Thrombophilia Flashcards
thrombosis can be _____ or _____
arterial or venous
**What is Virchow’s triad?
- Damage to the vessel wall
- Slowing of blood flow leading to stasis
- Changes in the coagulability of blood (leading to the hypercoagulable state)
**What are the 2 key players in arterial thrombosis?
platelets and vessel wall injury/abnormalities
**What is an arterial thrombosis due to?
Due to the adhesion, activation, and then aggregation of platelets
in arterial thrombosis, ______ and _____ may induce the release of procoagulants from endothelial cells
Bacterial and viral infections
In arterial thrombosis, ______ results in endothelial cell damage due to multiple etiologies, such as activated leukocytes, chemokine release, TNF, etc
Inflammation
????? induces an immune response, causing increased leukocyte activation and circulation
Platelet activation and aggregation
Patients with _____ or _____ are at an increased risk for thrombotic events
infection or significant inflammation
**What is a venous thrombosis due to ?
Most commonly caused by the activation of the coagulation cascade, due to stasis or hypercoagulability
Give some examples of abnormalities of blood flow
Atrial Fibrillation
Left Ventricular Dysfunction
Immobility
Vessel Obstruction
Hyperviscosity (e.g. polycythemia vera)
Sickle Cell Anemia
Heart Valve Disease/Replacement
Indwelling Catheters
Give some examples of pts who would have a higher risk to clot/ hypercoagulability
Protein C or protein S deficiency
Activated protein C resistance
Antithrombin (AT) deficiency
Antiphospholipid antibodies
Malignancy (Tumor Cell Procoagulants)
High Dose Estrogen Therapy
Pregnancy
thrombophilic pts are at a higher risk of an (arterial/venous) thrombosis
higher risk of venous thrombosis
What are some risk factors of developing a blood clot?
increased age, smoking, obesity, DM, HTN, HLP
Draw the clotting cascade picture Prof Adkins really likes
Name some inherited causes of venous thrombosis
Factor V Leiden mutation
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
Antithrombin (AT) deficiency
Dysfibrinogenemia
______ is the most common cause of inherited thrombophilia, accounting for 40 to 50 percent of cases
Factor V Leiden
How is Factor V Leiden inherited?
autosomal dominant
Describe what Factor V Leiden means?
pt has factor V present it is just defective, aka it is abnormal
What is Factor V important in the clotting process?
Activation by thrombin results in the formation of factor Va, which then serves as a cofactor in the conversion of prothrombin to thrombin.
(Factor V does not recognize active protein C, so a clot with form but it will not be able to get broken down: increased coagulation and decreased anticoagulation)
What is a classic pt presentation of factor V leiden?
DVT at young age
Family history of blood clots
A factor V leiden pt PTT with be ??
shortened or normal
What are the diagnostic tests you should order to confirm factor V leiden. What is the gold standard?
Protein C functional assay
DNA testing—— expensive!
**Describe the process for a protein C functional assay test
take purified protein C, mix it with the person’s plasma and measure the PTT before and after
**the protein C functional assay test results:
factor V leiden the PTT will be _____
normal pt, the PTT will be _____
stay the same
prolonged
How do you treat factor V leiden?
there is nothing to give prophylaxis
treat the clot with heparin
What are the exceptions in which you would treat factor V leiden prophlaxis
-high risk surgery
- pregnancy
-additional thrombophilic mutations
How is prothrombin gene mutations inherited?
autosomal dominant
prothrombin gene mutation it is a ______ which is synthesized in the liver and circulates with a half-life of approximately ______
vitamin K-dependent protein
3-5 days
Heterozygous carriers of the prothrombin gene mutation have ____ higher plasma prothrombin levels than normals. What is the gene?
30 percent
Prothrombin G20210A
Homozygous protein C deficiency causes ____
purpura fulminans neonatalis in newborns
protein C deficiency puts a pt at risk for ____. What is the treatment?
warfarin-induced skin necrosis
stop warfarin; start vit K, heparin, protein C concentrate/ FFP
Protein C deficiency imbalance between ____ and _____ increases your risk for ???
procoagulant and anticoagulant
5X increases your risk of venous thrombosis
Protein C acts as an anticoagulant by regulating the activities of ____ and _____
activated factor VIII and activated factor V
Patients with heterozygous protein C deficiency have _____ PT and _____ aPTT values.
normal
normal
Patients with homozygous protein C deficiency have _____ coagulation tests consistent with DIC
abnormal
Name some disorders that are associated with Vit K deficiency and protein C deficiency
including warfarin use, liver disease, malnutrition, DIC and nephrotic syndrome
Name some instances where you would see acquired protein S deficiency
pregnancy, oral contraceptive use, sickle cell anemia, inflammation, nephrotic syndrome and with coumadin therapy.
