Ch 7 Haemostasis Flashcards
where platelets from?
derived and released from progenitor megakaryocytes in the bone marrow
what do platelets release
major agonist of coagulation (2)
platelets synthesize prostanoids, notably thromboxane A2 (TxA2), from arachidonic acid.
ADP
Primary haemostasis (4)
- adherencce: endothelial disruption > Platelets adhere to subendothelial collagen, either directly or via collagen-bound von Willebrand factor (vWF)
- resulting in a shape change and activation
3.activation = release of agonists (Txa2 + ADP) from granules and via arachidonic acid metabolism
(4). Agonists recruit and activate additional platelets
(5) and alter the avidity and affinity of fibrinogen binding receptors, leading to aggregation
secondary haemostasis
cascade
Intrinsic and extrinsic pathways
* Extrinsic – initiated by tissue factor
* Intrinsic – initiated through contact activation of fXII
A Cell-Based Model of Coagulation
3 PHASES
(1) tissue factor = primary physiologic initiator of coagulation
(2) coagulation is localized to, and controlled by, cellular surfaces
3 overlapping phases
Initiation (on tissue factor-bearing cells)
vascular damage allows contact between plasma and tissue factor
fVII binds to TF (activated)
fVIIa-TF complex activates fX.
fX (cell surface) combines with fVa to produce thrombin.
fVIIa-TF complex also activates fIX, which diffuses into cell
amplification
platelets are fully activated, with cofactors V and VIII bound to their surfaces
thrombin amplifies the original signal
propagation (on platelets)
large scale thrombin generation occurs
fXI binds and activated by thrombin,
fXa generates fIXa.
fIXa complexes with fVIIIa to activate fX fXa-Va complexes activate prothrombin to produce burst of thrombin necessary to produce large quantities of fibrin.
Fibrin then complexed to form fibrin polymers and a stable thrombus
- Regulation of hemostasis (3)
- Platelets do not express tissue factor; coagulation can proceed only when extravascular tissue factor exposed
2.platelets are activated, markedly increases the speed of coagulation reactions > Prostacyclin limits the platelet response to TxA2, Ecto-ADPase metabolizes ADP released
- anticoagulant pathways:
- anticoagulant pathways
:
- **Antithrombin AT **
inactivates coagulation proteins that escape into the circulation from a site of injury
exerts potent antiinflammatory effect -
thrombin-thrombomodulin complex activates protein C
inactivate cofactors fVa and fVIIIa, and this slows the rate of thrombin
enhances fibrinolysis inactivation of plasminogen activator inhibitor-1 (PAI- 1) -
Tissue factor pathway inhibitor inhibits tissue factor
abrogates the initiation complex of factor VIIa-TF, as well as factor Xa
- Fibrinolysis
2 plasminogen activators?
o Plasminogen activators proteolytically convert the proenzyme, plasminogen, to plasmin
o Plasmin degrades fibrin into soluble degradation products
tissue-type plasminogen activator (t-PA
urokinase-type plasminogen activator (u-PA
plasminogen activator inhibitor-1 (PAI- 1)
stored in platelet α-granules
PAI-1 inhibits both tPA and uPA
α2-antiplasmin, synthesized in the liver, inhibits plasmin
- Platelet Enumeration and Estimation
Multiply average number of platelets per HPF by 15,000
o Pseudothrombocytopenia is a common artifact
- Buccal Mucosal Bleeding Time
prolonged by? 3
o 1-mm deep incisions in the mucosa of the upper lip
o Normal ranges are 1.7 to 4.2 minutes in the dog, and 1.4 to 2.4 minutes in the cat
o prolonged with thrombocytopenia, thrombopathia, and vasculopathy
- Prothrombin Time and Activated Partial Thromboplastin Time
o Prolongation of the PT indicates defective extrinsic and/or common pathways
o aPTT prolongation indicates defective intrinsic and/or common pathways
o short half-life of factor VII, the PT is very sensitive to vitamin K deficiency
- Activated Clotting Time
diatomaceous earth, which serves as a contact activator of factor XII
o normal ACT is less than 110 seconds for the dog, and less than 75 seconds for the cat
affected by: severe thrombocytopenia (<15,000/μL) or thrombopathia, anemia, altered blood viscosity, and assay incubation temperature
- d-Dimers
neo-epitope produced when soluble fibrin is crosslinked by fXIIIa
indicate the activation of thrombin and plasmin, and are specific for active coagulation and fibrinolysis
sensitive indicator of thrombotic conditions, such as DIC and thromboembolism
