Chapter 34 - Anticoagulation Flashcards
What are anticoagulants used for?
- Prevent blood clots from forming
- Keep existing clots from becoming larger
- They do not break down clots (like thrombolytics)
What are some indications for anticoagulants use?
- Acute coronary syndromes (ACS)
- Prevention of cardioembolic stroke
- Prevention/treatment of venous thromboembolism (VTE),
which refers to deep vein thrombosis (DVT) and/or pulmonary embolism (PE)
What is the most common side effect of anticoagulants?
Bleeding, which can be fatal.
Anticoagulants are high-alert medications for this reason.
Clotting factors are primarily made in the:
Liver
The coagulation cascade has two pathways which lead to fibrin formation:
1) The contact activation pathway (or the intrinsic pathway)
2) The tissue factor pathway (or the extrinsic pathway).
Anticoagulants inhibit the coagulation cascade and prevent (or reduce) clot formation
What factors do warfarin inhibits?
Factors II, VII, IX and X
(1972)
Protein C & S
What drug inhibit factor Xa
2- Direct
3- Indirect
Direct (PO)
- RivaroXAban
- ApiXAban
- EdoXAban
Indirect (IV/SQ)
- Fondaparinux
4- What drugs are Direct Thrombin Inhibitors
IV - Argatroban, Bivalirudin
PO - Dabigatran
Factor II Prothrombin –> Factor IIa Thrombin
5/6)What drugs have both anti Xa and anti IIa activities?
1- Unfractionated Heparin
- Has equal anti Xa & anti IIa activities
2- Low molecular weight heparin
- More anti Xa than anti IIa activities
What is the function of thrombin?
Thrombin converts fibrinogen into fibrin
Fibrin strands crosslink to hold the clot together
When do you use Injectable and oral anticoagulants
Injectable anticoagulants are used for:
- ACS (Heart) and VTE (Leg) (treatment and prevention)
Oral anticoagulants are used mainly for:
- VTE (Leg) (treatment and prevention)
- Stroke (Brain) prevention in patients with (AFib)
What are the oral anticoag drugs?
1- Warfarin (Vitamin K antagonists)
DOAC: Direct acting oral anticoagulants:
2- Factor Xa inhibitors
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Edoxaban
3- Thrombin Inhibitors
- Dabigatran (Pradaxa)
–> Treat/ Prevent blood clots in veins
–> Prevent stroke in A. Fib
DOACs Vs Warfarin?
1- Benefits of DOACs over Warfarin?
2- How do you dose DOACs?
3- What do you use for stroke prevention in Afib?
4- What do you use for VTE treatment?
1- DOACs benefits over warfarin:
- Less drug-drug interactions
- Less or comparable bleeding
- Shorter half-life
2- DOAC dosing is based on the indication and kidney/ liver function - there is no need to adjust the dose based on the INR (as with warfarin)
3- DOACs preferred for stroke prophylaxis in AFib
■ BUT - if there is moderate-to-severe mitral stenosis or a mechanical heart valve, use WARFARIN
4- Use DOACs for VTE treatment
■ BUT - if the patient has CANCER, use LMWH
■ BUT - if the patient has ANTIPHOSPHOLIPID syndrome, use WARFARIN
VITAMIN K ANTAGONISM (Warfarin)
1- Function of vitamin K
2- What happens if we antagonize Vitamin K
3- What should you watch for while on warfarin
1- Vitamin K is required for the carboxylation (activation) of clotting factors II, VII, IX and X
2- Without adequate vitamin K, the liver produces the clotting factors, but they have reduced coagulant activity.
3- Warfarin has a narrow therapeutic range and requires careful monitoring of the international normalized ratio (INR), which is affected by many drugs and changes in dietary vitamin K.
1- What is the function of antithrombin?
2- What drugs work on antithrombin? What do they do?
3- What drugs inhibit Factor Xa directly?
4- What should you monitor for efficacy?
1- Antithrombin (AT) is one of the body’s natural anticoagulants; it inactivates:
- Thrombin (factor Ila)
- Factor Xa
2- Drugs that work by binding to AT and causing a conformational change which increases AT activity 1,000-fold:
- Unfractionated heparin (UFH) (Xa = IIa)
- Low molecular weight heparins (LMWHs) (Xa > IIa)
- Fondaparinux (Arixtra) binds to AT, resulting in selective inhibition of factor Xa.
