Haemophilic emergencies & Transfusion medicine Flashcards
How many recognized canine blood types currently exist?
a. 3
b. 5
c. 7
d. 13
B
How many recognized feline blood types currently exist?
a. 1
b. 3
c. 5
d. 7
B
To ensure blood recipient health, which of the following pathogens should be screened for prior to blood donation?
a. Borrelia burgdorferi
b. Dirofilaria immitis
c. West nile virus
d. Brucella canis
D
Which of the following statements is true regarding blood transfusions in canines?
a. Dogs do not have naturally occurring alloantibodies to the DEA 1 group
b. For the first transfusion, the patient does not need to be typed or cross-matched
c. The DEA 1 group can cause a delayed antigenic reaction after a single transfusion
d. If a patient is cross-matched as compatible to a donor, there is no chance of a transfusion reaction
C
Which of the following blood components provides functional platelets?
a. Packed red blood cells
b. Fresh whole blood
c. Fresh frozen plasma
d. Cryoprecipitate
B
Both acute and delayed hemolytic transfusion reactions can be treated via which therapy?
a. Corticosteroids
b. Antihistamines
c. Supportive care
d. IVIG
C
Which blood type in felines could be thought of as a universal recipient?
a. Type A
b. Type B
c. Type AB
d. Type O
C
A major crossmatch examines the compatibility between which components?
a. Recipient plasma and donor RBCs
b. Donor plasma and recipient RBCs
c. Recipient plasma and recipient RBCs
d. Donor plasma and donor RBCs
A
Cryoprecipitate would be the treatment of choice for which coagulopathy?
a. Von Willebrand’s disease
b. Hemophilia B
c. DIC
d. Vitamin K1 antagonist rodenticide ingestion
A
he idea of using individual blood components as opposed to blood in its entirety for transfusion is referred to as what?
a. Component therapy
b. Novel transfusion
c. Tailored transfusion plan
d. Law of veterinary transfusion
A
Broad indications for transfusions
- Anaemia
- Coagulopathies
- Thrombocytopaenia
RBC transfusion
Treats anaemia and increases the oxygen carrying capacity of the blood and indicated where there is >20% acute blood loss, low RBC and evidence of transfusion triggers.
What percentage blood loss can healthy animals generally tolerate?
20%
(20ml/kg BW dogs; 10ml/kg BW cats)
PCV requirement for patients undergoing surgery/anaesthesia
At least 20% to ensure adequate O2 carrying capacity
When is an FFP transfusion indicated?
Coagulopathies with extensive bleeding
Colloidal oncotic pressure support
Hypoproteinaemia or hypoalbuminaemia (large volumes required)
Cryoprecipitate
fibrinogen-rich, factor VIII and vWF and useful in patients with factor deficiencies, plasma & protein deficiencies
Cryo-poor plasma indications
Coagulopathic and hyproteinaemic patients
Platelet transfusions are….
Rarely performed due to short storage life (<8 days) or <8h at room temperature.
FWB transfusion preferred method to give platelets
Blood typing & cross-matching
- performed before any transfusion
- cross matching performed on any patient with unknown or known previous transfusion history
- blood typing identifies a patient’s blood group but cross-matching does not but will detect presence of alloantibodies
Massive transfusion
Required for near exsanguination where half to full blood volume is transfused
90mL/kg dogs
66mL/kg Cats
Complications of massive transfusion
Electrolyte disturbances
Metabolic acidosis
Coagulopathy
Hypothermia
TRALI
Immunosuppression
Transfusion reaction
Erythrocytes developed by
haemopoietic progenitor cells via erythropoiesis
EPO
Erythropoietin
Released from the liver in response to a drop in oxygenation and is the primary hormone responsible for the production and regulation of RBC within the bone marrow.
Release of EPO begins a biochemical cascade which results in erythropoiesis and the production of new RBC to increase oxygen levels.
Determination of blood type
Presence or absence of antigens on the surface of RBC
positive = antigen present
negative = antigen absent
Which of IgM and IgG produces a more severe reaction?
IgM
Haemophilia affects which coagulation pathway?
Intrinsic
TACO & TRALI occur within….
