Thrombophilia Flashcards by Johannah Crumpton

thrombosis can be _____ or _____

arterial or venous

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**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)

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**What are the 2 key players in arterial thrombosis?

platelets and vessel wall injury/abnormalities

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**What is an arterial thrombosis due to?

Due to the adhesion, activation, and then aggregation of platelets

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in arterial thrombosis, ______ and _____ may induce the release of procoagulants from endothelial cells

Bacterial and viral infections

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In arterial thrombosis, ______ results in endothelial cell damage due to multiple etiologies, such as activated leukocytes, chemokine release, TNF, etc

Inflammation

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????? induces an immune response, causing increased leukocyte activation and circulation

Platelet activation and aggregation

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Patients with _____ or _____ are at an increased risk for thrombotic events

infection or significant inflammation

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**What is a venous thrombosis due to ?

Most commonly caused by the activation of the coagulation cascade, due to stasis or hypercoagulability

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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

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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

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thrombophilic pts are at a higher risk of an (arterial/venous) thrombosis

higher risk of venous thrombosis

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What are some risk factors of developing a blood clot?

increased age, smoking, obesity, DM, HTN, HLP

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Draw the clotting cascade picture Prof Adkins really likes

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Name some inherited causes of venous thrombosis

Factor V Leiden mutation
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
Antithrombin (AT) deficiency
Dysfibrinogenemia

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______ is the most common cause of inherited thrombophilia, accounting for 40 to 50 percent of cases

Factor V Leiden

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How is Factor V Leiden inherited?

autosomal dominant

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Describe what Factor V Leiden means?

pt has factor V present it is just defective, aka it is abnormal

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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)

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What is a classic pt presentation of factor V leiden?

DVT at young age
Family history of blood clots

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A factor V leiden pt PTT with be ??

shortened or normal

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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!

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**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

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**the protein C functional assay test results:

factor V leiden the PTT will be _____

normal pt, the PTT will be _____

stay the same

prolonged

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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