Endothelial_AJ0 Injury_NN1 
Autopsy_NN1 studies_NN2 early_AJ0 during_PRP the_AT0 pandemic_AJ0 revealed_VVD diffuse_AJ0 endothelial_AJ0 inflammation_NN1 in_PRP many_DT0 organs_NN2 ,_PUN including_PRP the_AT0 lung_NN1 ,_PUN heart_NN1 ,_PUN liver_NN1 ,_PUN and_CJC kidney_NN1 ,_PUN with_PRP evidence_NN1 of_PRF direct_AJ0 viral_AJ0 infection_NN1 of_PRF endothelial_AJ0 cells_NN2 by_PRP the_AT0 SARS-CoV-2_AJ0 virus_NN1 ._SENT Because_CJS in_PRP vivo_AJ0 biosynthesis_NN1 of_PRF von_NP0 Willebrand_NP0 factor_NN1 is_VBZ restricted_VVN to_PRP endothelial_AJ0 cells_NN2 and_CJC megakaryocytes_NN2 ,_PUN high_AJ0 plasma_NN1 von_NP0 Willebrand_NP0 factor_NN1 concentrations_NN2 in_PRP patients_NN2 with_PRP COVID-19_NN1 suggest_VVB significant_AJ0 endothelial_AJ0 cell_NN1 derangement_NN1 ._SENT Immune_AJ0 cell_NN1 arteritis_NN1 was_VBD found_VVN in_PRP the_AT0 lungs_NN2 of_PRF nearly_AV0 half_DT0 of_PRF those_DT0 who_PNQ had_VHD died_VVN of_PRF COVID-19_NN1 in_PRP one_CRD autopsy_NN1 series_NN0 ._SENT Endothelial_AJ0 injury_NN1 ,_PUN particularly_AV0 in_PRP the_AT0 context_NN1 of_PRF a_AT0 hypercoagulable_AJ0 milieu_NN1 ,_PUN likely_AJ0 is_VBZ responsible_AJ0 for_PRP the_AT0 high_AJ0 rates_NN2 of_PRF microthrombosis_NN1 noted_VVN in_PRP the_AT0 pulmonary_AJ0 vasculature_NN1 ._SENT Although_CJS pulmonary_AJ0 microthrombosis_NN1 has_VHZ been_VBN noted_VVN previously_AV0 in_PRP classical_AJ0 ARDS_NP0 ,_PUN the_AT0 extent_NN1 evident_AJ0 in_PRP COVID-19_NN1 is_VBZ significantly_AV0 greater_AJC ._SENT Ackerman_NP0 et_NP0 al_NP0 noted_VVD that_CJT autopsies_NN2 from_PRP patients_NN2 with_PRP COVID-19_CRD showed_VVD nine_CRD times_NN2 more_AV0 alveolar_AJ0 capillary_AJ0 microthrombi_NN1 compared_VVN with_PRP autopsies_NN2 from_PRP patients_NN2 with_PRP ARDS_NP0 secondary_AJ0 to_PRP H1N1_AJ0 influenza_NN1 ._SENT The_AT0 high_AJ0 rates_NN2 of_PRF microthrombosis_NN1 are_VBB not_XX0 limited_VVN to_PRP the_AT0 lungs_NN2 ;_PUN they_PNP also_AV0 have_VHB been_VBN reported_VVN in_PRP the_AT0 heart53_NN1 and_CJC skin_NN1 ._SENT Imaging_NN1 studies_NN2 demonstrate_VVB that_CJT thrombotic_AJ0 lesions_NN2 in_PRP COVID-19_NN1 are_VBB smaller_AJC and_CJC more_AV0 peripherally_AV0 located_VVN compared_VVN with_PRP those_DT0 in_PRP non-COVID_AJ0 acute_AJ0 PE_NN1 ,_PUN suggesting_VVG that_CJT some_DT0 filling_AJ0 defects_NN2 on_PRP CTPA_NP0 ,_PUN particularly_AV0 isolated_AJ0 subsegmental_AJ0 PE_NN1 ,_PUN may_VM0 reflect_VVI in_PRP situ_NN1 pulmonary_AJ0 thrombosis_NN1 instead_AV0 of_PRF the_AT0 typical_AJ0 embolization_NN1 of_PRF thrombi_NN2 originating_VVG from_PRP peripheral_AJ0 DVT_NP0 ._SENT Mirsadraee_NP0 et_NP0 al_NP0 reported_VVD that_DT0 of_PRF the_AT0 critically_AV0 ill_AJ0 patients_NN2 with_PRP COVID-19_NN1 found_VVD to_TO0 have_VHI pulmonary_AJ0 thrombosis_NN1 via_PRP screening_NN1 CTPA_NP0 ,_PUN 77_CRD %_NN0 did_VDD not_XX0 have_VHI radiologic_AJ0 evidence_NN1 of_PRF peripheral_AJ0 DVT_NP0 ._SENT 
Gas_NN1 Exchange_NN1 vs_PRP Lung_NN1 Compliance_NN1 