6h of a blood product transfusion
Treatment of mild transfusion reactions
antihistamines and stop transfusion
Treatment of moderate transfusion reactions
fluid boluses to 1/2 shock doses
Stop transfusion
Antihistamines (may not prove beneficial)
Treatment of severe transfusion reactions
Stop transfusion
epinephrine 0.01mg/kg IV
1/2 shock bolus of crystalloids
Oxygen (cats)
FFP contains
All coagulation factors
Fibrinogen and antithrombin III
Major crossmatch
recipient plasma against donor RBC
Minor crossmatch
Donor plasma againts recipient RBC
Common additive to closed collection blood bags
CPDA-1
Citrate-phosphate-dextrose-adenine
Open collection system for cats CPDA-1 ratio
1ml CPDA to 9mL blood
How FFP stored
Collection > separated/centrifuged > frozen to -20 within 8h of collection
PCV monitoring for transfusions
Before
During
6h after transfusion
24h after transfusion
FFP standard dose
10ml/kg
pRBC dose
vol (ml) = 2 X Desired PCV X BW
equiv. 2ml/kg = 1% rise
Monitoring and rate of blood transfusion
1-3ml for 5min
1-2ml/kg for next 15min
Complete over 4 hours
Monitoring continuous first 15min then hourly until finished
Standard filter size for blood
170um
When is warming of RBC indicated
Neonates, massive transfusion
Occurence of transfusion reactions
3-13% may be under represented due to clinical signs similar to critical illness
Top Immunological reaction to blood products
FNHTR & Urticaria
Top Non-immunological reaction to blood products
Infectious disease, sepsis, citrate toxicity, circulatory overload
FNHTR
Thought to be due to WBC inducing cytokine release, immunosuppression, thrombocytopaenia, TRALI
Intravascular haemolysis due to transfusion
Antibodies in recipient react with RBC surface antigen of donor and an IgG or IgM reaction activates the complement system forming a membrane attack complex leading to intravascular haemolysis
Severity of haemolytic reation
Amount of transfused blood
Amount of recipient alloantibodies
IgG or IgM response
Antibody cold or warm
Storage lesions causes and effects
Haemolysis
Microparticle aggregation
Decreased viability
Proinflammatory substances
Release of free Fe
Free Hb > reduced tissue perfusion > MODS
Induction of hypercoagulability
- Day 14-35 of storage
Leukoreduction
Eliminates inflammatory response to WBC and resultant immunosuppresion.
- reduces FNHTR
- reduced haemolysis
- reduces microparticle formation
- reduces cytokine reduction
Hypercoagulobility
Inappropriate thrombosis where the balance of anticoagulation and procoagulation is disrupted.
Virchow’s triad
Hypercoagulobility
Blood stasis
Endothelial damage
Glycocalyx
Large mesh work of glycosaminoglycans, proteoglycans and glycoproteins that is both a mechanoreceptor and crucial to coagulation.
Endothelial disruption
Exposes procoagulant substances to circulating blood I.e. tissue factor (TF) and activates the extrinsic pathway to start coagulation.
Endogenous anticoagulants
Restrict coagulation to the site of injury to prevent procoagulant state or systemic dissemination of coagulation.
Antithrombin, protein C, tissue factor pathway inhibitor (TFPI)
Antithrombin
Inhibits thrombin via factors 7, 9, 10 and is most defective when bound to heparin. AT is decreased in inflammation leading to bleeding.
