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Year 3 - Clinical > 24 - VTE > Flashcards

24 - VTE Flashcards

1
Q

What is the Virchow triad in thrombosis?

A
  • Endothelial injury (trauma to blood vessels)
  • Abnormal blood flow (ex: sitting w/ legs crossed for long time)
  • Hyper-coagulability (ex: genetics, infection, etc.)
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2
Q

Describe the intrinsic pathway

A

Injury -> exposure of collagen basement membrane (bloodstream should never see this protein matrix) (+contact activation) -> F12 -> F12a -> F11 -> F11a -> F9 -> F9a + F8C -> F10

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3
Q

Describe the extrinsic pathway

A

Injury -> tissue thromboplastins (tissue factor) -> 7 -> 7a -> catalyzes conversion of F10 -> F10a

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4
Q

Describe the common pathway

A

F10 -> F10a (+F5a) -> F-2 (prothrombin) -> F2a (thrombin) -> F1 (fibrinogen) + 13

F1 -> soluble fibrin (+13a) -> insoluble fibrin strands -> retracted fibrin thrombus “fibrin clot” -> soluble fibrin fragments

13 -> 13a (used to convert soluble fibrin to insoluble fibrin

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5
Q

Describe the platelet pathway

A

Injury -> vasoconstriction & endothelial adhesion (+stasis of blood flow) -> platelets (+adhesion) -> release reaction -> ADP + TxA2 + aggregation (this reaction produces all 3 but ADP -> TxA2 -> aggregation also) (+vWF) -> platelet thrombus -> retracted fibrin thrombus -> soluble fibrin fragments

Plasminogen -> plasmin -> retracted fibrin thrombus

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6
Q

What is important to note about thrombin?

A
  • Will always form a clot
  • Takes fibrinogen (floating in bloodstream) & catalyzes conversion to fibrin
  • Also works in platelet pathway
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7
Q

What is important to note about insoluble fibrin?

A

Acts as protein layer that attaches itself to vessel wall (after a few days the clot will be digested)

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8
Q

What is vWF?

A
  • Von Willebrand Factor

- Protein that binds to clump of platelets and collagen and then contracts and pulls platelets up against vessel wall

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9
Q

What is important to note about factor VIII (8)?

A
  • Synthesized by vascular endothelial wall and released into bloodstream
  • Factor 8C = coagulant material
    • Binds to Factor-8vWF on blood vessel wall (F8C on blood side, F8vWF on tissue side)
    • F8C pulls complex into bloodstream (“cleaves in the bloodstream”)
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10
Q

What are TxA2 and PGI? Where are each synthesized?

A
  • TxA2 (thromboxane A2) = platelet aggregator and vasoconstrictor
  • PGI (prostacyclin) = platelet anti-aggregator and vasodilator (prevents clotting)
  • In the blood vessel wall – AA (arachidonic acid) -> PGI catalyzed by COX (cyclooxygenase)
  • In platelets – AA -> TxA2 catalyzed by COX: TxA2 then exits platelets
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11
Q

Factors predisposing to bleeding

A
  • Open vessel (ex: recent surgery)
  • Platelet defects (ex: drugs – ASA, clopidogrel)
  • Pro-clotting factor deficiencies (ex: excess of protein C or S; deficiency of inactivated forms of any clotting factors)
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12
Q

Describe the PT and INR tests

A
  • Based on time for detection of clot formation in a test tube of px plasma after addition of thromboplastin and calcium
  • Interpretation = > 12 sec is suggestive of defective extrinsic & common pathway; test is sensitive to reductions in factor 2, 7, & 10 (note: warfarin reduces synthesis of factors 2, 7, 9, & 10)
  • Clinical notes = factor 7 is very sensitive to warfarin (b/c of its very short plasma t1/2), therefore PT (or INR) may rapidly become prolonged during warfarin therapy w/o adequate reduction of activated factors 2 or 10
    • Thrombotic state may still be evident since both factors 2 & 10 may continue to be activated via intrinsic pathway
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13
Q

Does thrombocytopenia or defective platelets affect PT, INR, or aPTT?