Early_AV0 in_PRP the_AT0 pandemic_AJ0 ,_PUN Gattinoni_NP0 et_NP0 al_NP0 noted_VVD that_CJT although_CJS many_DT0 patients_NN2 with_PRP COVID-19_NN1 technically_AV0 fulfilled_VVN the_AT0 Berlin_NP0 criteria_NN2 for_PRP ARDS_NP0 ,_PUN many_DT0 showed_VVD marked_AJ0 hypoxemia_NN1 and_CJC elevated_AJ0 shunt_NN1 fraction_NN1 with_PRP only_AV0 minimally_AV0 affected_VVN lung_NN1 compliance_NN1 ,_PUN particularly_AV0 early_AJ0 in_PRP the_AT0 course_NN1 of_PRF disease_NN1 ._SENT Chiumello_NP0 et_NP0 al_NP0 noted_VVD that_CJT venous_AJ0 admixture_NN1 was_VBD unrelated_AJ0 to_PRP the_AT0 fraction_NN1 of_PRF nonaerated_AJ0 lung_NN1 tissue_NN1 in_PRP COVID-19_NP0 ARDS_NP0 ,_PUN yet_AV0 was_VBD correlated_VVN to_PRP the_AT0 fraction_NN1 of_PRF nonaerated_AJ0 lung_NN1 tissue_NN1 in_PRP a_AT0 historical_AJ0 cohort_NN1 of_PRF patients_NN2 with_PRP non-COVID_AJ0 ARDS_NP0 who_PNQ were_VBD matched_VVN for_PRP both_DT0 Pao_NP0 2_CRD to_PRP Fio_NP0 2_CRD ratio_NN1 and_CJC compliance_NN1 ._SENT Additionally_AV0 ,_PUN many_DT0 nonintubated_AJ0 patients_NN2 with_PRP COVID-19_NN1 demonstrate_VVB dramatic_AJ0 hypoxemia_NN1 ,_PUN yet_AV0 lack_VVB proportional_AJ0 signs_NN2 of_PRF respiratory_AJ0 distress_NN1 ,_PUN a_AT0 condition_NN1 coined_VVD happy_AJ0 hypoxemia_NN1 ._SENT Some_DT0 have_VHB hypothesized_VVN that_CJT the_AT0 presence_NN1 of_PRF pulmonary_AJ0 thrombi_NN2 ,_PUN both_DT0 microthrombi_NN2 and_CJC macrothrombi_NN2 ,_PUN may_VM0 help_VVI to_TO0 explain_VVI the_AT0 disconnect_VVB between_PRP gas_NN1 exchange_NN1 and_CJC lung_NN1 compliance_NN1 in_PRP severe_AJ0 COVID-19_NN1 ._SENT 
Hemodynamic_AJ0 Perturbations_NN2 
Pulmonary_AJ0 emboli_NN2 increase_VVB pulmonary_AJ0 vascular_AJ0 resistance_NN1 (_PUL PVR_NP0 )_PUR and_CJC pulmonary_AJ0 artery_NN1 pressure_NN1 ,_PUN with_PRP higher_AJC thrombotic_AJ0 burden_NN1 correlating_VVG with_PRP higher_AJC PVR_NN1 and_CJC pulmonary_AJ0 artery_NN1 pressure_NN1 ._SENT With_PRP sufficiently_AV0 elevated_AJ0 right_AV0 ventricular_AJ0 (_PUL RV_NP0 )_PUR afterload_NN1 ,_PUN pulmonary_AJ0 emboli_NN2 can_VM0 induce_VVI RV_NP0 dilation_NN1 and_CJC dysfunction_NN1 ._SENT Somewhat_AV0 strikingly_AV0 ,_PUN patients_NN2 with_PRP COVID-19_NN1 requiring_VVG mechanical_AJ0 ventilation_NN1 show_VVB invasive_AJ0 hemodynamic_AJ0 profiles_NN2 that_CJT are_VBB characterized_VVN by_PRP low_AJ0 ,_PUN not_XX0 high_AJ0 ,_PUN PVR_NP0 ._SENT This_DT0 finding_NN1 is_VBZ surprising_AJ0 given_VVN the_AT0 high_AJ0 prevalence_NN1 of_PRF PE_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 in_PRP the_AT0 ICU_NN1 ,_PUN as_CJS well_AV0 as_CJS the_AT0 high_AJ0 prevalence_NN1 of_PRF elevated_AJ0 PVR_NN1 in_PRP non-COVID_AJ0 ARDS_NP0 ._SENT 
