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Thrombosis > Thrombosis > Flashcards

Thrombosis Flashcards

1
Q

Why anticoagulant medications are used?

A

To prevent and Treat Venous Thromboembolism with a precise dosing and monitoring.

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2
Q

What is hemostasis?

A

The balance between bleeding and clotting. It is the cessation of blood loss from the damaged vessel & Dissolution of the clot when it no longer needed!

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3
Q

In hemostasis, what are the 3 key players?

A

1) platelet function
2) Blood Coagulation
3) Fibrinolysis

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4
Q

What are the characteristics of Hemostasis? Elaborate

A

1) Normal Clotting Response: TF and platelets –> activate Coagulation Cascade –> Fibrin rich clot
2) Normal Dissolution Response: Tissue plasminogen Activator –> binds to plasmin –> break fibrin clot –> Restore Normal Blood Flow

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5
Q

What is Virchows Triad ? Elaborate

A

Risk Factors for thrombosis:
1) Blood stasis = immobility - paralysis
2) Vascular Injury = Surgery - Trauma - etc.
3) Hypercoagulation = inherited - Cancer - estrogen contraception etc.

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6
Q

What are the duration and Risk factor of VTE which is Categorized as “ TRANSIENT”?

A

Duration: 3 months
Risk Factors (Example):
Major:
1) Surgery with general anesthesia for >or = 30min
2) Confined to bed in hospital for >or = 3 days with acute
illness (bathroom privilege only)
Minor:
A) Surgery with general anesthesia < 30min
B) Admission to the hospital < 3d with acute illness
C) Estrogen therapy
D) Pregnancy and puerperium
E) Confined to bed out of hospital for > or = 3 d with acute illness
F) Leg injury associated with decreased mobility for > or =
3days

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7
Q

What are the duration and Risk factor of VTE which is Categorized as “Chronic / Persistant”?

A

Duration: persist after the development of VTE
Risk Factors (Example):
1) Active Cancer
2) Inflammatory bowel disease
3) Autoimmune disorders
4) Chronic infections
5) Chronic immobility (spinal cord injury)

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8
Q

List the two different Types of VTE
List difference in Prognosis, Subjective, objective , Diagnosis

A

A) Deep Venous Thrombosis
1) Prognosis: prognose into PE (pulmonary Edema)
2) Subjective: leg swelling , pain , warmth
3) Objective: D Dimers
4) Diagnosis: Duplex ultrasonography ; Venography

B) Pulmonary Edema
1) Prognosis: It may lead to death
2) Subjective: Cough , palpitations; chest pain ; Dyspnea .. Massive ( cyanotic - hypotensive- lightheadedness)
3) Objective: increase in HR , RR + Hypoxic on ABG
D dimers
4) Diagnosis: V/Q scan + CTPA

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9
Q

What are the goals of therapy for DVT prevention?
1) High risk
2) Low risk
3) High risk with bleeding

A

1) If high risk –> pharmacological
2) If lower risk –> no need or (non-pharmacological)
3) If high risk but patient is bleeding –> non-pharmacological until it’s safe to give pharmacologic

Giving anticoagulant in order to prevent VTE from developing

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10
Q

What are the strategies for “ Non Pharmacological Prevention”

A

A- Elastic Compression sticking
B- Leg elevation
C- leg Exercise
D- Early ambulation
E- Intermittent pneumatic Compression (IPC) worn at least 18hrs/day

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11
Q

What are the strategies for “Pharmacological Prevention”

A

A- Fixed low dose UFH: 5000 units SC every 8/12hrs

B- Low dose of LMWH
Enoxaparin 30mg SC BID
Enoxaparin 40mg SC once daily
Enoxaparin 30mg SC once daily (
CrCL< 30ml/min)

C- Fondaparinux: 2.5mg SC daily ( dont give CrCL < 30 ml/min or Weight =50kg)

D- Rivaroxaban 10mg po daily (inpatients total of 31-39 days) (dont use of CrCl < 30 ml/min)

E- NOACs - post operative
Apixaban 2.5mg PO BID
Dabigatran 220 mg po daily
Rivaroxaban 10mg po daily

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12
Q

IN the hospitalized Medical patient: there are 10 Risk factors of PADUA ; list them and indicate each risk factor with its relative points

when is it high risk of developing DVT?

