Clotting Conditions Flashcards
Clotting occurs in several steps:
- Vasoconstriction ← smooth muscle contraction
- Formation of platelet plug
- Clot reinforced by coagulation cascade→ Fibrin crosslinking
- Ends with fibrinolysis and restoration of blood flow
When a vessel is damaged- _____ is
exposed
collagen
Von Willebrand factor (vWF)
Forms a bridge between collagen of a damaged vessel and GPIb which is expressed on the surface of the platelet→ adhesion to the site
Platelet granules secret:
○ Adenosine diphosphate (ADP) released→ Activates nearby platelets
○ Arachidonic acid released which is converted to thromboxane A2
Eventually Factor X is activated by combination
of _____
IX and VIII and phospholipids
Measured with PT
Extrinsic pathway
Measured with aPTT
Intrinsic pathway
Intrinsic pathway is activated by ____
Activated by exposure to
collagen
Extrinsic pathway is activated by
Activated by presence of
tissue factor (III)
Ultimately both pathways lead
to activation of Factor ___
X
Factors that Inhibit Coagulation
○ Protein C
○ Protein S
○ Antithrombin III
Protein C and S are ____ dependent proteins
Vit K
_____ is a plasma protein which binds to
thrombin forming inert compound
Antithrombin III
Heparin acts to augment
____
Antithrombin III
What is Thrombophilia?
A condition where the blood has an increased tendency to form clots, potentially leading to life-threatening circumstances.
____ is a major cause of morbidity and mortality throughout the world
Thrombosis
_____ activates plasminogen into plasmin
tPA
The 19th century pathologist Rudolf Virchow proposed three independent processes which could increase the risk of abnormal thrombosis
○ Abnormal Flow / Stasis
○ Vessel Wall Injury
○ Hypercoagulability
Inherited Disorders of hypercoagulable state
○ Factor V Leiden Mutation
○ Prothrombin G20210A Mutation
○ Protein S Deficiency
○ Protein C Deficiency
○ Antithrombin III Deficiency
Acquired conditions of hypercoagulable states
○ Pregnancy-Related Hypercoagulability
○ Malignancy-Related Hypercoagulability
○ Antiphospholipid Antibody Syndrome
○ Heparin-Induced Thrombocytopenia
Factor V plays a crucial role in the conversion of Prothrombin to Thrombin and is normally inactivated by ____
Protein C (and S).
Factor V Leiden is ____ 10 times slower than
normal Factor V.
inactivated by Protein C
○ Leads to increased coagulation - more
Thrombin is created.
Factor V Leiden
Mutation of Factor V
____ is by far the most common
inherited risk factor for thrombophilia
Factor V Leiden mutation
The _____ triggers an overproduction of the Prothrombin protein (Factor II).
Prothrombin G20210A genetic mutation
Normally, Protein C works to ____
inactivate Factors VIII and V
in an effort to slow down or inhibit coagulation
(anticoagulant).
Antithrombin III normally inactivates several coagulation
factors, most importantly _____
Thrombin
_____ are at an increased risk of
thrombosis (DVT and PE)
Pregnant women
Antiphospholipid Syndrome
Antiphospholipid Antibody Syndrome is a condition in
which the body forms antibodies against proteins bound to
the phospholipids necessary for the coagulation cascade.
Antiphospholipid Syndrome includes:
○ Lupus Anticoagulant
○ Anticardiolipin Antibody
What is lupus anticoagulant
Those with Lupus Anticoagulant are at increased risk of venous thrombosis and recurrent miscarriage.
Anticardiolipin Antibody
Those with Anticardiolipin Antibody are at increased
risk of arterial thrombosis, concerning for myocardial
infarction and peripheral arterial occlusions.
Heparin-Induced TCP (HIT)
an adverse reaction to the medication
that occurs in 3% of those on
unfractionated Heparin and 0.6% of
those on LMWH.
HIT results from
formation
of antibodies to the
Heparin-Platelet Factor
4 (PF4) complex.
HIT usually occurs ____
5-10 days after initiation of Heparin.
A decline in baseline platelet count of 50% or more is diagnostic for
HIT
Treatment for HIT
○ Discontinue all forms of Heparin immediately.
○ Begin treatment with Direct Thrombin inhibitor (ie. Argatroban) or
Direct Factor Xa Inhibitor (ie. Rivaroxaban).
