approach to bleeding patient

approach to bleeding animal

attempt to quantify blood loss

identify life threatening situations

establish venous access and collect samoles for test

attempt to quatify blood loss

Total blood volume dog: 80-90ml/kg

Total blood volume cats: 60-70ml/kg

Most healthy animals can withstand 15-25% loss of blood volume

identify life threatening situations

Hypovolaemic shock (tachycardia, weak pulses, pale MM, prolonged CRT)

Location of bleeding:

• Pulmonary haemorrhage or pleural effusion (dyspnoea, tachypnoea)

• Bleeding into the abdomen (ascites, abdominal distension)

• GI haemorrhage (melaena, haematemesis, increased urea on biochemistry)

• CNS haemorrhage (neurological signs)

establish venous access and collect samples for test

PCV/total protein – Can take >4-6hrs for PCV to drop

Collect samples: Blood smear, full blood count (EDTA), coagulation profile (CITRATE), biochemistry (heparinized plasma or serum)

how to stabilise patient

control of haemorrhage - wound pressure

fluid replacement

• Volume replacement with buffered isotonic fluids if hypovolaemic

• Small volume resuscitation – assess perfusion parameters after each bolus

= Dogs: 10-20ml/kg over 15 mins

= Cats: 5-10ml/kg over 15 mins

= 75% of crystalloids leave intravascular space after 30 mins: shock rates as 40-50ml/kg in cats, 20-90ml/kg in dogs

• Blood transfusion if significant haemorrhage/anaemia

= Rule of thumb: Up to 25% blood loss replace with crystalloids; >25% blood transfusion

what to gather in signalment

age

sex

breed

history

when did bleed start

location

recent trauma or surgery

any drugs or accidental toxic ingestion - incl pills

physical exam

is bleeding due to local factor or systemic disorder

haemostasis overview

primary homeostasis

end results = formation of primary platelet plug

need

• subendothelial collagen exposure

• platelets

• von willebrand factor

clinical signs of primary homeostasis

small holes / capillary bleeding

due to lack of platelets or poor platelet function

• Petechiae (<3mm)

• Ecchymoses (>1cm)

• Epistaxis

• Ocular bleeding

• Haematuria

• GI haemorrhage

• Pulmonary haemorrhage

• CNS haemorrhage

primary vs secondary haemostasis

clinical signs of secondary haemostasis

Result of deficiency in clotting factors

Tend to present more acutely with life-threatening blood loss

Examples:

• Subcutaneous or cavity bleeding (haemothorax/haemoabdomen)

• Haematoma formation

• Haemarthrosis

in house lab tests

haematology

• smear examination and platelet estimation

biochemistry

assess clotting factors

• PT

• APTT

buccal mucosal bleeding time

• if thrombocytopenia is excluded

care with venepuncture sites

• Always sample from cephalic/saphenous vein if concerned there may be a bleeding disorder present

test of primary haemostasis

platelet count - machine or manual

buccal mucosal bleeding time

• only performed if platelet count and clotting times are normal

von willebrand factor antigen assay

test of secondary haemostasis

PT

APTT

activated clotting time - rarely used

test specific factor concentrations

tests of fibrinolysis

= breakdown of clot

fibrinigen degradtion products

D-dimers

disorders of primary homeostasis

Thrombocytopenia

• < 30 x109/L - spontaneous bleeding

• 30 – 50 x109/L - excessive bleeding with trauma

von Willebrand disease

Thrombocytopathia (very rare)

Vascular disorders (very rare)

thrombocytopenia

Most common cause of abnormal bleeding in the dog

Lack of production

• Bone Marrow Disorders: E.g., myelophthisis (e.g. myelofibrosis, neoplasia)

• Drug toxicosis: phenobarbitone, antimicrobials (chloramphenicol, penicillin, TMPS), methimazole, procainamide, oestrogen, chemotherapy drugs

Increased consumption

• Clot: e.g. Disseminated Intravascular Coagulation (DIC)

• Acute severe haemorrhage

= Normally platelet count >30,000/μL. If severe thrombocytopenia

then this is often the cause of the haemorrhage not vice versa

Increased destruction

• Immune-mediated destruction

Increased sequestration

• Splenic torsion or Splenomegaly

Spurious result – clotted sample in the tube!

inherited thrombocytopenia

Inherited macrothrombocytopenia

• Mutation in β1-tubulin gene in Cavalier King Charles Spaniels

= Other breeds with defect: Norfolk & Cairn terriers, Shih Tzu, Chihuahuas.