A

ARAR EHAA OO
1. Acute cancer (3)
2. Reduced mobility >3d (3)
3. Known Thrombophilia condition (3)
4. Trauma / Surgery less than 1 month (2)
5. Elderly age >70 yr (1)
6. Heart/ respiratory failure (1)
7. Acute myocardial Infarction or ischemic stroke (1)
8. Acute infection and/or rheumatologic disorder (1)
9. Obesity (BMI> 30) (1)
10.Ongoing hormonal treatment (1)

> or = 4 points –> high risk of developing DVT –> pharmacological prevention

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13
Q

Surgical Patients: list the two types of thrombosis , and there respective type of surgery ( with the list of examples if possible)

A
  1. High risk thrombosis
    a. Orthopedic surgery and open abdominal surgery:

i. Total Hip Arthroplasty (THA), Total Knee Arthroplasty (TKA): Duration for a minimum of 10 to 14 days, we can consider extending up to 35 days from the day of surgery.
Agents: heparin, LMWH, fondaparinux , NOACs are also options!

ii. Hip Fracture Surgery (HFS): Duration for a minimum of 10 to 14 days, we can consider extending up to 35 days from the day of surgery
Agents: heparin, LMWH, fondaparinux , NOACs NOT an option (studies are lacking)

  1. Low risk thrombosis
    a. Laproscopic surgeries
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14
Q

What are the goals of treating thrombosis?

A
  1. Prevent thrombus extension and embolization
  2. Reduce recurrence risk
  3. Prevent long-term complications such as the post-thrombotic syndrome
  4. Carefully use anticoagulant drugs to reduce the risk of bleeding associated with these agents
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15
Q

what are the types of VTE treatment? and duration of each?

A

1) Primary treatment:
Duration: 3-6months
Start Immediately
2) Secondary Treatment:
Duration: Lifelong
Always Assess (at least annually)

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16
Q

what are the guidelines for Venous thromboembolism

A

1st line = NOACs : dabigatran, apixaban, edoxaban or rivaroxaban
2nd line= Conventional treatment (VKA = Sintrom or warfarin) + paranteral anticoagulation

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16
Q

what are the steps regarding primary treatment?

A

1) Directly oral anticoagulants (NOACs) - Rivaroxaban 15mg PO BID for 21 days, followed by 20mg PO daily
Apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily

2) switching (NOACs): start parenteral anticoagulant for 7 days then either switch to Dabigatran 150mg PO BID or to Edoxaban 60mg daily (if CrCl 30-50ml/min & weight <60kg or taking pgp i –> 30mg PO daily)

3) Bridging: Conventional therapy : parenteral anticoagulant + bridge to oral therapy VKA both PO and IV @ the same time after 5 days -> remove AC , when VKA reach therapeutic range –> KEEP only PO VKA

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16
Q

what are the steps of secondary prevention ?

A

1) VKA+ INR 2-3

2)Direct AC PO :
Rivaroxaban 10mg PO daily (after 6m of full dose)
Rivaroxaban 20mg PO daily
Apixaban 2.5 mg po BID (after 6m of full dose)
Apixaban 5 mg po BID

Refusal –> give instead Aspirin

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17
Q

who are candidate for secondary prevention?

A

1) Provoked VTE by a transient risk factor: no need
2) Provoked VTE by a chronic risk factor: indefinite (considered if no risk of bleeding)
3) Unprovoked VTE: complete initial 3 months, then indefinite (considered if no risk of bleeding)

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18
Q

What are the 3 VTE treatment strategies?
Duration of each

A

A- Acute phase
Duration: 0-7 d

B- Early maintenance
Duration: 8-90 d

C- Extended
Duration: >91 d

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19
Q

What are different methods/ Strategies for treating VTE

A

ALL ORAL:

1) Apixaban 10mg PO BID for 7 days (acute) ——–> Apixaban 5mg PO BID (early maintenance and first days of extended phase) ——–> Optional: apixaban 2.5 mg PO BID after first 6m

