Coagulation Flashcards
What are the 4 steps of hemostasis?
- Vascular spasm
- Formation of platelet plug
- Coagulation and fibrin formation (secondary hemostasis)
- Fibrinolysis when the clot is no longer needed
What is collagen?
Procoagulant
Tensile strength
What is wVf?
Procoagulant
Platelet adhesion
What is fibronectin?
Procoagulant
Cell adhesion
What is protein C?
Anticoagulant
Degrades factor 5 and 8
What is protein S?
Anticoagulant
Cofactor for C
(S’ing that C “sucking that cock”)
What is antithrombin?
Anticoagulant
Inactivates 2a (thrombin) and factors 9, 10, 11, and 12
What is tissue pathway factor inhibitor?
Anticoagulant
Inhibits tissue factor
What is thrombomodulin?
Anticoagulant
Regulates naturally occurring anticoagulants
What is plasminogen?
Precursor to plasmin
What is tPA?
Activates plasmin
What is urokinase?
Fibrinolytic
Activates plasmin
What is alpha-antiplasmin?
Antifibrinolytic
Inactivates tPA/urokinase
What is plasminogen activator inhibitor?
Antifibrinolytic
Inhibits plasmin
What are the three vasoactive mediators that cause vasoCONSTRICTION?
Thromboxane A2
ADP
Serotonin
What are the two vasoactive mediators that cause vasodilation?
Prostacyclin
Nitric oxide
What do platelets lack?
Nucleus!
Where are platelets produced?
Bone marrow
What are some components for clot formation that are on the outside of the platelet?
Gylcoproteins ( repelled by healthy endothelium) ~ adhere to damaged endothelium
Phospholipids (substrate for prostaglandin synthesis) produce thromboxane A2~ activates platelets
What are some components inside the platelet that are part of clot formation?
Actin and myosin (help platelet contract for plug)
Thrombosthenin (assist with platelet contraction)
ADP (platelet activation)
Calcium (factor 4)
Fibrin-stabilizing factor (crosslinks fibrin)
Serotonin (activates other platelets)
Growth factor (helps repair damaged walls)
Platelet adhesion is associated with what?
von Willebrand
Platelet activation and adhesion is associated with what?
ADP and thromboxane A2
What two functions does vasospasm serve?
Reduces blood loss
Helps procoagulants remain in the affect area
What factor does von Willebrand factor bind to?
GpIb
What does the GpII receptor do?
Links activated platelets to each other to form the platelet plug
What are the 3 steps required to produce a platelet plug?
Adhesion
Activation
Aggregation
What is the final common pathway in the coagulation cascade?
Thrombin activation (2a)
When is the extrinsic pathway activated?
When Coagulation is initiated outside of the intravascular space
When is the intrinsic pathway activated?
Coagulation is initiates inside of the intravascular space
What is the intrinsic pathway?
12 > 11 > 9 (+8) > 10 (+5) > 2 > 1
It’s “IN a line” so it’s “INtrinsic”
Which lab value is for the intrinsic pathway?
PTT (intrinsic is longer just like PTT is longer)
What is the extrinsic pathway?
Tissue factor (3) > 7 (4+ ~ calcium) > 10 (+5) > 2 > 1
What lab value correlated with the extrinsic pathway?
PT (shorter than PTT~ just like the intrinsic pathway)
Which anticoagulant inhibits the EXtrinsic pathway?
WARFARIN
The extrinsic pathway looks like a little gun ~ you use guns in WAR
How is the extrinsic pathway activated?
When you have a gun (as in the extrinsic pathway ~ you need a trigger finger)
Trigger finger ~ TF ~ tissue factor
What factors are dependent on vitamin K?
Just remember 1972
10, 9, 7, and 2
What factors are in the common final pathway?
Remember they are all part of the money system.
10$, 5$, 2$, and 1$
How fast is the extrinsic pathway?
Fast! 15 seconds (think PT value)
What is the first factor to become deficient in patients with liver failure?
Factor 7! It has a very short half life
Which factor is missing in hemophilia A?
Factor 8
How fast is the intrinsic pathway?
Slow! Up to 6 minutes
What is activated fibrin-stabilizing factor?
13a
Where is plasminogen synthesized?
Liver
What is plasmin?
Proteolytic enzyme that degrades fibrin to fibrin degradation products
What are fibrin degradation products measured by?