• Homozygotes have high MPV and platelet counts often 25-75 x109/L

• Despite low counts, does not cause bleeding

Breed-associated thrombocytopenia

• Sighthounds associated with lower platelet counts than other breeds (>80 x109/L )

• Not associated with bleeding

immune mediated thrombocytopenia

involves immune-mediated destruction of platelets

primary IMTP

• IgG binding to platelets, resulting in destruction

• marked thrombocytopenia < 30×10^9/L = females and spaniel breeds predisposed

secondary IMPT

• Secondary to drugs, infectious disease or neoplasia

• Antibiotics (TMPS, cephalosporins) most common

= 5-7d of exposure of drug required to produce sensitisation

and onset of thrombocytopenia

= Case-control study of 48 dogs failed to find association with vaccination

• Infectious agents: Anaplasma, Babesia, Ehrlichia, Leptospira, Leishmania

diagnostic evaluation of IMTP

Full clinical history (including drug & travel history)

Full physical exam

Haematology with blood smear evaluation

Biochemistry

Idexx 4DX SNAP

Screen for underlying trigger (imaging)

• Thoracic radiographs

• Abdominal Ultrasound

Diagnosis of primary IMTP is presumptive, based on:

• severe thrombocytopenia

• exclusion of known causes of thrombocytopenia or underlying disease

• response to immunosuppressive therapy

treatment of IMTP

If a secondary cause is identified treat underlying disease or discontinue offending drug – often enough to resolve secondary IMTP

Otherwise: Glucocorticoids mainstay of therapy for primary disease

• Affects both the humoral and cell-mediated immune system

• Prednisolone

• Dexamethasone

Whole blood transfusions/Canine platelet concentrate can provide short-term haemostasis despite a negligible increase in platelet count post-transfusion

thrombocytopathia - platelet dysfunction - when to suspect it

animals who bleed excessibely despite normal platelet count and coagulation profile

thrombocytopathia - platelet dysfunction - causes

Systemic disease

• Hepatic disease

• Renal disease - Correlates with azotaemia

• Hyperproteinaemias (e.g. multiple myeloma)

• Bone marrow neoplasia

• Erythrocytosis

Drug therapy

• NSAIDS, aspirin, clopidogrel

Hereditary platelet dysfunction - rare

testing platelet function

Buccal Mucosal Bleeding Time

• very crude assessment of platelet function

• will be affected by thrombocytopenia

von willebrand disease

A platelet adhesion disorder cased by von Willebrand factor (vWF) deficiency

• Inherited

• Acquired (severe aortic stenosis) – very rare

vWF is synthesised and stored by endothelial cells

• Vital for platelet adherence & platelet aggregation

• Binds to factor VIII and prolongs its half life

BMBT increased

• Result only increased if vWf <20%

Measurement of Von Willebrand factor antigen in serum

• Test of choice

• Diagnosis based on low vWF antigen concentration

• Collect sample in citrated plasma (separate asap & freeze)

• Concentration does not correlate well with clinical disease

Genetic testing (Laboklin)

• Dobermann, Poodle, Manchester Terrier, Pembroke Welsh Corgi, Cockapoo, Red Setter, GSHP

• Can be used to detect affected dogs (homozygous) but also carriers (heterozygous) to avoid mating

Von Willebrand disease - when to suspect

Mucosal surface bleeding or excessive bleeding following surgery or trauma in a dog with a normal platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT) should prompt evaluation for vWD.