2) Rivaroxaban 15mg PO BID for 1st 21 days ( acute phase + some days of early maintenance ) ——–> rivaroxaban 20mg PO daily (early maintenance + some days extended phase) ——–> Optional: Rovaroxaban 10mg PO daily after 6m

Switching:
1) UFH , LMWH , Fondaparinux SC 1st 5 days ( acute) ——–> Dabigatran 150mg PO BID / Edoxaban 60mg PO daily (2 last days of acute phase + till the end of treatment = early maintenance and extended)

Overlap:
1) UFH , LMWH , Fondaparinux SC (acute phase) + warfarin PO daily overlapped with AC IV for @ least 5 days & INR > or = 2 —> dose adjust to target INR = 2.5 (2-3)

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20
Q

What is the treatment of Recurrent VTE?
Provoked / Unprovoked / while on treatment?

A
  • The old and recurrent VTE are both provoked due to transient risk Factor ——> No need for lifelong AC
  • Recurrent unprovoked VTE ——> extend therapy for 3m
  • Recurrent VTE while on warfarin treatment/NOAC - compliant ——> switch to LMWH temporarily @ least 1m
  • Recurrent VTE while on long term LMWH - compliant ——> increase LMWH dose about 1/4 - 1/3
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21
Q

how to treat Cancer associated with VTE ?

A

1) LMWH alone (less rate of recurrent VTE + keep on therapeutic range + compliance + withhold / adjust + can be used in thrombocytopenia or when invasive interventions are required

2) NOACs (Edoxaban, Apixaban and Rivaroxaban) ———> with caution in GI cancer

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22
Q

what are the risk factors for bleeding while on AC? and how assess (Moderate/High)

A
  • Age> 75 yo and frail
  • Previous bleeding
  • Renal or liver failure
  • Thrombocytopenia( ~ 100,000)
  • Concurrent antiplatelet use
  • Previous stroke
  • Poor anticoagulant control or non-compliance
  • Frequent falls or alcohol abuse
  • Presence of structural lesions that can bleed (tumor, recent surgery)

Moderate 1-2
High > or = 3

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23
Q

What is the treatment for Unstable PE?

A

Acute PE + Hypotension + no risk of bleeding ——–> fibrinolytics:
Alteplase rt-PA 100mg infusion over 2h ——-> institute or resume AC IV near end or immediately following it (when aPTTT returns to normal/almost normal)

24
Q

What to do with Patients who cant take AC (absolute Contraindicated) ? and how to differentiate them?

A

Given Inferior Vena Cava (IVC) filters

Absolute Contraindications:
1) Active bleeding
2) Hemophilia or other hemorrhagic tendencies
3) Severe thrombocytopenia (platelet count <20,000)
4) Inability to meticulously supervise and monitor treatment
(really difficult patient to deal with)

25
Q

what are the list of AC IV? and their properties (dosing/CI/ monitoring)?

A

1) UFC (unfractionated heparin) IV ——-> can be used during pregnancy
half life 1hr + not renally excreted

Dosing: 80 units/kg IV bolus , followed by a continuous IV infusion, starting dose of 18units/kg/hr {No max dose}
Weight used in the calculation: actual body weight ——–> if obese –> adjusted body weight

SC ——-> 333 units/kg, followed by 250 units/kg every 12 hours ——> not used much ——-> no need to monitor aPTT

Monitoring:
Efficacy:
check aPTT q 4-6hr (1.5-2.5 times the control - sec)

Safety:
signs of bleeding
Hb, Hct, Platelets (thrombocytopenia)

For special population: Anti Xa

SE: High incidence of thrombocytopenia + Osteoporosis

2) LMWH ( low molecular weight heparin) SC ——-> 1st line in pregnancy
Renally excreted ; half life 4 hr
A- Enoxaparin (lovenox) SC
Dosing:
if CrCl > 30 mL/min –> 1mg/kg BID or 1.5 mg/kg daily
if CrCl<30 mL/min –> 1 mg/Kg daily

B- Tinzaparin (innohep) SC

Monitoring: monitor special population; routinely for others not required
-LMWH anti Xa levels ( renal impairement ; Pregnancy; obesity ; prolonged therapy more than 2 w ; weight less than 50kg)