A

None

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14
Q

Does ASA or other NSAIDs affect PT, INR, or aPTT?

A

None

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15
Q

Describe the aPTT (activated partial thromboplastin time) test

A
  • Based on time for detection of clot formation in a test tube of px plasma after addition of activating agent and calcium
  • Interpretation = 33 sec is suggestive of defective intrinsic & common pathway; test is sensitive to reductions in factors 2, 8, 9, 10, 11, & 12
  • Clinical notes = heparin immediately accelerates binding & inactivation of activated forms of factors 2, 9, 10, 11, & 12 by antithrombin; PD action of heparin on PTT is immediate, but maximal effects are seen commonly after 6 h (4.5 half-lives of heparin)
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16
Q

Degradation rate of vit-K dependent clotting factors upon administration of warfarin

A
  • Warfarin = vitamin-K antagonist, so inhibits production of these clotting factors (2, 7, 9, & 10)
  • Factor 7 degrades in 4-7 h
  • Factor 9 in 21-30 h
  • Factor 10 in 27-48 h
  • Factor 2 in 42-72 h
  • Conclusion = can still form clot through intrinsic pathway in first 24-48 h after warfarin administration, but past that factors 2, 9, & 10 will diminish so no longer able to clot
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17
Q

Relationship between PT and INR

A
  • INR = (PT/PTc)^ISI
  • PT = px prothrombin time
  • PTc = mean prothrombin time for lab control
  • ISI = international sensitivity index
  • Don’t really care about actual PT, only care about INR
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18
Q

Difference between red thrombi and white thrombi?

A
  • White thrombi = arterial thrombi; primarily made of platelets but also fibrin & WBC’s (ex: coronary artery thrombosis, cerebral circulation thrombi)
  • Red thrombi = venous thrombi; primarily fibrin & RBC’s and a small platelet plug (ex: DVT, pulmonary emboli, ischemic limbs)
  • ASA plays no role in tx or prevention of venous thrombi
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19
Q

What are some examples of procoagulants and anticoagulants?

A
  • Clotting (procoagulants) – tissue thromboplastins, exposed collagen, activated factors, TxA2, vWF, factor-8 coagulant material
  • Bleeding (anticoagulants) – protein C, protein S, factor deficiencies, antithrombin (AT), prostacyclin, heparin, tPA, plasmin
20
Q

Common causes of hypercoagulable disorders?

A
  • DVT
  • MI
  • Prosthetic devices in contact w/ blood
  • Atrial fibrillation
21
Q

Pathophysiology of less common hypercoagulable disorders

A
  • Factor 5 Leiden & prothrombin gene mutations are relatively common inherited thrombophilic abnormalities in Caucasian population conferring the individual w/ small increase risk for venous thrombosis
  • Antithrombin, protein C, & protein S deficiency are less common that confer a significantly higher risk for venous thrombosis
  • Development of phospholipid antibodies is an autoimmune condition that predisposes an individual to arterial thrombosis, venous thrombosis, and/or pregnancy loss
  • Cancer is common cause of thrombophilia
  • Long-term anticoagulation often considered in these px; tx should be individualized, balancing risk of thrombosis vs. risk of bleeding w/ anticoagulants
22
Q

What are some risk factors for thrombogenesis?

A
  • Obesity
  • Age > 40 y/o
  • Malignancy
  • Immobilization
  • Major surgery
23
Q

Characteristics of deep vein thrombosis

A
  • Unilateral, warm, swollen, painful leg
  • Usually starts in calf (distal DVT)
  • May progress, moving up the thigh (proximal DVT)
  • Diagnosis based on symptomatology alone is correct in less than 50% of the time
24
Q

Characteristics of pulmonary embolism

A
  • Most common clinical presentation = tachypnea, chest pain, dyspnea, tachycardia (very acute onset)
  • Commonly found in px w/ recent history of DVT
  • Not an easy diagnosis; requires objective methods to establish
25
Q

Atrial fibrillation increases risk of ____ embolization

A

Cerebral

26
Q

What is important to note about px w/ prosthetic heart valves?