Von Willebrand disease treatment

Management aimed at controlling spontaneous bleeding or trauma/surgery- induced bleeding

Can be administered prophylactically to dogs with vWD prior to surgery

Cryoprecipitate

• Rich in factor VIII, fibrinogen and vWF

• vWF also present in whole blood and fresh frozen plasma

DDAVP

• 1-desamino-8-D-arginine vasopressin

• Increases vWF release from endothelial cells

disorders of secondary haemostasis

Inherited or acquired deficiencies of clotting factors

Most secondary haemostatic disorders seen in practice are acquired

• Vitamin K antagonism (deficiency) – rodenticide toxicity

• (Severe) liver disease

• DIC

• Angiostrongylus vasorum

Inherited disorders uncommon

• Haemophilia A (VIII deficiency) – more common

• Haemophilia B (IX deficiency – Christmas disease)

• Haemophilia C (XI deficiency) – extremely rare

vitamin K deficiency

Most commonly caused by ingestion of vitamin K antagonist rodenticides (coumarins and indandione derivatives)

Other causes: Decreased vitamin K absorption from the gut:

• Liver disease

• Biliary obstruction

• Exocrine Pancreatic Insufficiency

Vit K involved in production/activation of factors II, VII, IX, X

• dont need to know which factors

vitamin K deficiency - clinical signs

Typically observed 2-5 days after ingestion

Haemothorax, haemoptysis, haemoabdomen, haemarthrosis

Also: epistaxis, melena, haematoma, ecchymoses, haematuria, gingival bleeding

vitamin K deficiency - diagnosis

Clinical history, clinical signs and coagulation testing

PT/APTT

• Factor 7 = shortest half-life & therefore PT will be prolonged within 36- 72hours, prolongation of APTT follows later

vitamin K deficiency - treatment

Supplementation with Vitamin K1 therapy (do not give IV)

Recommended for 2-4 weeks

Fresh Frozen Plasma transfusion in emergency

liver disease

Coagulopathies are a rare clinical presentation of liver disease

• Acute fulminant hepatopathies

• End stage chronic hepatopathy (cirrhosis)

Clotting times (PT, APTT) may be prolonged in liver disease

Mechanisms:

• Vitamin K malabsorption

• Decreased production of clotting factors

Vitamin K is absorbed with fat and reduced excretion of bile (e.g. due to obstruction of the bile duct) can cause impaired lipid digestion and vitamin K absorption is reduced

Coagulation times recommended prior to liver biopsy

disseminated intravascular coagulation - DIC

Involves widespread systemic activation of coagulation

• = Microthrombi in vessels = ischemia and necrosis of organs

• = can lead to multiorgan failure

Consumptive coagulopathy

Many underlying causes

• Widespread inflammation

• Sepsis

• Neoplasia (esp. disseminated)

• Trauma

• Heat stroke

• Cardiac disease (esp. thromboembolism in cat)

• Angiostrongylus vasorum

DIC lab abnormalities

Thrombocytopenia

Prolonged clotting times (PT and aPTT)

Increased FDPs/D-dimer

Schistocytes

Decreased fibrinogen

DIC - treatment

poor prognosis

treat underlying cause

if bleeding = fresh frozen plasma

if anaemic = whole blood

tertiary haemostasis - fibrinolysis

Fibrinolysis activated concurrently with coagulation to restrict clot formation to the area of vascular injury

Laboratory assessment

• Fibrinogen degradation Products (FDPs): Produced following plasmin mediated lysis of fibrinogen and/or fibrin. However fibrinogen is present in circulation regardless of whether a clot has formed, as such the presence of FDPs is not specific for recent clot formation and lysis

• D-dimers: Specific form of FDPs produced following lysis of cross-linked fibrin. Increases indicate that activation of coagulation and fibrinolysis has occurred.

Hyperfibrinolytic disorders result in premature clot lysis and haemorrhage

Suspect in any bleeding patient (particularly following surgery or trauma) in which a disorder of primary or secondary haemostasis has been excluded

hyperfibrinolysis - congenital,acquired and treatment

Congenital

• Breed associated (Greyhounds): Delayed haemorrhage following trauma or surgery reported in up to 25% of greyhounds

Acquired

• Acute traumatic coagulopathy

• Lungworm (Angiostrongylus vasorum)

• Hepatic Failure

• DIC

• Chronic cavitatory effusions

Treatment

• Antifibrinolytic agents: Tranexamic acid 15mg/kg IV/PO every 8 hours