Counseling: under skin not into muscles + wash hands and area + syringe clear + don’t push any air or drug out + lie down and pinch a fold of skin + don’t rub the site + use different area of your body

SE: less incidence of thrombocytopenia

3) Fondaparinux SC:
half life 17-21 hr ; prolonged with renal impairment
renally excreted
Dosing:
if weight <50kg —-> 5mg daily
if weight 50 -100kg —-> 7.5 mg daily
if weight >100 kg —-> 10 mg daily

CI: if CrCl <30min/L

Monitoring: SrCr
special population: Anti Xa levels

26
Q

what are the list of DTI (DIRECT THROMBIN INHIBITORS) ? what are they used to? how to monitor?

A

IV DTI:
1) Argatroban
2) Bivalirudin
3) Lepirudin

USED: bridging VKA in heparin induced thrombocytopenia HIT
will work on factor X and II

Monitoring: SrCr, LFTs , aPTT

27
Q

what are the list of AC PO ? what are the main clotting factor’s half life? and their properties (dosing/CI/ monitoring)?

A

VKA are the only AC PO

Factor X 70 hr
Factor II 60 hr
Factor VII 4-6 hr

Warfarin (hydroxycoumarol): 20-60 hours –> takes time to reach steady state (add DTI for this reason)
half life 20-60hr
full effect: 5-7 d

Dosing:
- Starting 2.5-10mg
Lower Dosing: age > or = 60 and frail / poor nutritional status (hypoalbuminemia) / liver disease / CHF
Higher dosing: enzyme inducers + resistant to effects of warfarin
- Maintenance: Gradual increase in dose and avoid big jumps of INR

Monitoring: INR (not on AC and normal liver —> INR = 1; GOAL in DVT and PE 2-3) and PT
High INR —–> increase risk of bleeding
low INR —–> increase risk of clotting

SE: anaphylactic shock ; hypersensitivity, skin necrosis, gangrene, “purple toes” syndrome + Osteoporosis (long usage) + Bleeding

CI: Pregnancy except for women with mechanical heart valves (hi risk of Thromboembolism)

Sintrom (acenocoumarol ): 8 to 11 hours
full effect: 5 d —-> INR will change faster but doesnt mean full effect is reached
half life 8-11 hr

28
Q

What affects VKA dose/response to therapy?

A

1) Dietary Vitamin K intake: Food rich in vitamin K: green leafy vegetables, beef liver, green tea, herbal products ( more vitK —–> decrease in INR —–> increase in clots)

2) Disease states: CHF, Fluid congestion, fever, cirrhosis

3) Drug interactions
A- Bile acid sequestrants (cholestyramine) –> decrease warfarin absorption
B- Disruption of the gut flora –> less clotting factors –> increase INR
C- CYP inducers (such as phenobarbital, phenytoin,rifampin and carbamazepine ) —> increase metabolism of warfarin —-> decrease INR

D- CYP inhibitors (such as amiodarone, acute ethanol ingestion, cimetidine, miconazole, quinolone antibiotics, sulfonamide antibiotics ) —-> decrease metabolism of Warfarin –> increase INR

E- Highly bound proteins –> compete with warfarin (highly bound to proteins)
F- Antiplatelets , anticoagulants , NSAIDs —> increase risk of bleeding

29
Q

what are the list of NOACs ? and their properties (dosing/CI/ monitoring)?

A

SHOULD ONLY BE GIVEN IF CrCl < 30 ml /min (all except Apixaban ——> < 25 mL/min)
NO monitoring or adjusting the dose depending on INR // aPTT // PT

Monitor: Hb, Hct, Plt count, signs of bleed , SrCR or CrCl

A- Dabigatran: In switching: start AC IV for 7 d ——> switch to Dabigatran 150mg BID
mostly renally excreted
DONT CRUSH OR CHEW
Monitoring: No routine test + aPTT or thrombin time for dose adjustment + SrCr
—- half life 12-17hr —-

B- Rivaroxaban: 15mg BID for 21d ——-> 20mg daily
Can be crushed
TAKE with MEALS for bioavailability
Monitoring: No routine test , but PT or anti Xa for dose adjustment + SrCr
—- half life 7-11 hr —-