Protein S activity will be (increased/decreased) in patients receiving warfarin
decreased
Name some pt populations in which the protein S levels are decreased
pregnant women
oral contraceptives
liver disease
IBD
nephrotic syndrome
Name the 5 factors that antithrombin inactivates
thrombin
9a
10a
11a
12a
When does the initial clinical manifestations of Antithrombin III deficiency occur spontaneously in _____ (42%)
pregnancy
Where are the most common sites for a clot if you have a antithrombin III deficiency?
deep veins of the leg
mesenteric veins
What is the puerperium defined as ? What are you at a high risk for?
6 week period following delivery
higher risk of blood clot than pregnancy itself
What are some risk factors for thrombosis in pregnancy
Age (below 18 or greater than 35)
Cesarean delivery
Prolonged immobilization
Obesity
Previous thromboembolism
Coexistent thrombophilia
Why is the left leg more prone to thrombosis compared to the right?
Compression of the left iliac vein by the crossing right iliac artery
____ is an acquired hypercoagulable condition that results in recurrent venous or arterial thrombosis and/or pregnancy mortality
antiphospholipid syndrome
has arterial and venous blood clots
think pregnancy
Antiphospholipid Syndrome requires the presence of ????
autoantibody known as an antiphospholipid antibody (aPL) in the plasma
Antiphospholipid Syndrome is most commonly associated with ____
Lupus
or other underlying autoimmune disease
What are the 2 major clinical manifestations of Antiphospholipid Syndrome?
thrombotic events (usually DVT, arterial occlusions most common in cerebrovascular circulation)
pregnancy complications (usually around the 10 week mark)
Name some additional clinical manifestations of antiphospholipid syndrome?
Cardiac valvular disease
Pulmonary hypertension
Avascular necrosis of the hip
Cutaneous ulcers and/or Livedo reticularis
Adrenal insufficiency
Cognitive deficits
Thrombocytopenia
Ocular Complications
What is this picture describing? What syndrome is it associated with?
Libman-Sacks verrucous endocarditis
Antiphospholipid syndrome
Under _____ or ____ the emboli may travel to the systemic arterial circulation
PFO (patent foramen ovale)
ASD (atrial septal defect)
What is the classic clinical presentation of DVT?
dull aching pain
swelling, pain, and discoloration in the involved extremity
usually unilateral
warm and erythema
What is the Homan’s sign? Is it reliable?
hold the pt’s inner thigh and strongly dorsiflex the foot, positive sign if it is painful
What are some s/s of pulmonary embolism?
shortness of breath – abrupt onset
tachypnea
pleuritic chest pain
cough, hemoptysis
pleural effusion
pulmonary infiltrates
Right-sided heart failure
hypotension
syncope
sudden death (10% are fatal)
**What is the Wells score range for a DVT?
High: 3 or greater
Moderate: 1-2
Low: 0 or less
**What is the Wells score range for a PE?
high: greater than 4
low: 0-4
What are the top 2 choices for diagnostic testing if you are considered about a DVT?
Compression Venous Doppler Ultrasonography (approach of choice in most circumstances)
D-Dimer serum testing
What does a D-Dimer test for?
Byproduct of the degradation of blood clots, specifically, of the fibrin within a thrombus.
What does an elevated D-dimer suggest?
there is a thrombus in the body that is being degradated
What instances would a D-dimer may be a false positive?
Pregnancy, infection, cancer, recent surgery, inflammatory disease processes
____ Technique used to determine the speed of blood flow through arteries and veins
doppler ultrasound
If your pt has a low probability of a PE, what should you order? High probability?
if low probability - D-Dimer
High probability - Imaging
CT scan w/ IV contrast
What do you order if you have a high suspicion of a PE but the pt is allergic to contrast?
V/Q scan
ventilation/perfusion scan
What is the treatment for DVT?
Anticoagulant therapy is indicated for patients with DVT, since pulmonary embolism will occur in approximately 50%
heparin and warfarin
OR
Pradaxa, Xarelto, Eliquis, or Savaysa by themselves
If you decide to go the heparin/warfarin route, what is the treatment protocol?
heparin for 5 days and d/c once INR is between 2-3
Warfarin for min of 3 months
When is a Inferior Vena Caval filter indicated?
anticoag are contraindicated
high risk of proximal vein thrombosis or PE
pts who have recurrent thromboembolism despite adequate anticoagulation
What screening tests should you order for patients who are in a hypercoagulable state
Antithrombin
Protein C
Protein S
Factor V Leiden
Prothrombin gene mutations
Antiphospholipid antibodies
**Patient has abnormal coag studies or has had a thromboembolic event, when should you schedule repeat testing?
repeat in 2-3 months
_____ reduces protein C and protein S levels
Warfarin
____ can reduce antithrombin levels
Heparin
???? causes a reduction in the levels of any of the natural anticoagulants (protein C, protein S, antithrombin)
acute medical illness aka sepsis
When would long term anticoag therapy be indicated for pts with a history of PE
2 or more spontaneous events for all high-risk patients
1 spontaneous life-threatening thrombosis
1 spontaneous thrombosis at unusual sites (mesenteric or cerebral venous)
1 spontaneous thrombosis in association with the antiphospholipid antibody syndrome, active cancer, antithrombin III deficiency, or more than one genetic or allelic abnormality