o excellent negative predictive value in that few dogs with DIC or thromboembolism have normal d-dimer concentrations
not specific; DIC, thromboembolism, neoplasia, hepatic disease, renal failure, cardiac failure, or internal hemorrhage, and following surgical procedures
- Fibrinogen
endpoint of all clotting assays (PT, aPTT, ACT) is based on the formation of a fibrin clot
prolongation indicating hypofibrinogenemia
Viscoelastic Testing: Thromboelastography
global assessment of hemostatic system in whole blood
o reaction time (R) represents the enzymatic portion of coagulation (secondary hemostasis
o The clotting time (K) represents clot kinetics, largely determined by clotting factors, fibrinogen, and platelets
- Causes of Surgical Bleeding
o 4 Technical, disorders
o 4 Technical
Inadequate repair of vessels
Occult injury to vasculature
Damage to organs within surgical field
Damage to organs remote from surgical site
Primary – result from decreased circulating platelet numbers (thrombocytopenia), from platelet dysfunction (thrombopathia) or rarely, from vascular anomaly (vasculopathy)
Secondary – low conc or activity of coag factors
Acquired disorders usually affect both to variable degrees, inherited usually only affect one
primary haemostatic disease
decreased production
increased destruction (IMT, 1st - evans and idiopathic and 2nd- drugs, neoplasia)
cosumption (DIC, splenic dz, severe haemorrhage)
aquired (organi dz, drugs )
inherited (vWF)
secondary hemostatic disease
Aquired
* 1. 1. * Vit K def
* 1. 1. * hepatic dz
* 1. 1. * DIC
* 1. 1. * Drugs
* 1. 1. * shock/acid/hypothermia
inherited
haemophillia A (FVIII)
Hameophillia B (FIX)
recessive sex-linked traits
predisposing factors for coagulopathies (6)
- trauma/haemorrhage - tissue injury > TPA release which inhibits PAI-1
- Hemodilution: hypofibronigenemia thrombocytopenia and reduced factors, also triggered by massive transfusions (1 blood volume in 24 hours or 1/2 blood volume in 3 hours)
- Hypothermia: platelet adhesion effected
4..Acidemia:
- Shock: anticoagulant and hyperfibrinolytic state due to unknown mechanisms
- Critically ill patients:
- Preoperative Hemostatic Assessment
Patient-associated factors:
breed, diseased
Procedure bleeding risk
Tests and Their Limitations
* Routine hemostatic screening tests include the basic coagulogram (platelet count, PT, and aPTT) and/or the buccal mucosal bleeding time
Clinical signs of primary vs secondary haemostasis
Primary: ecchymoses, spontaneous bleeding from mucosal surfaces, Petechiae (more indicative of thrombocytopenia then pathia)
Secondary: hematomas, bleeding into body cavities, SQ, joints, or muscles
- Operative and Postoperative Bleeding
Blood loss of 25% to 30% of blood volume generally results in tachycardia and vasoconstriction
what % needs transfusion
blood pressure can be preserved until as much as 40% blood volume loss
determining cause of coagulopathies
Perform coag studies
* Normal TEG > indicates a technical cause of bleeding
Check for hypothermia and acidosis
Review medications
Review history
Additional coag studies : platetelt dysfunction with BMBT/smear. consider hyperfibrinolysis
management for coagulopathies
prevent bleeding
treat shock
Rule out technical
Restore normal hemostasis with medications and transfusions
Monitor coag parameters
Monitor for ongoing blood loss
Monitor for complications
“Damage control resuscitation” – aggressive correction of coagulopathies, while reducing hypoperfusion, hemodilution, and hypothermia
“Hypotensive resuscitation therapy”
Plasma transfusion options (3)
FFP: all (factors, Vwf, albumin)
cryoprecipitate: (vWf, fVII, fibrinogen)
crysupernatant: all but (vWf, fVII, fibrinogen)
o Platelet Transfusion
FWB: 10ml/kg
Platelet rich plasma: short self life, limited availability
hemostatic agents
Desmopressin: induces release of vWF via V2 receptors.
lasts 2 hours. (type 1 Wonvillibrands); 1-4 ug/kg SQ
Antifibrinolytics: aminocaproic acid and treanexamic acid (block activation of plasminogen)
Recombinant factor VIIa-
o Thrombocytopenia
Spontaneous bleeding generally does not occur until platelet counts fall below 50,000/μL
IMT
nonpathologic thrombocytopenia is reported in Cavalier King Charles Spaniels
majority of thrombocytopenic cats have underlying disease,
von Willebrand Disease
Dx: prolonged BMBT + normal platelet count.
