Clotting disorders Flashcards
How do platelets and clotting factors usually circulate
In inactive form
Vascular injury leads to
vascular spasm
Plt adhesion mediated by vWF
coagulation cascade
What are PT/INR measure
integrity of extrinsic (factor VII) and common pathway
Used for Warfarin check
What does PT represent
time in seconds for plasma to clot after you have added calcium and thromboplastin (activates the extrinsic pathway)
What causes a prolonged PT
Deficiencies or inhibitors of clotting factors within the extrinsic or common pathways
Why was INR created
to assess patient’s PT in comparison to a geometric mean of 20+ healthy males and females at THAT specific lab
What does aPTT measure
Integrity of intrinsic (VIII, IX, XI, XII)and common pathways of the coag cascade
What is PTT (partial thromboplastin time)
time in seconds it takes for patients plasma to clot after adding Calcium (phospholipid that activates the intrinsic pathway)
What is the clotting factor where intrinsic and extrinsic all come together
Factor Xa! It activates thrombin and causes a clot to form
What type of patient would we worry about if they have a deficient PT
Young, healthy patient; suspect something autoimmune, (liver disease, DIC)
Those are the patients you should prob preform a mixing study on
-Elderly with deficient PT you think, ok this might just be age related, or they could be on warfarin
What are the outcomes of a mixing study with aPTT
- if PTT corrects when you add “normal blood”: Pt has a factor deficiency* present in intrinsic path (8, 9, 11, 12). Essentially, when you add normal blood, the deficiency corrects bc you add those deficient factors in!
- If PTT stays prolonged: it must be something that is destroying any blood that comes in (drugs like heparin; AI hemophilia A; Lupus anticoagulant)
If PTT corrects and you determine it is 2/2 an intrinsic path factor deficiency, what should you do
Get a clotting factor assay to determine which factor is involved, and determine whether it is acquired or congenital
What is Lupus anticoagulant (LAC)
Prolonged PTT
MC in young females- do NOT have to have SLE!
Suspect if pt: No bleeding Hx or has a clot and baseline prolonged PTT before you started the anticoag
-AutoAbs are directed at phospholipid binding proteins, causes Ab mediated thrombosis
What are the outcomes of a mixing study with PT
PT corrects: deficiency in extrinsic path (factor 2, 7, 10, fibrinogen), liver disease
PT stays prolonged w/ prolonged PTT: inhibitor of extrinsic path, factor V inhibitor
Deficiencies in clotting factors found by PT or aPTT mixing studies are MCC by
Supratherapeutic warfarin (rat poison)
Etiologies that cause inhibition of all pathways found in PT/PTT mixing studies include (what causes to “stay prolonged”)
LAC
nonspecific factor inhibitors w/ lymphoproliferative d/o
monoclonal protein disorder (cause autoimmunity)
What is warfarin
Inhibits vitamin K dependent clotting factors (7, 9, 10, protein C&S)
Pregnancy category X
What can a supratherapeutic INR 2/2 warfarin lead to
elevated PTT
- for every 1.0 increase in PT, 16-17 sec. increase in PTT
- If pt comes in w/ an INR of 8 and they aren’t bleeding, hold dose then decrease
- if pt comes in w/ INR 4, hold dose 1-2 days then continue at same dose
- if pt comes in vomiting and can’t take warfarin, PR/INR will be high
2 MC reasons to use warfarin are
- AFIB (goal INR 2-3)
- VTE (goal INR 2-3)
- Mechanical valve replacement (goal INR 2.5-3.5)
What is UFH
Thrombin (factor IIa) and Xa inhibitor
Large molecule NOT well absorbed subQ, and can cause HIT
What is LMWH
Stronger Xa inhibit, only mild IIa (thrombin) inhibition w/ longer half life
Derived from UFH but defractionated to make a smaller molecule more well absorbed subQ
*SAFE for pregnancy= LOVENOX
(lovenox is dosed by weight)
-generally not good for those that are obese or w/ CKD/ESRD
Do you need to get labs or monitor LMWH
No! no need
But if you want to monitor your pt, you can check efficacy with anti-Xa levels 3-4 hours after Lovenox
-The only people you may need to monitor are obese or very thin patients
What is Fondaparinux
synthetic factor Xa inhibitor that causes ATIII to change in coag cascade. 17 hr half life
NO REVERSAL AGENT*
What are DOAC’s
Rivaroxiban/Epixaban: direct anti-Xa
Dabigatran: oral direct thrombin inhibitor used for AFib and VTE
What are reversal agents for anticoagulants
Heparin: protamine
Warfarin: vitamin K
Lovenox: Protamine wil only reverse 60%; give Plt, FFP, and DDAVP
Dabigatran (pradaxa): dialysis if bleeding in brain. if not, Idarucizumab
Xarelto: PCC
Arixtra: Novo 7 SSAVP
(know MC, use for life threatening bleeds)
What are RF for VTE and hypercoagulable states
Virchows triad: venous stasis + trauma/endothelial injury + hypercoagulable state = increased VTE risk
Hypercoag: cancer, smoking, pregnancy, estrogen, OCP, HRT, Tamoxifen/chemo drugs
List some common hypercoagulable states
Protein C&S or ATIII deficiency Factor V Leiden mutation prothrombin gene mutation LAC hyperhomocysteinemia Anticardiolipin antibody Paroxsymal nosturnal hemoglobinuria
What prevents over-clotting by regulating the coagulation cascade
Protein C&S, AT III
Deficiency in any can cause hypercoagulability
What is an ATIII deficiency
Mutations reduce levels or functional capacity of ATIII
Can also be low 2/2 liver disease, nephropathy, or heparin
What are Protein C&S
Vitamin K dependent proteins
Can be low in nephrotic syndrome or warfarin
If low, both carry increased risk for VTE
What is Factor V Leiden mutation
Normally, factor V helps convert prothrombin to thrombin, fibrinogen to fibrin, and forms a clot. And Protein C shuts this off so you do not over clot.
