Disseminated Intravascular Coagulopathy (DIC) PDF

1/13/25 Benjamin Brainard VMD University of Georgia Clinical syndrome where inflammation caused by disease triggers inappropriate activation of coagulation Activation of coagulation results in: – Platelet activation – Formation of thrombin...

1/13/25 Benjamin Brainard VMD University of Georgia Clinical syndrome where inflammation caused by disease triggers inappropriate activation of coagulation Activation of coagulation results in: – Platelet activation – Formation of thrombin Platelet activation à aggregation into microclots – Can travel to organs and obstruct arterial flow – If enough flow is obstructed, organ damage may result Thrombin production consumes coagulation factors – Eventually no longer enough to support clot formation à bleeding 1  1/13/25 Platelet adhesion supported through connections vonWillebrand Factor Collagen Fibrinogen 2  1/13/25 Endogenous anticoagulant molecules: Fibrinolysis: Antithrombin Triggered by clot formation Protein C/S Allows clot breakdown and restoration of flow Tissue Factor Pathway Inhibitor (TFPI) Plasmin/plasminogen How does coagulation happen without tissue damage? Monocyte or other cells trigger thrombin production – Tissue factor expression on cells Exposure of adhesion molecules on endothelial surface by degradation of endothelial glycocalyx – Cell adhesion molecules 3  1/13/25 Rabelink TJ. Nat Rev Nephrol. 2015;11(11):667-76. Wiesinger A. PLoS One. 2013;8(11):e80905. 4  1/13/25 Endothelial glycocalyx Glycoproteins on endothelial cell surface – Mediate interaction of WBC and platelets with EC surface – “hidden” by intact glycocalyx Cell adhesion molecules – Selectins (E, P) – Integrins Ligands for integrins on WBC and platelets Lawrence-Mills SJ. Vet J. 2022;285:105843. Mediate diapedesis Iba T. J Thromb Haemost. 2019;17(2):283-294. 5  1/13/25 ISTH definition “DIC is an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction” Diseases associated with DIC Sepsis Trauma – Septicemia (foals) Gastric dilatation volvulus (GDV) Endocarditis Organ torsions Cytauxzoonosis – Large colon voluvulus Neoplasia – Mesenteric torsion – Carcinomas Pancreatitis – Hemangiosarcoma Colitis (equine) IMHA Organ ischemia Heat stroke Snake envenomation 6  1/13/25 Non-overt DIC Stressed but compensated – Activation of coagulation buffered by anticoagulant mechanisms Thrombin—Antithrombin Tissue factor – Tissue factor pathway inhibitor (TFPI) – Best chance to reverse the progression – Predominantly hypercoagulable at this time Increased [fibrinogen] (inflammation) Risk of thrombosis/thromboembolism – Clots may lodge in capillaries and result in organ dysfunction or failure Overt DIC Decompensated – Exceeds body’s compensatory mechanisms Thrombocytopenia Decreased [fibrinogen] other factors – Hemorrhagic phenotype Petechiae Ecchymoses Epistaxis Cavitary bleeds – Activation of fibrinolysis by clots worsens hemorrhage – Organ failure may occur due to previously formed clots 7  1/13/25 PE Diagnosis of DIC: systemic inflammation SIRS criteria Toxic line (horses) Rectal temperature Brick red mm (dogs) – Hypothermia Evidence of predisposing disease – Hyperthermia – Snake bite Heart rate – Organ volvulus – Tachycardia – Neoplasia Dogs, horses – Bradycardia (cat) Tachypnea Laboratory diagnosis of DIC Platelet count Generally abnormalities in at Coagulation times least two of these markers plus Indicators of fibrinolysis physical exam findings or presence of inflammatory [Anticoagulant proteins] condition are necessary for Evidence of RBC fragmentation diagnosis Indicators of clot formation 8  1/13/25 Diagnosis of DIC: Platelets Consumptive thrombocytopenia – Platelet count between 40 – 100 x 103/μL (canine) Platelet clumping – Inflammatory