C- Apixaban : 10 mg BID for 7 days ——-> 5 mg BID
least renally excreted
Can be crushed
Take with/without meals
Monitoring: No routine test , but PT or anti Xa for dose adjustment + SrCr
—- half life 9-14 hr —-

D- Edoxaban: In switching: start AC IV for 7 d ——> switch to Edoxaban 60mg once daily
— if CrCrl 30-50ml/min, weight<60kg or taking potent pgp inhibitors) 30mg once daily —
—- half life 10-14 hr —-
NOT FOUND IN LEBANON

30
Q

Who shouldn’t receive NOACs?

A
  • Severe renal impairment
  • Liver disease (Child-Pugh B/C)
  • Pregnancy and lactation
  • Patients with antiphospholipid antibody syndrome
  • Compliance is a concern
  • Extreme body weight (caution avoid when weight > 120 kg or BMI> 40 kg/m2)
  • who is taking: Antimicrobials (antifungals, antibiotics, antiretrovirals) / Antiepileptics (Carbamazepine) / Immunosuppressants / Verapamil / Amiodarone
31
Q

If Patient prefers to avoid injections which NOACs should be given?

A

Apixaban or Rivaroxaban

32
Q

If Patient presents with Dyspepsia or Gerd which NOACs should be given?

A

Rivaroxaban, apixaban, edoxaban

33
Q

If Patient had a GI bleed before which NOACs should be given?

A

Apixaban, Edoxaban

34
Q

If Patient poor compliance with BID which NOACs should be given?

A

Rivaroxaban or edoxaban

35
Q

what is the antidote of Heparin?

A

1mg Protamine Sulfate IV for each 100 units of heparin
Maximum dose : 50mg

36
Q

what is the antidote of LMWH

A

1mg of protamine for earch 1mg of enoxaparin
neutralized around 60-70%

37
Q

what should be done in a life threatening bleed?

A

Give 10mg IV phytonadione (Vit K)
Also give blood derivatives:
– Fresh frozen plasma
– Prothrombin Complex concentrate
– Recombinant activated factor VII

38
Q

what should be done for a bleeding patient?

A
  1. Interrupt a VKA dose
  2. Give medium dose ~ 5mg of Vit K PO/IV (IV faster reversal than PO)
39
Q

What should be done if INR of a patient is > 3 and <20 {with no bleed}

A
  1. Interrupt VKA dose (skip a dose)
  2. Give Low doses oral vit K : between 1-2.5mg Vitk
40
Q

What should be done if patient had elective invasive procedure?

A

Interruption of VKAs may be sufficient (omit 1-2 doses)

41
Q

what are the low doses of VitK to reduce the INR at 24hr

A

IV 1mg ; PO 5mg to have similar effect

42
Q

what is the onset of action of VitK? to increase the coagulation factors

A

PO: 6-10hr
IV:1-2 hr

43
Q

what is the peak level of VitK? for the INR value to return to normal

A

PO: 24-48 hr
IV: 12-14 hr

44
Q

What is the main SE of VitK? and how to manage it?

A

SE: anaphylactoid Reactions
To minimize: VitK mixed with minimum of 50mL of IV fluid and administered using an infusion pump for minimum of 20min

45
Q

what is the antidote of Dabigatran?

A

Idarucizumab IV

46
Q

what is the antidote of Apixaban?

A

Andexanet Alfa IV

47
Q

what is the antidote of Rivaroxaban ?

A

Andexanet Alfa IV

48
Q

what is the antidote of Edoxaban ?

A

Andexanet Alfa IV

49
Q

What it is HIT and HITThrombosis?

A

HIT: heparin induced thrombocytopenia = immune mediated adverse effect - IgG when platelets count drop of >or = 50%

Onset: 5-14 d
Nadir platelets 30,000 - 50,000

If not thrombosis —> HIT
If thrombosis develops —> HITThrombosis

50
Q

what is HAT

A

A mild / transient drop of 10-30%
Onset 1-3 d
Nadir platelets 100,000
non immune
sequence BENIGN

51
Q

How is the pre - test scoring system? and what does each score tell us? how about the management done?

