Coagulation (exam 4) Flashcards
What is hemostasis?
Normal hemostasis is a balance between clot generation, thrombus formation, and regulatory mechanisms that inhibit uncontrolled thrombogenesis.
What are the goals of hemostasis?
- Limit blood loss from vascular injury
- Maintain intravascular blood flow
- Promote revascularization after thrombosis
What are the two stages of hemostasis?
- Primary Hemostasis
- Secondary Hemostasis
What occurs during Primary Hemostasis?
Immediate platelet deposition at the endovascular injury site leading to the initial platelet plug formation.
*Only adequate for minor injury
What occurs during Secondary Hemostasis?
Clotting factors are activated, leading to a stabilized clot formed and secured with crosslinked fibrin.
What role do vascular endothelial cells play in hemostasis?
They have antiplatelet, anticoagulant, and fibrolytic effects to inhibit clot formation.
What is the lifespan of platelets?
8-12 days.
What are the two types of storage granules in platelets?
- Alpha granules
- Dense bodies
What is the function of alpha granules?
Contain fibrinogen, factors V & VIII, vWF, and platelet-derived growth factor.
What is the function of dense bodies?
Contain ADP, ATP, calcium, serotonin, histamine, and epinephrine.
What is the Extrinsic Pathway in hemostasis?
The initiation phase of plasma-mediated hemostasis that begins with endothelial injury, exposing tissue factor (TF) to plasma.
What does the TF/VIIa complex do?
Activates factor X, converting it to Xa.
**IXa and calcium convert factor X to Xa
What is the role of factor Xa?
Begins the final common pathway in coagulation.
What initiates the Intrinsic Pathway?
Activation of factor XIIa upon contact with negatively charged surfaces.
What is the role of thrombin in hemostasis?
Converts fibrinogen (I) to fibrin (Ia) and is key in regulating hemostasis.
What is the Prothrombinase Complex?
Formed by Xa and Va, it converts prothrombin (II) into thrombin (IIa).
What is fibrinolysis?
The enzymatic breakdown of clots, primarily by plasmin.
What is the function of Tissue Factor Pathway Inhibitor (TFPI)?
Inhibits the TF/VIIa complex and factor Xa.
What is the significance of the Protein C system?
Inhibits factors II, Va, and VIIIa.
What are the common bleeding disorders?
- Von Willebrand’s Disease
- Hemophilia
- Drug-induced bleeding
- Liver disease
- Chronic renal disease
- Disseminated Intravascular Coagulation
- Trauma-induced coagulopathy
What is Von Willebrand’s Disease?
The most common inherited bleeding disorder affecting 1% of the population due to a deficiency in vWF. It causes platelet adhesion/aggregation
What is the hallmark of Hemophilia A?
Factor 8 (VIII) deficiency.
What is a common cause of intraoperative bleeding?
Anticoagulant medications.
What laboratory findings are common in liver disease related to hemostasis?
Prolonged PT and possible prolonged PTT.
What is Disseminated Intravascular Coagulation (DIC)?
A pathological hemostatic response causing excessive activation of the extrinsic pathway, leading to multi-organ dysfunction.
What is Trauma-Induced Coagulopathy (TIC)?
Acute coagulopathy seen in trauma patients, thought to be related to activated protein C decreasing thrombin generation.
What is Thrombophilia?
Inherited or acquired predisposition for thrombotic events.
What is the significance of the Factor V Leiden mutation?
Leads to activated protein C resistance and is present in 5% of the Caucasian population.
What is the main consequence of Heparin-Induced Thrombocytopenia (HIT)?
Platelet count reduction and activation of remaining platelets resulting in potential thrombosis.
What laboratory test assesses the integrity of the extrinsic and common pathways? It also measures the # of seconds until a clot forms
Prothrombin Time (PT).
What does Activated Partial Thromboplastin Time (aPTT) measure?
The effects of heparin
The integrity of the intrinsic and common pathways. Measures seconds until clot formation after mixing plasma with phospholipid, calcium, and an intrinsic pathway activator
What does the Anti-factor Xa activity assay evaluate?