3- Inhibit factor Xa directly
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
- Rivaroxaban (Xarelto)
4- These oral medications are taken once or twice daily and require no laboratory monitoring for efficacy.
1- How do UFH & LMWH inhibit thrombin & factor Xa?
2- How do Direct thrombin inhibitors work?
3- Why are IV DTis important clinically? When are they the drug of choice?
4- Name the IV and oral DTis?
1- UFH and LMWH indirectly inhibit thrombin and Factor Xa through AntiThrombin binding.
2- Direct thrombin inhibitors (DTis) block thrombin directly, decreasing the amount of fibrin available for clot formation.
3- IV DTis do not cross-react with heparin-induced thrombocytopenia (HIT) antibodies.
- Once HIT develops in the hospital setting, the injectable DTI ARGATROBAN is the drug of choice.
4- Oral: Dabigatran (Pradaxa)
IV: Argatroban, Bivalirudin
- How do fibrinolytics work?
- When do you use fibrinolytics?
- Fibrinolytics break down existing clots but are associated with a very high risk of bleeding.
- They are used when the patient could die without rapid restoration of blood flow:
– STEMI
– Acute ischemic stroke - Drugs: Streptokinase, Alteplase, urokinase
- When do you use antiplatelets?
- What is DAPT?
Antiplatelet drugs (aspirin, clopidogrel, ticagrelor) are used mainly for:
- ACS
- Stroke/TIA prevention
- Dual antiplatelet therapy (DAPT) refers to using both aspirin and a P2Y12 inhibitor (e.g., clopidogrel) together, which is very common in patients who have had an ACS.
- Antiplatelet drugs are NOT sufficient for treating DVT/PE.
- When are oral anticoags used?
- Oral anticoagulants are used mainly in AFib (for stroke prevention) and for DVT/PE (treatment and prevention).
- Oral medications like Xarelto or Eliquis are not indicated for ACS when platelet aggregation is the main target of drug therapy.
An acute drop in hemoglobin (>= … g/dL) could signify that bleeding is occurring (visible or not).
2
What could be some causes of epistaxis?
1) Epistaxis: From drugs, dry nasal mucosa (esp. with dry heat), nose-blowing
What could be some causes of gum bleeds?
2) Gums: New, or worse than usual from gingivitis, drugs
What could be some causes of bruising?
- From drugs (chronic steroids)
- Thrombocytopenia/clotting disorder
- Cushing’s syndrome
- Malnutrition
- Physical abuse
- Fracture/sprain
- Infection
What could be some causes of hematoma?
- From drugs
- On abdomen from LMWH injection that was rubbed (do not rub!)
- An epidural or spinal hematoma in a patient using a LMWH or DOAC who is given neuraxial anesthesia
- Spinal puncture
What could be some causes of emesis?
■ Coffee-ground emesis (vomit)- from bleeding in upper GI tract
■ Esophageal chronic reflux (esophagitis, Barrett’s)
■ Stomach From ulcer (NSADI-induced)
■ Duodenal From ulcer (H. pylori-induced)
What could be some causes of hematuria?
- From UTls
- Kidney stones (calculi)
- Prostatitis
- Kidney disease
What could be some causes of bleeding from anus?
- Light red: from hemorrhoids, rectal tear
- Black and “tarry” (sticky), smelly stool: from esophagus, stomach (NSAID-induced) or duodenum (H.pylori-induced)
- Other causes of rectal bleeding:
. Diverticulosis
. Colon cancer
. IBD (Crohn’s, ulcerative colitis)
. Colon polyps (benign or cancerous)
–> Rectal bleeding from polyps can be occult (not visible, requires tests (FOBT) to identify) - Bloody diarrhea (dysentery}- from infection (C.difficile, Shigella, Entamoeba histolytica)
Drugs that cause bleeding include:
- Anticoagulants
- Antiplatelets
- NSAIDs
- Natural products (ginkgo/SSRls, SNRls increase bleeding risk.
