Hemostasis Pt. 1 Flashcards
Components of Normal Hemostasis (3)
- Blood vessel
- Adequate platelet mass & function
- Adequate plasma coagulation factor levels & function
Hemostatic tests for intrinsic pathway
ACT, PTT
Hemostatic tests for extrinsic pathway
PT
What causes hemorrhage?
- blood vessel, platelet, and coagulation factor causes
Blood vessels
* Damage (e.g., trauma)
* Inflammation (vasculitis)
Platelets
* Reduced number (<50,000/uL; especially < 20,000)
* Impaired function
Coagulation factors
* Reduced levels
* (Impaired function)
Primary Hemostatic Defect; clinical signs? what are they due to?
- Clinical signs due to lack of platelet plug
- Widespread cutaneous & mucosal petechiae / ecchymoses:
- Gingival bleeding
- Epistaxis
- Hematuria
- Hematemesis / melena / hematochezia
- Hematoma after venipuncture
Secondary Hemostatic Defect; clinical signs?
- Clinical signs:
- Hemothorax
- Hemoabdomen
- Hemarthrosis
- Epistaxis
- Hematemesis / melena / hematochezia
- Large ecchymoses
- Petechiae typically not observed
what are primary and secondary hemostasis?
Hemostasis has two phases: primary and secondary hemostasis. In primary hemostasis, platelets aggregate to form a plug at the site of an injured blood vessel. While these platelets are aggregating, coagulation, or secondary hemostasis starts.
pre-surgery plan for breeds at risk of vWD?
- Pre-anesthetic CBC & mini-chemistry panel (liver/kidneys)
- Buccal mucosal bleeding time
- vWf: Ag level
Von Willebrand Disease - what does VWF circulate with, and what does it do? is this a common disorder?
- VWF circulates with factor VIII
- Promotes platelet-endothelial interaction
- Most common inherited hemostatic disorder in dogs
types of VWD and definitions
Type 1 VWD:
- Most common
- Reduction in all multimers of VWF
Type 2 VWD:
- Reduction in high molecular weight multimers
Type 3 VWD:
- Virtual absence of any VWF
VWD Clinical Signs
- Spontaneous hemorrhage, especially mucosal
- Severity highly variable
> Signs might only be seen after trauma - Petechial hemorrhage uncommon
Diagnosing VWD - helpful tests and what they mean?
- BMBT not specific for VWD
> Even when normal can still be at risk for bleeding - VWF Antigen Test
> Reported as a percentage of “normal”
> Normal range is 70-180% - VWF deficient:
> <50% = VWD carrier or affected
=> <35% = usually affected
> 50-69% = borderline (VWD carrier or normal) - VWF Function (collagen binding assay)
> Preliminary studies: appears to correlate well with bleeding risk
> Longer turnaround vs Antigen test - DNA test
> Often used to identify carriers (breeding stock)
> Does not correlate with risk of bleeding
Peri-Operative Risk management for dog with VWD?
- Pre-operative transfusion options
> Cryporecipitate plasma transfusion
: Concentrated source of VWF, Factor VIII (to stabilize existing VWF), fibrinogen
> Fresh frozen plasma
: VWF and all coagulation factors - DDAVP (Desmopressin)
> Stimulates VWF release
> Helps for 2-4 hours in some affected dogs
> Useful adjunct to plasma
> 1 microgram/kg SQ, 30 min prior to
surgery
> No additional benefit in repeated dosing
VWD Patients: Pre-Surgical Planning
- what do we do for dogs with low VWF titre but no previous bleeding episodes & normal BMBT
- Consider giving only DDAVP pre-op
- (Might not need plasma but ideal to have it in the clinic just in case)
how can we treat a VWD patient in the case of trauma or other factors causing excessive bleeding?
- DDAVP injection
- Cryoprecipitate or fresh frozen plasma transfusion
- +/- RBC replacement if marked hemorrhage
- Compression and other hemostatic techniques
Prognosis for VWD
Mild to moderate cases Type I (majority):
* Good prognosis
* Client education
* Treatment of trauma, pre-surgical care needed
other platelet conditions aside from VWD
- Immune mediated thrombocytopenia
- Platelet function disorders uncommon
> Often inherited, breed-related
Top differential diagnosis for petechial hemorrhage, mucosal bleeding
- Immune mediated thrombocytopenia
Types of hereditary Secondary Hemostatic Defects
- Hemophilia A, B
- Other factor deficiencies
Types of acquired Secondary Hemostatic Defects
- Liver dysfunction
- Toxicity (Vitamin K antagonism)
- Disseminated intravascular coagulation (DIC)
- Others
mechanism of Anticoagulant Rodenticide Toxicity
Inhibits recycling of Vitamin K1 from vitamin K1 epoxide reductase
- Vitamin K antagonism = lack of production of factors II, VII, IX, X
> FVII has shortest half-life, affected first - Several types of anticoagulant rodenticides exist, variable half-life
> Warfarin (and Similar 1st generation Anticoagulants): ~7 days
> Bromadiolone: ~14 days
> Brodifacoum (& Other “Super Warfarins”): 3-4 weeks
Clinical Signs of anticoagulant rodenticide toxicity and timing
- Develop 3-5 days following ingestion
- Common clinical signs:
- Dyspnea, coughing
- Exercise intolerance
- Hematomas
- Hematemesis, melena
- Hematuria
- Pale MMs
- Signs secondary to bleeding in other locations
Diagnosing Rodenticide Toxicity - common tests and findings