Functional assessment of heparin’s anticoagulant effect.
What is the standard component of coagulation labs?
Platelet Count.
What is the aPTT used to assess?
Integrity of intrinsic and common pathways
More sensitive to deficiencies in factor 8 & 9 (VIII, IX) than others
What does the anti-factor Xa activity assay measure?
Functional assessment of heparin’s anticoagulant effect
Plasma combined with Xa and an artificial substrate that releases a colorimetric signal after factor Xa is cleaved
What is the normal platelet count?
> 100,000 plts/microliter
Standard component of coagulation testing
What does Activated Clotting Time (ACT) assess?
Responsiveness to heparin. It is a variation of whole blood clotting time
Normal = 107 +/- 13 seconds
What does viscoelastic coagulation tests measure?
TEG (thromboelastogram) and ROTEM (rotational thromboelasometry)
All aspects of clot formation from early fibrin generation to clot retraction & fibrinolysis
Coagulation diagrams generated
What is the main mechanism of action of cyclooxygenase inhibitors?
Block Cox 1 from forming TxA₂
Important in platelet aggregation
How long do anti-platelet effects of Aspirin last after discontinuation?
7-10 days
ASA: anti-plt effects
What do P2Y12 receptor antagonists prevent?
GIIb/IIIa expression
Examples include Clopidogrel and Ticlopidine
What is the most common vitamin K antagonist?
Warfarin
DOC for valvular Afib & valve-replacements
What is the relative half-life of unfractionated heparin versus LMWH (short or long)?
Unfractionated heparin = short half-life
LMWH = longer half life
Unfractionated is fully reversible with Protamine
LMWH only partially reversible
What is a characteristic of Direct Oral Anticoagulants (DOACs)?
More predictable pharmacokinetics/dynamics
Fewer drug interactions
What is the primary use of thrombolytics?
To dissolve blood clots
May be given IV or directly into the site of blockage
What are the two categories of thrombolytics?
Fibrin-Specific and Non-Fibrin-Specific
Fibrin-Specific examples include Altepase (tPA), Reteplase, Tenecteplase
Non-fibrin specific: streptokinase
What do antifibrinolytics do?
Inhibit plasminogen from binding to fibrin
Examples include Epsilon-amino-caproic acid (EACA) & Tranexamic Acid (TXA)
What is the primary role of procoagulants?
Mitigate blood loss
Includes Antifibrinolytics & Factor Replacements
When should Warfarin be discontinued before surgery for low-risk patients?
5 days prior to surgery
Restart 12-24 hours postoperatively
What is the recommendation for stopping heparins before surgery?
UFH 4-6 hours prior, LWMH 24 hours prior
Resume after surgery based on type
What is the recommended delay for elective surgery after placement of bare-metal stents?
6 weeks
For drug-eluting stents, delay 6 months
What is the first DOAC approved for CVA prevention?
Dabigatran (Pradaxa)
Direct Thrombin Inhibitor
What is the antidote for Dabigatran?
Idarucizumab
Notably, most Direct Thrombin Inhibitors do not have a reversal agent
What is a characteristic of Direct Xa inhibitors?
Dosed daily without lab monitoring
Examples include Rivaroxaban (Xarelto), Apixaban (Eliquis)
Anti-clotting mechanisms of endothelial cells:
_____ charged to repel platelets
Produce platelet inhibitors such as _____ and _____
Excrete adenosine diphosphatase, which degrades into _____ _____, a platelet activator
Increases _____ __, an anticoagulant
Produce _______, which inhibits factor Xa and tissue factor VIIa complex
Synthesize _____ _____ _____
Negatively
Prostacyclin and nitric oxide
Adenosine diphosphate (ADP)
Protein C
Tissue factor pathway inhibitor
Tissue plasminogen activator (t-PA)
How many new platelets are formed daily?
120-150 billion
Upon exposure to the extracellular matrix, platelets undergo what 3 phases?
- adhesion
- activation
- aggregation
Current understanding is that the intrinsic pathway is an _____ _____ to propagate thrombin generation initiated by the extrinsic pathway
Amplification system
Which factor activates the final common pathway?
