Hematology Flashcards
Damage outside of blood vessels triggers release of Thromboplastin (III) from damaged cells
Extrinsic Pathway
Trauma to the blood itself or exposure of the blood to collagen in a traumatized blood vessel wall activates factor XII (XIIa).
Intrinsic Pathway:
IXa when complexed on the platelet surface with activated factor VIII:C (VIII:Ca) and Ca++ activates factor X (Xa).
Common Pathway?
Activated factor X (Xa) when complexed on the platelet surface with activated factor V (Va) and calcium (factor IV) on the platelet surface, converts prothrombin (factor II) to thrombin (IIa).
IIa converts fibrinogen (I) to fibrin (Ia), and in the presence of factor XIII, cross-linking occurs.
What does Heparin do?
Accelerates Anti Thrombin III (ATIII) which neutalizes thrombin (IIa) and Factor Xa.
Essentially it only binds to newer baby unbound clotting factors.
Heparin MOA
Increase the rate of Thrombin - ATIII reaction at least 1000 fold.
Uses of Heparin
-prophylaxis VTE, DVT, PE Tx
-A-fib, new heart valves
-tx of peripheral artery embolism
-CV surgery
-complications in pregnancy
Heparin metabolism
Reticuloendothelial system of the LIVER. Does Not cross the placenta.
Heparin Dose for VTE
5,000 units bolus then 1200-1600 units/hr
Keep aPTT 1.5-2.5 times normal level
What does aPTT measure? (Heparin monitoring)
Measures activity of the INTRINSIC and COMMON pathways time to clot formation
has issues with results
Anti-Xa (IU/mL) measure?
(Heparin monitoring)
More direct measurement of Heparin concentrations
has less factors that can affect levels but results may vary between labs
ACT (seconds) (activated clotting time) measure?
(Heparin monitoring)
-Whole blood sample
-measures INTRINSIC pathway
-used in procedures with significant Heparin use
-has good linear dose response
Issues that may lead to a prolonged baseline aPTT
-Intrinsic clotting factor pathway deficiency (8,9,11,12)
-Leukemia
-Meds (warfarin, DOACs)
-DIC
-Liver disease
-recent pregnancy or miscarriage
-polycythemia
-lupus
What is Heparin resistance and how is it caused?
-Requires high doses: > 35,000 units/day
-Due to increase in Factor VIII (8), ATIII deficiency, massive PE
-Acquired AT III deficiency in patients with cirrhosis, nephrotic syndrome or DIC, ECMO tx
Treatment for Heparin resistance?
Administer 2 units FFP to provide AT III
Check both aPTT and Anti-Xa
Heparin Toxicity presentation/symptoms
-Bleeding (major bleeds in 1-11.5% of pts.)
-Thrombocytopenia (HIT)
-abnormal LFTs
-infrequent risk of osteoporosis
-rare hyperkalemia d/t aldosterone suppression and natriuresis
What is HIT and how is it caused?
-< 100,000 drop from baseline
-Heparin dependent antiplatelet IgG antibodies (Type II HIT)
Direct, non-immunogenic platelet effect
-5-15 days after start of treatment
Earlier with previous exposure
Risks of getting HIT?
-1-15% with heparin (any dose)
-5% with heparin flush
-10x lower risk with LMWH
HIT Treatment
-Stop heparin products
-Administer non-heparin anticoagulants to prevent thrombosis
-Add allergy to the chart
-PROTAMINE SULFATE (ANTEDOTE)
How is Protamine Sulfate dose determined?
Determined by the dose of heparin, route of heparin administration and time elapsed since the heparin was administered.
1 mg Protamine : 100 units heparin
Protamine hypersensitivity reaction to….
fish
pre-treat with corticosteroid and antihistamine
LMWH MOA
Inhibition of Factor Xa by antithrombin.
Do not use ______ in patients with HIT
LMWH
Synthetic indirect specific inhibitor of Factor Xa only
Fondaparinux (Arixtra)
DOAC drug names
Oral Xa Inhibitors
Rivaroxaban (Xarelto ®)
Apixaban (Eliquis ®)
Edoxaban (Savaysa ®)
Taking over warfarin
XA
How long to hold Oral Xa inhibitor before surgery w/ low-mod bleed risk and high bleed risk?
1 day- low/mod
2/day- high
Apixaban, Edoxaban, Rivaroxaban
Dabigatran preop monitoring?
Bleed risk and CrCl (kidney function)
Oral Xa reversal?
(cannot measure INR)
D/C medication, mechanical compression, surgical hemostasis, transfusion support (blood products, activated charcoal)
Oral Xa Reversal?
Andexanet alpha (Andexxa)
Ciraparantag- pending since 2016
How does Andexxa work?
Reverses Factor Xa inhibitors- recombinant human Factor Xa
Binds competitively to Factor Xa inhibitors for complete reversal
Andexxa dosing
(Xa inhibitor reversal agent)
Low Dose
Initial IV bolus: 400 mg at 30 mg/min
Follow Infusion: 4 mg/min for up to 120 min
High Dose
IV Bolus: 800 mg at 30 mg/min
Infusion: 8 mg/min for up to 120 min
Andexxa Chart
Name Direct Thrombin Inhibitors
Argatroban, Hirudin Analogs (Bivalirudin, Lepirudin), Dabigatran
Argatroban MOA and Use
Small molecule.
Highly selective and reversible direct thrombin inhibitor (Factor IIa).
Used for the prevention and treatment of thrombosis in patients with HIT or HITTS (no reversal agent)