It_PNP is_VBZ possible_AJ0 that_CJT the_AT0 hemodynamic_AJ0 effect_NN1 of_PRF pulmonary_AJ0 thrombosis_NN1 is_VBZ mitigated_VVN by_PRP a_AT0 primary_AJ0 pulmonary_AJ0 vasodilatory_AJ0 process_NN1 in_PRP some_DT0 patients_NN2 with_PRP COVID-19_NN1 ._SENT Dual-energy_AJ0 CT_NN1 imaging_NN1 has_VHZ demonstrated_VVN pulmonary_AJ0 vessel_NN1 dilation_NN1 in_PRP COVID-19_AJ0 pneumonia_NN1 ._SENT Ackerman_NP0 et_NP0 al_NP0 ,_PUN in_PRP addition_NN1 to_PRP demonstrating_VVG high_AJ0 rates_NN2 of_PRF pulmonary_AJ0 microthrombosis_NN1 in_PRP COVID-19_NN1 ,_PUN also_AV0 noted_VVN high_AJ0 rates_NN2 of_PRF intussusceptive_AJ0 and_CJC sprouting_AJ0 angiogenesis_NN1 ._SENT Reynolds_NP0 et_NP0 al_NP0 reported_VVD that_CJT 83_CRD %_NN0 of_PRF mechanically_AV0 ventilated_AJ0 patients_NN2 with_PRP COVID-19_NN1 showed_VVD positive_AJ0 bubble_NN1 study_NN1 findings_NN2 as_CJS assessed_VVN by_PRP contrast-enhanced_AJ0 transcranial_AJ0 Doppler_NP0 imaging_NN1 ,_PUN likely_AJ0 indicative_NN1 of_PRF abnormal_AJ0 pulmonary_AJ0 capillary_AJ0 dilation_NN1 ,_PUN pulmonary_AJ0 arteriovenous_AJ0 malformations_NN2 ,_PUN or_CJC both_AV0 ._SENT Additionally_AV0 ,_PUN the_AT0 degree_NN1 of_PRF transpulmonary_AJ0 bubble_NN1 transit_NN1 correlated_VVN with_PRP Pao_NP0 2_CRD to_PRP Fio_NP0 2_CRD ratio_NN1 ,_PUN suggesting_VVG that_CJT these_DT0 pulmonary_AJ0 vascular_AJ0 dilations_NN2 may_VM0 be_VBI a_AT0 significant_AJ0 cause_NN1 of_PRF hypoxemia_NN1 in_PRP COVID-19_NP0 ARDS_NP0 ._SENT Whereas_CJS pulmonary_AJ0 macrothrombi_NN1 and_CJC microthrombi_NN1 increase_NN1 PVR_NN1 ,_PUN pulmonary_AJ0 vasodilation_NN1 decreases_VVZ PVR_NN1 ;_PUN when_CJS both_DT0 processes_NN2 occur_VVB simultaneously_AV0 ,_PUN each_DT0 can_VM0 "_PUQ cancel_VVI out_AVP "_PUQ the_AT0 hemodynamic_AJ0 effect_NN1 of_PRF the_AT0 other_AJ0 (_PUL Fig_NN1 2_CRD )_PUR ._SENT The_AT0 coexistence_NN1 of_PRF both_DT0 obliterative_AJ0 and_CJC vasodilatory_AJ0 processes_NN2 in_PRP the_AT0 pulmonary_AJ0 vasculature_NN1 is_VBZ reminiscent_AJ0 of_PRF what_DTQ can_VM0 occur_VVI in_PRP chronic_AJ0 liver_NN1 disease_NN1 ,_PUN specifically_AV0 portopulmonary_AJ0 hypertension_NN1 (_PUL obliterative_AJ0 )_PUR and_CJC hepatopulmonary_AJ0 syndrome_NN1 (_PUL vasodilatory_NN1 )_PUR ._SENT Ultimately_AV0 ,_PUN in_PRP COVID-19_NP0 ARDS_NP0 ,_PUN the_AT0 obliterative_AJ0 processes_NN2 may_VM0 dominate_VVI ,_PUN leading_VVG to_PRP severe_AJ0 RV_NP0 failure_NN1 and_CJC cardiogenic_AJ0 shock_NN1 ._SENT 
Although_CJS the_AT0 vasodilatory_AJ0 and_CJC obliterative_AJ0 processes_NN2 may_VM0 offset_VVI each_DT0 other_NN1 hemodynamically_AV0 ,_PUN their_DPS coexistence_NN1 may_VM0 amplify_VVI hypoxemia_NN1 in_PRP COVID-19_NN1 ._SENT Vasodilated_AJ0 regions_NN2 experience_VVB increased_AJ0 blood_NN1 flow_NN1 ,_PUN creating_VVG low_AJ0 V˙_NN1 /_PUN Q˙_NN1 ratios_NN2 ._SENT Microthrombi_NN1 and_CJC vasoconstriction_NN1 in_PRP other_AJ0 areas_NN2 of_PRF the_AT0 lung_NN1 reroute_VVI additional_AJ0 blood_NN1 flow_NN1 to_PRP the_AT0 vasodilated_AJ0 regions_NN2 and_CJC drive_VVB down_AVP the_AT0 V˙_NP0 /_PUN Q˙_NP0 ratio_NN1 further_AV0 ._SENT Mathematical_AJ0 modeling_NN1 demonstrates_VVZ that_CJT the_AT0 large_AJ0 amount_NN1 of_PRF pulmonary_AJ0 venous_AJ0 admixture_NN1 in_PRP the_AT0 setting_NN1 of_PRF relatively_AV0 minor_AJ0 parenchymal_AJ0 involvement_NN1 observed_VVN in_PRP early_AJ0 COVID-19_NN1 can_VM0 be_VBI explained_VVN reasonably_AV0 by_PRP a_AT0 combination_NN1 of_PRF pulmonary_AJ0 thrombosis_NN1 and_CJC vasodilation_NN1 ._SENT 
