Platelets 2 Flashcards
Disorders of platelet function?
> Glanzmann’s thrombasthenia (defect in GPIIbIIIa)
- otterhounds and great Pyrenees
- quarter horses
- defective platelet aggregation and abnormal clot retraction
canine thrombopathia - abnormal GPIIbIIIa exposure and impaired degranulation
- bassett hounds
Bovine thrombopathia - defect not known
- simmentals
- mild-severe bleeding
Causes of thrombocytosis? LOOK
> physiological transient
- epinephrine induced splenic contraction
reactive (2*)
- ^ thrombopoietin +- IL6
- inflammation, haemorrhage, Fe deficinecy
essential thrombocythemia
- myeloproliferative disorder
- persistent ^ platelet nos.
- BM megakaryocytes ^ +- abnormal morphology
- function variable (may see pettechiae/echymoses or thrombosis)
- TPO normal/increased
What is vWF? Where is it synthesised and how does it circulate?
- vWF = plasma glycoprotein for platlet adherence to collagen and formation of 1* haemostatic plug
- synthesised by endothelial cells, platelets and megakaryocytes
- circulates bound to FVIII (protective function for FVIII)
- maysee concurrent v in FVIII
- exists in small, medium and large multimers (large multimers most active in haemostasis)
Clinical signs of vWF dz?
- mucosal bleeding (GI, epistaxis, haematuria)
- NO peticheia
- bleeding may be absent
- prolonged buccal mucosal bleeding time despite no thrombocytopenia
- clotting times usually NORMAL (PTT may be ^ d/t factor VIII decrease)
Which species is vWF dz common in?
- common dogs
- rare cats and horses
- pigs used as human model
What forms of VW dz exist? LOOK
Type 1 - decreased conc of all multimers
Type 2 - qualitative abnormalities in vWF structure/function
Type 3 - absence of all vWF multimers
Type 1 vW dz?
- all multimers present at decreased concentrations
- variable severity of bleeding (not until [vWF]
Type 2 vW dz?
- qualitative abnormalities in vWF structure function
- disproportionate decrease in LARGE multimers
- severe and uncommon
Breeds type 1 vWD
- Doberman
- autosomal inheritance so males and females == affected
breeds type 2 vWD
- german shorthaired and wirehaired pointers
- one horse case
- autosomal recessive
type 3 vWD
- absence of all vWF multimers (
breeds type 3 vWD
- Scottish terriers, Chesapeake Bay Retrievers, Shetland Sheepdogs and Dutch Kooiker
- autosomal recessive
How can vW dz be tsted for?
> measure levels of vWF Ag
- collect blood into EDTA or citrate
- if using citrate as a coagulant dilute 1:9
- vWF decreased by clots in the sample and heamolysis but unaffected by lipaemia
- separate plasma immediately, freeze and ship overnight w/ ice
Specific vWF tests?
> ELISA - Ab > Immunoelectrophoresis - separate relative amounts of different multimers (required for diagnosis of type II disease) > genetic test to detect carriers
How is interpretation of vWF ELISA perfmored? ie. what do differneing levels of Ags indicate?
Tx vWD?
> transfusion to supply factor
- cryoprecipitate best (^ conc vWF) 1U/10kg
- plasma can be given @6-12ml/kg if cryo not available
- whole blood if anaemic too
desmopressin
- doesnt tx dz
- pre-op prophylaxis with type 1 dz
- causes release of vWF from endothelium
- human intranasal/1ug/kg SQ 30min pre-op
What type of sample is needed for coagulation tests?
- citrated plasma
- ratio of anticoag:blood 1:9
- NB: vPCV anaemic patients will have more plasma!*
- do not sample thorugh heparinised catheters
- minimise trauma to prevent platelet activation and coagulation
- centrifuge to separate plasma within an hour
- analyse within 4hrs or freeze plasma
- always include species specific control ???
What do citrate tubes look like? What should be checked in tube?
blue/purple/green (small)
- check for clots! Need to resample
What coagulation test can be used in practice with patient?
ACT: Activated clotting time (=PTT in lab)
- point of care test
- INTRINSIC and COMMON pathways
- 2ml whole blood into ACT tube with diatomaceous earth
- incubate 60s @37* check for clot formation q5-10s
- time to initial signs of clot is ACT time (s)
- less sensitive than PTT
- prolonged with thrombocytopenia
What is the PTT?
> partial thromboplastin time
- intrinsic and common pathways
- incubate citrated plasma with excess phospholipid [ usually comes from platelet cell membrane as this is NOT a test of platelet number] , contact activator and calcium
- measure time to formation of clot
What can interfere with PTT?
- lipemia, hemolysis, oxyglobin tx, icterus interfere with clot detection
Can PTT be used to detect hypercoagulation?
No too crude
- only look for prologed time
What does prolonged PTT time indicate?
- defect in INTRINSIC (factors XII, XI, IX, VIII) or COMMON (X, V, II, fibrinogen) pathways
- factor activity must be
What is PT?
= prothrombin time
- screening test for defects in EXTRINSIC or COMMON pathway of coagulatino
- incubate citrated plasma with tissue thromboplastin (TF) and calcium
- measure time to clot formation
What does prolonged PT time indicate?