Antigen assay (VWF:Ag (below 50%) are predicted at risk)
genetic test
type 1,2,3
multimeric plasma glycoprotein that facilitates platelet adhesion to exposed subendothelium
participates in platelet aggregation and binds fVIII
Hereditary VWD is an autosomal trait. 1 x abnormal gene increase risk. Antigen screening test required > * <50% are considered deficient
Type 1
all multimers, but in reduced concentrations
Doberman Pinschers, Poodles, Shetland Sheepdogs, GSD
Type 2
disproportionate loss of high-molecular-weight multimers
GSP
Type 3
quantitative deficiency, almost complete absence of vWF (<0.1%)
* Shetland Sheepdogs, Scottish Terriers
Tx: FFP, cryopreciptate (4hr life) desmopressin b4 surgery
o Other Thrombopathies
requires the administration of platelets
o Vitamin K Deficiency
anticoagulant rodenticide toxicity
factors II, VII, IX, and X, as well as for the synthesis of proteins C and S
PT prolongation occurs first, reflecting the short half-life of fVII (4 to 6 hours).
aPTT follows when other factors are depleted (approximately 2 days
Vitamin K1 therapy is initiated at 2.5 to 5.0 mg/kg SC or IM
o Hepatic Disease
synthesizing clotting factors (with the exception of fVIII), coagulation inhibitors (AT, protein C), and fibrinolytic protein
significantly decreased functional hepatic mass (>70%)
Vitamin K deficiency due to malabsorption of fat-soluble vitamins or biliary obstruction
Hyperfibrinolysis + Thrombocytopenia
80-90% have bleeding anomoly, but unpredicatble bleeding risk
THROMBOEMBOLIS
venous or arterial
macrovascular obstruction by a thrombus that develops locally (primary thrombosis), or that translocates from a distant site (embolism).
Arterial > aortic (FATE)
Venous > PTE, hepatic/portal, caudal venacava
Virchow’s triad
risk factors for thromboembolism
- abnormalities of the vessel wall (endothelial injury)
- abnormalities of blood flow (vascular stasis)
- abnormalities of blood constituents (hypercoagulability)
Hypercoagulability
imbalance between prothrombotic and anticoagulant activities
- Hypoalbuminemia increases TxA2 synthesis
- Acquired AT deficiencies
- Activated protein C deficiency,
hypercoagulable state
causes
IMHA and surgery > venous thromboembolism
others: Neoplasia, pancreatitis, HyperA, sepsis, DM
TEG ~ diagnosis of hypercoagulability
- Postoperative Thromboembolism
82% THR have PTE
imaging studies
(1) the exclusion of other potential causes; (2) laboratory evidence of hypercoagulability, if possible; and (3) identification of an underlying disorder
Pulmonary Thromboembolism
pulmonary hypertension
> heart failure, reduced CO and death
xray
radiolucency, hypovascular lung regions
blood gas
increased A-a gradient, hypoxemia, hypocapnia, and decreased oxygen responsiveness
d-dimer increased
Dx: CT pulmonary angiography (CTPA)
Tx: Antiplatelet drugs
aspirin: irreversible functional defect in platelets by inactivating COX-1
* ultralow-dose standard primary thromboprophylaxis
Anticoagulants: inhibit 2nd hemostasis, venous thromboprophylaxis
* Unfractionated Heparin (needs monitoring)
* Low-molecular-weight heparin
* Warfarin
oxygen supplementation (patient support)
reduce sx risk: minimise trauma, hypoperfusion and compression
DISSEMINATED INTRAVASCULAR COAGULATION
systemic activation of coagulation, leading to widespread microvascular thrombosis that compromises organ perfusion and can contribute to organ failure > progress to consumption and bleeding
CS: organ dysfunction
Dx: hypercaog (TEG), thrombocytopaenia, increased PT, aPTT, hypofibrinogen, and d-dimers
Tx: underying dz, o Adequate perfusion must be restored and maintained via appropriate fluid therapy +/- transfusion
Preoperative autologous blood donation and transfusion in
dogs undergoing elective surgical oncology procedures with
high risk of hemorrhage
Sharma 2020 Vet Surg
Study design: Prospective study.
Animals: Twelve dogs.
minimum of 6 days
mandibulectomy, maxillectomy,
chest wall resection, and liver lobectomy
Ten of the 12 dogs received autologous transfusion.
No dog developed transfusion-related complications
Prospective evaluation of the utility of cross-matching prior to first transfusion in cats: 101 cases
Humm 2020
Transfusion reactions occurred in 20 cats, most commonly febrile non-haemolytic transfusion reactions (n = 9) and haemolytic transfusion reactions (n = 7)
Twelve autologous blood
transfusions in eight cats
with haemoperitoneum
Cole 2019
retrospective descriptive study
Autologous transfusion appears to be a safe and effective technique for stabilising cats with haemoperitoneum.
Xenotransfusion of canine blood to cats: a review of 49 cases and their outcome
Gal 2020
Xenotransfusion of canine packed red blood cells to cats is possible but haemolysis should be expected between 1 and 6 days after transfusion