- Prolongation of PT, PTT, ACT
> PT prolonged first - CBC findings:
> May see anemia, mild thrombocytopenia
Radiographs - Radiographs
> Thoracic or abdominal effusions
Less Common Tests for Rodenticide toxicity
PIVKA:
* Proteins induced by vitamin K antagonism
* Levels will be increased
* Not widely available
()
Definitive diagnosis requires serum levels (or tissue levels, stomach contents)
* Rarely performed
Initial Treatment for warfarin toxicity
- Vitamin K1
- Transfusion depends on clinical signs
> Plasma - replace coagulation factors
> RBC replacement may be needed
Supportive Treatment for warfarin toxicity
- Supportive care as indicated:
- IV fluids
- Oxygen supplementation
- Cage rest
- Other:
> Thoracocentesis if effusion interfering with respiration (give plasma first)
Ongoing Vitamin K1 therapy for rodenticide toxicity protocol
- 2.5 mg/kg PO q 12 hours
- Administer with (high fat?) food
- For 1-4 weeks depending on specific anticoagulant
- Recheck PT 48 hours after last dose
> If still elevated, resume treatment for 1 week and recheck again
what to do for acute rodenticide ingestion
If ingestion witnessed <24 hours ago decontamination indicated:
* Induce emesis
* Activated charcoal
()
* Not effective if clinical signs are present
* Ingestion has occurred days ago
how long does it take for PT/PTT to increase after rodenticide ingestion
- Takes several days
how do we know if we should start vit K therapy after rodenticide toxicity based on PT/PTT?
- Takes several days for PT/PTT to increase
- Monitor at baseline, 48, and 72 hours
> If normal at 72 hours, no additional treatment - If PT/PTT increasing, start Vitamin K1
Prognosis: Anticoagulant Intoxication
- Good with prompt care
- Factors that might influence prognosis:
- Costs associated with care
- Compliance
- Possible adverse reactions to plasma transfusions
what is hemophilia A and in what species is it reported?
What coagulation test(s) will be abnormal?
- Haemophilia A
- Deficient in factor VIII
- Reported in dogs & cats
> intrinsic pathway abnormal - PTT, ACT
what is hemophilia B and in what species is it reported? is it common compared to A?
What coagulation test(s) will be abnormal?
Haemophilia B
* Deficient in factor IX
* Reported in dogs & cats (less common than A)
> intrinsic pathway will be abnormal - PTT, ACT
Factor deficiency secondary to liver failure - what signs will we see?
- Clinical signs of liver failure predominate
- Prolonged PT/PTT, could see hemorrhage
- Seen in hepatic lipidosis, chronic severe hepatitis, acute hepatopathy
how do we treat factor deficiency secondary to liver failure?
- Treat liver disease
- Vitamin K +/- plasma
what type of coagulation disorder is Disseminated Intravascular Coagulation? often associated with what?
- Mixed coagulation disorder
- Thrombosis and bleeding
- Complication of an underlying disorder
- Often associated with heightened inflammatory response
DIC: Common Underlying Conditions
- Neoplasia (e.g. hemangiosarcoma, others)
- Sepsis, infections
- Immune mediated disorders (e.g. IMHA)
- Snake envenomation
- Heatstroke
- Gastric dilation & volvulus (GDV)
- Massive inflammation (e.g. severe pancreatitis)
- Trauma
DIC: Pathophysiology
- Systemic disease causes excessive thrombosis in microcirculation due to one or more of:
> Endothelial damage (e.g., heatstroke)
> Activated platelets (e.g., sepsis, IMHA)
> Procoagulants released into circulation (e.g., trauma, pancreatitis) - Excess thrombosis eventually consumes most of the platelets & coagulation factors; fibrinolysis is activated
> Bleeding can result
Diagnosing DIC
- Evidence of fibrin clot lysis
*Fibrin degradation products
* D-dimers - Thrombocytopenia (usually mild to moderate)
- Increasing PT/PTT
- CBC – schistocytes/RBC fragments
Treating DIC
- Treatment of underlying disorder
- Supportive care
> Maintain perfusion & oxygenation - Treatment of coagulation abnormality depending on phase of DIC
> (Hyper or hypocoagulability)
DIC Prognosis
- Overall a guarded prognosis
- Can support some patients through the crisis
- Depends partially on underlying cause
- Need intensive care
most common Thromboembolic Diseases
- Arterial thromboembolism (ATE) in cats with hypertrophic cardiomyopathy
- Pulmonary thromboembolism (venous) in dogs and cats
diseases associated with pulmonary thromboembolism
- neoplasia
- immune-mediated hemolytic anemia
- cardiomyopathy
Diagnosis of Thromboembolism - clinical signs? required diagnostic method?
- Clinical signs depend on site that is not perfused
> Lack of arterial perfusion to an area (e.g., cold limb in ATE cat)
> Lack of venous drainage (e.g., edematous limb, effusion in cavity)
> Dyspnea with PTE - Imaging required to identify the thrombus
Treatment of TE
- Direct lysis of clot difficult (referral procedure)
> High complication rate
> Streptokinase infusion - Provide thromboprophylaxis to prevent new TE formation
> Often combine anti-platelet and anticoagulant therapy
> E.g., clopidogrel plus rivaroxaban