Diagnosis_NN1 
In_PRP the_AT0 absence_NN1 of_PRF systematic_AJ0 screening_NN1 ,_PUN the_AT0 diagnosis_NN1 of_PRF PE_NN1 begins_VVZ with_PRP clinical_AJ0 suspicion_NN1 ._SENT Unexplained_AJ0 dyspnea_NN1 and_CJC hypoxemia_NN1 ,_PUN particularly_AV0 in_PRP the_AT0 setting_NN1 of_PRF normal_AJ0 chest_NN1 radiography_NN1 findings_NN2 ,_PUN raises_VVZ the_AT0 clinical_AJ0 suspicion_NN1 for_PRP PE_NN1 ._SENT Clinical_AJ0 suspicion_NN1 of_PRF PE_NN1 in_PRP a_AT0 patient_NN1 with_PRP COVID-19_AJ0 pneumonia_NN1 often_AV0 is_VBZ diminished_VVN because_CJS the_AT0 signs_NN2 and_CJC symptoms_NN2 of_PRF COVID-19_AJ0 pneumonia_NN1 mimic_VVB those_DT0 of_PRF PE_NN1 ;_PUN a_AT0 patient_NN1 's_POS dyspnea_NN1 and_CJC hypoxemia_NN1 may_VM0 be_VBI attributed_VVN solely_AV0 to_PRP COVID-19_AJ0 pneumonia_NN1 ,_PUN and_CJC further_AV0 diagnostic_AJ0 testing_NN1 for_PRP potential_AJ0 PE_NN1 may_VM0 be_VBI deferred_VVN ._SENT Although_CJS clinical_AJ0 probability_NN1 scores_NN2 ,_PUN such_DT0 as_PRP the_AT0 Wells_NP0 score_NN1 ,_PUN are_VBB helpful_AJ0 in_PRP raising_VVG clinical_AJ0 suspicion_NN1 of_PRF PE_NN1 in_PRP patients_NN2 ,_PUN they_PNP have_VHB not_XX0 been_VBN validated_VVN in_PRP patients_NN2 with_PRP COVID-19_AJ0 and_CJC likely_AJ0 underestimate_NN1 the_AT0 probability_NN1 of_PRF PE_NN1 in_PRP COVID-19_NN1 ._SENT 
D-dimer_NN1 ,_PUN in_PRP conjunction_NN1 with_PRP clinical_AJ0 probability_NN1 assessment_NN1 ,_PUN has_VHZ great_AJ0 usefulness_NN1 in_PRP ruling_VVG out_AVP PE_NN1 in_PRP patients_NN2 with_PRP low_AJ0 or_CJC intermediate_AJ0 probability_NN1 of_PRF PE_NN1 ,_PUN although_CJS its_DPS usefulness_NN1 in_PRP COVID-19_NN1 is_VBZ unclear_AJ0 ._SENT Although_CJS D-dimer_NN1 levels_NN2 in_PRP COVID-19_AJ0 correlate_NN1 with_PRP rates_NN2 of_PRF thrombosis_NN1 ,_PUN it_PNP is_VBZ not_XX0 clear_AJ0 whether_CJS a_AT0 particular_AJ0 D-dimer_NN1 value_NN1 "_PUQ rules_NN2 in_PRP "_PUQ or_CJC "_PUQ rules_NN2 out_AVP "_PUQ PE_NN1 ._SENT In_PRP the_AT0 study_NN1 by_PRP Mirsadraee_NP0 et_NP0 al_NP0 in_PRP which_DTQ screening_NN1 CTPA_NP0 was_VBD performed_VVN for_PRP patients_NN2 with_PRP COVID-19_NN1 on_PRP admission_NN1 to_PRP the_AT0 ICU_NN1 ,_PUN D-dimer_NN1 levels_NN2 did_VDD not_XX0 discriminate_VVI between_PRP patients_NN2 with_PRP and_CJC without_PRP PE_NN1 ._SENT Li_NP0 et_NP0 al_NP0 developed_VVD a_AT0 three-factor_AJ0 score_NN1 consisting_VVG of_PRF admission_NN1 fibrinogen_NN1 ,_PUN admission_NN1 D-dimer_NN1 ,_PUN and_CJC D-dimer_NN1 increment_NN1 >_NN1 1.5_CRD fold_NN1 ,_PUN the_AT0 score_NN1 performing_VVG with_PRP a_AT0 sensitivity_NN1 of_PRF 0.93_CRD and_CJC specificity_NN1 of_PRF 0.71_CRD for_PRP symptomatic_AJ0 VTE_NN1 ._SENT 
