Clotting Disorders Flashcards
Platelets and clotting factors circulate normally in an _________ form.
Platelets and clotting factors circulate normally in an inactive form.
Vascular injury disrupts endothelium and leads to what 3 things?
- Vascular spasm
- Platelet adhesion mediated by Von Willebrand factor
- Coagulation cascade
What does PT represent?
time in seconds for plasma to clot after addition of calcium and an activator of extrinsic pathway (thromboplastin)
What leads to a prolonged PT?
Deficiencies or inhibitors of clotting factors within extrinsic or final common pathways
Why was INR created?
PT results for identical patients vary with different labs
What is INR?
mathematical conversion of patient’s PT compared to geometric mean of PT of at least 20 healthy subjects of males and females at THAT lab
What does PTT (Partial Thromboplastin Time) measure?
integrity of intrinsic and final common pathways of coag cascade
What does PTT represent?
time in seconds for patient’s plasma to clot after the addition of phospholipid, an intrinsic pathway activator- calcium
if clotting times remain prolonged what should you think?
inhibitor
if clotting times normalize or decrease to near-normal what should you think?
factor-deficiency
What does PTT correct?
Factor DEFICIENCY of intrinsic pathway like factors VIII, IX, XI, or XII
How can you determine which clotting factor is involved with an abnormal PTT?
clotting factor assay
PTT stays prolonged with what?
an inhibitor: heparin, LMWH, AIH/Factor 8 inhibitor
Lupus anticoagulant
What do you see in pts w/LAC (lupus anticoag)?prolonged PTT
prolonged baseline PTT
Seen more in young females
When would you suspect LAC?
pt w/no bleeding hx
pt w/clot w/baseline prolonged PTT before Ant-coag was started
What should you think if a PT corrects with normal PTT?
DEFICIENCY of factors II, VII, and X or fibrinogen (2, 7, 10)
Liver dz (prolonged PT)
What should you think if PT is still prolonged with prolonged PTT?
Factor 5 inhibitor
PT and PTT MIxing study:
deficiencies caused by what?
supratherapeutic warfarin or rat poison
what inhibitors will you see in lymphoproliferative d/o or monoclonal protein d/o?
LAC
nonspecific factor inhibitors
Pts with what 2 disorders can develop antibodies against self (have autoimmune characteristics)?
lymphoproliferative d/o
monoclonal protein d/o
Warfarin:
What can supratherapeutic INR lead to?
elevated PTT
every 1.0 increase of PT is what of PTT?
16-17 sec PTT
3 MC reasons to use Warfarin
1) A-Fib INR 2-3
2) VTE INR 2-3
3) Mechanical valve replacement- INR 2.5-3.5
Warfarin interferes with what factors and proteins?
factors VII, IX, X and proteins C & S
Can you use warfarin in pregnancy?
No: Preggo X
UFH inhibits which factors?
IIa (thrombin)
Xa
UFH PK and risk
PK: large molecule: 30 units long and not well absorbed subcutaneously
risk of HIT
What does LMWH inhibit?
More of Xa
some of IIa
LMWH benefits
smaller so well absorbed subcutaneously
predictable 1/2 life
Ex: Enoxaparin, Dalteparin
Risk of HIT
Can give with preggos
T/F: No need to draw blood tests to see if anticoag is therapeutic unless pt. is very obese or very thin
What would you draw if you had to?
TRUE
anti-factor Xa levels 3-4 hrs post LMWH administered
synthetic pentasaccharide that inhibits factor Xa and binds to antithrombin III causing antithrombin III to go through conformational change inhibiting coag cascade
Half-life 17 hrs. long and NO reversal agent
Which med?
Fondaparinux
Direct Xa inhibitors
Rivaroxaban
Apixaban
ex of DOAC
dabigatran
what are fondaparinux, rivaroxaban/apixaban and dabigatran used for?
A-fib & VTE
What agents should be used to reverse overdose in the following meds?
