Disorders Flashcards
What is Virchow’s triad
- Endothelial dysfunction
- Hypercoagulability of blood
- Blood stasis / altered blood flow
Briefly describe the mechanisms of prothrombosis induced by endothelial damage
- Decreased anticoagulant molecules that are normally found in the endothelial glycocalyx (TFPI, thrombomodulin, heparan sulfate)
- Release of ultra-large multimers of vWF and fVIII
- Exposure of procoagulant substances (tissue factor)
What are the effects of neutrophil extra-cellular traps promoting immunothrombosis
- Cell-free DNA activates FXII and prekallikrein -> contact pathway
- Bind to clotting factors, TF, fibrin -> fortifie clots
- Histones activate platelets via platelet TLR-2 and TLR-4 and increase thrombin generation
- Histones inhibit activation of protein C
- Cell free DNA forms complexes with plasmin and fibrin, inhibit tPA ->inhibit fibrinolysis
- Neutrophil elastase degrades TFPI
How can microparticles have a procoagulant effect
- Expression of phosphatidylserine on their surface (external membrane)
- Expression of tissue factor
What are the 4 big factors contributing to a hypercoagulable state
- Endothelial disturbances (-> loss of anticoagulants + release of vWF + exposure of TF)
- Increased procoagulant elements (TF expressed on inflammatory cells, microparticles, NETs)
- Decreased endogenous anticoagulants (decreased hepatic production of AT / protein C / protein S, consumption, loss of endothelial anticoagulants)
- Decreased fibrinolysis (loss of endothelial tPA/uPA, increase in PAI-1, inhibition of fibrinolysis by NETs)
What are 2 types of tests that can be used for assessment of global coagulation and what parameters to they give
- Viscoelastic testing (thromboelastography, rotational thromboelastometry) -> time to initial fibrin crosslinking, rate of clot formation, viscoelastic properties of clot, time to clot lysis
- Calibrated automated thrombography (CAT) -> endogenous thrombin potential
Name a few potential laboratory markers of hypercoagulability
- Increased D-dimers
- Increased fibrin degradation products
- Increased fibrinogen
- Increased thrombin-antithrombin complexes
- Increased clotting factors activity
- Decreased protein C
- Decreased antithrombin
- Increased vWF multimers
- Increased thrombin generation on calibrated automated thrombography (CAT)
- Decreased fibrinolysis and/or increased clot formation on viscoelastic testing
In the CURATIVE guidelines, what are the conditions for which antithrombotic therapy is recommended? What are the conditions for which it is recommended only if other risk factor(s) are present?
- Recommended:
- IMHA in dogs
- PLN and PLE in dogs
- Cardiomyopathy in cats especially if prior ATE, spontaneous echocontrast, reduced LA flow velocity
- Necrotizing pancreatitis in dogs - If other risk factor(s):
- Neoplasia in dogs
- Hyperadrenocorticism or corticosteroid administration in dogs
- Sepsis in dogs
- Heartworm in cats and dogs
- PLN and PLE in cats
What are causes of procoagulant state found in PLN in dogs
- Urinary loss of AT
- Decreased fibrinolysis (higher alpha2-antiplasmin)
- Higher fibrinogen activity
- Increased fVIII activity
What are causes of procoagulant state found in IMHA in dogs
- Increased TF (due to microparticles and endothelial expression stimulated by free heme)
- Erythrocyte membrane becomes procoagulant +/- release microparticles
- NET formation due to hypoxia
What is the main mechanism suggested for hypercoagulability in neoplasia
Release of TF-bearing microparticles from neoplastic cells
What are possible causes of vitamin K deficiency
- Impaired intestinal absorption = impaired fat absorption (usually a consequence of failure of bile secretion = hepatic or post-hepatic issues)
- Impaired vitamin K recycling by vitamin K epoxide reductase (usually from rodenticide toxicity)
What is the overall survival to discharge for cats with FATE? What are negative prognostic factors
About 30-45% survival to discharge
Negative factors = lower rectal temperature, higher affected limb lactate, presence of CHF, both limbs affected, absence of motor function
What are the thromboprophylaxis recommendations for cats with FATE
- Clopidogrel 18,75 mg PO q24 (with suggested loading dose)
- OR UFH 250 U/kg SC QID
- OR Dalteparin 75 U/kg SC QID
- OR Rivaroxaban 0.5-1 mg/kg PO q24
What is the recurrence rate of FATE for cats on clopidogrel
About 50% (time to recurrence or cardiac death of 1 year)
What are autoantibodies directed against in ITP
Platelet integrin αIIbβ3 (fibrinogen receptor) or glycoprotein Ibα (vWF receptor)
What is a proposed mechanism for uremia-induced platelet dysfunction
Decreased platelet adhesion due to decreased vWF binding activity (similar to type II vWD)
What are the 3 types of von Willebrand diseases with their breed predispositions
- Type I = quantitative vWF deficiency, reduced quantity of all multimers (Doberman Pinschers, Corgis, Poodles, Irish Setters, Westies)
- Type II = qualitative vWF abnormalities, some multimers missing (German Wirehaired and Shorthaired Pointers)
- Type III = absence of vWF (Chesapeake Bay Retriever, Shetland Sheepdogs, Scottish Terriers)
What are mechanisms of platelet dysfunction induced by hydroxyethyl starch
- Binding to αIIbβ3 or glycoprotein Ibα inhibits platelet aggregation and adhesion
- Interference with fVIII-vWF complex
- Interference with intracellular signaling function
List some diagnostics available for evaluation of platelet disorders
- Tier 1 tests (rule out easy things):
- Platelet count with smear
- Platelet size and morphology
- Clotting times
- vWF concentration (Ag) or binding assay - Tier 2 tests (confirm platelet disorder)
- Buccal mucosal bleeding time
- Platelet function analyzer
- Clot retraction assay
- Viscoelastic testing - Tier 3 tests (definitive diagnosis)
- Flow cytometry
- Platelet aggregometry
- Western blot
- Genetic molecular testing
List causes of acquired platelet dysfunction
- Uremia (decreased vWF binding activity)
- Liver disease (unknown mechanism)
- Drug induced: anti-platelets, anticoagulants, NSAIDs (theoretically only salicylic acid, but COX-2 selective NSAIDs can decrease platelet activity in situations of increased thrombopoiesis), phosphodiesterase inhibitors, NO donors, beta-lactams
How long before a procedure should antiplatelet drugs be discontinued in low-to-moderate-risk patients? What is the recommendation for high risk patients?
- 5-7 days before for low-to-moderate risk
- For high risk patients, if on dual anti-platelets then one should be discontinued ; if only on one anti-platelet it should be continued
What are preventative treatment options for a dog with vWD undergoing surgery
- Cryoprecipitate 1 unit / 10-15kg
- FFP 6-10 mL/kg
- DDAVP (desmopressin) 1-3 ug/kg IV or SQ
(ONLY for type 1 or type 2 vWD)
What is the estimated platelet count in a unit of platelets derived from whole blood
8x10^10 platelets -> give 1 unit / 10kg