Protein c
Inhibits factors 5 and 8a reducing fibrinolysis and is less functional in the face of systemic inflammation
Fibrinolysis
The final step to prevent vascular occlusion
Diagnosis of hypercoagulobility
Often diagnosed when a thrombotic event occurs in an at risk patient
Can look at factor levels and TEG as well as other methods
- Tests used to identify hypocoagulable states ineffective (PT/aPTT)
Systemic inflammation effect on coagulobility
Increases TF expression
Activates endothelial cells
Disrupts the glycocalyx
Impairs anticoagulation
Abates fibrinolysis
Coagulation in septic patients
Usually initially a short state of hypercoagulobility but then followed my a much longer period of hypocoagulobility
Types of conditions that are prone to hypercoagulobility
PLN
IMHA
Hypercortisolaemia/hyperadrenocorticism
Cardiomyopathies (HCM particularly)
Neoplasia
Isolated brain injury
Treatment of hypercoagulable states
Antithrombotics i.e. clopidogrel, rivaroxaban, aspirin and LMWH may be indicated for for PLN, ATE, IMHA and neoplasia but in instances of systemic inflammation, HAC TBI these may be contraindicated
Bleeding disorders
Disruption of haemostatic mechanisms which lead to bleeding
Haemostasis and fibrinolysis maintain…
Integrity of the close, high-pressure circulatory system after vascular damage
Primary v. secondary haemostasis
Primary: injury > clot formation (interactions between platelets and endothelium)
Secondary: proteolytic reactions that involve clotting factors
Fibrinolysis
Dissolution of the fibrin clot to restore normal vascular patency
Cell based coagulation model
TF initiates coagulation on TF-bearing cell surface generating thrombin which amplifies initial signal by activating PLT & co-factors. Complexes from application propagate on the surface of the activated platelet and large scale thrombin formation occurs > large quantities of fibrin to stabilise a thrombus.
** INITIATION, AMPLIFICATION AND PROPAGATION **
Platelet count and enumeration
Quantitative measure on the number of platelets
PLT a estimate = PLT/hpf X 15,000/uL
BMBT
The only reproducible and reliable method in small animals to identify primary haemostatic disorder I.e. vWD or NSAID thrombopathia
Gauze around maxilla to occlude upper lip > two 1mm deep incision not where vessels located > blot shedded blood carefully > record time
PT/aPTT
Used to identify secondary haemostatic defect of extrinsic or intrinsic pathway.
PT = extrinsic = fVII, vit K deficiency
aPTT = intrinsic
Not predictive of bleeding and if only slightly prolonged may not be completely accurate
Fibrin split products (FSPs)
Occur when fibrin is lysed by plasmin and tested with agglutination testing
High FSP can indicate: DIC, neoplasia, IMHA, TE, hepatic dysfunction, SIRS, trauma, HF, GDV…
D-dimers
Produced when soluble fibrin is cross-linked with fXIII and indicate the activation of thrombin and plasmin (active coagulation and fibrinolysis)
Critical patients are often? (haemostasis)
Hypocoagulable so are at risk of spontaneous bleeding that is either direct or induced. Secondary factors like dilution, acidaemia and hypothermia increase the chances of a bleed in these patients
Dilutional coagulopathy
In hypovolaemic shock there is a drop in intravenous hydrostatic pressure and when a patient is resuscitated with factor-deficient fluid (crystalloid/colloids/MT) there is low circulating factors and platelets resulting in bleeding. Fibrinogen is the first factor affected and therefore will rely on other factors to keep up with consumption however once breakdown>synthesis clot stability is reduced.
What fluid has the most profound haemodilution effect and why
Hetastarch because affects vWF and fVIII
Hypothermia in relation to hypocoagulopathy
Platelets are very sensitive to temperature changes even between 33-37. Under 33 degrees there is reduced platelet function, reduced enzyme activity and reduced TF-fVIIa complexes > coagulopathy
Acidaemia in relation to hypocoagulopathy
Acidaemia occurs with hypoperfusion and MT of stored CPDA cells which increases fibrinogen degradation and impaired coagulation
pH 7.2 = <50% reduction in fX and fV activity (70% reduction at 7.0)
pH 7.0 = <90% reduction in fVIIa
** can not be reversed using a buffer **
Antifibrinolytics in the management of bleeding disorders
TXA/EACA
Aprotonin
Thrombocytopenia
Low platelet count and spontaneous bleeding can occur when reduced <30,000 and 50,000/uL
Thrombopathia
May have adequate platelets but platelets can be non-functional.
Hereditary, NSAIDs, ehrliciosis, drugs, snake envenomation, DIC, hypothermia, anaemia….
Inherited coagulopathies
Usually just involve one factor however can have rare deficiency of vitamin k factors (II, VII, IX and X) I.e. Devon Rex
Most are identified within first year of life
fVII may be diagnoses later on in life = extrinsic only = PT prolonged
Haemophilia = intrinsic factors = aPTT prolonged
Cryoprecipitate use for bleeding disorders
fVIII and hypofibrigenaemia
Cryosupernatant for bleeding disorders
Vit K deficiency (FFP alternatively)
Vitamin K deficiency
Involves factors: II, VII, IX, X and alters secondary haemostasis
PT will be prolonged first but as factor depletion occurs there will be prolongation of aPTT as well, then the common pathway.