With this mutation, factor V is resistant to protein C, so it does not get shut off, so you end up clotting more 2/2 high thrombin
Heterozygous is MC and risk is only 5x higher
Homozygous is rare and risk is 80x higher
MC in white
What is the prothrombin gene mutation
Mutation of nucleotide substitution in 3’ untranslated region of prothrombin gene= greater fxn of prothrombin (factor II)
3x higher VTE risk
What is Homocysteine
High levels of Homocystein increase risk for VTE (arterial), vascular injury, platelet aggregation, smooth muscle hypertrophy, intimal thickening, elastic lamina disruption, and impaired NO activity
What is hyperhomocysteinemia
MTHFR deficiency (valine replaces alanine) Can be caused by B6, B12. and folic acid deficiency , smoking, fibrates, and nicotinic acid Can Tx with B12 and folate, but they don't reduce risk of VTE
What is antiphospholipid Ab syndrome (APS)
Antibodies to phospholipids cause recurrent venous or atrial thrombosis, pregnancy morbidity/fetal loss
The associated Abs are LAC, anticardiolipin antibody, and anti-beta 2 glycoprotein
How do you treat APS
Lovenox!
Stops you from forming clots that can lead to thrombi 2/2 autoantibodies
LAC and anticardiolipin antibody are both diseases where
the body forms IgG or IgM against phospholipids
Phospholipids are involved in the coag cascade and cause more arterial clotting
Sneddon syndrome causes
Livedo reticularis and neurologic abnormalities
Typical of patients that have very progressive Lupus, may cause tissue hypoxia leading to the bruise that looks like mottled skin
S/Sx of a DVT are
Swelling
Erythema
Pain/ache
May be of LE (more common) or UE
What tests are used to evaluate VTE
Doppler US**: can be falsely - below knee. if you are very susp and it comes -, repeat in 2-3 days
CT angio: PE
VQ scan: good if w/ renal insufficiency, pregnant, or allergic to contrast dye
D-dimer: + is acute clot, but - if chronic clot or no clot! only use if you are really susp and US is (-)
Your patient comes in and you do a doppler and determine they have a DVT. How do you proceed
Do they have RF? (surgery, pregnant, cancer, HRT, travel)
Start UFH/LMWH (preventive) first, then warfarin (must run coag panel)
Or start on a DOAC
Wait until you d/c warfarin for 3 WKS before you run confirmatory tests
Why do you start UGH/LMWH before warfarin?
Warfarin initially drops protein C&S levels and puts a patient at higher risk for VTE before it “thins” the blood
Start on UFH to provide blood thinning while warfarin gains efficacy
How long should you be on anticoags if you’ve had a VTE
1st VTE: 3-6 months
1st VTE + hypercoagulable (RF): 3-6 months
Life threatening VTE: may need lifelong (controversial)
Recurrent VTE + hypercoag: Lifelong anticoags
Idiopathic VTE: may need lifelong, 90% re-thrombose
What is tPA (tissue plasminogen activator)
Thrombolytic therapy! given IV vs catheter-directed
Indicated for pts w/ extensive, life threatening clot -OR- w/ PE causing significant hemodynamic instability and RV strain (saddle embolism!)
What is an IVC filter
Umbrella placed into the IVC
Reserved for pts that can’t take anticoags and are high risk for LE DVT, to prevent propagation
Also used if you had a BIG PE to avoid future lung injury -OR- if high risk of bleeding complications
If you have a permanent IVC filter, you need
Lifelong anticoag therapy!
How do you treat SF thrombophlebitis
NSAIDs/ASA + warm compress AC if: >5cm very symptomatic clot w/in 2cm of where SF vein enters deep vein if SF thrombosis occurs while on ASA
