Role of Anticoagulant in

treatment protocol of
COVID 19 patients

: By
Amira Abdelrazek Nemr
COVID-19 has been associated with inflammation and a
prothrombotic state, with increases in fibrin, fibrin degradation
products, fibrinogen, and D-dimer levels. In some studies,
elevations in these markers have been associated with worse
.clinical outcomes

Patients with COVID-19, which is caused by the novel severe

acute respiratory distress syndrome coronavirus 2, may develop
hemostatic abnormalities. 

Early reports demonstrated high rates of VTE for patients who are
acutely ill or hospitalized with COVID-19, including those receiving
critical care. 
The optimal strategy for thromboprophylaxis in these patients
remains uncertain.

Coagulation abnormalities in COVID-19

Patients diagnosed with mild-to-moderate COVID-19 not requiring

hospitalization do not benefit from starting anticoagulation, either
as thromboprophylaxis or to prevent progression of COVID-19,
based on a very low event rate in stable outpatients, from the
ACTIV-4b RCT comparing placebo, aspirin, or two different doses
.of apixaban in ambulatory patients older than 40 years

We advise not starting anticoagulation for acutely ill COVID-19–

 .positive outpatients

Abnormalities caused by SARS-CoV-2, is associated with several

coagulation abnormalities which may be responsible for thrombotic
manifestations related to this disease such as venous
thromboembolism (VTE) and PE.
What dose of anticoagulation should be empirically used in
hospitalized COVID-19 patients in the absence of confirmed or
suspected VTE?

All hospitalized adults with COVID-19 should at a minimum receive

pharmacologic thromboprophylaxis, unless the risk of bleeding
even on prophylactic dosing outweighs the risk of thrombosis.
LMWH is preferred over unfractionated heparin (UFH). In the
setting of heparin-induced thrombocytopenia, fondaparinux is
recommended. In patients for whom anticoagulants are
contraindicated or unavailable, mechanical thromboprophylaxis
(e.g., pneumatic compression devices) can be used. Combined
pharmacologic and mechanical prophylaxis is not generally
recommended.

Hypercoagulable state :

A number of changes in circulating prothrombotic factors have

been reported or proposed in patients with severe COVID-19:
•Elevated factor VIII
•Elevated fibrinogen
•Circulating prothrombotic microparticles
•Neutrophil extracellular traps (NETs)
•Hyper viscosity

Coagulation testing

•Prothrombin time (PT) and aPTT normal or slightly prolonged

•Platelet counts normal or increased (mean, 348,000/microL)
•Fibrinogen increased (mean, 680 mg/dL; range 234 to 1344)
•D-dimer increased (mean, 4877 ng/mL; range, 1197 to 16,954)
●Other assays
•Factor VIII activity increased (mean, 297 units/dL)
•VWF antigen greatly increased (mean, 529; range 210 to 863),
consistent with endothelial injury or perturbation
•Minor changes in natural anticoagulants
-Small decreases in antithrombin and free protein S
-Small increase in protein C

One of the most striking features of COVID-19 is the wide

spectrum of clinical manifestations and outcomes, from
asymptomatic to various degrees of organ dysfunction to death.

VTE 
 Venous thromboembolism (VTE), including extensive deep vein
thrombosis (DVT) and pulmonary embolism (PE), was very
common in acutely ill patients with COVID-19 during the early
stages of the pandemic, seen in up to one-third of patients in the
intensive care unit (ICU), even when prophylactic anticoagulation
was used .
However, there has been a general trend over time from a higher
VTE risk in hospitalized patients earlier in the pandemic towards a
lower risk later in the pandemic, although VTE risk in hospitalized
patients remains a serious concern
The reasons for the decrease in risk remain unclear; earlier
diagnosis and improved treatment may have played a role.

Clinical implications
Higher-dose anticoagulation, mostly performed using LMWH,
significantly reduced the risk of venous thromboembolic events, at
the expense of a significantly increased risk of major bleeding.
However, higher-dose anticoagulation had no effect on all-cause
death. Consequently, this meta-analysis does not support the
routine use of therapeutic-dose anticoagulation in patients
hospitalized with COVID-19. Therapeutic-dose anticoagulation
might improve outcomes in selected patients.

In noncritically ill patients, we found a numerically lower risk of

death with higher-dose anticoagulation than with prophylactic-dose
anticoagulation, but without reaching statistical significance. Future
studies may investigate whether early initiation of higher-dose
anticoagulation in noncritically ill patients is associated with
improved outcomes.
 As of now, there is insufficient evidence of survival benefit of
higher-dose anticoagulation compared with prophylactic-dose
anticoagulation in noncritically ill and in critically ill patients.

antithrombotic Therapy for Nonhospitalized Patients Without

Evidence of Venous Thromboembolism

For patients who are at high risk for VTE and at low risk of bleeding,
extended VTE prophylaxis can be considered, as per the protocol
for patients without COVID-19.

Antithrombotic Therapy for Hospitalized, Nonpregnant Adults

Without Evidence of Venous Thromboembolism

In hospitalized patients, low molecular weight heparin (LMWH) or

unfractionated heparin (UFH) is preferred over oral anticoagulants,
because these 2 types of heparin have shorter half-lives and the
effect can be reversed quickly, can be administered intravenously or
subcutaneously, and have fewer drug-drug interactions.

When heparin is used, LMWH is preferred over UFH.

For adults who require low-flow oxygen and do not require

intensive care unit (ICU)-level care:

Contraindications for the use of therapeutic anticoagulation in

patients with COVID-19 are a platelet count <50 x 109/L, hemoglobin
<8 g/dL, the need for dual antiplatelet therapy, bleeding within the
past 30 days that required an emergency department visit or
hospitalization, history of a bleeding disorder, or an inherited or active
acquired bleeding disorder.

In patients without VTE who have begun a therapeutic dose of

heparin, treatment should continue for 14 days or until hospital
discharge, whichever comes first.

switching from the therapeutic dose to a prophylactic dose of

heparin, unless VTE is confirmed.
Hospitalized Children

For hospitalized children with COVID-19, indications for VTE

prophylaxis should be the same as those for children without COVID-
19.

Chronic Anticoagulant or Antiplatelet Therapy

Outpatients with COVID-19 who are receiving warfarin and are in
isolation and unable to have international normalized ratio
monitoring may be candidates for switching to direct oral
anticoagulant therapy.

Patients with a mechanical heart valve, ventricular assist device,

valvular atrial fibrillation, or antiphospholipid antibody syndrome or
who are lactating should not discontinue treatment with warfarin.

The COVID-19 Treatment Guidelines recommends that

hospitalized patients with COVID-19 who are receiving
anticoagulant or antiplatelet therapy for underlying medical
conditions continue this treatment unless significant bleeding
develops or other contraindications are present.

: Reference

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432456

https://www.uptodate.com/contents/covid-19-hypercoagulability

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/
2785005