoagulant factor V is not inactivated by protein C
- 5% presence in population
- heterozygous = 3x risk of thrombus
- homozygous = 18x risk of thrombus
12
Q
Dysfibrinogememia
A
- high levels or structurally defective fibrinogen, variants are either more or less susceptible to clot formation
- high levels = 2x increase arterial thrombus
- fibrinogen >450mg/dL = poor outcome for CVA pts
13
Q
Protein C Deficiency
A
- genetic anticoagulant issue
- circulating anticoagulant
- vitamin K dependent proteins that inhibit procoagulant factors V and VIII
- decrease = 5x increased risk of VTE
14
Q
Antithrombin III Deficiency
A
- protease inhibitor that binds to thrombin
- heparin facilitates this
- heterozygous deficiency in 50% of pop
- acquired ATIII deficiency after Heparin or DIC
- homozygous ATIII deficiency is fatal
15
Q
Lipoprotein(a)
A
- inhibits fibrinolysis - similar to plasminogen
- increased levels associated w VTE and CAD
16
Q
tPA abnormalities
A
- 2-3x increased risk of VTE
17
Q
Exogenous Causes of HYPERcoagulability (visual)
A
18
Q
Coagulopathic States Associated w Increased Risk of Bleeding (just because of genetics or comorbidities)
A
- hemophilia
- inherited plt disorders
- von Willebrand dx
- liver failure
- renal failure (uremia)
- DIC
- dilutional coagulopathy
- anticoagulant/antiplatelet therapy
- other coagulation disorders (factor deficiencies)
19
Q
Risk Factors for Bleeding in Surgical Patients (iatrogenic reasons)
A
- advanced age
- small body size, preop anemia (low RBC volume)
- antiplatelet/antithrombotic drugs
- preexisting coagulopathy
- prolonged operation (long bypass time)
- emergency operation (no preop labs)
20
Q
Risk Factors for Bleeding in Surgical Patients (comorbidities)
A
- HF
- COPD
- HTN
- PVD
- liver/renal failure
21
Q
Antiphospholipid Antibodies
A
- disease state associated w hypercoagulability
- ie: lupus anticoagulants, anticardiolipin antibody, anti-B2-glycoprotein-1 antibody
- thought to be 2/2: decreased thrombomodulin expression, increased TF expression, impaired protein C anticoagulation pathway
- at risk for recurrent thrombotic events
- usually require anticoagulation (coumadin)
22
Q
Liver or Renal Failure
A
- decreased production of anticoagulant factors (ATIII, Protein C and S, plasminogen)
- increases platelet activation
23
Q
Blood Stasis
A
- pre-op or post-op immobility
- low CO, afib
- Virchow’s Triad
- metabolic syndrome
- cancer
- age
24
Q
Virchow’s Triad
A
- low flow state
- endothelial damage
- dysfunctional blood components
25
Q
Metabolic Syndrome
A
- abdominal obesity
- HTN
- increased glucose
- increased cholesterol
- associated w endothelial dysfunction and increased platelet aggregation
26
Q
HIT
A
- 0.5-5% incidence in pts tx w heparin in past 5 days
- unexplained drop in platelets by 50% (<150,000)
- 7% to 50% of heparin-treated patients generate heparin-PF4 antibodies, especially following cardiovascular surgery (also ortho and neuro)
- antibody T1/2 90 days
- increased risk of thrombosis
- if HIT suspected, start treatment immediately, don’t wait for labs!*
27
Q
Heparin/HIT MOA
A
- heparin binds to platelet factor 4 (PF4)
- antibodies recognize the complex, release microparticles that stimulate thrombin aggregation and thrombin are formed
- excessive thrombus leads to endothelial damage and TF production and more prothrombosis
- increased risk of DVT, VTE, PE, MI, CVA, arterial occlusion
- -* thrombus risk 40-75%
28
Q
High Risk HIT Pops
A
- females
- malignancy
- high PF4 titer
- increased risk of DVT, VTE, PE, MI, CVA, arterial occlusion
29
Q
HIT Diagnosis
A
- platelet drop by 50% (<150,000)
- new thrombus within 5-14 days of heparin tx
- R/O sepsis, IABP destruction of platelets, drug induced thrombocytopenia
30
Q
Rapid Onset HIT S/S
A
- platelet drop within minutes to hours 2/2 previous exposure to heparin within past 3 months
- hypotension, pulmonary hypertension, and/or tachycardia, occur 2 to 30 minutes after intravenous heparin bolus
- observed intraoperatively and can present as anaphylaxis, usually accompanied by acute thrombocytopenia
- can also occur days to weeks after stopping heparin (“delayed onset HIT”), and should be considered if a recently hospitalized, heparin-treated patient presents with thrombosis
31
Q
HIT Treatment
A
- STOP heparin and eliminate all sources (flushes)
- initiate anticoagulation w direct thrombin inhibitor (ie: lepirudin, argatroban, desirudin, or bivalirudin)
32
Q
Direct Thrombin Inhibitor
A
- argatoban
- lepirudin
- desirudin
- bivalirudin
33
Q
Risk Factors for Bleeding
A
- advanced age
- low preop RBC volume
- antiplatelet or antithrombotic medications preop
- redo or emergency surgery
- comorbidities on previous flashcards
34
Q
Thrombocytopenia
A
- platelet <50,000
- high risk for bleeding!
