Date Released: April 12, 2020

The world today is in turmoil. The COVID-19 pandemic has engulfed the whole world in the wake of this silently raging onslaught. It has created worry and unpredictable challenges among health care providers and in the health care systems. The medical crisis continuously causes morbidity and mortality threats to overwhelming proportions. Up to this moment, no immediate cure or panacea has been discovered. This makes the battle against COVID-19 a very desperate struggle. However, the medical and scientific sectors in collaboration with the government authorities, have pooled their best collective efforts to device certain safety measures and protocols to contain and lessen the spread of the virus, and to look for the best possible therapeutic intervention to ultimately put an end to this pandemic. We, in our society can do no less. Hopefully we can prove ourselves worthy and equal to this critical challenge.

The Philippine Society of Vascular Medicine (PSVM) has developed safety protocols and guidelines on the approach to vascular procedures and treatment interventions, with the hope of mitigating the spread of infection and ensuring safe and efficient health care delivery in the midst of this pandemic.

PSVM Guidance consists of two parts, namely:

1. Anticoagulation and COVID-19
2. Safety protocols and guidelines during COVID-19 pandemic

Disclaimer on the recommendations

• These should not be considered as rigid guidelines and are not intended to supplant clinical judgement or the development of consensus regarding institutional approaches to treatment. There is a great deal of uncertainty around this evolving pandemic and information may change
• It is possible that some of the strategies outlined in this document may in time be replaced as our understanding of the unique challenges that COVID-19 poses in each country or locality

Role of Anticoagulation in COVID-19: Recommendations on its use

COVID-19 patients are at risk for VTE especially the critically-ill and those with high Padua prediction scores, where the incidence can be as high as 20%¹. Additionally, admitted COVID-19 patients can develop coagulopathy (COVID-associated coagulopathy or CAC) that is associated with high mortality. Ning Tan and others reported lower mortality rates in those who received prophylactic dose anticoagulation against those who did not.2,3  This benefit may not only have resulted from prevention of VTE and mitigation of pulmonary microthrombosis,⁴ but also by abatement of pulmonary inflammation and fibrosis due to the anti-inflammatory properties of heparin^5,6 [which may be an added benefit in COVID infection where proinflammatory cytokines are markedly increased⁷].

Therefore, based on the available evidence and expert opinion, we make the following recommendations:

1)            We suggest initiation of anticoagulation using prophylactic dose heparin on admission (or at any time during the hospital course) if ANY of the following are present: (Please see Appendix A for the algorithm)

1. International Society of Thrombosis and Hemostasis( ISTH) criteria^8,9: D-dimer

> 2ug/ml, ± prolonged protime, ± platelet < 100 x 10⁹/L

1. PADUA score of ³ 4 (Appendix B) ¹
2. Sepsis-induced coagulopathy (SIC) score of ³ 4 (Appendix C) ²
3. Critically ill (admission to ICU requiring mechanical ventilation or FiO2 of 60% or higher)¹

*Recommended dose as follows^11-15:

*           For patients with acute kidney failure, end stage renal disease, dialysis dependent or conditions where eGFR may be inaccurate, unfractionated heparin (UFH) is more preferred.

• While Fondaparinux has been suggested as a non-heparin anticoagulant that may be used as an alternative in heparin-induced thrombocytopenia (HIT)²¹, there are presently no data on its use specifically in COVID-19 patients.

• It is reasonable to shift patients maintained on NOACS before admission, to LMWH or UFH and follow the appropriate dosing and shifting guide- lines,²² since there are no available data as yet on the use of NOACS in COVID-19.

• Contraindications to prophylactic-dose anticoagulation include⁸:
  • Platelet count < 25 x 10⁹/L
  • Active bleeding

*abnormal PT or APTT is not a contraindication

• For those with contraindications to pharmacologic anticoagulation, use mechanical prophylaxis¹³ in patients who are critically-ill or with Padua score of ³ 4, using in this order of preference: intermittent pneumatic compression device (IPC), thigh-high or knee-high graduated compression stockings (GCS)¹⁶ which provides at least 18 mmHg ankle pressure¹⁷.

