Thrombotic Disorders- Lecture Flashcards
Thrombophilias are _ disorders
Thrombophilias are clotting disorders
The three common risk factors that make up Virchow’s triad and increase the risk of DVT are _ , _ , and _
The three common risk factors that make up Virchow’s triad and increase the risk of DVT are endothelial damage , abnormal blood flow or venous stasis , and hypercoagulability
_ is a cause of endothelial damage (virchow)
Atherosclerosis is a cause of endothelial damage (virchow)
Abnormal blood flow or venous stasis (virchow) may be caused by:
- Prolonged immobilization
- Varicose veins
- Atrial fibrillation
- Cardiac valve stenosis
Hypercoagulability (virchow) may be caused by:
- Smoking
- Oral contraceptives
- Pregnancy
- Malignancy
- Age
- Trauma/surgery
What are some clinical indications that a thrombi is secondary to a thrombotic disorder?
- Thromboses in abnormal places
- History of recurrent thromboses
- Family history
- Less than 50 years old
- One or more miscarriages
_ is a particular malignancy that is associated with DVTs due to its production of a mucin that acts as a procoagulant
Adenocarcinoma is a particular malignancy that is associated with DVTs due to its production of a mucin that acts as a procoagulant
Name four hereditary thrombotic disorders:
- Factor V Leiden
- Factor II gene mutation
- Protein C and S deficiencies
- Antithrombin deficiency
_ is an autoimmune condition that is most commonly idiopathic or acquired and leads to hypercoagulability and thromboembolitic events
Antiphospholipid antibody syndrome (APS) is an autoimmune condition that is most commonly idiopathic or acquired and leads to hypercoagulability and thromboembolitic events
Explain APS and the two-hit hypothesis
- About 5% of the population has antiphospholipid antibodies without having APS
- An additional risk factor is needed to proceed to APS
Clinical features of APS
Antiphospholipid antibody syndrome:
* Recurrent venous and arterial thromboses
* Recurrent fetal loss
* Pulmonary emboli
* Heart valve disease
* Nephropathy
* Livedo reticularis
PT and PTT values are _ with APS due to _
PT and PTT values are prolonged with APS due to antibodies inhibiting coagultion in vitro (the medium used is a phospholipid)
* Mixing study does not correct PT/ PTT
If the PT/ PTT remains prolonged after a mixing study, we can confirm an APS diagnosis by adding _
If the PT/ PTT remains prolonged after a mixing study, we can confirm an APS diagnosis by adding excess phospholipid to soak up the antiphospholipid antibodies
False positive syphilis screens may be seen in patients with _
False positive syphilis screens may be seen in patients with anticardiolipin antibodies (APS)
We can use _ testing to determine the type of antiphospholipid antibody syndrome
We can use ELISA testing to determine the type of antiphospholipid antibody syndrome
* Lupus anticoagulant
* Anticardiolipin antibodies
* Anti-beta 2 glycoprotein I antibodies
_ is associated with an inability of Protein C to cleave the mutated factor V protein
Factor V Leiden is associated with an inability of Protein C to cleave the mutated factor V protein
_ is the most common hereditary thrombotic disorder
Factor V Leiden is the most common hereditary thrombotic disorder
Atypical clotting locations include:
- Mesenteric veins
- Portal veins
- Hepatic veins (Budd Chiari)
- Ovarian veins
- Renal veins
Factor II is activated by factors _ + _
Factor II is activated by factors Va + Xa
Factor II gene mutation is a point mutation _ that causes _
Factor II gene mutation is a point mutation G20210A that causes an overproduction of prothrombin
* G –> A
Protien C and S work together to stop clotting by inactivating factors _ and _
Protein C and S work together to stop clotting by inactivating factors VIII and V
Protein (C/ S) is the sidekick and (C/ S) cleaves
Protein S is the sidekick and Protein C cleaves
Protein C and S deficiency can be inherited or acquired from _ , _ , _
Protein C and S deficiency can be inherited or acquired from liver disease , vitamin K deficiency , chemotherapy
Warfarin blocks the enzyme _
Warfarin blocks the enzyme vitamin K epoxide reductase
The reduced form of vitamin K is needed for _ and activation of _ factors
The reduced form of vitamin K is needed for gamma-carboxylation of glutamate and activation of X, IX, VII, II, protein C and protein S factors
Why should warfarin not be given without a heparin bridge?
- Wafarin inhibits X, IX, VII, II and Protein C and S
- Protein C and S have the shortest half life so when they are first to be depleted, the patient ends up in a hypercoagulable state
- This increases the risk of thrombosis
- Microthrombi in cutaneous and subcutaneous venules can lead to lessions –> bullae –> necrosis
Treatment for warfarin skin necrosis includes _ , _ , and _
Treatment for warfarin skin necrosis includes stop warfarin , provide vitamin K , and fresh frozen plasma (replenish C and S), start heparin product
Purpura fulminans is also known as _
Purpura fulminans is also known as Waterhouse-Friderichsen syndrome
* It is essentially warfarin skin necrosis but without warfarin
Waterhouse-Friderichen syndrome is _
Waterhouse-Friderichen syndrome is acute, widespread thrombi causing rapid progression of bruising and skin erythema to black-blue bullae and necrotic plaque
Purpura fulminans and TTP and ITP can present very similarly, however, _ has the most rapid progression
Purpura fulminans and TTP and ITP can present very similarly, however, Waterhouse-Friderichsen has the most rapid progression
Antithrombin deficiency can be acquired or hereditary; it is inherited in _ pattern
Antithrombin deficiency can be acquired or hereditary; it is inherited autosomal dominant
Antithrombin deficiency can be acquired from decreased production like in _ , increased use like in _ , or loss of antithrombin from _
Antithrombin deficiency can be acquired from decreased production like in liver disease , increased use like in trauma, surgery , or loss of antithrombin from nephrotic syndromes
Type I antithrombin deficiency is a _ mutation that results in _
Type I antithrombin deficiency is a nonsense mutation that results in complete loss of antithrombin function
Type II antithrombin deficiency is a _ mutation that results in _
Type II antithrombin deficiency is a point mutation that results in defective antithrombin protein
* End up with normal circulating levels, just not as functional
* This is more commont than type I
_ is a unique consequence of antithrombin deficiency that can often lead to its diagnosis
Heparin resistance is a unique consequence of antithrombin deficiency that can often lead to its diagnosis
* Heparin normally induces a conformational change in AT that increases its affinity for X and II
* It cannot enhance this anticoagulation in people with AT deficiency
