Disorders of Hemostasis in Small Animals Flashcards
what is hemostasis
stopping of a flow of blood
what is reduced hemostasis
bleeding
what is increased hemostasis
thrombosis
what are primary bleeding disorders (3)
- thrombocytopenia
- thrombocytopathia
- vWD
what are secondary bleeding disorders (3)
- rodenticide toxicity
- liver disease
- congenital factor deficiencies (hemophilia)
what are tertiary bleeding disorders
hyperfibrinolysis
what are mixed bleeding disorders
- DIC
- angiostrongylus vasorum
what are the steps in normal hemostasis
- primary
- secondary
- tertiary
what is primary hemostasis
formation of platelet plug
what is the secondary hemostasis
stabilization of the platelet plug –> fibrin formation
what is tertiary hemostasis
breakdown of platelet plug
aka fibrinolysis
what are the steps in primary hemostasis (4)
- vessel injury causes the release of tissue factor (TF) which is naturally found on the surface of the subendothelial collagen. Becomes exposed to the blood following injury
- blood vessel constricts in response to injury: slows the flow of blood
- platelets bind to exposed tissue factor using vWF as a bridge and become activated
- a loose plug of activated platelts is formed over the defect in vessel wall. This is only loosley held in place by vWF and interactions between platelets. Red cells are trapped amongst the platelets
what does primary hemostasis require to occur successfully (4)
- normal platelet number
- normal platelet function
- normal vWF activity
- normal vessel wall function (vasoconstriction)
what occurs during secondary hemostasis
clotting cascade (intrinsic, extrinsic, common pathways)
culminates in formation of fibrin –> cross linked into a mesh around the platelets
describe the clotting cascade pathway
what occurs in tertiary hemostasis
plasminogen is converted into plasmin which breaks down fibrin into fibrin degredation products (FDPs)
what other clinical diseases can cause epistaxis (5)
- hemostatic disorder
- hypertension
- nasal tumour
- aspergillosis
- nasal foreign body
what other clinical diseases can cause hemoabdomen (4)
- hemostatic disorder
- trauma
- post surgical
- neoplasia (splenic tumour, hepatic tumour, vena cava invasion)
what are 3 key things to diagnose a hemostatic disorder
- history
- clinical exam
- tests of hemostasis
what are specific primary hemostatic disorder clinical signs (8)
- petechiae
- echymoses
- oozing from wounds
- intraoperative bleeding
- capillary ooze
- epistaxis
- melena
- hematuria
what are the clinical signs for secondary hemostatic disorders (7)
- echymoses
- hematomas
- hemoarthrosis
- hemothorax
- hemoabdomen
- large body cavity bleeds
- subcutaneous hematomas
what are typical owner reported problems in primary hemostatic disorders
- melena
- bleeding from gums
- epistaxis
what are tests of primary hemostasis (4)
- buccal mucosal bleeding time
- platelet count
- platelet function
- vWF assays
what are tests of secondary hemostasis
- prothrombin time (PT)
- activated partial thromboplastin time (APTT)
- measure fibrinogen levels
what are tests of tertiary hemostasis
- fibrin degredation products (FDPs)
- D-dimers
what are mixed tests (viscoelastic tests)
- TEG
- TEM
- ROTEM
what is the first step when interpreting the platelet count
do you trust the hematology analyzer?
how do assess whether or not the platelet count is accurate
blood smear
check feathered edge for clumping
count # of platelets in 10 oil immersion fields and multiply by:
dogs 1.5 x 10^9/l
cats: 2 x 10^9/l
what is the reference range of platelet count in dogs and cats
dogs: 200 x 10^9/l
cats: 300-800 x 10^9/l
what platelet count value do you start to worry and what value does spontaneous bleeding occur at
worry at <50 x 10^9/l
spont bleeding: <30 x 10^9/l
what are common platelet count problems
- platelet clumping is present
- red cell platelet overlap
- large platelets in certain breeds (ex. CKCS have larger size than normal and fewer #)
what is thrombocytopenia
decreased platelet #
what are the causes of thrombocytopenia (5)
- decreased production (bone marrow disorder)
- increased destruction: immune mediated thrombocytopenia (IMTP), infectious disease (Ehrlichia)
- sequestration
- increased consumption: bleeding, DIC (angiostrongylus vasorum)
- breed idiosyncrasy (CKCS)
what does the platelet count need to be in order to be the primary cause of bleeding
<50
what are the 3 scenarios that lead to thrombocytopenia
- platelets are being destroyed
- severely used up
- failure of production
what should you look at if you think that there is a failure of production of platelets
look for other cytopenias (anemia, leukopenia, etc)
chemotherapy
what are the diagnostic work up for thrombocytopenia
look for causes of destruction
- rule out infectious diseases (anaplasma, ehrlichia, angiostrongylus vasorum)
- rule out neoplasia
- +/- bone marrow assessment?