○ Check US Doppler of LEs and monitor Platelet count.
○ When platelet # recovers, can transition to Warfarin for at least 30
days
Deep Vein Thrombosis S/S
○ Most commonly, patients present with…
■ Unilateral leg pain
■ Unilateral calf tenderness
■ Unilateral leg/ankle swelling
DVT diagnostic testing
○ The use of a Clinical Prediction Tool is suggested.
■ Wells Score System for DVT
○ If low probability based on Prediction Tool:
■ Order High-Sensitivity D-Dimer (blood test)
● Negative D-Dimer rules out DVT
○ If moderate probability of DVT:
■ High-Sensitivity D-Dimer or Compression Ultrasound
○ If high probability of DVT:
■ Compression Ultrasound is diagnostic test of choice
High-sensitive D-Dimer is very sensitive for ____
VTE
The presence of D-Dimer
indicates that clotting
_____
has occurred
Treatment and Management of DVT
○ Prevention in high-risk patients is critical!
○ Once diagnosed, Systemic Anticoagulation is treatment.
Inpatient treatment for DVT recommended if…
● Massive DVT
● Symptomatic Pulmonary Embolism
● High risk of bleeding with anticoagulation
● Significant comorbid conditions
Acute DVT treatment
○ Anticoagulation started immediately
○ Oral anticoagulant preferred for maintenance treatment
○ Anticoagulation is continued for at least 3 months.
In the treatment of acute DVT, Recent studies have shown that____
early ambulation is safe and
recommended over bedrest
If there is a high degree
of concern for a PE, an
_____ can be placed
endovascularly.
Inferior Vena Cava (IVC)
Filter
_____ is the
most significant complication of
DVT.
Pulmonary Embolism
Pulmonary Embolism
● If a DVT breaks loose, it can
travel through the heart and into
the lungs.
Characteristic Signs and Symptoms of Pulmonary embolism
○ Sudden onset dyspnea
○ Tachypnea
○ Tachycardia
○ Pleuritic Chest Pain
○ Cough
○ Sometimes a fever
○ Symptoms of shock (massive PE)
○ Hemoptysis (not common)
○ Signs and symptoms of DVT are common
Diagnostic testing for pulmonary embolism
○ Pulmonary Embolism Rule-out Criteria (PERC)
○ The use of a Clinical Prediction Tool is suggested.
○ Low probability, D-Dimer is used to rule out PE
● If positive advance to CT Angio
○ Moderate probability, D-Dimer or below imaging.
○ High probability of PE, D-Dimer is not indicated.
Test of choice for pulmonary embolism
CT Pulmonary Angiography is test of choice
Treatment for PE If patient is hemodynamically stable
■ SC LMWH (Lovenox) is preferred over IV UFH.
■ More common- DOACs-Rivaroxaban or Apixaban.
Treatment for PE If massive PE with concern for shock
■ IV unfractionated Heparin is preferred.
■ IV Alteplase (a fibrinolytic called tPA) can also be used.
■ Endovascular pulmonary embolectomy is used as a measure of last resort
○ Long-term (at least 3-6 months) anticoagulation with an oral agent is recommended (Warfarin or NOAC ie. Novel oral anticoagulant)
____ occurs when platelet aggregation
and the coagulation cascade are triggered by
disease of the artery
Arterial thrombosis
Characteristic Presentation of arterial thrombosis
■ Myocardial Infarction
■ Unstable Angina
■ Ischemic Stroke
■ Acute Limb Ischemia of Peripheral Arterial Disease
Risk factors of arterial thrombosis
smoking, obesity, diabetes,
hypertension, dyslipidemia, advancing age, atherosclerosis,
and positive family history.
Treatment of Arterial thrombosis
○ Treatment specific to acute arterial thrombosis will be
discussed in the above listed courses.
■ Mostly uses antiplatelet drugs
○ Prevention of atherosclerosis (by addressing modifiable
risk factors) is critical to prevention of arterial
thrombosis.
Virchow’s Triad
○ Venous Stasis
○ Vessel Wall Injury
○ Hypercoagulability
Patient with a DVT are at very high risk
of ____
that clot breaking loose and traveling
to the lungs, causing a Pulmonary
Embolism.
Prevention of _____ is critical to prevention of arterial thrombosis.
atherosclerosis (by addressing modifiable
risk factors)
