COAGULOPATHY OF PATIENTS INFECTED WITH COVID-19 Reza aghabozorgi MD - - PowerPoint PPT Presentation

MANAGEMENT OF COAGULOPATHY OF PATIENTS INFECTED WITH COVID-19

Reza aghabozorgi MD medical oncologist and hematologist

• we will review data for coagulation abnormalities that
• ccur in association with COVID-19, and clinical

management questions likely to arise

• Our considerations are based on evolving data and

consensus

• Evidence of abnormal coagulation parameters associated with

COVID-19 appeared in early reports from China

• a D-dimer level greater than 1.0 mcg/mL at admission was

associated with increased mortality with an OR of 18.42 (2.64- 128.55, p=0.003)



elementary data showed that LMWH or UFH are associated with a reduced 28-day mortality in more severe COVID-19 patients displaying a sepsis-induced coagulopathy (SIC) score ≥4 (40.0% vs 64.2%, p=0.029) or D-dimer levels >6-fold the upper limit of normal (32.8% vs 52.4%, p=0.017)

INFLAMMATION AND COAGULATION

• In addition to respiratory failure, patients with

severe illness are also likely to have coagulopathy Infection pathogens initiates complex systemic inflammatory responses as part of innate immunity

mechanisms of thrombus formation

■ imbalance of pro and anticoagulant states during infection ■ the endothelium plays an important role in homeostasis regulation and it is disrupted in viral infections ■ viral infection-induced elevation of von Willebrand factor ■ tissue factor pathway activation

thromboinflammation or immunothrombosis

■ Activation of host defense systems ■ subsequent activation of coagulation and thrombin generation ■ critical communication components among humoral and cellular amplification pathways

 Polyphosphates, derived from microorganisms, activates

platelets, mast cells, and FXII in the contact pathway of coagulation, and exhibit other downstream roles in amplifying the procoagulant response of the intrinsic coagulation pathway

 Complement pathways contribute to activation of

coagulation factors The inflammatory effects of cytokines also result in activated vascular endothelial cells and endothelial injury with resultant prothrombotic properties

 Given the tropism of the virus for ACE2 receptors,

endothelial cell activation and damage with resultant disruption of the natural antithrombotic state is likely

 This inflammation associated withCOVID-19 and

subsequent activation of coagulation is the probable cause for the elevated Ddimer levels

EN ENDO DOTHELIAL THELIALOP OPATHY THY an and COVID VID19 19

■ The receptor for viral adhesion is an ACE 2 receptor on endothelial cells ■ ■ viral replication causing inflammatory cell infiltration, endothelial cell apoptosis, and microvascular prothrombotic effects ■ microcirculatory dysfunction contributes to the clinical sequelae in patients with COVID-19.

RECOMMENDATION

• All patients presenting to hospital for COVID-19 should

have the following test obtained at baseline: D-dimer, PT, PTT, fibrinogen and CBC with differential

■ All patients admitted to hospital for COVID-19 should have the following tests obtained at baseline and every 2 days: D-dimer, PT, PTT, fibrinogen daily y if ini nitial l or subse seque uent t D-dimer imer is elevated ed

■ The most common pattern of coagulopathy observed in patients is characterized by elevat ations ions in f n fibri brinogen

• gen and

nd D- dimer er levels els ■ prolongation of the aPTT and/or PT is minimal, thrombocytopenia is mild (platelet count ~100 x109/L)

■ Rarely patients with severe COVID-19 infection and multiorgan failure progress to a coagulopathy meeting criteria for overt DIC ■ moderate to severe thrombocytopenia (platelet count <50 x109/L), prolongation of the PT and aPTT, extreme elevation

• f D-dimer, and decreased fibrinogen (< 1.0 g/L)

■ Worsening of coagulation parameters, specifically the D-dimer, indicates progressive severity of COVID-19 infection and predicts that more aggressive critical care will be needed ■ experimental therapies for COVID-19 infection might be considered in this setting ■ Improvement of these parameters along with stable or improving clinical condition provides confidence that stepping down of aggressive treatment may be appropriate