how do you diagnose immune mediated thrombocytopenia (IMTP)
dx of exclusion if all secondary causes ruled out
what is the signalment of immune-mediated thrombocytopenia (IMPT)
median age 4-5 years, but can be ANY
cocker spaniels seem predisposed
what are the presenting signs of IMTP
primary hemostatic disorder: surface/capillary bleeding
how is IMTP managed (3)
gentle handling
- blood transfusion only if anemia enough to CV compromised
- treatment of underlying trigger if secondary (infection, neoplasia?)
- immunosuppression: steroids (1-2mg/kg/24h), +/- second line agent
can a transfusion replace platelet number
no you can’t give enough to increase the platelet number substantially and reduce risk of bleeding
even whole blood will not replace PLT
if the platelet count is >50 but <200, why would that be?
this count isn’t low enough to cause spont bleeding
bleeding is causing PLT to be used up
what is the workup if the PLT is >50 but <200 (3)
- is there bleeding? remember not all bleeding is a coagulopathy
- is there a secondary hemostasis disorder?
- is there a mixed disorder? DIC?
what does prothrombin time (PT) test
extrinsic and common pathways
what does activated partial thromboplastin time (APPT) test
intrinsic and common pathways
what are common disorders of secondary homeostasis (3)
- vitamin K antagonism (rodenticide toxicity)
- vitamin K deficiency (hepatic/cholestatic disease)
- specific factor deficincies (hemophilia A and B, hageman effect factor XII)
what is the cause of vitamin K antagonism
coumarin based rodenticides
first generation: warfarin
second generation brodifacoum, etc etc –> many types
inhibit enzymes that activates the vitmain K dependent factors –> II, VII, IX, X
what are the clinical signs of vitamin K antagonism
secondary hemostatic: cavity bleeds
known intoxication: initally asymptomatic (~3 days)
how is vitamin K antagonism diagnosed
history: any access?
testing: PT and APTT times
what does vitamin K antagonism diagnosed using clotting times
PT: prolongs first (usually within 48 hours, before clinical bleeding starts –> factor VII has the shortest 1/2 life)
APTT: prolongs second
how is vitamin K antagonism treated if there is a known recent ingestion
emesis, decontamination
monitoring PT (starting 48 hours post ingestion)
how is vitamin K antagonism treated if there is increasing PT or active bleeding
- vitamin K: subcutaneous for 24-48h and then ongoing oral (several months)
- supportive care: thoracocentesis only if dyspnea with pleural effusion, transfusion (whole bood if CV unstable), fresh frozen plasma more specific to replace factors
what are the casues of vitamin K deficiency (2)
- end stage liver disease: reduced production of clotting factors, reduced activation of vitamin K dependent factors
- severe cholestasis: reduced liver ability to recycle vitamin K dependent factors
what are the clinical signs of vitamin K deficiency (3)
- secondary homeostasis: except cavity bleeds
- clinically spontaneous bleeding unlikely
- increased bleeding risk with surgery/biopsy
how do you test between vitamin K antagonism or deficiency
- prolongation of both PT and APTT can be seen
- is there concurrent signs of liver/cholestatic disease? (increased liver enzymes, increased bilirubin, reduced albumin, reduced urea)
what are the clotting factor deficiencies
- hemophilia A (factor VIII)
- hemophilia B (factor IX)
- factor XII deficiency (factor XII in cats)
- others: rare deficiency of factors II, VII, X, XI, XII
what are the clinical signs in factor X deficiency
causes high neonatal mortality
what are the clinical signs of hemophilia A and B
young animals: usually <1 year old
X-linked recessive: MALE animals
unexpectedly severe/spontaneous hemorrhage
prolonged APTT, normal PT
what are the clinical signs of factor XII (hagemen trait)
asymptomatic
prolongs APTT
when should a BMBT test not be done
not before you have done a platelet count
when should bleeding stop in a BMBT
2-4 mins
if there is a prolonged of BMBT
vWD
thrombocytopathia
if there is a normal BMBT, clotting time and platelet count what could the cause be
angiostrongylus
hyperfibrinolysis
what is von willebrand’s disease caused by
reduced vW factor concentration or function
congenital: breed predisposition (dobermann)
what are the clinical signs of von willebrand’s disease
excessive hemorrhage with trauma or surgery
how do you test for von willebrand disease
<50% vWF:Ag = affected
what is the treatment of von willebrand disease
may be none needed
in the face of bleeding or prior to surgery –> desmopressin, cryoprecipitate
what is thrombocytopathia
due to defective pseudopod formation and lack of spreading of platelets, i.e., defective adhesivity in contact with wettable surfaces.
