Coagulation Flashcards
Mechanisms that limit size of the clot
- vasodilation: washing out ADP and TxA2
- anti-thrombin: inactivating thrombin
- tissue factor pathway inhibitor: neutralizing TF
- Protein C & S: inhibit factors III, V, VIII
Protein C & S inhibit which factors?
III, V, VIII
Mechanisms that breakdown the clot (fibrinolysis)
- plasminogen
- plasmin
Plasminogen
- proenzyme
- synthesized in the liver
- incorporated into clot dormant until activated
Plasmin
- proteolytic enzyme
- degrades fibrin into fibrin degradation products
Plasmin activation involves what substances?
- tPA
- Urokinase
When is tPA released?
- released by injured tissue over a period of days (major mechanism)
Where is Urokinase produced?
- produced by the kidneys and released into circulation (minor mechanism)
What are the mechanisms that turn off Fibrinolysis
- tPA inhibitor
- alpha-2 antiplasmin
What is the action of tPA?
inhibits conversion of plasminogen to plasmin
What is the action of alpha-2 antiplasmin?
inhibits the action of plasmin on fibrin
Contemporary Cell-Based coagulation cascade consists of what 3 phases?
- initiation: TF/VIIa rxn activates factor X (common pathway) - makes small amt of thrombin (IIa)
- amplification: activates plts, V, and XI
- propagation: produces enough thrombin to activate fibrin
Activated Partial Thromboplastin Time (aPTT)
- assesses intrinsic and common pathways
- 25-32 sec
- measures time it takes to form a clot using phospholipid, calcium, & an activator
International Normalized Ration (PT/INR)
- assesses extrinsic and common pathways
- 12-14
- measures time it takes to form clot w/ TF and Ca+
INR
- Normal: 1
- target for warfarin: 2-3 x control
Plt Count
- monitors # of plts (not how well they fxn)
- 150,000 - 300,000
- < 50,000 inc. surgical bleed risk
- < 20,000 inc. spontaneous bleed risk
Bleeding Time
- monitors plt fxn
- 2-10 min
- ASA and NSAIDs prolong bleeding time
- not commonly used in practice
Activated Clotting Time (ACT)
- guides heparin dosing
- 90-120
- ACT >400 sec before CPB
- measured before heparin, 3 min. after its given, & every 30 min thereater
TEG - R Time
- time to begin forming clot
- problem: coagulation factors
- tx: FFP
TEG - K Time
- time until clot has achieved fixed strength
- problem: fibrinogen
- tx: cryo
TEG - Alpha Angle
- speed of fibrin
- problem: fibrinogen
- tx: cryo
TEG - Max Amplitude (MA)
- highest vertical amplitude on TEG
- measures clot strength
- problem: plts
t- tx: plts +/- DDAVP
Amplitude at min. after max aimplitude (A60)
- height of vertical amplitude 60 min. after max amplitude
- problem: excess fibrinolysis
- tx: Tranexamic, aminocaproic acid
Endogenous heparin is produced by…
- basophils
- mast cells
- liver
Exogenous heparin is produced by…
- bovine and porcine GI mucosa
Heparin MOA
- inhibits intrinsic and final common pathways
- Antithrombin III: natural anticoagulant in the plasma
- Heparin binds to antithrombin and accelerates it 1000 fold
- AT complex neutralizes thrombin and factors X, XII, XI, & IX
- inhibits plt fxn
- failed heparin should consider AT deficiency
Heparin Pharmacokinetics
- metabolized by heparinase
- elimination: degradation by macrophages & renal excretion
- doesn’t cross the placenta & is safe in pregnancy
aPTT therapeutic normal
- 1.5-2.5x normal (25-35 sec)
ACT is affected by…
- hypothermia
- thrombocytopenia
- deficiency of fibrinogen, factor VII, or factor XII
Heparin side effects
- hemorrhage
- Heparin Induced Thrombocytopenia (HIT)
- allergic rxn
- Hypotension
- dec. ATIII Concentration
Heparin contraindications
- neurological procedures
- Heparin induced thrombocytopenia
- regional anesthesia
Protamine
- derived from salmon sperm
- 1mg per every 100 u
Another name for vitamin k
Phytonadione
IV administration of vitamin k is associated with?
- life threatening anaphylaxis
- if given IV, rate should not exceed 1 mg/min
Cryoprecipitate contains which factors?
VIII, XIII, fibrinogen, & vWF
Which coagulopathies prolong PTT but no PT?
Hemophilia A
Hemophilia B
What lab values are increased and decreased in DIC?
PT/PTT: inc
D-dimer: inc
Plts: dec
fibrinogen: dec
3 conditions associated with high risk of DIC
- sepsis (highest risk = gram - bacilli)
- OB complications (highest risk = preeclampsia, placental abruption, amniotic fluid embolism)
- malignancy (highest risk = adenocarcinoma, leukemia, lymphoma)
What are the supportive treatments for DIC?
- Hypovolemia: tx w/ IV fluids
- coagulopathy: replace consumed blood components w/ FFP, plts, cryoprecipitate
- severe microvascular thrombosis: IV heparin or LMWH
Antithrombin deficiency
- antithrombin captures factors XII, XI, X, and IX which ultimately leads to thrombin (IIa) inhibition
- heparin works by inc anticoagulant effect of AT by 1000 fold
- pts w/ AT deficiency are unresponsive to Heparin
- repeated heparin administration can consume the body’s supply of AT & produce an acquired form of AT deficiency
- tx: AT concentrate and FFP
Triggers of sickle cell anemia
- pain
- hypothermia
- hypoxemia
- acidosis
- dehydration