disease – Always look at blood smear – One platelet at 100X (hpf) Approx 15 x 103/μL platelets Diagnosis of DIC: Coagulation profile Coagulation times – Prothrombin time (PT) Non-Overt: normal Overt: prolonged – Activated partial thromboplastin time (aPTT) Non-overt: 1.2-1.5 x high normal value Overt: 2+ X prolonged – Fibrinogen concentration ↑ with inflammation (non-overt) ↓ with consumption (overt) 9  1/13/25 Diagnosis of DIC: Fibrinolysis markers D-dimer – Increased in circulation D E D FDP – No longer measured PLASMIN Wiinberg B et al, Vet J, 2010 Decreased anticoagulant proteins Protein C/Protein S – Inactivate coagulation factors Antithrombin – 1:1 binding to Thrombin à TAT complex Tissue Factor Pathway Inhibitor (TFPI) Wiinberg B et al, Vet J, 2010 10  1/13/25 Plan, overall Identification of inciting cause à treatment Elimination of inciting cause à resolve DIC Treat treatable – Replace fibrinogen/factors if bleeding – Consider anticoagulation if clotting Jude 13 y FS Labrador Ret. Presenting complaint: – Lethargy – Anorexia – Vomiting – Fever Physical exam: – Quiet, alert, responsive – T 102.9, RR 20 bpm, HR 130 bpm – Mm pale, sl. icterus – HR regular, soft II/VI murmur – Abdomen soft, non-painful Systolic BP: 120 mm Hg 11  1/13/25 Jude, lab data WBC: 9.3K – NΦ: 7.8K (84%) x 109/L (2.9 – 12) Bands: 174 (2%) (0 - 0.45) – LΦ: 837 (9%) 0.4 - 2.9 – MΦ: 465 (5%) 0.1 - 1.4 Hct 40% Platelets: 45 x 103/μL PT: 7.9 sec (6.4 - 8.9) aPTT: 19.8 sec (8.7 - 13.4) Jude, workup plan Find inflammatory nidus: – Imaging: Thoracic radiographs Abdominal radiographs Abdominal ultrasound Consider echocardiogram (murmur) – Urinalysis/urine culture – Tick-borne disease titers Erlichia, Rickettsia 12  1/13/25 How do we treat DIC? Resolve underlying cause Medical – Resolve inflammation – Antibiotics (if infection) – Supportive care Nutrition Support oxygen delivery (fluids, RBC, oxygen) Prevent additional inflammation Surgical – Drain/flush/remove inflammatory nidus. – Neoplasia/abscess/sepsis 13  1/13/25 Stop hemorrhage (if present) Fresh frozen plasma/fresh whole blood – Restores consumed coagulation factors – Only source of anticoagulant factors Pros: – Partially resolves coagulopathy – May provide additional anticoagulant factors AT may be anti-inflammatory – Restores the glycocalyx Decrease coagulation? In the presence of overt thrombosis High risk patients – IMHA – Cardiac disease (cats) – Severe sepsis – Severe sustained systemic inflammation Colitis Ischemia/shock Risk/benefit should be considered 14  1/13/25 Prophylactic anticoagulation? Anticoagulant drugs – Heparin Unfractionated or low-molecular weight heparins Bind and neutralize factors II and X May result in hemorrhage Antiplatelet drugs – No evidence in DIC Jude Urinalysis: – No abnormal findings Thoracic/abdominal radiographs: – No abnormal findings Abdominal ultrasound – No abnormal findings – Hepatic aspirate and culture 15  1/13/25 Jude Liver aspirate: – “vast quantaties of degenerate neutrophils” – “occasionally contain intravellular, long bacterial rods” – “severe septic suppurative inflammation” Rx: – Broad spectrum antibiotics, supportive care Ampicillin, Enrofloxacin IV crystalloid fluids – Hepatoprotectant medications Urosodiol, Denamarin Antifibrinolytics No indication for the use in the treatment of DIC. In rare cases where the inciting cause may be hyperfibrinolysis leading to further consumptive coagulopathy, drugs such as ε-aminocaproic acid or tranexamic acid may be indicated. 16  1/13/25 So… how to treat DIC… Depends. Assess: – Clinical status of patient – Progression of patient – Individual patient risk – Coagulation tests – Fibrinolytic tests And monitor. – Coagulation status – Oxygen delivery – Organ function [email protected] 17