TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy
Abstract
:1. Introduction
1.1. Disseminated Intravascular Coagulopathy (DIC) and COVID-19: An Uncommon Phenomenon?
1.2. The Progression of the Disease, If Untreated Is a Two-Phase ‘Rollercoaster’ of Events, Characterized by Thrombotic Pathology Followed by Bleeding or Thrombocytopenia Pathologies
1.3. A Place for Existing Point-Of Care Techniques to Guide COVID-19 Treatment
2. The Early Treatment of Patients with Anticoagulation Medication
Anticoagulation Trails
- Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day);
- or intravenous unfractionated heparin (to achieve a 0.3–0.7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30;
- Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin.
3. Fluorescence Microscopy Can Be Used to Provide a Marker of Microclot Formation and Platelet Hyperactivation
3.1. Methods Used to Analyse Microclots in Platelet Poor Plasma
3.2. Methods Used to Prepare Platelets
3.3. A Grading System for Plasma Microclot Formation and Platelet Activation, Spreading and Clumping
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Circulating Biomarkers | Selected References |
---|---|
P-selectin | [7,51] |
Fibrin(ogen) and D-dimer | [38,42,45,47,52,53,54,55,56,57,58] |
Von Willebrand Factor | [17,36,59,60] |
(A) Thromboelastography® | ||
TEG® Parameters | Explanation | |
R value: reaction time measured in minutes | Time of latency from start of test to initial fibrin formation (amplitude of 2 mm); i.e., initiation time. | |
K: kinetics measured in minutes | Time taken to achieve a certain level of clot strength (amplitude of 20 mm); i.e., amplification. | |
A (Alpha): Angle (slope between the traces represented by R and K) Angle is measured in degrees | The angle measures the speed at which fibrin build up and cross linking takes place, hence assesses the rate of clot formation, i.e., thrombin burst. | |
MA: Maximal Amplitude measured in mm | Maximum clot size: it reflects the ultimate strength of the fibrin clot, i.e., overall stability of the clot. The larger the MA the more hypercoagulable the clot. | |
Maximum rate of thrombus generation (MRTG) measured in Dyn.cm−2.s−1 | The maximum velocity of clot growth observed or maximum rate of thrombus generation using G, where G is the elastic modulus strength of the thrombus in dynes per cm−2. | |
Time to maximum rate of thrombusgeneration (TMRTG) measured in minutes | The time interval observed before the maximum speed of the clot growth. | |
Total thrombus generation (TTG) measured in Dyn.cm−2 | The clot strength: the amount of total resistance (to movement of the cup and pin) generated during clot formation. This is the total area under the velocity curve during clot growth, representing the amount of clot strength generated during clot growth. | |
Lysis at 30 min (LY30) measured in % | The LY30 parameter (measured in %) is recorded at 30 min, measured from the point where the maximum amplitude (MA) of the clot is reached. | |
G value measured in Dyn.sec | G-value is a log-derivation of the MA and is meant to also represent the clot strength Elevated G-value is associated with a hypercoagulable state and therefore increases the risk for venous thromboembolic disease. | |
(B) PFA-200 Platelet Test Interpretation: | ||
Citrated whole blood is aspirated at high shear rates through disposable cartridges. These cartridges contain an aperture within a membrane coated agonist. The agonist cartridges are Col/EPI, Col/ADP and P2Y and they report data in closure time. The PFA-200 test induces platelet adhesion, activation and aggregation using the three cartridges. Closure times increase progressively as the platelet counts falls below 100 × 109/L. | ||
Agonist cartridges [66] | Test principle | Closure time interpretations: measured in seconds |
Collagen and epinephrine (Col/EPI): This cartridge has a collagen (2 μg equine type I) and epinephrine (10 μg)-coated membrane (C/Epi). | Co-stimulation by shear stress, collagen, epinephrine. Gives an indication of effectiveness of aspirin and GP IIβ/IIIα inhibitor dosage. | Col/EPI closure time is 82–150 s with a value >150 s regarded as prolonged. |
Collagen and ADP (Col/ADP): This cartridge has a collagen (2 μg equine type I) and adenosine-diphosphate (50 μg)-coated membrane (Col/ADP). | Co-stimulation by shear stress, collagen, ADP. Gives an indication of effectiveness of aspirin and clopidogrel and GP IIβ/IIIα inhibitor dosage. | Col/ADP closure time is 62–100 s with a value >100 s regarded as prolonged. |
P2Y: This cartridge has a prostaglandin E1 (5 ng) and ADP (20 μg)-coated membrane. | Co-stimulation by shear stress, ADP, PGE1 and Ca2+. Gives an indication of effectiveness of clopidogrel and GP IIβ/IIIα inhibitor dosage | Shortened PFA P2Y closure times >106 s are viewed as prolonged. |
Score | Spreading | Score | Clumping |
---|---|---|---|
1 | Activation with pseudopodia | 1 | None |
2 | Mild | 2 | Mild |
3 | Moderate | 3 | Moderate |
4 | Severe | 4 | Severe |
Score | Presence of Microclots in Platelet Poor Plasma |
---|---|
1 | Very few areas of plasma protein misfolding (≤1 µm) visible with a few ≤10 µm microclots |
2 | Very few areas of plasma protein misfolding (≤1 µm) visible with scattered/mild ≤10 µm microclots |
3 | Moderate areas of plasma protein misfolding visible as microclots ≥15 µm |
4 | Severe areas of plasma protein misfolding visible as large microclots |
Control/Healthy | Mild | Moderate | Severe |
---|---|---|---|
=3 | 4–7 | 8–10 | 11–12 |
Platelets + PPP scores = |
Prognostic Indicator | |||
---|---|---|---|
Points assigned | 0 | 1 | 2 |
Age (years) | ≤44 | 45–64 | ≥65 |
Effort intolerance above baseline | No | Yes | |
Hypoxemia, O2 saturation | >95 | 92–95 | <92 |
Chest X-ray/CT scan | Normal | ≤1 quad | ≥1 quad |
Obesity (BMI) | <26 | 26–36 | >36 |
Co-morbidities: 1 point for each comorbid condition | Type 2 Diabetes Mellitus, coronary artery disease (CAD), non-atrial fibrillation (AF) stroke, smoking, deep vein thrombosis (DVT), hyperparathyroidism (HPT), chronic kidney disease (CKD) | ||
TEG: MA | <69 | 69–75 | >75 |
TEG: G-score | <10 | 10–15 | >15 |
TEG: Ly-30 | >0 | None (1 point) | |
Score | |||
Low Risk | Moderate Risk | High Risk | |
0–3 | 4–10 | ≥11 |
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Laubscher, G.J.; Lourens, P.J.; Venter, C.; Kell, D.B.; Pretorius, E. TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy. J. Clin. Med. 2021, 10, 5381. https://doi.org/10.3390/jcm10225381
Laubscher GJ, Lourens PJ, Venter C, Kell DB, Pretorius E. TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy. Journal of Clinical Medicine. 2021; 10(22):5381. https://doi.org/10.3390/jcm10225381
Chicago/Turabian StyleLaubscher, Gert Jacobus, Petrus Johannes Lourens, Chantelle Venter, Douglas B Kell, and Etheresia Pretorius. 2021. "TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy" Journal of Clinical Medicine 10, no. 22: 5381. https://doi.org/10.3390/jcm10225381