what are the clinical signs of thrombocytopathia
primary disorder
what are the causes of thrombocytopathy (4)
- congenital
- infectious (Ehrlichia)
- systemic diseases (uremia/hepatic disease)
- drugs: NSAIDs, aspirin, clopidogrel
how do you test for thrombocytopathy
difficult most commonly a diagnosis of exclusion
PFA/platelet aggregometry –> not available clinically
how is thrombocytopathy managed
supportive
treat underlying disease
what is hyperfibrinolysis
excessive breakdown of fibrin
what are the causes of hyperfibrinolysis (4)
- liver disease
- angiostrongylus
- trauma
- congenital (suspected cause for increased bleeding in greyhounds ex. post dental extractions)
how do you test for hyperfibrinolysis
FDPs, D-dimers
global tests –> TEG
how do you manage hyperfibrinolysis
supportive
tranexamic acid
transfusion: fresh frozen plasma
how does tranexamic acid work
inhibits the activation of plasminogen and prevents breakdown of fibrin
what are the clinical signs of angiostrongylus vasorum
how does angiostrongylus cause bleeding
can affect all parts of homeostasis
how does angiostrongylus disrupt primary hemostasis (4)
- acquired vWF deficiency
- thrombocytopenia (immune mediated or consumptive)
- abnormal platelet function
- blood vessel endothelial disruption
how does angiostrongylus disrupt secondary hemostasis (2)
- immune complex activation of clotting factors
- parasite secretes anticoagulant factors
how does angiostrongylus disrupt tertiary hemostasis (2)
- reduced serum fibrinogen levels
- hyperfibinolysis
how is angiostrongylus vasorum diagnosed
- fecal baermanns for L1 larvae
- in house ELISA: IDEXX angiodetect
how is angiostrongylus vasorum treated
supportive care for hemorrhage
parasite kill
steroids: for worm kill immune side effects
what medications kill the angiostrongylus parasites
imidacloprid/moxidectin and milbemycin
fenbendazole also effective but unlicensed
how is angiostrongylus prevented
slug and snail control
prophylactic monthly parasite prevention
how do you clinically judge if both platelet count and coagulation times are abnormal (3)
- if PT and APTT massively prolonged, PLT slightly low –> probably just consumption of PLT
- PLT <30, PT and APPT a second or two prolonged –> focus on thrombocytopenia
- both markedly abnormal –> concern for DIC
what is DIC
disseminated intravascular coagulation
what causes DIC
systemic coagulation and fibrinolysis together
what are the effects of DIC
mix of thrombosis and bleeding: spectrum of signs over time
what disorders can cause DIC and how
due to widespread endothelial damage/release of tissue thromboplastins
- inflammatory
- traumatic
- neoplasia
- angiostrongylus vasorum
how do you test for DIC
- increased APTT (first) and PT
- thrombocytopenia (consumptive)
- decreased fibrinogen
- increased FDPs and D-dimer
- TEG/ROTEM: various curve shapes
what are the treatment principles for DIC
- eliminating initiating cause
- ensuring adequate tissue perfusion
- supporting target organs usceptible to microthrombi, ischemia or hemorrhage
- replacement of blood components
- anticoagulants (heparin?)