CTPA_NP0 is_VBZ the_AT0 first-choice_AJ0 method_NN1 for_PRP the_AT0 diagnosis_NN1 of_PRF PE_NN1 because_CJS of_PRF its_DPS high_AJ0 accuracy_NN1 ,_PUN wide_AJ0 availability_NN1 ,_PUN and_CJC ability_NN1 to_TO0 assess_VVI for_PRP other_AJ0 pulmonary_AJ0 pathologic_AJ0 features_NN2 ._SENT Its_DPS use_NN1 may_VM0 be_VBI limited_VVN in_PRP critically_AV0 ill_AJ0 patients_NN2 with_PRP COVID-19_NN0 who_PNQ are_VBB not_XX0 stable_AJ0 enough_AV0 for_PRP transfer_NN1 and_CJC in_PRP patients_NN2 with_PRP renal_AJ0 failure_NN1 ,_PUN a_AT0 common_AJ0 complication_NN1 in_PRP severe_AJ0 COVID-19_NN1 ._SENT V˙_NP0 /_PUN Q˙_NP0 scanning_NN1 can_VM0 be_VBI used_VVN for_PRP patients_NN2 in_PRP whom_PNQ CTPA_NP0 is_VBZ contraindicated_AJ0 or_CJC inconclusive_AJ0 ._SENT Scans_NN2 performed_VVN on_PRP patients_NN2 with_PRP abnormal_AJ0 chest_NN1 radiography_NN1 findings_NN2 ,_PUN as_CJS is_VBZ often_AV0 the_AT0 case_NN1 in_PRP patients_NN2 with_PRP COVID-19_AJ0 pneumonia_NN1 ,_PUN are_VBB more_AV0 likely_AJ0 to_TO0 result_VVI in_PRP false-positive_AJ0 results_NN2 because_CJS the_AT0 images_NN2 rarely_AV0 appear_VVB as_PRP normal_AJ0 or_CJC showing_VVG a_AT0 low_AJ0 probability_NN1 of_PRF PE_NN1 in_PRP such_DT0 patients_NN2 ._SENT Compression_NN1 ultrasonography_NN1 can_VM0 be_VBI performed_VVN to_TO0 assess_VVI for_PRP DVT_NP0 when_CJS chest_NN1 imaging_NN1 is_VBZ contraindicated_AJ0 or_CJC indeterminate_AJ0 ;_PUN however_AV0 ,_PUN the_AT0 absence_NN1 of_PRF DVT_NP0 does_VDZ not_XX0 imply_VVI the_AT0 absence_NN1 of_PRF pulmonary_AJ0 thrombosis_NN1 ,_PUN especially_AV0 because_CJS in_PRP situ_NN1 pulmonary_AJ0 thrombosis_NN1 is_VBZ a_AT0 potential_AJ0 mechanism_NN1 in_PRP COVID-19_NN1 ._SENT A_AT0 diagnosis_NN1 of_PRF DVT_NP0 may_VM0 eliminate_VVI the_AT0 need_NN1 to_TO0 evaluate_VVI for_PRP PE_NN1 because_CJS the_AT0 indication_NN1 for_PRP therapeutic_AJ0 anticoagulation_NN1 will_VM0 have_VHI been_VBN established_VVN ._SENT Echocardiography_NN1 can_VM0 raise_VVI suspicion_NN1 for_PRP the_AT0 diagnosis_NN1 of_PRF PE_NN1 with_PRP the_AT0 presence_NN1 of_PRF clot_NN1 in_PRP the_AT0 right_AJ0 side_NN1 of_PRF the_AT0 heart_NN1 or_CJC new_AJ0 right_AJ0 heart_NN1 strain_NN1 ._SENT Although_CJS it_PNP has_VHZ limited_VVN diagnostic_AJ0 value_NN1 ,_PUN echocardiography_NN1 is_VBZ most_AV0 useful_AJ0 for_PRP risk_NN1 stratification_NN1 of_PRF confirmed_AJ0 PE_NN1 ._SENT 
Prophylaxis_NN1 
Considering_VVG that_CJT PE_NN1 is_VBZ one_CRD of_PRF the_AT0 most_AV0 common_AJ0 preventable_AJ0 causes_NN2 of_PRF hospital_NN1 death_NN1 ,_PUN thromboprophylaxis_NN1 is_VBZ a_AT0 crucial_AJ0 component_NN1 in_PRP the_AT0 care_NN1 of_PRF hospitalized_AJ0 patients_NN2 ,_PUN and_CJC COVID-19_NN1 is_VBZ no_AT0 exception_NN1 ._SENT A_AT0 retrospective_AJ0 study_NN1 by_PRP Rentsch_NP0 et_NP0 al_NP0 demonstrated_VVD that_CJT the_AT0 administration_NN1 of_PRF prophylactic_AJ0 anticoagulation_NN1 within_PRP 24_CRD h_ZZ0 of_PRF admission_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 was_VBD associated_VVN with_PRP decreased_AJ0 mortality_NN1 when_CJS compared_VVN with_PRP no_AT0 prophylactic_AJ0 anticoagulation_NN1 ._SENT Multiple_AJ0 society_NN1 guidelines_NN2 recommend_VVB prophylactic_AJ0 anticoagulation_NN1 for_PRP hospitalized_AJ0 patients_NN2 with_PRP COVID-19_NN0 who_PNQ do_VDB not_XX0 have_VHI a_AT0 contraindication_NN1 to_PRP treatment_NN1 ._SENT However_AV0 ,_PUN standard_AJ0 doses_NN2 of_PRF prophylactic_AJ0 anticoagulation_NN1 likely_AJ0 are_VBB insufficient_AJ0 for_PRP the_AT0 prevention_NN1 of_PRF VTE_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 ;_PUN many_DT0 VTE_NN1 events_NN2 are_VBB diagnosed_VVN within_PRP the_AT0 first_ORD 24_CRD h_ZZ0 after_PRP admission_NN1 ,_PUN and_CJC the_AT0 reported_AJ0 rates_NN2 of_PRF VTE_NN1 are_VBB notably_AV0 high_AJ0 despite_PRP the_AT0 use_NN1 of_PRF anticoagulant_AJ0 thromboprophylaxis_NN1 ._SENT 
As_CJS a_AT0 result_NN1 of_PRF the_AT0 high_AJ0 rates_NN2 of_PRF VTE_NN1 despite_PRP standard-dose_AJ0 thromboprophylaxis_NN1 ,_PUN many_DT0 institutions_NN2 have_VHB implemented_VVN protocols_NN2 using_VVG higher_AJC doses_NN2 ,_PUN including_PRP an_AT0 intermediate_AJ0 dose_NN1 and_CJC even_AV0 a_AT0 therapeutic_AJ0 dose_NN1 ._SENT Tacquard_NP0 et_NP0 al_NP0 reported_VVD in_PRP a_AT0 study_NN1 of_PRF 538_CRD patients_NN2 with_PRP COVID-19_CRD in_PRP eight_CRD French_AJ0 ICUs_NN2 that_CJT high-dose_AJ0 prophylactic_AJ0 anticoagulation_NN1 (_PUL intermediate_AJ0 or_CJC therapeutic_AJ0 dose_NN1 )_PUR was_VBD associated_VVN with_PRP a_AT0 significant_AJ0 reduction_NN1 in_PRP thrombotic_AJ0 complications_NN2 (_PUL hazard_NN1 ratio_NN1 ,_PUN 0.81_CRD )_PUR without_PRP an_AT0 increase_NN1 in_PRP bleeding_AJ0 risk_NN1 ._SENT In_PRP more_AV0 than_CJS 4_CRD ,_PUN 000_CRD patients_NN2 with_PRP COVID-19_NN1 at_PRP a_AT0 New_AJ0 York_NP0 hospital_NN1 with_PRP an_AT0 aggressive_AJ0 anticoagulation_NN1 protocol_NN1 ,_PUN Nadkarni_NP0 et_NP0 al_NP0 noted_VVD a_AT0 trend_NN1 toward_PRP a_AT0 mortality_NN1 reduction_NN1 with_PRP therapeutic_AJ0 anticoagulation_NN1 compared_VVN with_PRP prophylactic_AJ0 anticoagulation_NN1 ,_PUN a_AT0 finding_NN1 that_CJT did_VDD not_XX0 meet_VVI statistical_AJ0 significance_NN1 (_PUL P_ZZ0 =_NN1 .08_CRD )_PUR ._SENT 
However_AV0 ,_PUN recent_AJ0 randomized_AJ0 controlled_AJ0 trials_NN2 do_VDB not_XX0 support_VVI the_AT0 use_NN1 of_PRF higher_AJC than_CJS standard_AJ0 doses_NN2 for_PRP prophylactic_AJ0 anticoagulation_NN1 in_PRP critically_AV0 ill_AJ0 patients_NN2 with_PRP COVID-19_NN1 ._SENT In_PRP 600_CRD critically_AV0 ill_AJ0 patients_NN2 ,_PUN intermediate-dose_AJ0 anticoagulation_NN1 with_PRP enoxaparin_NP0 1_CRD mg_NN0 /_PUN kg_NN0 daily_AJ0 was_VBD not_XX0 superior_AJ0 to_PRP standard_AJ0 prophylactic_AJ0 anticoagulation_NN1 with_PRP enoxaparin_NP0 40_CRD mg_NN0 daily_AJ0 in_PRP reducing_VVG the_AT0 composite_AJ0 outcome_NN1 of_PRF venous_AJ0 or_CJC arterial_AJ0 thrombosis_NN1 ,_PUN treatment_NN1 with_PRP extracorporeal_AJ0 membrane_NN1 oxygenation_NN1 ,_PUN or_CJC mortality_NN1 within_PRP 30_CRD days_NN2 ._SENT Although_CJS bleeding_AJ0 events_NN2 were_VBD rare_AJ0 ,_PUN major_AJ0 and_CJC clinically_AV0 relevant_AJ0 nonmajor_AJ0 bleeding_AJ0 events_NN2 were_VBD nonsignificantly_AV0 more_AV0 frequent_AJ0 with_PRP intermediate-dose_AJ0 anticoagulation_NN1 (_PUL 6.2_CRD %_NN0 for_PRP intermediate_AJ0 dose_NN1 ,_PUN 3.1_CRD %_NN0 for_PRP standard_AJ0 dose_NN1 ;_PUN P_ZZ0 =_NN1 .08_CRD )_PUR ._SENT A_AT0 large_AJ0 National_AJ0 Institutes_NN2 of_PRF Health_NN1 multiplatform_NN1 randomized_VVD controlled_AJ0 trial_NN1 incorporating_VVG three_CRD global_AJ0 networks_NN2 (_PUL A_AT0 Randomised_AJ0 ,_PUN Embedded_AJ0 ,_PUN Multi-factorial_AJ0 ,_PUN Adaptive_AJ0 Platform_NN1 Trial_NN1 for_PRP Community-Acquired_AJ0 Pneumonia_NN1 [_PUL REMAP-CAP_NP0 ]_PUR ,_PUN Anti-Thrombotic_AJ0 Therapy_NN1 to_TO0 Ameliorate_VVI Complications_NN2 of_PRF COVID-19_NN1 [_PUL ATTACC_NP0 ]_PUR ,_PUN and_CJC Accelerating_VVG COVID-19_AJ0 Therapeutic_AJ0 Interventions_NN2 and_CJC Vaccines-4A_NP0 [_PUL ACTIV-4A_NP0 ]_PUR )_PUR examining_VVG the_AT0 benefit_NN1 of_PRF therapeutic_AJ0 dose_NN1 vs_PRP standard_AJ0 dose_NN1 prophylactic_AJ0 anticoagulation_NN1 in_PRP more_AV0 than_CJS 1_CRD ,_PUN 000_CRD critically_AV0 ill_AJ0 patients_NN2 with_PRP COVID-19_AJ0 discontinued_AJ0 enrollment_NN1 because_CJS statistical_AJ0 criteria_NN2 for_PRP futility_NN1 were_VBD met_VVN ._SENT Importantly_AV0 ,_PUN despite_PRP therapeutic_AJ0 anticoagulation_NN1 decreasing_VVG major_AJ0 thrombotic_AJ0 events_NN2 ,_PUN an_AT0 89_CRD %_NN0 probability_NN1 was_VBD found_VVN that_CJT therapeutic_AJ0 anticoagulation_NN1 was_VBD inferior_AJ0 to_PRP standard_AJ0 dose_NN1 prophylactic_AJ0 anticoagulation_NN1 in_PRP achieving_VVG the_AT0 primary_AJ0 outcome_NN1 of_PRF survival_NN1 or_CJC days_NN2 free_AJ0 of_PRF organ_NN1 support_NN1 ._SENT The_AT0 mechanism_NN1 for_PRP this_DT0 likely_AJ0 harm_NN1 is_VBZ unclear_AJ0 ,_PUN given_VVN that_CJT major_AJ0 bleeding_NN1 was_VBD increased_VVN only_AV0 mildly_AV0 with_PRP therapeutic_AJ0 anticoagulation_NN1 (_PUL 3.1_CRD %_NN0 vs_PRP 2.4_CRD %_NN0 )_PUR ._SENT These_DT0 findings_NN2 suggest_VVB that_CJT initiating_AJ0 therapeutic_AJ0 anticoagulation_NN1 after_PRP severe_AJ0 COVID-19_NN1 has_VHZ developed_VVN may_VM0 be_VBI too_AV0 late_AJ0 to_TO0 alter_VVI the_AT0 clinical_AJ0 course_NN1 beneficially_AV0 ._SENT In_PRP contrast_NN1 ,_PUN for_PRP moderately_AV0 ill_AJ0 hospitalized_AJ0 patients_NN2 with_PRP COVID-19_NN1 ,_PUN the_AT0 National_AJ0 Institutes_NN2 of_PRF Health_NN1 recently_AV0 announced_VVN via_PRP press_NN1 release_NN1 that_CJT therapeutic-dose_AJ0 anticoagulation_NN1 was_VBD superior_AJ0 to_TO0 standard-dose_VVI prophylactic_AJ0 anticoagulation_NN1 in_PRP reducing_VVG the_AT0 need_NN1 for_PRP organ_NN1 support_NN1 and_CJC mortality_NN1 ._SENT The_AT0 full_AJ0 results_NN2 and_CJC official_AJ0 publication_NN1 of_PRF these_DT0 studies_NN2 are_VBB awaited_VVN anxiously_AV0 because_CJS they_PNP undoubtedly_AV0 will_VM0 help_VVI to_TO0 establish_VVI the_AT0 optimal_AJ0 anticoagulation_NN1 dosing_VVG strategies_NN2 for_PRP patients_NN2 with_PRP COVID-19_NN1 ._SENT 
