Unit 9 - Coagulation Pt 2 Flashcards
examples of ADP receptor inhibitors
Clopidogrel
Ticlodipine
Prasugrel
Ticagrelor
how long should ADP receptor inhibitors be stopped prior to surgery
Clopidogrel: 5-7 days
Ticlodipine: 14 days
Prasugrel: 7-10 days
Ticagrelor: 5-7 days
how long should GpIIb/IIIa receptor antagonists be stopped before surgery
Abciximab: 3 days
Eptifibatide: 1 day
Tirofiban: 1 day
how long should non-specific COX inhibitors be stopped before surgery
Aspirin: 7 days
NSAIDs: 1-2 days
how long should COX2 inhibitors be stopped prior to surgery
None
(rofecoxib, celecoxib)
when should unfractionated heparin be stopped prior to surgery
6 hours
when should LMWH be stopped prior to surgery
1-2 days
(enoxaparin, daltaparin, tinzaparin)
when should thrombin inhibitors be stopped prior to surgery
Argatroban: 4-6 hours
Bivalirudin: 2-3 hours
when should Fondaparinux be stopped prior to surgery
4 days
when should warfarin be stopped prior to surgery
2-4 days
MOA of Fondaparinux
factor 10 inhibitor
examples of plasminogen activators
tPA
streptokinase
when to stop tPA before surgery
1 hr
when to stop streptokinase before surgery
3 hrs
how do non-specific COX inhibitors prevent platelet aggregation
by blocking COX-1
stops conversion of arachidonic acid to prostaglandins and ultimately thromboxane A2
MOA of Amicar
plasminogen activator inhibitor
MOA of aprotinin
inhibits plasma, kallikrein, thrombin, and protein C
MOA of TXA
plasminogen activator inhibitor
MOA of DDAVP
Stimulates factor 8 and vWF factor release
purpose of antifibrinolytics in surgery
help preserve integrity of fibrin clot during surgery
synthetic derivative of the amino acid lysine
TXA
MOA of TXA
binds to lysine binding site on plasminogen & prevents conversion to plasmin
affinity of TXA at modest doses
- strong affinity for 5 lysine binding sites on plasminogen
- competitively prevents activation of plasminogen to plasmin
affinity of TXA at high doses
noncompetitive plasmin inhibitor
Most common inherited disorder of platelet function
von willebrand disease
plt count in von willebrand disease
normal - it’s a qualitative plt disorder
how is von willebrand factor synthesized
by vascular endothelium & megakaryocytes
2 key functions of von willebrand factor
- Anchors platelet to vessel wall at site of vascular injury (platelet adhesion)
- Carries inactivated factor 8 in the plasma
type 1 von willebrand disease
mild-moderate reduction in amount of vWF produced
type 2 von willebrand disease
the vWF that is produced doesn’t work well
type 3 von willebrand disease
severe reduction in the amount of vWF produced
lab findings with von willebrand disease
- PTT and bleeding time ↑
- No change in PT/INR, plt count, or fibrinogen
synthetic analogue of ADH
DDAVP
in what type of von willebrand disease can DDAVP be used
type 1, type 2
Patients with type 3 do not respond because they don’t produce cVW
MOA of DDAVP
stimulates endogenous vWF release and increases factor 8 activity
dose of DDAVP
0.3 mcg/kg IV
how long does a dose of DDAVP improve bleeding time
12-24 hours
contents of cryo
factors 8, 13, fibrinogen, and vWF
what can be used to treat any type of von willebrand factor disease
cryo
FFP
1st line for type 3 vWF disease
purified 8-vWF concentrate
treatment of vWF that reduces risk of transfusion-related infection
Purified 8-vWF concentrate:
disease of factor 8 deficiency
hemophilia A
pt population more likely to be affected by hemophilia A
males
X-linked
pt population more likely to be affected by hemophilia A
males
X-linked
factor 8 activity assoc with spontaneous bleeding
< 1%
(severe disease)
factor 8 activity assoc with spontaneous bleeding
< 1%
(severe disease)