A
  • Px w/ prosthetic heart valves are at increased risk of developing valvular thromboembolism (most common clinical manifestation = cerebral embolism)
  • Embolization greater w/ mechanical than bioprosthetic valves
27
Q

Describe the difference between tx for mechanical and bioprosthetic valves

A
  • Mechanical valves – warfarin ING target 2.5 recommended for valves in aortic position w/ no risk factors for TE; if risk factors present then target 3; target 3 recommended for valve in mitral position
  • Bioprosthetic valves – generally lower risk for systemic embolization; ASA 75-100 mg reasonable in all px w/ bioprosthetic valves; for first 3-6 months after bioprosthetic valve surgery target warfarin INR 2.5
28
Q

What are the goals and monitoring parameters for UFH and warfarin?

A
  • Goals – maintain aPTT w/in the labs specific therapeutic range (ex: 59-99 sec)
  • Heparin provides immediate anticoagulant effect, so check aPTT’s q6h initially and adjust heparin infusion to maintain aPTT w/in desired range as early as possible (ie: w/in first 24 h)
  • Check platelet count daily
  • Start warfarin on day 1 at 5 mg po & adjust subsequent daily dose according to INR goal (individualized to thromboembolic disorder)
  • Stop heparin after at least 5 days of combined therapy & when INR is greater than target for at least 2 consecutive days
  • Exceptions – px w/ major pulmonary embolism or iliofemoral vein thrombosis – run heparin for up to 10 days & start warfarin after a delay of 4 days
  • Possible indications – pulmonary embolism w/ shock; massive DVT w/ limb gangrene
29
Q

Parameters to monitor therapy for UFH, LMWH, or warfarin

A
  • aPTT, INR, Hgb, PLTS, & clinical signs of bleeding
  • Clinical signs of bleeding (melena (black tarry stools), hematuria, ecchymosis, hematemesis, hemoptysis, epistaxis) monitor at least daily
30
Q

What are the drugs and duration recommendations for DVT and PE?

A
  • UFH or LMWH and start on warfarin at the same time
  • UFH or LMWH usually d/c after 5 days provided that INR has been in therapeutic range (> 2) for at least 24 h
  • Heparin should be continued longer (ie: 10 days) in those w/ massive pulmonary embolism or iliofemoral vein thrombosis
  • For provoked VTE, continue warfarin for 3 months maintaining INR target 2.5
  • For idiopathic or unprovoked VTE, therapy recommended for 3 or more months (up to 2.5 years)
  • Continue warfarin indefinitely if pt has risk factors (ex; malignancy, AT deficiency)
  • If pt has thrombotic/embolic recurrence despite anticoagulation, continue warfarin indefinitely, but increase INR target to 3
31
Q

Which DOAC has the longest t1/2?

A

Dabigatran

32
Q

What factors do LMWH, dabigatran, rivaroxaban, and apixaban target?

A
  • LMWH = factors 2a and 10a
  • Dabigatran = factor 2a
  • Rivaroxaban and apixaban = factor 10a
33
Q

Should LMWH, dabigatran, rivaroxaban, and apixaban be avoided in CrCl < 30?

A
  • Yes

- Avoid apixaban if CrCl < 25

34
Q

Drug interactions for LMWH, dabigatran, rivaroxaban, and apixaban?

A
  • LMWH = none known
  • Dabigatran = P-gP inhibitors/ inducers
  • Rivaroxaban and apixaban = CYP 3A4 and P-gP inhibitors/ inducers
35
Q

Which DOAC has the overall lowest risk of bleeding?

