DIC Flashcards
describe DIC pathogenesis
- clinical syndrome where inflammation caused by disease triggers inappropriate activation of coagulation (without damage to vascular system)
- activation of coagulation results in:
-platelet activation
-formation of thrombin - platelet activation results in aggregation into microclots, which can travel to organs and obstruct arterial flow
-if enough flow is obstructed, organ damage may result - thrombin production consumes coagulation factors
-eventually, there is no longer enough to support clot formation, which leads to bleeding
-if happens quickly and at high volume, use up platelets beyond which bone marrow can supply more and also exceed the liver’s ability to catch up and make more clotting factors (move from hypercoagulable state to a non-coagulable state where you are no longer able to form clots)
what supports platelet adhesion?
connections via
- vWF
- collagen
- fibrinogen
allows you to make initial platelet plug over vessel injury and eventually stable mature clot
what are 3 endogenous anticoagulant molecules?
- antithrombin: binds and inactivates thrombin
- protein C/S: shut off factor V
- tissue factor pathway inhibitor
at the same time that you’re generating the clot and activating platelets, body should also be producing these anticoagulant molecules to turn off the clotting cascade = why when you cut yourself you don’t turn into a massive clot
-these molecules are very busy if you are making a lot of thrombin, so there will be less circulating in the blood
-all are made in the liver! liver failure = decrease in these molecules
-some diseases may cause you to lose one of these preferentially = at risk for thrombosis
describe fibrinolysis
- triggered by clot formation
- allows clot breakdown and restoration of flow
- via plasmin/plasminogen (plasminogen enzyme, activated by endothelium in the area of clot formation to plasmin)
how does coagulation happen without tissue damage?
2 main mechanisms
- monocyte or other cells trigger thrombin production
-tissue factor expression on cells when monocyte activated by inflammation, shoots up tissue factor on membrane so can bine to factor 7 and go on to clot without any endothelial damage - exposure of adhesion molecules on endothelial surface by degradation of endothelial glycocalyx
-cell adhesion molecules
describe the endothelial glycocalyx
- glycoproteins on endothelial cell surface
-mediate interaction of WBC and platelets with extracellular surface
-hidden by intact glycoclayx - cell adhesion molecules:
-selectins: E and P
-integrins: ligands for integrins on WBC and platelets, mediate diapedesis
when glycolcalyx starts to fall apart (due to disease) will expose these adhesion molecules to passing WBC and platelets, leading to platelet activation and clot formation
define DIC
an ACQUIRED syndrome characterized by the intravascular activation of coagulation with loss of localization (forming clots in areas without vessel damage)
-can originate from and cause damage to microvasculature, which can produce organ dysfunction if severe enough
describe diseases associated with DIC
inflammatory!
- sepsis: septicemia (foals)
- endocarditis
- cytauxzoonosis
- neoplasia: carcinomas, hemangiosarcoma
- IMHA
- heat stroke
- snake envenomation
- trauma: can also cause widespread endothelial damage so massive coag activation can be enough to overwhelm protective mechanisms
- gastric dilation volvulus (GDV)
- organ torsions:
-large colon volvulus
-mesenteric torsion - colitis (equine)
- organ ischemia
- pancreatitis
describe non-overt DIC
- stressed but compensated
-activation of coagulation buffered by anticoagulant mechanisms
-thrombin-antithrombin
-tissue factor-tissue factor pathway inhibitor - best chance to reverse the progression at this stage
- predominantly hypercoagulable at this time
-increased fibrinogen
-risk of thrombosis/thromboembolism - clots may lodge in capillaries and result in organ dysfunction or failure
describe overt DIC
- decompensated
-exceed’s body’s compensatory mechanisms
-thrombocytopenia
-decreased fibrinogen and 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
describe PE diagnosis of DIC: systemic inflammation
- SIRS criteria
- rectal temp:
-hypothermia or hyperthermia - heart rate:
-tachycardia: dogs, horses
-bradycardia (cats) - tachypnea
- toxic line (horses)
- brick red MM (dogs)
- evidence of predisposing dz: snake bite organ volvulus, neoplasia
PE not indicative of DIC, just of inflammation
describe lab diagnosis of DIC
- platelet count
- coagulation times
- indicators of fibrinolysis
- concentration of anticoagulant proteins
- evidence of RBC fragmentation
- indicators of clot formation
generally, abnormalities in at least 2 of these markers plus physical exam findings or presence of inflammatory condition are necessary for diagnosis
describe platelets in DIC
using up, but not destroying platelets
- consumptive thrombocytopenia
-plt count between 40-100x10^3 (moderate) - platelet clumping:
-inflammatory disease
-ALWAYS look at blood smear
describe coagulation profile of DIC
- coag times:
a. prothrombin time
-non-overt = normal
-overt = prolonged
b. activated partial thromboplastin time (aPTT)
-non-overt: 1.2-1.5x high normal value
-overt: 2x prolonged (no meas)
c. fibrinogen: acute phase protein that increases with inflammation
-increases with inflammation (non-overt)
-DECREASES with consumption (overt)
describe fibrinolysis markers of DIC
- D-dimer: increased in circulation
- FDP: no longer measured
describe anticoagulant proteins in DIC
DECREASED!!
- protein C/S: inactivate coagulation factors, when decreased = clotty clotty
- antithrombin:
-1:1 binding to thrombin to make TAT complex, when decreased = thrombin goes crazy and more clotty clotty - decreased tissue factor pathway inhibitor so even MORE clotty clotty
describe the overall plan of dealing with DIC
- ID inciting cause to guide treatment
- eliminate inciting cause to resolve DIC
- treat what’s treatable
-replace fibrinogen/factors if bleeding
-consider anticoagulation if clotting
describe how to treat DIC
- resolve underlying cause!!
a. medical:
-resolve inflammation
-antibiotics if infection
-supportive care: nutrition, support oxygen delivery (fluids, RBC, oxygen)
-prevent additional inflammation
b. surgical:
-drain/flush/remove inflammatory nidus
-for neoplasia/abscess/sepsis
- stop hemorrhage (if present)
a. fresh frozen plasma/fresh whole blood: restores consumed coag factors, only source of anticoag factors
b. pros: partially resolves coagulopathy, may provide additional anticoag factors (AT may be anti-inflammatory), restores glycocalyx
- decrease coagulation?
-in the presence of overt thrombosis
-in high risk patients: IMHA, cardiac disease cats, severe sepsis, severe sustained systemic inflammation (colic, ischemia/shock)
-risk versus benefit should be considered - +/- prophylactic anticoagulation
a. anticoag drugs:
-heparin: unfractionated or low-molecular weight heparins, bind and neutralize factors II and X but MAY result in hemorrhage (works with antithrombin so if don’t have antithrombin may not work)
b. anti-platelet drugs: no evidence of helping in DIC
describe the use of antifibrinolytics in DIC treatment
- no indication for use in treatment of DIC
- in rare cases where the inciting cause may be hyperfinrinolysis leading to further consumptive coagulopathy, drugs like e-aminocaproic acid or tranexamic acid may be used
