DVT Flashcards
Tobacco Use Disorder (DSM-5)
- at least 2 of the following over 12 months:
- larger amounts, longer period, craving, time spent obtaining, affects life, etc.
Treatments for smoking cessation? Side effects?
- interventional and behavioural support VERY effective (advice from doctors helps people quit! brief intervention, etc.)
- NRT –> transdermal patch, gum, lozenge, inhaler, etc. (no superiority of one over the other)
- skin reactions due to adhesives, insomnia, heart palpitations, chest pain, N/V, GI, mouth ulcers, hiccups
- Vareniciline –> partial agonist (release of DA) and antagonist (reduces effect of nicotine) at the alpha-4-beta-2 receptor, effect increases if taken with NRT
- nausea, insomnia, constipation, weird dreams
- Buproprion –> serotonin/NE re-uptake inhibitor
- only given if varenciline/NRT contraindicated
- insomnia, dry mouth, decreased appetite
- cannot give to patients w seizure
Stages of change in motivational interviewing?
- Pre-contemplation (no intent to change)
- Contemplation (aware of issue)
- Preparation (intent on taking action)
- Action
- Maintenance
- Repair
Describe primary hemostasis
- occurs in minutes
- vessel wall injury –> vasoconstriction –> circulating VWF binds to sub-endothelial collagen –> VWF binds GPIb on platelets –> platelets are activated leading to a hemostatic plug at the site of injury
- platelets aggregate via GPIIbIIIa receptors and fibrinogen
What are signs of defects in primary hemostasis? What are possible etiologies?
- excessive bruising, mucosal bleeds (epistaxis, gums, GI, menses), post-operative bleeds
- PLATELET ISSUE –> either quantitative (thrombocytopenia) or qualitative (platelet function defect aka PFD)
- VON WILLEBRAND DISEASE –> either quantitative (type I which is moderate, type III which is severe, or acquired/autoimmune) or qualitative (type II)
What is the most common congenital bleeding disorder?
Type I Von Willebrand Disease
What tests could you order to assess primary hemostasis issues?
- CBC (platelet count)
- Aggregometry (ability to aggregate with platelet agonists)
- VWF testing - quantity with Ag, quality with VWF and F8 activity (VWF stabilizes F8)
Describe secondary hemostasis
- occurs over hours
- cascade of coagulation factors leading to a fibrin net that stabilizes the hemostatic plug
- TF (F7a) from endothelium binds F8a –> cleaves F10 to F10a
- F10a cleaves prothrombin (F2) to thrombin (F2a)
- Thrombin cleaves fibrinogen to fibrin, activates platelets via PAR receptors, and produces F11a which drives more thrombin production
- Fibrin and F13a link to produce an insoluble fibrin clot
Describe fibrinolysis.
What is an example of an antifibrinolytic drug?
- occurs over days/weeks
- tPA released by endothelium converts plasminogen to plasmin which breaks down the fibrin clot
- this results in fibrin degradation products such as D-dimer (reflects systemic clotting activity, really only useful in ruling things OUT if low pre-test probability i.e. high sensitivity)
- tranexamic acid (TXA)
- Alpha-2-PI inhibits plasmin and PAI inhibits plasminogen
What are signs of a defect in secondary hemostasis? What could possible etiologies be?
- umbilical stump bleed, joint or IM bleeds, delayed post-operative bleeding
- Hemophilia A (F8) and Hemophilia B (F9) (both x-linked recessive)
- An acquired inhibitor (most common is against F8)
What do PTT and PT (INR) measure?
PTT –> intrinsic pathway (8/9/11/12)
PT (INR) –> extrinsic pathway (7)
What is INR standardized for? What is considered normal?
Standardized for warfarin therapy (should be 2-3)
1 is considered normal (including if on DOAC/ heparin)
What could be a cause of an abnormal PTT/INR?
- traumatic venipuncture, heparin contamination, hemolysis, lipemia, increased hematocrit, hyperbilirubinemia
What do the results of a PTT mixing study indicate?