- defect in EXTRINSIC (factor VII) or COMMON
-
Which factor has the shortest half life? Clinical implications?
Factor VII of extrinsic pathway
- will decrease first if problem with production of clotting factors
- so prolonged PT will be seen first before PTT/ACT
> eg. Vit K deficiency may see prolonged PT with normal PTT early on
If PT and PTT are both prolonged what scenarios could be occouring?
> problems
- common
- extrinsic + common
- intrinsic + common
- extrinsic + intrinsic
- extrinsic+ intrinsic + common
What does PT elongation time indicate?
- factor VII deficiency
- DIC
- Vit K deficiency
- LIver failure
> NOT affected by thrombocytopenia
What further tests can be used to assess coagulation?
> specific factor analysis
- detect specific factor deficiencies
- usually for hereditary deficicenies
- correct PT and PTT of test plasma to that of normal plasma
What tests of fibrinolysis are available?
> FDPs (fibrin degradation products)
- use latex agglutination (special test and kit)
- done on serum (needs to be separated within 30mins)
- test immediately or freeze
What do ^ FDPs indicate?
> DIC most commonly
- but not specific
- may also increase with haemorrhage, jugular vein thrombosis (horse), liver dz
- will be + if fibrinogen broken down as well as fibrin
more specific = D-dimers
- plasmin mediated degradation of cross-linked fibrin
Disorders of coagulatioin - most common?
- acquired factor deficiencies
- most common = vit K
- rodenticide toxicity (coumarin, indanedione) or sweet clover ingestion (cattle)
Which factors are vit K deoendant?
- II, VII (PT affected first), IX, X
Mechanism of vit K deficiency?
- factors produced in the liver
- activated by vit K depdednant carboxylase (requires reduced vit K)
- production of reduced vit K requires activation of vit K reductase
- vit K reductase inhibited by coumarin-type rodenticides
- > lack of active FII, VII, IX, X -> coagulopathy
Random details on vit K deficiency pathway
- vit K from gut (fat soluble)
- proenzyme needs to be carboxylated (2,7,9,10) /activated to take part in coagulation
- vit K reduced back again once used
- Coumarins block vit K recycling
Which pathways are affected by vit K? What coagulation tests affected first?
- all pathways
- PT see nfist as factor VII affected
CLinical signs of vit K deficency?
- haemorrhage
- ^ PT and PTT
- platelet nos and buccal mucosal bleeding time SHOULD be normal, but mild thrombocytopenia poss d/t consumption of clotting factors with haemorrhage
Tx vit K deficiency?
- Emetics, cathartics, activated charcoal if ingestion of rodenticide recent
- transfusions (whole fresh blood/fresh frozen plasma)
- +- packed RBCs if severe anaemia present
> Vit K tx (K1) - orally/parenterally (SQ)
- NOT IV (risk of anaphylaxis)
- NOT IM (risk of haematoma)
- O/D -> haemolytic anamiea
- can give loading dose SQ + lower dose q8hrs
- same dose gien orally w/ fatty meal
- can take 12hrs before vit K tx shortens PT/decreases bleeding
> if warfarin/1st gen rodenticide = 1 week tx
> 2nd/3rd gen need to tx min 3 weeks ( check PT 24-48hrs after last dose, if prolonged reinstate tx for another 2 weeks and recheck
Causes of thrombocytopenia?
-
Give egs. of herediatary defects of coagulation
- factor VII deficiency
- haemophilia A (factor VIII deficiency)
- Haemophilia B (factor IX deficiency)
- factor XI/XII deficiency
Tx inherited coagulation defects?
- transfusion (whole blood/plasma) to replace factors and RBCs
- fresh/frozen plasma gives smaller factor
- cryoprecipitate has 10x more factor VIII cf. plasma
What is DIC?
- mixed haemostatic defect
- d/t excessive coagulation -> widespread thrombosis
- haemorrhage -> consumption of clotting factors
(platlets and fibrinogen both lost) - 2* to underlying diseases (neoplasia, liver dz, immune mediated dz, infectious dz)
- may be chronic/acute
What haemostatic abnormalities are seen with DIC?
- THROMBOCYTOPENIA
- PROLONGED pt AND ptt
- ELEVATED fdpS
- DECREASED FIBRINOGEN
- DECREASED ANTITHROMBIN iii
Tx DIC?
> stop coagulation
- heparin
- transfusion whole blood/plasma/cryoprecipitate (source of antithrombin III)
- aspirin to stop platelet activation
correct other underlying abnormalities
prog poor
Outline the approach to the bleeding patient
> haemorrhage peticheal/ecchymotic?
= platlet defect
frank haemorrhage
= coagulation defect
- consider age and hx (toxins)
CBC
- Hct and platlet count
thrombocytopenia?
- check clots. smear
- if >100x10^9 haemorrhage = cause of thrombocytopenia likely
- if if plt within interval but haemorrhage (=vWD) or ecchymoses (platlet function)
check BMBT
assay vWF Ag
check clotting function (PTT may be ^ d/t concurrent v FVIII)
check PT and PTT
- if both prolonged consider vit K deficiency/ DIC
- PTT only = intrinsic pathway defects (haemophilia A/B)
- OT only = early vit K deficiency, liver dz, early DIC