- Heparin
- Enoxaparin
- Pradaxa
- Xarelto
- Fondaparinux
- Heparin: Protamine
- Lovenox/Fragmin: Protamine
- Pradaxa: Dialysis (if bleeding in brain) or Idarucizumab (if no bleeding)
- Xarelto/Eliquis- PCC
- Fondaparinux (Arixtra)- Novo 7, DDAVP
RF for VTE & hypercoagulable state
stasis
recent trauma/surgery and hypercoagulable state
increased risk for venous thromboembolism (VTE)
CA (Trousseau’s syndrome)
pregnancy
smoking
estrogen
Protein C & S along with antithrombin III deficiencies
Factor V Leiden mutation
Prothrombin gene mutation
Lupus anticoagulant
Hyperhomocysteinemia
Anticardiolipin antibody
Paroxysmal nocturnal hemoglobinuria
These are all…
hypercoagulable states
what 3 things prevent overclotting?
Protein C, Protein S, and Antithrombin III
Both are vitamin K dependent proteins
Both can be low in nephrotic syndrome
Protein C &S
Can be low d/t liver disease, nephropathy or heparin
Mutations reduce levels or decrease its functional capacity
AT III deficiency
essential cofactor to allow conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin –> clot
This is inactivated by protein C
What Factor?
Favtor Va
single AA substituted allowing resistance to inactivation or activated protein C resistance so continues to clot d/t high levels of prothrombin –> thrombin (factor IIa)
WHat mutation?
Mutation Arg506Gln
Mutation of nucleotide substitution in 3’-untranslated region of prothrombin gene which results in greater function of prothrombin (factor II)
What mutation?
Prothrombin Gene G20210A Mutation
High levels of homocysteine lead to what?
Vascular injury
Intimal thickening
Elastic lamina disruption
Platelet aggregation
Smooth muscle hypertrophy
Impairs nitric oxide activity
MTHFR deficiency- alanine to valine substitution at 677 amino acid position
Deficiencies of vitamins B6, B12 and folic acid
Fibrates and nicotinic acid increase
What condition?
Hyperhomocysteinemia
What do you treat Hyperhomocysteinemia with?
Vit B12 & folate
Recurrent arterial or venous thrombosis, pregnancy morbidity/fetal loss and presence of antiphospholipid antibodies including
Lupus anticoagulant (LAC)
Anticardiolipin antibody
Anti-Beta 2 glycoprotein
What dz?
Antiphospholipid Ab Syndrome (APS)
body forms IgG or IgM antibodies against phospholipids
Phospholipids are involved in coag cascade
More arterial clotting
Sneddon syndrome (livedo reticularis and neurologic abnormalities)
What dz?
LAC and Anticardiolipin Ab
Best test to evaluate VTE?
Doppler US: can be falsely negative with DVT below the knee
fi high suscpicion = repeat in 2-3 day
Dx test for PE
CT angiogram
If pt has renal insufficiency, pregnancy or anaphylaxis to iodine, what dx test would you do if they have VTE?
VQ scan
How do you approach a pt with VTE?
- Find out if they have risk factors: Surgery, pregnancy, cancer, HRT, travel
- Start UFH or LMWH first and then warfarin: Sounds paradoxical but warfarin initially will drop protein c & s levels placing pt. at higher risk of VTE before actually taking effect to “thin” blood out
Can start with DOAC
If pt. started on UFH, LMWH, or warfarin, recommended not to run hypercoagulable panel because some tests will be falsely low
_Wait until off warfarin for at lease 3 weeks before running tests**_
VTE & AC duration:
1st VTE
AC for 3-6 mos
VTE & AC duration:
1st VTE and hypercoagulable
no need for lifelong AC
Recurrent VTE & hypercoagulable
lifelong AC
Who is tPA indicated for?
pts who have extensive clot burden
PE causing significant hemodynamic instability & RV strain
When would you use an IVC filter?
pts who cannot take AC and have or are at risk for lower extremity DVT to prevent propogation of clot.
pt that had a BIG PE to avoid possible future lung injury
pts with high risk of bleeding complications
SF thrombophlebitis TX
NSAIDS/ASA + warm compresses
Consider AC if:
>5cm
very symptomatic
clot is within 2 cm of where SF vein enters the deep vein
if pt had SF vein thrombosis while on ASA