- Mix patient and normal plasma
- If clot time corrects it is a factor issue
- If it does not correct there is an inhibitor present
What are some examples of natural coagulation inhibitors?
- Protein C and S (inactivate F5a and F8a, vitamin K dependent)
- Antithrombin (prevents cleaving of prothrombin to thrombin)
- Tissue factor pathway inhibitor (TFPI - inhibits TF aka F7a)
What is Virchow’s triad?
- factors leading to thrombophilia
1. Endothelial injury
2. Stasis
3. Hypercoagulability
What are some factors that can cause thrombophilia?
- Cancer, pregnancy, OCPs, androgens, post-op, myeloproliferative neoplasm
What are two cofactors involved in the coagulation pathway?
calcium and phospholipids
What can cause superficial vein thrombosis?
IV/catheters/etc.
Risk factors for VTE?
- immobility (in-patient hospitalization), age, pregnancy, obesity, trauma, surgery, malignancy, OCPs, inflammation, antiphospholipid Ab syndrome
- hereditary causes –> protein C/S/antithrombin deficiencies, factor V Leiden, increased F8
- these risks are supra-additive
Post-Thrombotic Syndrome
- chronic venous insufficiency leading to venous HTN
- edema, hypoxia, inflammation, swelling, pain, ulcers, rash/ skin changes
- consider TPA to prevent
Symptoms of a DVT?
Symptoms of a PE?
- swelling, painful, red, warm
- SOB, chest pain (pleuritic), hemoptysis
Best imaging methods for DVT? P/E?
- Compression U/S best for proximal DVT
- if (+), venous compression will be limited or gone - CT pulmonary angio for P/E
- will see filling defect, failure of PA opacification
- V/Q scan is an alternative (no contrast or radiation
but takes longer and less accesible)
*VQ scan is best screening tool for CTEPH
What is a measure of DVT likelihood?
Well’s Score
When should you consider hereditary testing for VTE?
- unprovoked, recurrent, family Hx, purpura fulminans in young
How long should DVT treatment be? What can you give for prophylaxis?
- 3-6 months for DVT/ transient factor
- 6-12 months fro PE
- indefinite if high risk/ unprovoked/ persistent factor/ cancer assx thrombosis
- LMWH or DOACs
What reverses warfarin? Heparin
Warfarin –> vitamin K
Heparin –> protamine
What is the MOA of DOACs?
Which DOACs can be given as monotherapy for VTE?
- direct inhibitors of thrombin (Dabigatran) (good if antithrombin deficient)
- direct inhibitors of Factor 10a (Rivaroxaban, Apixaban, Edoxaban)
- only rivaroxaban and apixaban are given for VTE
*DOACs are dosed differently for different indications
Benefits of DOAcs
Cons of DOACs (who cannot take them?)
(+) –> faster acting, no monitoring, fewer dietary and drug interactions
(-) –> expensive, cannot give if renal insufficiency, only Dabigatran is reversible, cannot give if antiphospholipid syndrome/ mechanical heart valves/ on rifampin or phenytoin
Definition of pulmonary HTN
- Mean pulmonary pressure (PAP) greater than 20mmHg
- Note: this is in the pulmonary circulation, not bronchial
What is the transpulmonary gradient? How is it calculated? What is a normal value?
- Pressure decreases as the blood flows from the R heart across the pulmonary circulation to the L heart due to resistance
TPG = mean pulmonary artery pressure (mPAP) - mean left atrial pressure (LAP)
*mPAP = 2/3 dPAP + 1/3 sPAP
*LAP estimated from pulmonary capillary wedge pressure (PCWP), arterial puncture, or LVEDP via L heart catheter
- normal is under 10mmHg
How do you calculate pulmonary vascular resistance? What is a normal value?
PVR = TPG/CO
- normal is 150-250
Different Groups of Pulmonary Hypertension
Which groups do pre-capillary HTN and isolated post-capillary PH belong to?