factor 8 activity assoc with increased surgical bleeding
activity 6-30% of normal
lab values in hemophilia A
- PTT ↑
- No change in PT/INR, Plt count, bleeding time, or fibrinogen
SE of giving DDAVP rapidly
hypotension
r/t vasodilation
disease of factor 9 deficiency
hemophilia B
severe vs mild hemophilia B disease
- Severe disease (factor 8 activity < 1%) assoc. with spontaneous bleeding
- Mild disease (factor 8 activity 6-30% normal) doesn’t cause spontaneous bleeding but is assoc with increased surgical bleeding
half life of factor 8 concentrate
8-12 hours
half life of factor 9 concentrate
18-24 hours
risk of giving factor 9 concentrate
thromboembolic complications
when might recombinant factor 7 be needed in a hemophilia patient
when they develop inhibitors that prevent exogenous factors from achieving therapeutic goals
MOA of recombinant factor 7
Exact MOA unclear
both classic and contemporary cell-based theories of coagulation suggest that factor 7 contributes to thrombin generation by facilitating tissue factor at the site of vascular injury and on the surface of the platelet
risks of recombinant factor 7
arterial & venous thrombosis
MI, embolic stroke, DVT, PE
3 Conditions Assoc. with High Risk DIC
- Sepsis (highest risk = gram negative bacilli)
- OB complications (highest risk = preeclampsia, placental abruption, and AFE)
- Malignancy (highest risk = adenocarcinoma, leukemia, lymphoma)
dose of recombinant factor 7 for hemophilia pts
90-120 mcg/kg
MOA of recombinant factor 7
exact MOA unclear
classic and contemporary cell-based theories of coagulation suggest that factor 7 contributes to thrombin generation by facilitating tissue factor at the site of vascular injury and on the surface of the platelet
adverse effects assoc with recombinant factor 7
Can increase the risk of arterial thrombosis (Ml and embolic stroke) as well as venous thrombosis (DVT or pulmonary embolism)
what is DIC
disordered clotting & fibrinolysis that leads to simultaneous occurrence of hemorrhage and systemic thrombosis
lab values assoc with DIC
↑ PT/PTT, D-dimer
↓ platelets, fibrinogen
how are procoagulants kept at bay in normal physiology
antithrombin and tissue factor pathway inhibitor (TFPI)
how does DIC lead to organ failure
systemic activation of coagulation = increased fibrin formation = microvascular thrombosis = organ failure
what leads to hemorrhage in DIC
Widespread fibrin deposition consumes the body’s supply of fibrinogen, coagulation factors, and platelets = hemorrhage
s/s DIC
- ecchymosis
- petechiae
- mucosal bleeding
- bleeding at IV puncture sites
- prolonged PT and PTT
- increased D-dimer and fibrin split products
- decreased fibrinogen and antithrombin
3 conditions assoc with high risk for DIC
- Sepsis
- OB complications
- Malignancy
infections at highest risk for DIC
gram negative bacilli
OB complications at highest risk for DIC
preeclampsia
placental abruption
AFE
malignancies at highest risk for DIC
adenocarcinoma
leukemia
lymphoma
treating DIC
- Definitive treatment: reverse cause
- Treat hypovolemia with IV fluids
- Replace consumed blood components with FFP, platelets, and cryo
- IV heparin or LMWH for severe microvascualr thrombosis
factors inactivated by antithrombin
factors 9, 10, 11, & 12
ultimately leads to thrombin (factor 2a) inhibition
factors inactivated by antithrombin
factors 9, 10, 11, & 12
ultimately leads to thrombin (factor 2a) inhibition
causes of antithrombin deficiency
- congenital
- acquired from repeated heparin admin (consumes body’s supply of AT)
treatment for antithrombin deficiency
- AT concentrate
- FFP
Patients with antithrombin deficiency are unresponsive to heparin
treatment for antithrombin deficiency
- AT concentrate