• We suggest routine determination of D-dimer, Prothrombin Time and Platelet Count in all PUI/COVID -19 patients, on admission⁸. This may help to stratify patients who may need close monitoring or not. These tests are repeated every 2-3 days thereafter (or more frequently if with rapid clinical deterioration) to identify worsening coagulopathy. Any underlying condition (e.g. liver disease) or medication (e.g. anti-platelets) which may alter the parameters and potentially increase the bleeding risk should be taken into

3)            We suggest to discontinue anticoagulation in the following scenarios:

1. Platelet count ≤ 20 x 10⁹/L in non-bleeding patients⁸
2. Platelet count ≤ 50 x 10⁹/L an PT ratio ³ 5 (not the same as INR) in bleeding patients⁸
3. General ISTH major bleeding criteria:
   • Fatal bleeding, and/or
   • Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or
   • Bleeding causing a fall in hemoglobin level of 2 g/dl (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red

4)            We suggest that prophylactic dose of  anticoagulation  be  continued,  in the absence of contraindications, until resolution of COVID-19 and/or patient's discharge.

• In admitted COVID-19 patients diagnosed to have DVT (or PE), we suggest adjusting anticoagulation therapy to therapeutic

• We suggest that if D-dimer is disproportionately high (ie, does not track with other inflammatory markers such as CRP, ESR, or ferritin), or when clinical symptoms or signs suggest DVT (eg. unilateral leg swelling), screening with compression ultrasonography may be done, and anticoagulation dosage adjusted .

• We suggest that therapeutic dose of anticoagulant in patients diagnosed with VTE be continued according to standard VTE treatment protocols,²³ with regular evaluation of treatment risk-benefit

• Knowledge of this disease is continually evolving and recommendations may be changed and updated. Clinicians are advised to keep abreast with the latest developments and evidences.

The ISTH also recommends measurement of serum fibrinogen as a hemostatic marker to identify worsening coagulopathy, but because of its cost and limited availability locally, we decided not to include it in our recommendations.

Anticoagulation strategy for patients with Acute Limb Ischemia should follow the standard protocol (as no new data so far have emerged on this amidst the COVID pandemic), with diligent and careful monitoring of coagulation and bleeding parameters.

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Appendix A: Algorithm for anticoagulation

Appendix B: Padua Prediction Score for Risk of VTE in hospitalized medical patients¹⁸

Padua Score <4: Low risk for VTE

Padua Score ³4: High risk for VTE, Prophylaxis is highly suggested

Appendix C: Sepsis-induced Coagulopathy (SIC ) Scoring System¹⁹

Total Score ³ 4 = SIC is suspected

Appendix D: Sequential Organ Failure Assessment (SOFA) Scoring:²⁰

SOFA scoring is used to assess organ dysfunction in critically-ill patients. As one of the parameters to determine presence of sepsis-induced coagulopathy (SIC), we just have to look into the first 4 categories: namely respiratory, cardiovascular, hepatic and renal functions and get the cumulative points to be used for SIC scoring (for example, if the cumulative SOFA from the 4 categories score is 3, then it is given 2 points for SIC scoring. If the cumulative points is 1, then the score for SIC scoring is 1).

References:

1. Xu et al. Risk assessment of venous thromboembolism and bleeding in COVID-19 patients. Research Square. 24 Mar 2020. [Preprint]

2. Tang et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. Journal of Thrombosis and Haemostasis. 27 March

3. Tang, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 18 Feb

4. Luo, W.; Yu, H.; Gou, J.; Li, X.; Sun, Y.; Li, J.; Liu, L. Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19). Preprints 2020, 2020020407.

5. Chen Shi et al. The Potential of Low Molecular Weight Heparin to mitigate cytokine storm in severe COVID-19: a retrospective

6. Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti- inflammatory effects? Thromb Haemost. 2017 Feb 28; 117(3):437-444.

7. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506.

8. Thachil, et al. International Society of Thrombosis and Hemostasis (ISTH) interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis. 25 March

9. Yao, et al. D-dimer as a biomarker for disease severity and mortality in COVID-

19        patients: A Case Control Study. April 3, 2020 [Preprint].