- How does UFH work?
- UFH binds to antithrombin (AT)
- Which then inactivates thrombin (factor Ila) and factor Xa (as well as factors IXa, Xla, Xlla and plasmin)
- And prevents the conversion of fibrinogen to fibrin
Unfractionated Heparin:
- Indications
- Dosing
1) Prophylaxis of VTE: 5,000 units SC Q8-12H
2) Treatment of VTE: 80 units/kg IV bolus; 18 units/kg/hr infusion
3) Treatment of ACS/ STEMI: 60 units/kg IV bolus (max 4,000 units); 12 units/kg/hr infusion (max 1,000 units/hr)
Which weight should you use for dosing UFH?
Total body weight
What is the onset of action of IV and SC heparin?
Onset:
- IV: immediate
- SC: 20-30 min
– t1⁄2 =1.5 hrs
Can you give LMWH instead of heparin in HIT?
HIT antibodies have cross-sensitivity with LMWHs
CONTRAINDICATIONS with heparin
- Uncontrolled active bleed (intracranial hemorrhage)
- Severe thrombocytopenia
- History of HIT
- Hypersensitivity to pork products
Some products contain benzyl alcohol as a preservative (do not use in neonates, infants, pregnancy and breastfeeding)
Warning with heparin (Med safety)
Fatal medication errors:
- Verify the correct concentration is chosen
SIDE EFFECTS with heparin
- Bleeding (Epistaxis, bruising, gingival, GI)
- Thrombocytopenia
- HIT
- Hyperkalemia
- Osteoporosis (with long-term use)
- Alopecia
MONITORING with heparin
- When do you suggest possible HIT?
- aPTT or anti-Xa level:
. Check 6 hours after initiation and
. Every 6 hrs until therapeutic
. Then every 24 hrs
. With every dosage change - aPTT therapeutic range: 1.5-2.5 x control
- Anti-Xa therapeutic range: 0.3-0.7 units/ml
- aPTT and anti-Xa monitoring are not required for SC (prophylactic) dosing
- Platelets, Hgb, Hct at baseline and daily (dec in platelets > 50% from baseline suggests possible HIT)
Antidote of Heparin
Protamine
- When do we commonly use Heparin continuous IV infusion? Why?
- Unpredictable anticoagulant response (has variable and extensive binding to plasma proteins and cells)
- Continuous IV infusions are common for treating VTE and ACS because heparin has a very short half-life
When do you give Heparin IM?
Do not give IM due to hematoma risk
What is HepFlush and why do we use it?
Heparin lock-flushes (HepFlush) are only used to keep IV lines open.
Medication Errors with Heparin:
- Fatal errors, especially in neonates, occurred when the incorrect heparin strength (higher dose) was chosen.
- Heparin injection 10,000 units/ml and flushes 10 or 100 units/ml look and sound alike.
LMWH drugs and brand
- Enoxaparin (Lovenox)
- Dalteparin (Fragmin)
- Lovenox come in different doses:
- 1 mg = … units antiXa activity
1 mg= 100 units anti-Xa activity
LMWH - Enoxaparin (Lovenox)
- Indications
- Dose
1) Prophylaxis of VTE: 30 mg SC Q12H or 40 mg SC daily
– CrCI < 30 ml/min: 30 mg SC daily
2) Treatment of VTE & UA/ NSTEMI
- 1 mg/kg SC Q12H or
- 1.5 mg/kg SC daily (only for inpatient VTE treatment)
– CrCI < 30 ml/min: 1 mg/kg SQ daily
– Use total body weight for dosing
3) Treatment of STEMI
- Patients < 75 years: 30 mg IV bolus plus 1 mg/kg SC dose followed by 1 mg/kg SC Q12H
– CrCI < 30 ml/min: 30 mg IV bolus plus 1 mg/kg SC dose followed by 1 mg/kg SC daily
- Patients >= 75 years: 0.75 mg/kg SC Q12H (no bolus)
– CrCI < 30 ml/min: 1 mg/kg SC daily (no bolus)
LMWH - Dalteparin
- Brand
- Indication
- Fragmin
- Prophylaxis of VTE: 2,500 - 5,000 units SC daily
- Treatment of UA/NSTEMI: 120 units/kg (max 10,000 units) SC Q12H
LMWH BBW
- Patients receiving neuraxial anesthesia (epidural, spinal) or
- Undergoing spinal puncture
–> Are at risk of hematomas and subsequent paralysis
LMWH CI
- History of HIT
- Active major bleed
- Hypersensitivity to pork
LMWH SE
- Bleeding
- Anemia
- Injection site reactions (pain, bruising, hematomas)
- Dec platelets (thrombocytopenia, including HIT)
LMWH monitoring
- Platelets, Hgb, Hct, SCr
- Anti-Xa monitoring:
– No need (More predictable anticoagulant response than UFH
– Monitor in pregnancy
– Obtain peak anti-Xa levels 4 hours post SC dose - Monitoring may be done in obesity, low body weight, pediatrics, elderly or renal insufficiency
- aPTT is not used
– It measures how long it takes for your blood to form a clot
- Antidote of lmwh?