D-diner
What three phases does the coagulation cascade consist of?
- Initiation: (tissue factor is expressed)
- Amplification: (platelets and cofactors lay groundwork for large scale production)
- Propagation: (large quantities of thrombin are produced)
What type of feedback mechanism does the coagulation cascade express?
Positive!
What is the BEST predictor of bleeding during surgery?
History and physical
What does the PTT measure?
Value: 30ish seconds
Measures: Intrinsic and common pathway
Unfractionated heparin
What does PT measure?
Value: 13ish
Measures: extrinsic pathway and final
Med: warfarin
What is INR?
Value: 1ish
Standardization if the PT. Patients PT/standard mean
Med: warfarin target ~ 2-3x control
What is activated clotting time? (ACT)
Value: 90-120
Guides heparin dosing ~ should be measured before heparin, 3 mins after, and 30 mins following
> 400 for CPB
What platelet count increases surgical bleeding risk? What count increases spontaneous bleeding?
< 50,000 surgical
< 20,000 for spontaneous
What does bleeding time measure?
Platelet function
Value: 2-10 mins
What does a D-Dimer measure?
Fibrinolysis (fibrin degradation products)
If Fibrinolysis is increased ~ likely a clot somewhere
Normal < 500
**think DDP ~ DIC, DVT, and PE
What is a thromboelastogram? (TEG)
Real time visualization of disorders of coagulation and Fibrinolysis
What is the R time in the TEG?
Time to begin clot formation
Think coagulation factors ~ FFP
What is the K time on the TEG?
Time until clot has achieved strength
**think fibrinogen ~ cryo
What is the alpha angle on the TEG?
Speed of fibrin accumulation
**fibrinogen ~ Cryo
What is the maximum amplitude (MA) on the TEG?
Measures clot strength
**(platelets) ~ platelets and DDAVP
What is the amplitude at minutes after maximum amplitude (A60)
Determines Fibrinolysis
**excessive Fibrinolysis ~ TXA/Amicar
What does heparin inhibit?
***Intrinsic and final common pathways
Binds antithrombin and accelerates it’s ability.
Is heparin positively or negatively charge?
Negative!!
Does heparin cross the placenta?
No! It’s large and is SAFE during pregnancy
What is the standard dosing for heparin in cardiac surgery patients?
Cardiac surgery: 300-400 U/kg
VTE prophylaxis: 5,000 U SC
Active VTE: 5,000 U IV ~ 1250 U/hr
Acute MI: 5,000 IV ~ 100U/hr
What is protamine derived from?
Salmon sperm
What charge does protamine have?
Protamine is POSITIVE
What is the dose of protamine?
1 unit of protamine for every 100 units of heparin
What are the 3 main side effects of protamine?
Hypotension (histamine release)
Pulmonary HTN: (TxA2 and serotonin release)
Allergic reaction: previous sensitization to NPH, vasectomy and/or fish allergy
What total factors does Warfarin inhibit?
1972 ** and C and S
What are antidotes to vitamin K?
FFP and vitamin K
(In an emergency ~ warfarin should be reversed with FFP, factor 7a or prothrombin complex)
What can impair fat absorption and the production of vitamin K?
Malabsorptive disorders and decreased bile production
What are some risk factors for vitamin K deficiency?
Poor diet
Abx therapy (requires bacteria to manufacture)
Malabsorption
Hepatocellular dx
Neonates must receive vitamin K IM (no bacteria yet)
What is the risk associated with IV phytonadione (vitamin K)?
Life threatening anaphylaxis
What is clopidogrel?
ADP receptor antagonist
What is abciximab?
GpIIb/IIIa receptor antagonist
What is warfarin?
Vitamin K antagonist
What is Enoxaparin?
Antithrombin cofactor
What are the ADP receptors inhibitors? How long should you hold?
Ass: “girls/grel don’t like it is in the ass”
Dick: only wait 7ish days for a dick apt, except for ticlopidine
Pussy: Plavix (clopidogrel) is the main one
What are the GpIIb/IIIa receptor antagonists?
“Fib and fab(mab) hit the G[pll]b”
Abciximab (3 days)
Eptifibatide (1 day)
Tirofiban (1 day)
What are the COX inhibitors (non specific)?