A

Apixaban

36
Q

Reversal agents for anticoagulant related bleeding

A
  • *Effectiveness if anticoagulant specific
  • Protamine (IV)
  • Vit K (PO, SC, IV)
  • FFP (fresh frozen plasma)
  • fRVIIA (recombinant factor VIIa 7a)
  • 4-PCC (4 factor prothrombin complex concentrates)
  • Idarucizumab (monoclonal Ab fragment specifically targeted at dabigatran)
37
Q

Warfarin - indication, onset, monitoring, reversal options

A
  • Tx of major thrombosis
  • Causes clotting factor depletion (factors 2, 7, 9, 10)
  • Oral only
  • Slow onset (days); full effects > 1 week
  • INR for monitoring
  • Stop 1 week prior to planned surgeries
  • Use w/ any degree of renal function
  • Reversal = vit K, FFp, rFVIIa, 4-PCC; dialysis not effective in overdose
38
Q

Dabigatran - indication, onset, monitoring, reversal options

A
  • For prevention of stroke w/ A fib
  • Binds to & inhibits thrombin (2a)
  • Oral only
  • Fast onset (1 h); full effects in 3 days
  • Increases aPTT test (but not recommended for monitoring according to manufacturer)
  • Stop 1-2 days prior to planned surgeries
  • Use CI if ClCr < 30
  • Reversal = hemodialysis, rFVIIa; no role for FFP b/c dabigatran provides anticoagulation by inhibition not by clotting factor depletion; 4-PCC not effective
39
Q

Rivaroxaban/ apixaban - indication, onset, monitoring, reversal options

A
  • For prevention of stroke w/ A fib
  • Binds to & inhibits factor 10a
  • Oral only
  • Fast onset (3-4 h), full effects in 2 days
  • Increases INR test (but not recommended for monitoring according to manufacturer)
  • Stop 1-2 days prior to planned surgeries
  • Use CI if ClCr < 30
  • Reversal = 4-PCC (octaplex); hemodialysis removal not effective; no role for FPP b/c these agents provide anticoagulation by inhibition, not be clotting factor depletion
40
Q

Describe the Greenfield filter. What are some indications?

A
  • Mechanical device placed in inferior vena cava to “filter” emboli origination from lower extremities
  • Possible indications – CI to anticoagulant therapy (ex: bleeding PUD – peptic ulcer), recurrent PE despite adequate anticoagulation
41
Q

Counselling issues for px on LMWH, warfarin, or DOAC’s

A
  • Inform all HCP’s of anticoagulant use
  • Avoid ASA and other NSAIDs, and some dietary supplements as may exacerbate bleeding
  • Discuss w/ pharmacist before taking any new medication (Rx or OTC) b/c lots of drug interactions
  • Maintain usual diet; we will dose warfarin to your diet (can be affected by diets high in vitamin K); avoid changes in diet
  • Recommend medic-alert bracelet identifying anticoagulant use
  • For warfarin, instruct pt they will be undergoing weekly or biweekly monitoring of blood INR values
  • Inform Dr. immediately if experience any of the following
    • Bleeding after cuts that don’t stop reasonably quickly
    • Black or blue spots or bruises on skin
    • Bleeding from nose or mouth
    • Red or dark brown urine
    • Red or black appearing stools
42
Q

Describe hemophilia

A
  • Result is the same despite the type (can’t catalyze 10 -> 10a)
    • Type A = deficiency of Factor 8C w/ normal factor 8-vWF; referred to as “classical hemophilia”
    • Type B = deficiency of factor 9; referred to as “Christmas disease”
43
Q

What is von Willebrand’s disease?

A

Diminished factor 8-vWF, but normal factor 8C

44
Q

What is disseminated intravascular coagulation?

A

Simultaneous clotting and bleeding; commonly seen w/ severe sepsis

45
Q

What is thrombocytopenia?

A
  • Platelet count < 100,000
  • Decreased platelet count from either decrease in bone marrow production or due to increased peripheral (ie: circulating blood) destruction (give platelet infusion if < 30,000 b/c could have spontaneous bleed in brain)
46
Q

What effect does severe liver disease have on clotting/bleeding?

A
  • Bleeding secondary to factor deficiencies
  • Decreased hepatic synthesis of factors 1-13, except factor 8
  • Also, have decreased synthesis of AT, plasminogen, and alpha 2-antiplasmin
  • DIC may also occur

Year 3 - Clinical (30 decks)

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