A
  • High probability (6-8 points) —-> HIT or HITT –> discontinue heparin like agents + stop AC + dont start warfarin until platelets back to normal ( 150 x 10 ^9) / bridge VKA + non heparin AC for 5 d —-> continue treatment for 3 m
    Intravenous DTI: argatroban or Subcutaneous Pentasaccharides: Fondaparinux
    NOACs HITT : rivaroxaban 15 mg twice daily for 21 days, then 20 mg once daily
    for a duration of 3-6 months
  • Intermediate probability (4-5 points) —-> apply clinical judgment or diagnosis for treatment
  • Low probability (≤ 3 points) —-> HAT —–> keep patient on Heparin or LMWH and expect platelet to resolve alone
52
Q

which drugs induces Thrombocytopenia?

A

abciximab
cephalosporins
diltiazem
eptifibatide
quinine
tirofiban
vancomycin

53
Q

what are the 4 factors of 4T score?

A

1) thrombocytopenia
2)Timing of platelet count fall
3) thrombosis or other sequelae
4) other causes of thrombocytopenia

54
Q

what are the diseases that might cause thrombocytopenia ?

A

Bone marrow disease
cardiac surgery
vitamin B12 deficiency
folic acid deficiency
idiopathic thrombocytopenia
thrombotic thrombocytopenic purpura
post transfusion purpura

55
Q

During surgery , what should be taken into consideration regarding AC?

A

avoid risk of bleeding –> evaluate need to discontinue AC

Due to high clotting risk –> AC should be given –> short acting IV (UFH,LMWH as a bridge)

56
Q

what are example of Minor bleeding risk surgery?

A

Endoscopy with biopsy; electrophysiological study or simple
radiofrequency catheter ablation; angiography

57
Q

what are example of Major bleeding risk surgery

A

spinal or epidural anaesthesia; lumbar diagnostic puncture; thoracic
surgery; abdominal surgery; major orthopaedic surgery; liver biopsy;
transurethral prostate resection; kidney biopsy.

58
Q

how to manage Periprocedural (surgeries) using VKA?

Specify the management also for WARFARIN & LMWH

what is the dose of LMWH

A

1) Discontinue warfarin 4 d before surgery
2) Clear of VKA –> short acting IV (UFH,LMWH at prophylactic or treatment doses)
3) prior to surgery discontinue IV AC (UFH 6 hr before ; LMWH before 24hr)
4)Resume IV AC after surgery overlap with Warfarin

if high blood risk:
Warfarin: discontinue before 5 days , and re-take it after the surgery
LMWH: discontinue before 1 day and take it after 1-2 days after surgery

If low to moderate risk:
warfarin same as high
LMWH: discontinue before 1 day and take it after 1 day of surgery

If minimal bleed risk: warfarin (no need to stop)

LMWH:
full dose: enoxaparin 1mg/kg BID or 1.5mg/kg Daily / Dalteparin 100IU/kg BID or 200 IU/kg daily
low dose: 40mg daily Enoxaparin / Dalteparin 5000 IU daily

59
Q

What is the appropriate timing to withhold DOACs Perioperatively? - Interruption

A

High Bleeding risk:
—> before 3 days: Apixaban + Dabigatran ( CrCl>or= 50) + Edoxaban + Rivaroxaban
—> before 5 days: Dabigatran ( CrCl <50)

Low/Mod Bleeding risk:
—> before 1 day: Apixaban + Dabigatran ( CrCl>or= 50) + edoxaban + Rivaroxaban
—> Before 2 days: Dabigatran ( CrCl <50)

60
Q

What is the appropriate timing to withhold DOACs Perioperatively? - Resumption

A

Directly after Procedure/surgery:
All low /Mod bleeding risk with Any of the medication: Apixaban + Dabigatran ( CrCl>or= 50) + Edoxaban + Rivaroxaban +Dabigatran ( CrCl <50)

After 2-3 days:
All high bleeding risk with any of the medications:Apixaban + Dabigatran ( CrCl>or= 50) + Edoxaban + Rivaroxaban +Dabigatran ( CrCl <50)

Thrombosis (1 decks)

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