Group 1 –> pulmonary arterial HTN (increased resistance to flow)
- intima proliferation, medial hypertrophy
- CT disease, HIV, portal HTN, congen heart disease
Group 2 –> Left heart disease (high back pressure from the left heart)
Group 3 –> Lung Disease/ Hypoxia (destruction of pulmonary parenchyma)
Group 4 –> Pulmonary Artery Obstructions
- Chronic Thromboembolic PH (CTEPH)
- P/E increases PVR (mPAP over 20) leading to small
vessel arteriopathy
Group 5 –> Unclear/ Multifactorial
pcPH –> 1/3/4/5
IpcPH –> 2/5
Pre-capillary PH vs isolated post-capillary PH?
pcPH –> increased TPG (arterial)
ipcPH –> normal TPG (venous)
How does Pulmonary HTN kill you?
- overtime get increase PAP/ PVR and decreased CO
- this leads to systemic hypotension –> decreased RV tissue perfusion –> RV ischemia –> right heart dysfunction with increased right arterial pressure
- RV overload leads to RV dilation –> LV compression
Symptoms of Pulmonary Hypertension?
How to diagnose?
Treatment?
- SOBOE, fatigue, palpitations, hemoptysis, weight gain, syncope
- echocardiogram (will see increased systolic peak tricuspid regurgitation velocity)
- 1 –> neurohormonal (target endothelin/ prostacyclin/ NO-SGC-cGMP pathways)
- 2 –> underlying cause
- 3 –> underlying cause
- 4 –> surgical endarterectomy, balloon angioplasty (+/- NH modulation)
- 5 –> underlying cause
What does a long history of productive cough suggest?
Chronic bronchitis often secondary to smoking
Causes of bronchiectasis?
Causes of hemoptysis?
Causes of atelectasis?
- obstruction, CF, measles, pertussis
- pneumonia, TB, bronchiectasis, cancer, SLE, trauma, P/E, left heart failure, aortic rupture, mitral stenosis, cocaine
- obstruction or compression i.e. mucus/ malignancy/ fluid/ foreign body/ hemo or pneumothorax
Which cancer is often linked to smoking and is more common in men?
What are histo signs of this cancer?
- Squamous cell carcinoma
- single cell keratinization, keratin pearls, intercellular bridges
Which cancers are centrally located?
- Squamous cell carcinoma
- Small cell carcinoma
What are common lung metastases sites?
- Brain, Bone, Liver, Adrenal gland
What does an adenocarcinoma look like? What does small cell cancer look like?
- glandular appearance, mucus formation
- small dark cells in non-cohesive clusters, hyperchromatic nuclei, absent nucleoli, scant cytoplasm, crush artifact (DNA strands)
What is Pancoast syndrome?
- Horners (anhydrosis, ptosis, constricted pupils) AND brachial plexus issues
- Commonly caused by an apex lung tumor (OFTEN squamous cell carcinoma)
- Will see a cavitary pancoast tumor
What is extrinsic allergic alveolitis?
- hypersensitivity pneumonia (i.e. mushrooms)
- chronic interstitial inflammatory infiltrate, granulomas
- treat w steroids
Heparin
- how does it work?
- different forms?
- endogenously released by mast cells
- potentiates antithrombin I/III which inactivates 9/10/11/12 and thrombin
- unfractionated, LMWH (dalteparin, enoxaparin), fondaparinux (only anti-10a)
Pros of LMWH
Cons of LMWH
(+) –> decreased risk of thrombocytopenia compared to unfractionated heparin, good for chronic use
(-) –> injection
Warfarin (aka Coumadin)
- how does it work?
- vitamin K antagonist (essential for 2/7/9/10) - all of these factors must be depleted for it to work, although INR will increase if even one is
Pros of Warfarin
Cons of Warfarin
(+) –> easily reversed, cheap, no renal excretion, effective and familiar
(-) –> slow acting so must be given with LMWH, requires monitoring, drug and dietary interactions, difficult to use with procedures, chemo interactions, nausea and vomiting
*note antigoagulants protein C+S are also vitamin K dependent
Percutaneous Coronary Intervention (PCI)
Percutaneous Transluminal Coronary Angioplasty (PTCA)
- minimally invasive but can cause restenosis, manageable with antiplatelets but more issues if diabetic
- often use with dual antiplatelet therapy for 3m-2y post
P2Y12ADP Receptor Inhibitors
Which can you not give in surgery
- block platelet activation (primary hemostasis)
- used in PCI
- often part of dual antiplatelet therapy with aspirin
- clopidogrel, ticagrelor, prasugrel
- cannot give clopidogrel in surgery
Thrombin receptor antagonist
- voraxapar
- cannot use if active stroke or bleeding, VERY high risk of bleeds
Clot busters (thrombo/fibrinolytics)
- TPA –> activates plasmin
- need catheter access
- use during MI/ stroke/ VTE/ PE if severe risk outweighs the increased bleed risk
How does dosing of warfarin with LMWH work?