Management

COVID-19 infection infrequently leads to bleeding despite abnormal coagulation parameters blood product transfusion should be individualized Blood component therapy should not be instituted on the basis

• f laboratory results alone, but reserved for those with active

bleeding

■ There are no data to support any particular “safe” cut-off for hematological parameters ■ In patients who are not bleeding, there is no evidence that correction of laboratory parameters with blood products improves outcomes ■ Replacement might worsen disseminated thrombosis and further deplete scarce blood products

■ actively bleeding, transfuse platelets (one adult dose) if the platelet count is less than 50 x 109/L ,give plasma (4 units) if the INR is above 1.8 and order cryoprecipitate (10 units) if the fibrinogen level is less than 150 mg/L

ANTICOAGULATION

• Patients should receive standard prophylactic

anticoagulation with LMWH in the absence

• f any contraindications (active bleeding or platelet

count less than 25,000) abnormal PT or APTT is not a contraindication

• Heparin has been implicated in binding to COVID-19 spike

proteins as well as downregulating interleukin-6 (IL-6)

• unfractioned heparin or LMWH remains as the best choice
• f anticoagulant for admitted patients

• If LMWH contraindicated due to renal failure (Creatine

Clearance <30mL/min), UFH can be used as an alternative In obese patients, the recommended dose is 40 mg bid

■ If a patient is on a DOAC at time of admission but then requires COVID-19 therapy that interacts with the DOAC, or is/becomes severely ill, that patient should be switched to LMWH (preferred over UFH)

■ prophylactic dose LMWH is recommended for all patients despite abnormal coagulation tests in the absence of active bleeding, and held only if platelet counts are less than 25 x 109/L

Renal adjustment enoxaparin

■ CrCl 15-29:30mg Q24 h ■ CrCl<15 or renal replacment thrapy: avoid use

Prophilaxis dosing obecity

■ UFH 5000 unit Q 8 houre SC ,IF BW is 120 to 150kg ■ UFH 7500 unit Q 8 houre SC ,IF BW is >150kg ■ Enoxapari 40 mg Bid if Crcr>30 ■ Enoxaprin 40mg daily if Crcr 30 >

Low body weight

■ UFH:5000 q12h ■ Enoxaparin:30mg q 24h

non-hospitalized patients

there are currently insufficient data to recommend for or against using this data to guide management decisions

Pat atie ients nts wi with th COVID ID-19 9 Wh Who A

• Are

Dis ischa harge rged d from rom th the Hos e Hospi pita tal

■ Routine post-discharge VTE prophylaxis is not

• t recom

comme mend nded ed for patients ents with h COVID VID-19 19 ■ for high-risk patients one regimens is optional ■ rivar aroxaban aban 10 10mg daily y for r 31 to 39 39 days ys

Modified IMPROVE-VTE score

VTE risk score VTE risk factor 3 Previous VTE 2 Known thrombophilia a 2 Current lower limb paralysis or paresis b 2 History of cancerc 1 ICU/CCU stay 1 Complete immobilization d ≥ 1 d 1 Age ≥60 y

• aA congenital or acquired

condition leading to excess risk of thrombosis (e.g., factor V Leiden, lupus anticoagulant, factor C or factor S deficiency).

• bLeg falls to bed by

5 seconds, but has some effort against gravity (taken from NIH stroke scale)

• cCancer (excluding

nonmelanoma skin cancer) present at any time in the past 5 years (cancer must be in remission to meet eligibility criteria)

• dImmobilization is being

confined to bed or chair with

• r without bathroom

privileges

■ Modified IMPROVE-VTE score ≥4 ■

• Modified IMPROVE-VTE score ≥2 and D-dimer level >2

times the upper limit of normal ■

• Age ≥75 years

■

• Age >60 years and D-dimer level >2 times the upper limit of

normal ■

• Age 40 to 60 years, D-dimer level >2 times the upper limit
• f normal and previous VTE event or cancer

EUROPEAN HEART JOURNAL - CARDIOVASCULAR PHARMACOTHERAPY

THANKS