Anticoagulation Dosing Guideline for Adult COVID-19 Patients
Enoxaparin is the preferred first line anticoagulant for patients diagnosed with COVID-19. The incidence of HIT with enoxaparin is less than 1%.
1. 2. 3.

VTE Prophylaxis:
 
VTE prophylaxis will be considered for COVID-19 patients who are low risk.

Low risk COVID-19 patient

Not receiving mechanical ventilation

D-Dimer < 6 mg/L

ESRD on iHD without clotting
Kidney Function
BMI (kg/m2)
Dosing of Enoxaparin

Concern for HIT or LMWH Failure
CrCL ≥ 30 mL/min
18.5-39.9
30mg SUBQ Q12H
Consult Hematology
40-49.9
40mg SUBQ Q12H
≥ 50
60mg SUBQ Q12H
CrCL < 30 mL/min OR
ESRD/AKI on RRT
18.5-39.9
30mg SUBQ Q24H
Consult Hematology
≥ 40
40mg SUBQ Q24H
Special Population:
 
< 18.5 (or weight < 50kg)

Heparin 2500 SUBQ Q8H
Consult Hematology

*Contraindications: Platelets < 25 K/uL or Fibrinogen < 50 mg/dL or active bleeding
Therapeutic anticoagulation
Therapeutic anticoagulation will be considered for COVID-19 patients who are considered high risk or diagnosed with an acute VTE.
High risk COVID-19 patient (for all hospitalized patients):
Receiving mechanical ventilation AND D-dimer > 6 mg/L OR
Acute kidney injury (Scr increase 0.3 mg/dL above baseline) +/- CVVHD/AVVHD/SLED or IHD with clotting
Anti-Xa level goals for enoxaparin therapy (when indicated):
1. Therapeutic peak LMWH level (Drawn 4 hours after 3rd dose): 0.6-1 anti-Xa units/mL
2. Therapeutic trough LMWH level (Drawn 1 hour prior to 3rd dose): < 0.5 anti-Xa units/mL
  

Kidney Function
 
BMI
(kg/m2)
Dosing of Enoxaparin

Concern for HIT or LMWH Failure
CrCL ≥ 30 mL/min
12-49.9
1 mg/kg SUBQ Q12H
Bivalirudin infusion (see Anticoagulation COVID- 19 guidelines for dosing)
≥ 50
0.8 mg/kg SUBQ Q12H
**monitor peak anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti- Xa level and dose adjustment
CrCL < 30mL/min
12-49.9
1 mg/kg SUBQ 24H
Bivalirudin infusion (see Anticoagulation COVID- 19 guidelines for dosing)
≥ 50
0.8mg/kg SUBQ Q24H
**monitor peak anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti- Xa level and dose adjustment
ESRD or AKI on RRT

 
0.8 mg/kg SUBQ Q24H (MAX dose 1mg/kg Q24H) **monitor peak and trough anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti- Xa level and dose adjustment
Bivalirudin infusion (see Anticoagulation COVID- 19 guidelines for dosing)

If minor bleeding prior to obtaining steady state anti- Xa levels
Decrease dose to 0.5 mg/kg and monitor anti-Xa peak and trough with 1st dose of new regimen
Consult pharmacist to assist with obtaining anti- Xa levels and dose adjustment
*Contraindications: Platelets < 50 K/uL or fibrinogen < 100 mg/dL or active bleeding
Intra-dialytic anticoagulation for renal replacement therapy
Nephrology service will determine the need for a booster dose of IV enoxaparin when ordering renal replacement therapy Renal replacement therapy (iHD/SLED/CRRT)
o Enoxaparin 30 mg IV x 1 preferably prior to or within an hour of starting dialysis o If HIT positive or enoxaparin failure, recommend switching to bivalirudin
 
This guideline/pathway is not intended to be a substitute for clinical judgement. The risk of bleeding must be weighed against the risk of thrombosis and its consequences.
Anticoagulation in Pregnant Patients: Antenatal and Postpartum
Management of anticoagulation therapy during labor and delivery requires specialized care and planning and should be managed similarly in pregnant patients with COVID-19 as other conditions that require anticoagulation in pregnancy.
Prophylactic anticoagulation o
Therapeutic anticoagulation
o For a high risk critically ill pregnant patient less than 22 weeks gestation or post-partum, enoxaparin should be considered
 
All low risk pregnant women with suspected or confirmed COVID-19 infection should receive prophylactic unfractionated
 
heparin upon admission to reduce risk of
venous thromboembolism
Trimester
Dosing of Heparin
Concern for HIT
1st
5000-7500 units SUBQ Q12H
Consult Hematology
  
