Thrombotic disorders Flashcards
_ are clots that form within blood vessels, usually within the venous system
Thrombi are clots that form within blood vessels, usually within the venous system
_ are pieces of clot that travel through the bloodstream to other places in the body where they become lodged in vessels
Emboli are pieces of clot that travel through the bloodstream to other places in the body where they become lodged in vessels
A _ is a clot that forms in one of the deep veins of an extremity, such as the femoral or brachial vein
A deep vein thrombosis (DVT) is a clot that forms in one of the deep veins of an extremity, such as the femoral or brachial vein
_ is most commonly caused by a piece of clot that breaks off from a DVT and lodges in the pulmonary arterial system
Pulmonary embolism (PE) is most commonly caused by a piece of clot that breaks off from a DVT and lodges in the pulmonary arterial system
DVT patients usually present with _
DVT patients usually present with unilateral swelling of the leg often with pain and redness
* A palpable cord may be present
What is a positive Homan sign
Positive homan sign: increased pain with passive dorsiflexion of the ankle with a DVT
Three components of Virchow Triad
- Endothelial damage
- Hypercoagulable state
- Abnormal blood flow/venous stasis
Name some common causes of endothelial damage
- Smoking
- Hypertension
- Surgery
- Trauma
Name some common causes of abnormal blood flow
Abnormal blood flow means blood either moves in a disorganized manner (turbulence) or slows down (stasis); this allows platelets and clotting factors to mingle
* Immobility
* Central venous catheters
* Varicose veins
* Atrial fibrillation
Name some common causes of hypercoagulability
- Cancer
- Estrogen-containing contraceptives
- Pregnancy
- Obesity
- Hereditary disorders
Postthrombotic syndrome is _ that occurs in up to 50% of patients after a DVT
Postthrombotic syndrome is chronic venous insufficiency that occurs in up to 50% of patients after a DVT
* Causes leg pain, edema, skin ulcers, discoloration
_ is a massive iliofemoral DVT that completely occludes the venous drainage of the extremity –> edema, cyanosis, gangrene
Phlegmasia cerulea dolens is a massive iliofemoral DVT that completely occludes the venous drainage of the extremity –> edema, cyanosis, gangrene
Patients with a low to moderate Wells score will first get _ testing for DVT; Patients with high Wells score will first get _ test
Patients with a low to moderate Wells score will first get D-dimer test for DVT; Patients with high Wells score will first get D-dimer and ultrasonography
An elevated D-dimer test indicates _
An elevated D-dimer test indicates thrombus formation and breakdown
D-dimer test has high (specificity/sensitivity) but low (specificity/sensitivity)
D-dimer test has high sensitivity but low specificity
* Smoking, infection, surgery, pregnancy can cause D-dimer to be positive
_ is the best radiographic modality to diagnose DVT
Compression ultrasonography is the best radiographic modality to diagnose DVT
* If there is a clot present in the vein, the ultrasound transducer will fail to collapse the vein like a normal vein
Patients at risk of DVT in the hospital normally get _ and _ as prophylaxis
Patients at risk of DVT in the hospital normally get low-molecular-weight heparin and leg-compression devices
The prefered DVT treatment is _
The prefered DVT treatment is direct oral anticoagulants
* Ex: Rivaroxaban (Xarelto)
* Ex: Apixaban (Eliquis)
_ is the most common hereditary thrombotic disease
Factor V Leiden is the most common hereditary thrombotic disease
Factor V Leiden involves a _ mutation in the _ gene
Factor V Leiden involves a single-point mutation in the factor V gene
* Makes it invinsible to protein C cleavage and inactivation
* Causes fibrin to continuously be made –> clots
Factor V Leiden is a _ to _ substitution; specifically at the location where _
Factor V Leiden is a arginine to glutamine substitution; specifically at the location where protein C cleaves factor V to inactivate it
When should we be concerned about herditary thrombosis disorders?
- Young age (< 45)
- Family history
- Lack of risk factors
How do we test for Factor V Leiden?
