Coagulation: schoenwald Flashcards
Acquired Conditions and Risk Factors
- Venous stasis–> Long periods of immobilization-travel, illness
- Antiphospholipid syndrome-autoimmune
- Atrial fibrillation
-Cancer–> Mass affect pressing on vein
or Tumor produces substances promoting clotting
- Treatments (chemo/radiation)
- Trauma/surgery
Acquired Conditions and Risk Factors (cont.)
Central line catheters Pregnancy Medications Hormone replacement therapy Oral contraceptives Tamoxifen Heparin in heparin induced thrombocytopenia Atherosclerosis Obesity
Antiphospholipid syndrome= ______ antibodies
Autoimmune-cardiolipin antibodies
Antiphospholipid syndrome:
-clinical criteria=
-Vascular thrombosis-validated by imaging or biopsy
-**Pregnancy complications:
1 or more unexplained deaths of physically normal fetus at or after 10 weeks or pregnancy
1 or more premature births of physically normal newborn at or before 34 weeks due to pre-eclampsia, eclampsia or abnormally functioning placenta
3 or more unexplained consecutive miscarriages before the 10th week
Antiphospholipid syndrome:
-lab criteria
-Positive test for 1 autoantibody on 2 or more occasions 12 weeks apart
- -Lupus anticoagulant
- -Anticardiolipin antibody
- -Anti B2GP1 antibody
Antiphospholipid Syndrome: Treatment
- Lifelong anticoagulation
- *Warfarin contraindicated in pregnancy (category X)
- **Transition to LMWH during pregnancy
- NOACS?
Inherited Clotting conditions:
Factor V Leiden mutation (activated protein C resistance)
- Mutation causes single amino acid replacement at 1 of 3 cleavage sites of Factor V
- Protein C cannot inactivate the cleavage Factor V in presence of Factor V Leiden mutation-slows the clotting cascade because of persistent Factor V Leiden activity=increase in thrombin generation
- **Most common hereditary blood coagulation disorder in US-5% of Caucasians, 1.2% African Americans
Inherited Clotting conditions:
-Prothrombin ______ mutation
- *Prothrombin 20210 mutation
- -Results in increased prothrombin (Factor II)
Inherited Clotting conditions (List others)
- MTHFR mutation: Predisposes to high levels of homocysteine and MAY increase clotting risk
- Protein C: Helps regulate speed of coagulation cascade by degrading factors V and VIII
- Protein S: Cofactor with Protein C
Inherited clotting disorders:
dx by?
running factor assays or specific genetic tests
- Can be heterozygous (inherited one mutated gene copy and one normal copy) or homozygous (inherited 2 mutated gene copies)
- *Homozygous usually more severe
-Hypercoagulation panel:
Factor V Leiden
Prothrombin gene 20210 mutation
Protein C and Protein S activity
MTHFR gene-Methylenetetrahyrofolate Reductase
Homocysteine
Anticardiolipin antibodies-antiphospholipid syndrome
Hyper coag panels include?
Factor V Leiden
Prothrombin gene 20210 mutation
Protein C and Protein S activity
MTHFR gene-Methylenetetrahyrofolate Reductase
Homocysteine
Anticardiolipin antibodies-antiphospholipid syndrome
inherited clotting disorders: tx?
lifelong anticoag
Anticoagulation Agents:
describe warfarin
MOA: inhibits vitamin K dependent factors
Usage:prophylaxis and treatment of DVT and PE, afib
Only anticoagulant that prevents activation of new clotting factors
Slow onset of action: 3-5 days to become therapeutic
Stabilizes clot
Oral delivery
Multiple drug interactions
- **Therapeutic Drug Monitoring is INR
- **Reversal Agent: Vitamin K or FFP
Anticoagulation Agents:
-describe unfractionated heparin
MOA: binds to antithrombin, inhibits Factors II, IXa,Xa,Xia,XIIa
Used for prophylaxis and treatment of DVT/PE/Afib
IV
- *Monitoring PTT and CBC(HIT monitoring)
- Reversal agent-protamine sulfate
Anticoag agents:
-describe Low molecular Weight Heparin (LMWH)
=aka Dalteparin (Fragmin) or Enoxaparin (Lovenox)
- MOA :binds to antithrombin to inhibit factors Xa and Iia (mostly Xa-Xa activity of LMWH much higher than unfractionated heparin
- Used in prophylaxis and treatment of DVT/PE, unstable angina, nonQ wave MI
- Stabilizes clot
- Used with warfarin as bridge until INR therapeutic
- **May be used in pregnancy
Reversal agent is protamine sulfate
What is the blackbox warning regarding LMWH??***
Spinal procedures such as epidural catheter placement,lumbar puncture can result in epidural or spinal hematoma=paralysis
Describe NOACS-Novel oral anticoagulants
-which ones are direct thrombin inhibitors?
- Bivalirudin (Angiomax)- direct thrombin inhibitor
- Dabigatran (Pradaxa)- direct thrombin inhibitor
Describe NOACS-Novel oral anticoagulants
-which ones are Factor Xa inhibitors?
Apixaban (Eliquis)-Factor Xa inhibitor
Rivaroxaban (Xarelto)-Factor Xa inhibitor
Edoxaban (Savaysa)-Factor Xa inhibitor
What are all Pts at risk for that take NOACs?
Spinal hematoma a risk for all of these agents if used during spinal/epidural procedures
Direct Thrombin Inhibitors
-MOA?
MOA: prevent cleavage of fibrinogen to fibrin monomers and thrombin induced platelet aggregation
Stabilize active clots and prevent formation of new clots
-Bivalirudin (used mainly as IV med in acute coronary syndromes)
-and Dabigatran
When is Dabigatran used?
(a direct thrombin inhibitor)
-Used in afib, prophylaxis and treatment of DVT/PE
Oral alternative to warfarin therapy
No laboratory monitoring
Reversal agent: idarucizumab (Praxbind)-monoclonal antibody
Factor XA inhibitor
-MOA?
MOA: inhibit Factor Xa
Used for a fib, prophylaxis and treatment of DVT/PE including post op prophylaxis
Apixaban (Eliquis), Rivaroxaban (Xarelto), edpxaban (Savaysa)-oral
No lab monitoring
Stabilize clot and prevent new formation of clots, slowly dissolve pathologic clots
Factor XA inhibitor
Reversal agent: for apixaban and rivaroxaban only?
Factor Xa(recombinant) inactivated-Andexxa- acts as decoy for binding cost=$50,000/dose
Von willibrand disease
-describe
=Deficiency of vonWillibrand factor
-VWF is a carrier for Factor VIII and platelets
-Deficiency causes: prolonged bleeding, Frequent nosebleeds, Easy bruising
Excessive bleeding with procedures
-DDAVP (synthetic vasopressin) stimulates cellular release of VWF
Von willibrand disease:
-what labs should you order?
prolonged bleeding time, normal PT,
*PTT MAY be slightly elevated.
DIC=
Inappropriate clotting mechanism-futile clotting and bleeding
DIC results from
Result of organ injury, sepsis, amniotic fluid embolism, retention of dead fetus, malignancy, liver cirrhosis, surgery, trauma, burns
–Organ injury results due to intravascular clots and subsequent ischemia/anoxia
DIC: tx?
Heparin as treatment to limit futile clotting
Labs of DIC:
- Which ones are prolonged?
- which ones are decreased?
-prolonged: bleeding time, PT, PTT, thrombin time
**Platelets are decreased