- Should you expel air bubble from syringe?
- When do you administer IM?
- Where should you store it?
- Antidote: protamine
- Do not expel air bubble from syringe prior to injection (can cause loss of drug)
- Do not administer IM
- Store at room temperature
UFH/LMWH Drug Interactions
- Other anticoagulants
- Anti platelet drugs
- Some herbal supplements
- NSAIDs, SSRIs, SNRls
- Thrombolytics
HEPARIN-INDUCED THROMBOCYTOPENIA:
- What is HIT
- It has a high risk for:
- What happens if left untreated?
- What is HITT and what can it cause?
- Whats the estimated incidence of HIT?
- What is the typical onset of HIT?
- How do you diagnose it?
- What is the most common sign of HIT?
- An immune-mediated IgG drug reaction
- Has a high risk of venous and arterial thrombosis.
- The immune system forms antibodies against heparin bound to platelet factor 4 (PF4), the antibodies then join with heparin and PF4 to create a complex, and this complex binds to the Fc receptors on platelets.
- This causes platelet activation and a release of pro-coagulant microparticles.
- If left untreated, HIT can lead to a prothrombotic state causing many complications including heparin-induced thrombocytopenia (most common sign of HIT) and thrombosis (HITT).
- HITT leads to amputations, post-thrombotic syndrome and/or death.
- The estimated incidence of HIT is -3% of patients exposed to heparin for more than four days.
It is lower with a shorter duration of treatment. - The typical onset of HIT occurs 5 - 14 days after the start of heparin or within hours if a patient has been exposed to heparin within the past 3 months.
- A diagnosis is made by:
– A compatible clinical picture
– An unexplained drop in platelet count (defined as > 50% drop from baseline) and
– Laboratory confirmation of antibodies (ELISA test and confirmatory serotonin release assay) or
– Platelet activation by heparin
MANAGEMENT OF HIT COMPLICATED BY THROMBOSIS (HITT)
1) What should you do if HIT was suspected
2) What should you do if the pt is on warfarin and got diagnosed with HIT?
3) What anticoagulant is recommended for pts with HIT?
4) When can you start warfarin therapy?
5) At what dose should you start warfarin?
6) Should you overlap with another anticoag?
7) Do other anticoags increase INR?
8) What anticoag is preferred if urgent cardiac surgery or PCI is required?
1) Stop all forms of heparin and LMWH including heparin flushes and heparin-coated catheters.
2) Stop warfarin & Give vitamin K
– Although the patient is at a high risk of thrombosis, warfarin use with a low platelet count has a high correlation with warfarin-induced limb gangrene and necrosis.
3) Non-heparin anticoagulants (in particular, Argatroban) over heparin, LMWH or vitamin K antagonists.
4) Do not start warfarin therapy until the platelets have recovered to > 150,000/mm3
5) Warfarin should be initiated at lower doses (5 mg maximum).
6) Overlap warfarin with a non-heparin anticoagulant for a minimum of five days and until the INR is within target range for 24 hours.
7) Argatroban can increase the INR; the value must be interpreted cautiously.
8) If urgent cardiac surgery or PCI is required, bivalirudin is the preferred anticoagulant.