10. Yu et al. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a restrospective analysis. Research Square. 31 Mar 2020. [Preprint]

11. Israel Society of Thrombosis and Hemostasis (IsSTH) Guidelines

12. PSMID Interim Guidelines on the Management of Patients with Suspected and Confirmed COVID, March 26,

13. Prevention of VTE in Nonsurgical Patients. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012,

14. Anticoagulation in chronic kidney disease: from guidelines to clinical practice. Clinical Cardiology. 2019,Aug.
15. Guideline for the Prevention of venous Thromboembolism (VTE) in Adult hospitalized Patients. Published by the State of Queensland, December

16. Thigh-high stockings appear better knee-high stockings for Ann DVT prophylaxis in stroke Med. Published Online September 20, 2010.

17. Type of compression for reducing venous stasis. A study of lower extremities during inactive recumbency. Arch Surg. 1975 Feb;110(2):171-5.

18. Barbar, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism. the Padua Prediction Score. Journal of Thrombosis and Hemostasis 2010;8:2450-7.

19. Iba et al. New Criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 27 Sep

20. Lambden, et al. The SOFA Score - development, utility and challenges of accurate assessment in clinical trials. Critical Care (2019) 23:374.

21. Cuker et al. American Society of Hematology (ASH) 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv.2018 Nov 27; 2(22):3360-3392.

22. Non-Vitamin K Antagonist Oral Anticoagulants (NOAC) Guidelines. Clinical Excellence Commission. updated July

23. Kearon et al. Antithrombotic Therapy for VTE Disease. CHEST Guideline and Expert Panel Report. CHEST 2016; 149(2):315-352.

Safety Protocols and Guidelines During COVID-19 Pandemic

1. Patient Encounters and Interpretation of Imaging
   1. We encourage the practice of telemedicine/private messaging for non-emergent consults and refill of medications
   2. We encourage using available technology and software for remote viewing and interpretation of vascular procedures
   3. If it is necessary to make a hospital visit, we strongly encourage the use of personnel protective equipment, at least N95 masks and gloves, and if warranted, overall protective suits and

1. Vascular Imaging Procedures
   1. Vascular imaging procedures should be limited to acutely symptomatic emergent/urgent cases. We strongly discourage procedures for chronic, stable vascular
   2. These are the cases considered to be emergent/urgent:
      1. Acute DVT
      2. Acute limb ischemia

• Procedure Protocols
  1. All patients undergoing vascular laboratory procedures should undergo routine pre- procedural screening for
  2. If red flags for suspicion of (PUI), or confirmed COVID arise, protocol for such cases should be
  3. Vascular Imaging Protocol for non-COVID patients
     1. The vascular technologist must wear an N95 mask and clean gloves while performing the procedure. Standard infection precautions must still be
  4. Vascular Imaging Protocol for PUI/COVID patients
     1. There should be a dedicated machine and probe for this patient
     2. Ideally, procedures for in-patients should be done at bedside. Transporting a patient from his/her room to the Vascular Laboratory may increase the chances of contamination. If bedside procedures are not possible (i.e. no available portable machines in the hospital) and for ER or out-patients depending on current hospital policies and set-up, there should be a dedicated room/cubicle where the insonation of suspected and confirmed COVID cases can be
     3. If feasible, patients should wear an N95 mask during the entire imaging acquisition
     4. The vascular technologist should wear full personnel protective equipment (PPE) during the entire
     5. Deep cleaning of the room is performed after each patient
     6. After imaging, the downtime is typically between 30 minutes to 1 hour for room decontamination and passive air

1. Equipment
   1. All ultrasound machines should undergo standard disinfection on a daily basis, or intensified disinfection after every use for COVID or suspected COVID dedicated machines.
   2. Machines dedicated for COVID or suspected COVID patients must be covered in at least 2 layers of impermeable plastic (i.e. cling wrap as first layer that aligns to the

contour of the unit and does not significantly compromise screen view, followed by a single-piece plastic on top that covers the entire machine including the wheels).