Treatment_NN1 
Anticoagulation_NN1 is_VBZ the_AT0 mainstay_NN1 of_PRF the_AT0 treatment_NN1 for_PRP acute_AJ0 PE_NN1 ,_PUN both_AV0 for_PRP patients_NN2 with_PRP and_CJC without_PRP COVID-19_NN1 ,_PUN to_TO0 prevent_VVI further_AJC thrombosis_NN1 and_CJC thromboembolism_NN1 ._SENT Initial_AJ0 treatment_NN1 options_NN2 for_PRP anticoagulation_NN1 include_VVB unfractionated_AJ0 heparin_NN1 ,_PUN low-molecular-weight_AJ0 heparin_NN1 ,_PUN fondaparinux_NN1 ,_PUN and_CJC ,_PUN in_PRP low-risk_AJ0 patients_NN2 ,_PUN direct_AJ0 oral_AJ0 anticoagulants_NN2 ._SENT As_CJS is_VBZ the_AT0 case_NN1 with_PRP non-COVID-19_AJ0 PE_NN1 ,_PUN risk_NN1 stratification_NN1 is_VBZ the_AT0 central_AJ0 tool_NN1 used_VVN to_TO0 identify_VVI patients_NN2 at_PRP increased_AJ0 risk_NN1 of_PRF early_AJ0 death_NN1 who_PNQ may_VM0 benefit_VVI from_PRP reperfusion_NN1 therapy_NN1 (_PUL ie_AV0 ,_PUN thrombolysis_NN1 or_CJC embolectomy_NN1 )_PUR ,_PUN mechanical_AJ0 circulatory_AJ0 support_NN1 ,_PUN or_CJC both_AV0 ._SENT Per_PRP the_AT0 European_AJ0 Society_NN1 of_PRF Cardiology_NN1 guidelines_NN2 ,_PUN high-risk_AJ0 PE_NN1 is_VBZ characterized_VVN by_PRP cardiac_AJ0 arrest_NN1 ,_PUN systolic_AJ0 BP_NP0 <_NP0 90_CRD mm_ITJ Hg_NP0 ,_PUN or_CJC requiring_VVG vasopressors_NN2 ,_PUN inotropes_NN2 ,_PUN or_CJC both_AV0 ._SENT Intermediate-risk_NN1 PE_NN1 is_VBZ characterized_VVN by_PRP normotension_NN1 with_PRP signs_NN2 of_PRF RV_NP0 dysfunction_NN1 on_PRP echocardiography_NN1 or_CJC CTPA_NN1 ,_PUN elevated_AJ0 troponin_NN1 levels_NN2 ,_PUN or_CJC an_AT0 elevated_AJ0 PE_NN1 severity_NN1 index_NN1 score_NN1 ._SENT Of_PRF note_NN1 ,_PUN the_AT0 role_NN1 of_PRF troponin_NN1 levels_NN2 as_PRP a_AT0 prognostic_AJ0 biomarker_NN1 for_PRP PE_NN1 in_PRP COVID-19_NN1 is_VBZ confounded_VVN by_PRP the_AT0 fact_NN1 that_DT0 troponin_NN1 frequently_AV0 is_VBZ elevated_VVN in_PRP patients_NN2 with_PRP COVID-1982_NP0 ;_PUN in_PRP that_DT0 context_NN1 ,_PUN it_PNP likely_AV0 reflects_VVZ myocardial_AJ0 inflammation_NN1 ,_PUN cardiac_AJ0 microthrombosis_NN1 ,_PUN or_CJC both_AV0 ,_PUN rather_AV0 than_CJS RV_NP0 pressure_NN1 overload_NN1 ._SENT Low-risk_AJ0 PE_NN1 is_VBZ characterized_VVN by_PRP normotension_NN1 ,_PUN lack_NN1 of_PRF RV_NP0 dysfunction_NN1 ,_PUN and_CJC a_AT0 low_AJ0 PE_NN1 severity_NN1 index_NN1 score_NN1 ._SENT Figure_NN1 3_CRD summarizes_VVZ the_AT0 European_AJ0 Society_NN1 of_PRF Cardiology_NN1 risk_NN1 stratification_NN1 algorithm_NN1 and_CJC treatment_NN1 strategy_NN1 ._SENT 
If_CJS possible_AJ0 ,_PUN patients_NN2 with_PRP high-risk_AJ0 PE_NN1 should_VM0 undergo_VVI reperfusion_NN1 therapy_NN1 ,_PUN mechanical_AJ0 circulatory_AJ0 support_NN1 ,_PUN or_CJC both_AV0 ._SENT Patients_NN2 with_PRP intermediate-risk_AJ0 PE_NN1 should_VM0 be_VBI monitored_VVN closely_AV0 for_PRP signs_NN2 of_PRF clinical_AJ0 deterioration_NN1 ,_PUN with_PRP select_AJ0 patients_NN2 proceeding_VVG to_PRP reperfusion_NN1 therapy_NN1 ._SENT 