ASA (7 days)
NSAIDS (1-2 days)
What are the COX 2 inhibitors?
Rofecoxib (none)
Celecoxib (none)
What are the anticoagulants? (Heparins) how long should you hold?
Unfractionated: 6 hours
Low molecular heparin (parin): 1-2 days
What are the anticoagulants? (Thrombin inhibitors) how long should you hold?
Argatroban (4-6 hours)
Bivalirudin (2-3 hrs)
What is the factor for factor 10 inhibitors?
Fondaparinux (4 days)
What are the factors for the vitamin K anticoagulants?
Warfarin (hold for 3 days)
Which medication inhibits protein C and plasmin?
Aprotinin
Which medication stimulates factor 8 and vWF release?
DDAVP
What are the three types of von Willebrand?
Type 1: mild ~ reduction in the amount
Type 2: vWF doesn’t work well
Type 3: severe reduction in the amount
Which type of vWF is DDAVP good for?
TYPE 1
What two factors does vWF affect?
Bleeding time (affect platelets)
And PTT (affects the intrinsic pathway because of factor 8)
What is the dose of Desopressin?
0.3 mcg/kg IV
Which two blood products can be used for all three type of vWF?
FFP and cryo
What is the first line agent for a patient with type 3 vWF?
Purified 8-vWF
Which lab value is prolonged with Hemophilia A and hemophilia B?
PTT ( hemophilia a ~ deficient factor 8 and hemophilia B ~ deficient factor 9 are part of the INTRINSIC pathway)
What is considered the “last ditch” treatment for bleeding without an identifiable cause?
Recombinant Factor 7
What is DIC?
Disseminated Intravascular Coagulation ~ disorganized clotting and Fibrinolysis
How are lab values affected in DIC?
Increased PT/PTT
Increased D-Dimer
Decreased fibrinogen
Decreased platelets
What are some signs of DIC?
Ecchymosis
Petechiae
Mucosal bleeding
Bleeding at IV sites
What are the 3 type of patients at HIGHEST risk for DIC?
Sepsis ~ highest (gram negative)
Obstetric ~ preeclampsia, placental abrupt
Malignancy: leukemia, lymphoma
What is the definite treatment for DIC?
Reversing the underline cause
Otherwise treatment is supportive!
IV fluids, FFP, platelets, cryo, IV heparin
What is contraindicated in a patient with type 2 HIT? What should he used instead?
Heparin is contraindicated
Bivirudin is a direct thrombin inhibitor
What are some traits of HIT type 1?
Heparin induced platelet aggregation
Occurs with LARGE heparin dose
1-4 days after administration
Platelets < 100,000
Morbidity: min
Tx: resolves spontaneously
What are some traits of Type 2 HIT?
If you get hit twice, it’s BAD
Anti platelet antibodies ~ form immune complexes
Occurs after ANY heparin dose
Platelets < 50,000
Hypercoagulable state causes high risk of death or amputation
Heparin MUST be discontinued.
What is factor 5 Leiden mutation?
Causes a resistance to the anticoagulant effect of protein C
Lifelong anticoagulation is unwarranted
What four factors are inhibited by antithrombin?
9, 10, 11, 12
What is sickle cell disease?
Inherited disorder that affects erythrocytes
In sickle cell dx, what is substitution in the RBC?
Valine is substituted for glutamic acid (that is what is on the beta chain in sickle cells)
**this happens on the BETA chain
Ultimately alters RBC geometry
What are the triggers to avoid in sickle cell crisis?
Pain
Hypothermia
Hypoxemia
Acidosis
Dehydration
What are the main complications of sickle cell?
Vaso-occlusive: impaired tissue perfusion > ischemic injury (most common)
Acute chest: thrombosis, embolism and infection > common in kids > new lung infiltrates and AT LEAST ONE [cough, cp, Dyspnea, wheezing]
Sequestration crisis: spleen removes RBCs faster than bone marrow produces >anemia
Aplastic crisis: bone marrow suppression > anemia (usually with viral infections)
What resp disorder occurring in 50% of sickle cell patients?
Asthma
What is sickle cell trait?
Heterozygous sickle cell disease
DO NOT advance to crisis unless hypoxic!!!
For the ABO system, what is O traits?
RBC antigen: O
Plasma antibodies: anti-B; Anti-A
Compatibility: O