2nd
7500-10000 units SUBQ Q12H

3rd
10000 units SUBQ Q12H
Gestational age
Kidney Function
BMI (kg/m2)
Dosing of Enoxaparin
Concern for HIT or LMWH Failure
Less than 22 weeks

CrCL ≥ 30 mL/min
12-49.9
1 mg/kg SUBQ Q12H
**monitor peak anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti-Xa level and dose adjustment
Consult Hematology
≥ 50
0.8 mg/kg SUBQ Q12H
**monitor peak anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti-Xa level and dose adjustment
CrCL < 30mL/min
12-49.9
1 mg/kg SUBQ 24H
**monitor peak anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti-Xa level and dose adjustment
Consult Hematology
≥ 50
0.8mg/kg SUBQ Q24H
**monitor peak anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti-Xa level and dose adjustment
ESRD or AKI on RRT


0.8 mg/kg SUBQ Q24H (MAX dose 1mg/kg Q24H)
**monitor peak and trough anti-Xa level with 3rd dose
Consult pharmacist to assist with obtaining anti-Xa level and dose adjustment
Consult Hematology
If minor bleeding prior to obtaining steady state anti-Xa levels
Decrease dose to 0.5 mg/kg and monitor anti-Xa peak and trough with 1st dose of new regimen
Consult pharmacist to assist with obtaining anti-Xa levels and dose adjustment

*Contraindications: Platelets < 50 K/uL or fibrinogen < 100 mg/dL or active bleeding
o For a high risk critically ill pregnant patient greater than 22 weeks gestation, unfractionated heparin should be considered due to its short half-life and reversibility
aPTTs should be monitored according to institutional protocol
Unfractionated heparin, low molecular weight heparin, and warfarin do not accumulate in breast milk and do not induce an
anticoagulant effect in the newborn; therefore, they can be used in breastfeeding women with or without COVID-19 who require VTE prophylaxis or treatment
o Direct-acting oral anticoagulants are not routinely recommended due to lack of safety data
o Direct thrombin inhibitors should be used as a last line option with an assessment of benefit versus risk in patients who
require anticoagulation and are unable to receive heparin products (e.g., heparin-induced thrombocytopenia) due to limited data available

Thisguideline/pathwayisnotintendedtobeasubstituteforclinicaljudgement. Theriskofbleedingmustbeweighedagainsttheriskofthrombosisanditsconsequences.
Bivalirudin: therapeutic anticoagulation
Due to the liver injury that may be seen in patients with COVID-19, bivalirudin is the preferred direct thrombin inhibitor for the treatment of HIT, enoxaparin failure, or patients receiving extracorporeal membrane oxygenation (ECMO).
IHD – intermittent hemodialysis, CRRT – continuous renal replacement therapy Dose adjustments:
* If aPTT >3x baseline, consider holding infusion for 1 hour and re-starting at 50% lower rate
Monitoring:
o aPTT q 4 hours following initiation of infusion and following dosing adjustment – target aPTT 50-80 o If 2 consecutive aPTTs are at goal, check aPTT q 24 hours
o CBC as appropriate based upon clinical status of patient
Bivalirudin for renal replacement therapy
CVVH: no loading dose, bivalirudin 2 mg/hour one hour prior to RRT until completion o If doses of 2 mg/hour are ineffective, increase bivalirudin dose by 20%
Transition from therapeutic enoxaparin to an oral anticoagulant
Prior to discharge:
o All high-risk patients previously on therapeutic anticoagulation without a confirmed VTE may transition to a DOAC at
prophylactic doses
Rivaroxaban 10 mg daily (for patients with a CrCl > 30 ml/min) OR apixaban 2.5 mg bid x 4 weeks
In patients who do not have insurance coverage for a DOAC or in whom a DOAC may be contraindicated, prophylactic doses of enoxaparin may be used for the time frame listed above
Warfarin may be considered in patients who have confirmed HIT
o All high-risk patients on therapeutic anticoagulation for a confirmed VTE may transition to a DOAC at treatment doses
Rivaroxaban 15 mg bid x 21 days followed by 20 mg daily thereafter OR apixaban 10 mg bid x 7 days followed by 5 mg bid thereafter
In patients who do not have insurance coverage for a DOAC or in whom a DOAC may be contraindicated, treatment doses of enoxaparin may be continued for the time frame listed above
Warfarin may be considered in patients who have confirmed HIT