Add activated protein C to aPTT assay –> clotting time is prolonged in normal patients but not as prolonged in FVL patients
Recurrent thrombosis and history of miscarriages are hallmark signs of _
Recurrent thrombosis and history of miscarriages are hallmark signs of antiphospholipid antibody syndrome
Antiphospholipid antibodies can be idiopathic in some patients; more commonly they are caused by systemic disease like _
Antiphospholipid antibodies can be idiopathic in some patients; more commonly they are caused by systemic disease like lupus (SLE)
Explain the two hit hypothesis of antiphospholipid antibody syndrome
- Presence of antiphospholipid antibodies
- Additional risk factor for hypercoagulability
What are the common clinical manifestations of antiphospholipid antibody syndrome?
- Venous thrombosis
- Arterial thrombosis
- Pulmonary embolism
- Stroke
- Livedo reticularis
- Fetal loss
- Heart valve disease
- Neuropathy
APS can affect any organ in the body because phospholipids are everywhere
_ is discoloration of skin in a reticular pattern due to obstruction of superficial capillaries
Livedo reticularis is discoloration of skin in a reticular pattern due to obstruction of superficial capillaries
Patients with APS will have a _ PTT and PT
Patients with APS will have a prolonged PTT and PT and thrombocytopenia
* Because antiphospholipid antibodies interfere with the reagents in coagulation studies
* The antibodies inhibit coagulation in vitro but act as procoagulants in vivo
* Ex: “lupus anticoagulant”
How do we test for APS in the lab?
- Mixing study: we expect PTT to remain prolonged
- We can then add phospholipids to pick up some of the antibodies –> correction of clotting time confirms ddx
- ELISA can identify nature of antibody specifically
Name 3 ways of acquiring antithrombin deficiency
- Liver disease (cirrhosis): decreased production of antithrombin
- Acute thrombosis, surgery, trauma: consumption of antithrombin
- Nephrotic syndromes: urinary loss of antithrombin
Antithrombin deficiency will cause excessive clotting due to the inability for AT to shut off its normal clotting factors _
Antithrombin deficiency will cause excessive clotting due to the inability for AT to shut off its normal clotting factors XIa, IXa, Xa, VIIa, IIa
Hereditary antithrombin deficiency is [inheritance pattern]
Hereditary antithrombin deficiency is autosomal dominant
Type I antithrombin deficiency. is a _ that results from a _
Type I antithrombin deficiency. is a complete loss of the mutant antithrombin that results from a nonsense mutation at the AT gene
Type II antithrombin deficiency is a _ that results from _
Type II antithrombin deficiency is a functionally defective antithrombin that results from missense mutation at a reactive site; defective antithrombin is still synthesized in normal levels
Two key clinical features of antithrombin deficiency:
- Increased risk of thrombosis
- Heparin resistance
Heparin mechanism of action:
Heparin works by binding antithrombin and inducing a conformational change that increases the affinity of AT for thrombin and factor X
* Increases the inactivating ability of antithrombin and promotes anticoagulation
We an use a _ assay to test for antithrombin deficiency; this is then followed by a _ test to measure the level of antithrombin antigen in the plasma
We an use a heparin cofactor assay to test for antithrombin deficiency; this is then followed by an ELISA to measure the level of antithrombin antigen in the plasma (and we can distinguish between type I and type II)
* We do not commonly test for AT deficiency because it is very rare
Factor _ is very important because it catalyes the conversion of fibrinogen to fibrin; if we have a mutation in this factor that causes its overproduction we tip the balance towards clotting
Factor II (thrombin) is very important because it catalyes the conversion of fibrinogen to fibrin; if we have a mutation in this factor that causes its overproduction we tip the balance towards clotting
Most patients with an overproduction of factor II have a point mutation known as _
Most patients with an overproduction of factor II have a point mutation known as G20210A (guanine –> adenine)
How common is factor II genetic mutation?
Factor II mutation (G20210A) is the second most common thrombophilia in white people, behind factor V Leiden
To test for factor II genetic mutation we can use _
To test for factor II genetic mutation we can use PCR
Protein S serves as _ while Protein C is able to _
Protein S serves as sidekick (cofactor) while Protein C is able to directly inactivate Va and VIIIa
Thrombophilias cause _
Thrombophilias cause excessive clotting