The liver in haemostasis
The liver synthesises clotting factors, coagulation inhibitors and fibrinolytic proteins and thus liver dysfunction may result in bleeding or deficiencies.
In saying this 70% of hepatic mass is lost before evidence of this due to large reserve stored within it but fVII will be the first to go.
< 93% of patients with liver disease will have haemostatic dysfunction
To combat potential resuscitation associated coagulopathy (RAC)
Permissive hypotension (50mmHg MAP)
FFP:RBC 1:1
CP = 1u/7-10kg
Use TEG to guide treatment
DIC
Systemic activation of coagulation that leads to widespread micro vascular thrombosis, compromising organ perfusion and inducing MODS. Mostly associated with SIRS and sepsis
Diagnosis of DIC
Underlying dz with risk of DIC + 1 or more of the following:
- thrombocytopaenia
- prolonged PT
- prolonged aPTT
- elevated D-dimers
- hypofibrinogenaemia
- reduced antithrombin
- schistocytes
Delayed bleeding in greyhounds
Occurs in about 26% of greyhounds 36-72h post surgery and is accompanied with illness, widespread bleeding, haemolysis, mildly low platelet, increased hepatic and muscle enzymes and is considered a fibrinolytic system anomaly due to it NOT reflecting a primary or secondary haemostatic disorder.
Treated by prophylactic EACA for 5 days before undergoing elective procedures.
Normal values for BMBT, PT, aPTT
BMBT 1.7-4.2 sec; 1.4-4.2
PT 6-12
aPTT 10-25
Normal PLT count
200-800 X 10^9/L
8-15/hpf
Signs of thrombocytopaenia
Petechiae & ecchymoses
Mucosal bleeding
Epistaxis
Hyphema
Haematochezia
Melena
Haematuria
CNS abnormalities
Excessive bleeding at venipuncture sites
Large platelets on smear
May indicate regeneration from bone marrow but could be normal for some breeds
Mechanisms of thrombocytopaenia
- Increased production
- Consumption
- Sequestration
- Increased destruction
Interventions for thrombocytopaenia
Depends on the cause but sometimes no therapeutic measures are needed or aimed at treating underlying disorder. If <30X10^9/L therapy generally indicated. Some options (depends on cause but focused on immune mediated):
- glucocorticoids: pred 2-4mg/kg/day
- immunomodulation; IVIG, cyclosporine, azathioprine, mycophenalate
- chemo agents: vincristine 0.02mg/kg IV
- splenectomy
- platelet transfusions (fWB usually used)
Platelet transfusion
Can increase PLT number < 40X10^9/L
Extrinsic v. intrinsic platelet disorders
Extrinsic - lack of functional protein required for adhesion and aggregation therefore normal platelet structure and function. I.e. vWD where vWF is dysfunctional
Intrinsic - inherent to platelets I.e. Chediak-hibachi syndrome and glanzmann’s thromboaesthesia
vWD
Dysfunction of vWF that normally mediates platelet function and stabilises fVIII. It is autosomal dominant or recessive, resulting in suspicious bleeding during or shortly after surgical procedures. There is no petechiae and ecchymoses generally and can be confirmed with BMBT and lab testing.
BMBT usually 6-11min
Type 3 = absolute deficiency of vWF
Some examples of acquired platelet disorders
Uraemia, vWD, drugs
Treatment options for platelet disorders
Avoid trauma
fWB
Cryoprecipitate 1u/10kg
DDAVP 1u/kg SQ
Identify and treat underlying cause
Testing for disorder I.e. vWD
Anaemia
Reduction in the oxygen-carrying capacity of the blood that results from low haemoglobin and low RBC mass
1. Blood loss
2. Reduced erythropoiesis
3. Haemolysis
Haemophilia A and B only affect
Male dogs
Clinical signs of anaemia
Pallor
Icterus
Pigmenturia
Hypovolaemia
Lethargy
Tachycardia
Tachypnoea
Signs of haemorrhage
Petechiae/ecchymoses
Minimum database for anaemic patients
PCV/TS
CBC/Smear
Biochemistry
Coagulation profile
Agglutination test
Imagine
Blood typing
Faecal exam
Polychromasia
May indicate regenerative anaemia when accompanied by reticulocytes
Rouleaux formation
Stacking of RBC
Hypochromasia
May indicate a chronic anaemia
Spherocytes
Often seen and associated with IMHA
Schistocytes
DIC
Heinz bodies
Indicative of toxic and oxidative damage
What are some other causes of haemolytic anaemia that aren’t IMHA
Chemical induced or oxidative injury - onions, zinc, copper, hypophosphataemia
Hereditary - phosphofructokinase deficiency, pyruvate kinase deficiency
Infectious process
Haemolysis
Therapeutic approaches to anaemic patients
Depends on their presentation and what their underlying disorder is.