CrCl (ml/min)
Bivalirudin Initial dose (mg/kg/hour)
> 60
0.15 +/- 0.1
30-60
0.08 +/- 0.04
< 30
0.05 +/- 0.02
IHD (25% clearance by HD filters) or CRRT
0.07 +/- 0.03

aPTT (seconds)

Dose adjustment
Monitoring recommendations
<50

Increase infusion rate by 20%

Re-check aPTT 4 hours after rate change
50-80
No change
Re-check aPTT at 4 hours; if 2 consecutive aPTTs are at goal, check aPTT q 24 hours
>80*
Decrease infusion rate by 20%
Re-check aPTT 4 hours after rate change
  

All patients initiating enoxaparin should have a baseline and q48h fibrinogen, D-dimer, aPTT and PT/INR.
Determine COVID risk status
  
Low risk:*
Not receiving mechanical ventilation
D-dimer < 6 mg/L
ESRD on iHD without clotting
High risk:○
Receiving mechanical ventilation AND D-dimer > 6 mg/L
Acute kidney injury (Scr increase 0.3 mg/dL above baseline) +/- CVVHD/AVVHD/SLED or IHD with clotting
     
Recommend Prophylactic Dose Enoxaparin□
Recommend Therapeutic Dose Enoxaparin■
  
 
BMI 18.5**– 39.9 kg/m2
CrCl > 30 ml/min: Enoxaparin 30 mg SUBQ q 12 hours
CrCl < 30 ml/min: Enoxaparin 30 mg SUBQ q 24 hours
BMI > 40 kg/m2
CrCl > 30 ml/min: Enoxaparin 40 mg SUBQ q 12 hours
CrCl < 30 ml/min: Enoxaparin 40 mg SUBQ q 24 hours
  

 
ESRD/AKI on RRT◊ Enoxaparin 0.8 mg/kg SUBQ q 24 hours
If minor bleeding, decrease enoxaparin dose to 0.5 mg/kg
If concern for HIT, switch to bivalirudin infusion^
Concern for HIT, LMWH failure, or patients receiving ECMO Recommend bivalirudin infusion^
      
  
Concern for HIT/ LMWH failure Consult hematology
BMI 12– 49.9 kg/m2
CrCl > 30 ml/min: Enoxaparin 1 mg/kg SUBQ q 12 hours
CrCl < 30 ml/min: Enoxaparin 1 mg/kg SUBQ 24 hours
BMI > 50 kg/m2◊
CrCl > 30 ml/min: Enoxaparin 0.8 mg/kg SUBQ q 12 hours
CrCl < 30 ml/min Enoxaparin 0.8 mg/kg SUBQ q 24 hours
   
BMI > 50 kg/m2
CrCl > 30 ml/min: Enoxaparin 60 mg SUBQ q 12 hours
CrCl < 30 ml/min or ESRD on iHD Enoxaparin 40 mg SUBQ q 24 hours
  
If receiving RRT and concern for circuit clot on prophylactic enoxaparin: Recommend additional Enoxaparin 30 mg IVP ONCE prior to or within one hour of initiating dialysis
 
If receiving RRT and concern for circuit clot on therapeutic enoxaparin: Recommend additional Enoxaparin 30 mg IVP ONCE prior to or within one hour of initiating dialysis
Anti-Xa goals (when indicated)◊
Therapeutic peak LMWH level (drawn 4 hours after the 3rd dose): 0.6-1 anti-Xa units/mL
Treatment trough LMWH level (drawn one hour prior to 3rd dose): < 0.5 anti-Xa units/mL
□Patients should not receive prophylactic dose enoxaparin if fibrinogen < 50 mg/dL, platelets < 25,000 K/uL, or active bleeding.
■ Patients should not receive therapeutic dose enoxaparin if fibrinogen < 100 mg/dL, platelets < 50,000 K/uL, or active bleeding.
*If patients transition from low-risk to high risk based upon criteria or develop a VTE on prophylaxis, full-dose anticoagulation is warranted
**If BMI < 18.5 kg/m2 or weight < 50 kg, recommend Heparin SQ 2500 units q 8 hours
◊If BMI > 50 kg/m2 or AKI/ESRD, recommend anti-Xa monitoring (consult pharmacy for assistance)
^Bivalirudin is preferred to argatroban given likelihood of elevated transaminases (e.g., secondary to medications, ischemia, among other causes) in the COVID patient
○Upon discharge, apixaban 2.5 mg bid x 4-6 weeks should be continued in patients without a confirmed VTE and normal renal function and 2 weeks for patients with AKI/ESRD. Warfarin may be considered in cases
of confirmed HIT. Patients with a confirmed VTE should be discharged on therapeutic anticoagulation.
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