Xa
_______ _______ is the key step in regulating homeostasis
Thrombin generation
(4) major coagulation counter mechanisms (clot control):
_______ :endovascular TPA & urokinase convert plasminogen to plasmin
______ __ system inhibits factors II, Va & VIIIa
______ ______ ______ ______ forms complex with Xa that inhibits VIIa complex, along with Xa; thereby downregulating the extrinsic pathway
______ ______ ______: antithrombin; heparin; heparin cofactor II
Fibrinolysis
Tissue factor pathway inhibitor (TFPI)
Protein C
Serine protease inhibitors (SERPINs)
Inhibits thrombin and factors 9a-12a
Antithrombin (AT)
Binds to AT, causing a conformational change that accelerates AT activity
Heparin
Inhibits thrombin alone
Heparin cofactor II
Mild vWF disease is often responsive to _______
DDAVP: increases vWF
With hemophilia, _____ is normally prolonged and _____, _____, _____ labs are usually normal
PTT (intrinsic pathway)
PT, plts, bleeding
Which 8 drugs increase the risk of intraop bleeding?
- heparin
- warfarin
- direct oral anticoags
- beta-lactam abx
- nitroprusside
- NTG
- NO
- SSRIs
The liver is the primary source of which clotting factors?
5, 7, 9, 10, 11, 12
*Along with protein C & S and antithrombin (clot control)
In chronic renal patients _______ and correction of _______ are shown to shorten bleeding times
- dialysis
- anemia
Treatment of platelet dysfunctio includes (3):
- cryoprecipitate (rich in vWF)
- DDAVP
- Conjugated estrogens given pre-operatively x5 days
DIC labs:
Plts are _____
PT/PTT/thrombin time are _____
Soluble fibrin & fibrin degradation products are _____
Decreased
Prolonged
Increased
Trauma induced coagulopathies occur due to _____, _____, and/or _____
Acidosis, hypothermia, hemodilution
A _______ _______ causes increased PT concentration, leading to hypercoagulation
Prothrombin mutation
_______ _______ is an autoimmune disorder with antibodies against the _______-_______ proteins in the coagulation system
Antiphospholipid syndrome
Phospholipid-binding
How long after heparin treatment can HIT occur (the first time)?
5-14 days
**Can occur in 1 day if pt has received a prior heparin dose
T/F: Unfractionated heparin carries a lesser risk than LMWH
False: unfractionated heparin carries a GREATER risk than LMWH
Antibodies produced in HIT are typically cleared in _____ months
3
What is the normal activated clotting time (ACT)?
107 seconds. +/- 13 seconds
_______ _______ _______ determines the perioperative heparin concentration
Heparin concentration measurement
_______ mg of protamine will inhibit _______ mg of heparin
1mg; 1mg
How long do antiplatelet effects of NSAIDS last after discontinuation?
3 days
P2Y12 receptor antagonists. Anti-platelet effects duration:
Clopidogrel: ______ after d/c
Ticlopidine: ______ - ______ after d/c
Ticagrelor & Cangrelor: ______ after d/c
7 days
14-21 days
<24 hours
What are the vitamin k dependent factors?
2, 7, 9, 10, and protein C & S
What are the (4) direct thrombin inhibitors?
- Hirudin: leeches
- Argatroban: synthetic; reversibly binds to thrombin
- Bivaliruden: shortest halflife; DOC for renal or liver impairment
- Dabigatran: first direct oral anticoagulant (DOAC)
Surgery is contraindicated within _______ days of thrombolytic treatment
10
What are the 2 classes of procoagulants?
Antifibrinolytics
Factor replacements
When should aspirin be d/c’d prior to surgery? Low vs high risk patients
Moderate/high risk: continue ASA
Low risk: stop 7-10 days prior to surgery
What is the recommended delay in elective surgery after drug-eluding stent placement?
6 months
What are the (3) warfarin reversals?
- Prothrombin complex concentrates
- Vitamin K
- FFP
What is the antidote for DOAC factor Xa inhibitors?
Andexanet - a derivative of factor Xa