35
Q
Hemophilia
A
- recessive X linked disorder
- A: factor VIII deficiency
- 1:5k - 10k males
- recombinant Factor VIII
- B: factor IX deficiency
- 1:20k - 34k makes
- recombinant Factor IX
36
Q
von Willebrand Factor
A
- glycoprotein that allows platelet adhesion and aggregation under arterial flow
- a carrier for coagulation factor VIII
37
Q
von Willebrand Disease
A
- partial quantitative deficiency (Type I) may respond to DDAVP
- qualitative deficiency (Type II) has 4 variants
- total deficiency (Type III)
- can be acquired
38
Q
Treatment for von Willebrand Disease
A
- measure vWF activity
- administer factor VIII/vWF concentrate, IGG, cryoprecipitate, plasma pheresis
- short t1/2 of vWF may require redosing
39
Q
DIC
A
- thrombocytopenia (platelets <100k in 50-60% and <50k in 10-15%)
- >4 dats ICU or 50% decrease in ICU = 4-6x mortality
- coagulopathy: prolonged PT or aPTT, bleeding
- fibrinogen consumption: low levels indicate severe DIC, fibrinogen and D-dimer are innacurate
- reduced antithrombin and Protein C levels
40
Q
PT
A
- prothrombin time
- normal 11-13 seconds
- addresses the extrinsic and common coagulation pathways
- primarily used to monitor long-term use of anticoagulant therapy through the INR
41
Q
aPTT
A
- activated partial thromboplastin time
- normal is 25-38 seconds
- adresses the intrinsic and common coagulation pathways
- used to monitor heparin therapy, screen for hemophilia A and B, detect clotting inhibitors
42
Q
Fibrinogen
A
- normal is 2-4 g/L
- decreased levels indicate DIC, liver disease or dilutional coagulopathy
- fibrinogen (Factor I) is a glycoprotein synthesized in the liver and cleaved by thrombin to produce fibrin monomer, the basis of clot formation
43
Q
Platelet Aggregation Studies
A
- done if pt has normal platelets but is not clotting
- used to classify qualitative platelet abnormalities in adhesion, release, or aggregation
- normal range is >65%
44
Q
TEG (visual)
A
45
Q
Components
A
46
Q
PRBCs remain in circulation for how long?
A
- 120 days
- old or dysfunctional cells removed by the spleen
- shelf life up to 42 days
- old = increased 2,3 DPG (10% at 42 days)
47
Q
Synthesis of PRBC
A
- synthesis dependent upon erythropoietin and iron
- erythropoietin increases w anemia or hypoxia
48
Q
CADET face Right
A
- increases HbB affinity for 02
CO2
Acid
DPG
Exercise
Temperature
49
Q
Universal Donor
A
Type O
50
Q
Universal Acceptor
A
Type AB
51
Q
Rh Compatibility
A
Rh- gets Rh-
Rh+ can get either Rh- or Rh+
always give Rh- to Rh- women of childbearing age
52
Q
Acute Hemolytic Reaction
A
- ABO incompatibility
- occurs in 1:30k
- s/s = agitation, N/V, dyspnea, fever, flushing, hypotension, tachycardia, HgBnuria
- renal failure from ATN or DIC is worst case scenario
- fever, nonhemolytic rxn occurs 0.1-1% of transfusions
53
Q
Platelets
A
T1/2 7-10 days
- 150 - 300,000
- transfused in 4- or 8-packs (can expect plt count to increase 15-30)
- total count and function of plts important
- avoid elective surgery w platelet count <50k*
- see if pt was taking ASA or ibuprofen*
54
Q
FFP
A
- contains procoagulants, anticoagulants, albumin, and immunoglobulins from plasma that aren’t in PRBCs
- indicated for the treatment of complex coagulopathies in which multiple coagulation factors and inhibitors are depleted
- must be kept cold between 1C (34F) and 6C (42F)
- can be kept thawed 5 days at these temps
- ABO compatibility but not Rh
- AB is universal donor for FFP
- INR >1.5 times normal to be effective tx
55
Q
Adverse Side Effects of FFP
A
- 1-3% risk of allergic reaction
- Hypocalcemia w high volume FFP (tx w calcium chloride 500-1000 mg or 1/2 to 1 amp)
- TRALI occurs 1:2k to 1:7.5k transfusions (but incidence is down since FFP from males)
56
Q
Albumin
A
- colloid osmotic pressure of 5% albumin similar to that of plasma
- volume expander
- no effect on hepatic or renal function
- no effect on coagulation parameters
57
Q
Hydroxyethyl Starches
A
- synthetic colloids
- effective volume expanders
- high dose (>20 ml/kg) may affect bleeding
58
Q
Cryoprecipitate
A
- 150-250mg fibrinogen per unit
- each bag contains 5-10 u of cryoppt
- each unit increases plasma fibrinogen 100mg/dL/5kg body weight
- proper level of fibrinogen not known (>150-200mg/dL?)
59
Q
Recombinant Factor VIIa (NOVOseven)
A
- indicated for hemophilia w F8, F9 antibodies and F7 deficiency
- dose 90-100 ug/kg (up to 400ug have been given without thrombosis)
- used for trauma and surgical bleeding (but not supported by literature)
- initial dose 20-70 ug/kg
- decreases bleeding and re-ops but increases CVA and thrombosis