- FFP
Patients with antithrombin deficiency are unresponsive to heparin
treatment for antithrombin deficiency
- AT concentrate
- FFP
Patients with antithrombin deficiency are unresponsive to heparin
what causes Heparin-Induced Thrombocytopenia
- Occurs when the body mounts an immune response against heparin after it binds to PF4
- IgG antibodies activate platelets
- results in uncontrolled clot formation
patho of HIT type 1
- Heparin-induced platelet aggregation
- Occurs after large heparin dose
onset of HIT type 1
1-4 days after heparin admin
plt count in HIT type 1 vs type 2
type 1 = < 100,000
type 2 = < 50,000
treatment of HIT type 1
resolves spontaneously even if heparin is continued
patho of HIT type 2
- antiplatelet IgG antibodies attack factor 4 immune complex = plt aggregation
- occurs after any heparin dose
onset of HIT type 2
5-14 days after heparin admin
morbidity of HIT type 1 vs type 2
type 1 = minimal morbidity
type 2 = high risk of amputation and death
treatment of HIT type 2
- d/c heparin
- anticoagulate with direct thrombin inhibitor (Bivalirudin, Hirudin, Argatroban)
risks of protein C or S deficiency
can produce hypercoagulable state and ↑ risk thrombus
Creates a feedback mechanism that prevents unnecessary clot formation
risks of protein C or S deficiency
can produce hypercoagulable state and ↑ risk thrombus
Creates a feedback mechanism that prevents unnecessary clot formation
treatment of protein C and S deficiency
- Start thromboembolism treatment with heparin - pt will switch to Warfarin
- May require life-long anticoagulation with warfarin
factor 5 leiden mutation
Causes resistance to anticoagulant effect of protein C
treatment of Factor 5 Leiden Mutation
- anticoagulation only for pts with thromboembolism
- Lifelong anticoagulation is unwarranted unless pt has recurrent thrombotic events
Patho of sickle cell anemia
- Inherited disorder that affects erythrocytes
- Amino acid substitution (valine is substituted for glutamic acid) on the beta globulin chain alters BC geometry
- alters RBC function
how does sickle cell anemia alter RBC function
- deoxygenation of HgbS leads to sickling
- if severe, sickling causes RBCs to clump together and cause mechanical obstruction
- sickled cells more prone to hemolysis and removal by spleen
lifespan of sickled cells vs normal blood cells
sickled = 12-17 days
normal = 120 days
anesthetic management of sickle cell anemia
focuses on avoiding triggers that promote sickling
avoid: pain, hypothermia, hypoxemia, acidosis, dehydration
most common manifestation of sickle cell disease
Vaso-Occlusive Crisis
med that reduces incidence and severity of sickle cell crisis
hydroxyurea
causes of acute chest syndrome
thrombosis
embolism
infection
diagnosis of acute chest syndrome
requires new lung infiltrates on CXR and at least one: chest pain, cough, dyspnea, wheezing
potential causes of acute chest syndrome
hypoventilation, narcotics, splinting, pain
what causes sequestration crisis in sickle cell
Occurs when spleen removes RBCs from circulation at a faster rate than the bone marrow produces them
consequences of sequestration crisis in sickle cell
anemia
hemodynamic instability
why are pts with sickle cell at risk for aplastic crisis
RBCs with HgbS have a short half life
even a small amount of bone marrow suppression can cause anemia
common cause of aplastic crisis in sickle cell pts
parvovirus B19
sickle cell patients at highest risk for pneumococcal disease
children
pneumococcal disease prophylaxis in sickle cell pts
pneumococcal vaccination and daily penicillin up to 5 yrs of age
diagnosis seen in 50% of sickle cell patients
asthma
complication in 10% of sickle cell patients
pulmonary HTN