- Oxygen
- supportive care
- blood products
- surgery
- vitamin K 2-5mg/kg
- DDVAP 1-4ug/kg
- Pred 2-4mg/kg/day
- AB
- parasitic treatment
Haemolysis
Premature destruction of RBC either in the extra vascular or intra vascular space
Haemolytic anaemia
Occurs when destruction of RBC exceeds the rate of production and can be due to many things and either classed as regenerative or non regenerative
Signs of haemolytic anaemia
Decrease O2 carrying capacity and delivery of O2
- exercise intolerance
- anorexia
- malaise
- syncope/collapse
- pallor +- icterus
- tachycardia
- tachypnoea
- bounding pulse
- soft, systolic murmur
IMHA
Antibody mediated destruction of a patients own RBC and either primary or secondary due to drug, infection or cancer. Female dogs over-represented.
Treatment involves immunosuppressive agents (pred, dex, cyclosporine), IVIG, blood products, supportive care, anticoagulants
Anticoagulant rodenticides
Antagonise action of vitamin K factors (II, VII, IX, X) inducing coagulopathy. There is a lag of 3-5 days whilst factor VII depletes and then clinical signs of bleeding into lungs, abdomen, CNS, joints and trachea occurs. Treatment with initial decontamination, activated charcoal, Vit K and FFP. Monitor PT.
Cholecalciferol rodenticides
Increase iCa as rapidly absorbed and converted by hepatocytes and further converted into the kidneys and therefore there is reduced excretion, increased Ca GIT absorption and resorption from the bone. Commonly prevents with AKI and cardiac arrhythmias. Labs include: low phos, inc Ca, metabolic acidosis, inc protein, azotaemia. Can have soft tissue mineralisation. Treatment with 0.9% saline to increase caliuresis0, furosemide, pamidroante, glucocorticoids
Bromethalin
Uncouples oxidative phosphorylation reducing ATP > CA forced into cells > cellular swelling > inc ICP > neurological signs, hyperthermia, hyperexcitability, paresis/paralysis.
fWB components
All factors, RBC and platelets if used within 8h of collection
FFP components
Contains all labile and non-labile factors but not platelets
If stored > year is classed as FP and this will have loss of factors 8 & vWF V and IX (still has II, VI and X)
Liquid plasma components
Kept at 1-6 degrees
Has factors V and VIII for 14 days
Facts about FNHTR
Usually self limiting and due to incompatibility to donor WBC & PLT
Over 1 degree temp rise usually within 1-2h of transfusion; usually resolves within 12-24h
Use leukoreduction filters
DHTR
Usually occur over 24h after transfusion finished (most common 3-5 days)
Antibody production to foreign antigen I.e. DEA -ve given DEA +ve blood
Jaundice, fever, anorexia
Decreasing RBC lifespan (normal 4-6weeks)
AHTR
RB-antigen incompatibility leading to an inflammatory response, haemolysis and SIRS
Usually occurs within 20-30min of transfusion but occur <24h after
Very severe in cats
Type III sensitivity reaction
Formation and depositing of immune complexes in areas like the glomeruli, endothelial cells, lymph nodes, and synovium leading to neutrophil migration, activation and inflammation
Citrate toxicity
Normal citrate processing by the liver overwhelmed > hypocalcaemia > seizures, panting, pyrexia, PU/PD etc
Hyperammonaemia
Breakdown of stored RBC release potassium and ammonia > hepatic disease and hepatic encephalopathy especially if patient already has liver dysfunction