3. Transducer covers can be condoms, or commercial transducer covers and should be for single use

1. Focused Vascular Ultrasound Procedures
   1. We encourage the use of shortened ultrasound protocols (Please see Appendices A and B) to focus on areas of concern and reduce the exposure of vascular technologists.
   2. Bilateral limbs (upper or lower extremities) should be insonated for patients in whom acute deep venous thrombosis is
   3. Only the affected limb (upper or lower extremities) should be insonated if acute limb ischemia is
   4. Vascular imaging procedures should strictly be done in 10 minutes. If the patient presents with challenging sonographic windows and views, then clinical judgement should supersede, or other diagnostic modalities should be considered to aid in the diagnosis.

1. Surgical and Interventional Procedures
   1. In keeping with the general guidelines and recommendations, we are highly discouraging elective vascular surgeries and interventional procedures. Only procedures deemed as emergent or urgent that will significantly and immediately impact clinical care and outcomes should be considered during this time. Emergent or urgent conditions needing intervention are:
      1. Ruptured aortic aneurysms
      2. Acute limb ischemia (SVS classification IIa and IIb)
      3. Acute proximal aortic and branch dissection

2. Need for intervention for a large (>5.5 cm) aortic aneurysm has to be assessed vis a vis its risk of rupture in the next few months, risk of intervention, and availability of resources.

3. A list of procedures for possible deferral and rescheduling is provided in the

Appendix C.

• Training
  1. For institutions with Vascular Medicine training, the health and safety of our trainees are still of primary concern. We strongly encourage the use of PPE, at least an N95 mask and gloves, and full PPE if warranted while in the hospital
  2. Trainees should observe standard infection
  3. We encourage the use of web meetings for continuing medical education

Appendix

1. Three-point Ultrasound technique for Deep Vein Thrombosis
   • Compressibility of the following venous segments are assessed: the common femoral vein (CFV), femoral vein (FV), and popliteal vein

source: Needleman L, Cronan J, Ultrasound for Lower Extremity Deep Venous Thrombosis Multidisciplinary Recommendations From the Society of Radiologists in Ultrasound Consensus Conference; Circulation. 2018;137:1505–1515

Lee J, Lee S, Comparison of 2-point and 3-point point-of-care ultrasound techniques for deep vein thrombosis at the emergency department, A meta-analysis. Medicine: May 2019 - Volume 98 - Issue 22 - p e15791

1. Focused vascular lower limb arterial duplex scan (F - VLAD)
   • This method includes the scanning of the common femoral artery, deep profunda, superficial femoral artery, and popliteal artery, followed by the distal segments of the anterior tibial and posterior tibial

source: Normahani P, Pashlan M, The impact of a focused vascular lower limb arterial duplex (F-VLAD) scan in management decisions for acute limb ischaemia, Perfusion 2017, Vol. 32(1) 74–80

1. List of Vascular Surgical/Interventional Procedures that may be deferred or rescheduled
2. Repair of asymptomatic ascending aortic aneurysm (<5.5 cm)
3. Endovascular or open treatment of an unruptured abdominal aortic aneurysm (AAA)

<5.5 cm

3. Peripheral limb angiography, and/or revascularization (surgical and endovascular intervention) for claudication and/or non-healing wounds (without impending limb/tissue loss)
4. Carotid angiography with or without intervention (surgical or endovascular) in asymptomatic patients
5. Renal angiography with or without intervention
6. Creation of dialysis access (AV fistula)
7. Venous ablation
8. Venous stenting

Sources

1. American College of Cardiology, General Guidance on Deferring Non-urgent CV testing and Procedures During the COVID-19 Pandemic
2. Limiting of Vascular Ultrasound Procedures due to COVID-19 Pandemic, Section of Vascular Medicine, Dr. H.B. Calleja Heart and Vascular Institute, St. Luke’s Medical Center, QC
3. Limiting Vascular Ultrasound Studies due to Corona Virus Pandemic, Section of Vascular Medicine, Heart Institute, St. Luke’s Medical Center, BGC:
4. Philippine Heart Center Vascular Lab Policies during COVID Pandemic
5. Philippine Society of Echocardiography Interim Guidelines for Enhanced Quality and Safety 20200403 V1
6. Vascular Society of Great Britain and Ireland Guidance on COVID-19 and vascular surgery