- looking for therapeutic INR range of 2-3
- have to give LMWH for a minimum of 5 days no matter what (or longer if still not therapeutic)
- also need at least 2 days of therapeutic overlap
What are some anticoagulant drug limitations based on kidneys/ liver/ blood?
- LMWH and DOACs are dependent on renal excretion
- DOACs are dependent on liver metabolism
- microcytic anemia may indicate active bleeding
Which anticoagulants are often first line/ safest in terms of major bleeds?
Which anticoagulant can be taken in pregnancy?
- DOACs
- LMWH
What treatments are appropriate for cancer associated thrombosis?
- DOACs as long as there is no increased risk of bleeds
- If there is a high bleeding risk or GI cancer –> LMWH
Stable vs unstable CAD
- stable –> lifestyle disease, plaques, 70%+ occlusion
- unstable –> morbid disease, thrombus (due to shear stress, oxidative stress, inflammation), any size
Treatments for CAD
- antithrombotics/ antiplatelets (revascularization)
- clopidogrel has a 2 step metabolism, slower onset
than prasugrel and ticagrelor - if high bleed risk do not continue dual anti-platelet
therapy (DAPT) for long
- clopidogrel has a 2 step metabolism, slower onset
- anti-ischemics (pre/afterload, HR, contractility)
- anti-arrhythmics/ anti-inflammatory (cardioprotection)
What are some platelet agonists?
- serotonin, epinephrine, ADP, TXA2, collagen, thrombin, tissue factor
Aspirin (ASA)
- How does it work
- When is it recommended
- concerns
- inhibits TXA2
- better for MI in males and ischemic stroke in females
- only recommended for males 45+ if MI risk is greater than GI hemorrhage and woman if ischemic CVA risk is greater
- do NOT use for CV protection in women under 55 and men under 45
- increases risk of serious bleeding events with age
Explain the mechanism behind SOB in P/E
Acute hypoxemia due to V/Q mismatch –> chemoreceptors –> increased respiratory drive
CHADS65 Criteria
CHADS2 Criteria
- If over 65 (OAC), if under 65 but stroke/TIA/HTN/CHF/DM (OAC), if under 65 but CAD/arterial vascular disease (ASA)
CHF
HTN
Age over 65
DM
Stroke/TIA (2)
What factors can affect INR?
- Diet (low vitamin K intake when sick)
- Interactions (metronidazole will increase INR)
- Diarrhea
- Non-compliance with medication
Course of action if INR is minorly supratherapeutic (under 5)?
omit one dose or lower dose
What is bridging?
Substituting LMWH for warfarin when warfarin is interrupted –> this shortens the period of time that a patient is not anticoagulated
- warfarin has a long t1/2 so it takes 5 days to normalize after starting/stopping
- especially needed if at high risk for thromboembolism i.e. mechanical mitral valve
Proximal deep veins
Distal deep veins
Superficial veins
- external iliac, femoral, popliteal (70-80%)
- anterior tibial, peroneal, posterior tibial (20-30%)
- greater and lesser saphenous veins
*distal DVT and superficial vein thrombosis dont always need anticoagulation
What are DOAC contraindications?
- liver disfunction, eGFR <30, pregnant or breastfeeding, extremes of body weight, impaired absorption in the stomach or small intestine
What is the indication for an IVC filter?
- acute VTE and anticoagulation contraindication
- can provoke thrombosis itself, take out ASAP
