Bleeding disorders

Anticoagulant rodenticide toxicity (vitamin K deficiency)

first generation anticoagulant warfarin

short half life 12 h

relatively low toxicity in target species

repeated or massive exposure required to cause clinical bleeding in dog

second generation coumarin derivatives (bromadiolone and brodifacoum) and indandione rodenticides (pinion and diaphacinone)

more potent

longer lasting effects (half life 4-6 days)

more completely bound to plasma proteins and have an enhanced tendency to accumulate in hepatic tissue

most likely via secondary poisoning through ingestion of killed target species

inactivate vitamin K enzyme and prevents carboxylation of vitamin K dependent coagulation proteins and cannot lead to fibrin formation

clinical signs

onset delayed for several days post exposure while the concentrations of the vitamin K dependent clotting factors become depleted

may be non-specific if internal bleeding

depression

weakness

pallor

dyspnoea

abdominal swelling

sudden death

anaemia

external haematomas

bruising

excessive bleeding from venipuncture sites or other sites of injury

epistaxis

haematemesis

haematochezia

melaena

haematuria

lameness

diagnosis

coagulation screening tests unlikely to reveal abnormalities until at least 36-72 hours post-exposure

pro-thrombin time generally prolonged first (36-48h)

Proteins induced by vitamin K antagonism (PIVKA) can be detected by some labs, usually cleared within 12h of administration of vitamin K, collect samples before vitamin K therapy

partial thromboplastin time and activated clotting time usually prolonged to 48-72 hrs post exposure

factor VII has the shortest half life (approx. 6h)

other possible confirmatory tests:

quantification of vitamin K epoxide concentrations and determination of the specific anticoagulant in blood, liver +/- stomach

treatment

supportive to correct hypovolaemia and coagulopathy

fresh blood or plasma will help correct the hypovolaemia and enhance haemostasis by restoring depleted clotting factors

vitamin K1 (5mg/kg) loading dose subcutaneously at multiple sites

followed by s/c or oral doses (1.25-2.5mg/kg) at 8-12hr intervals for as long as necessary until toxin metabolised or excreted

duration of tx depends on anticoagulant, 1 week tx may be undertaken initially

PT + PTT must be checked 48-72h after cessation of vitamin K1 tx

if prolonged indicates residual toxic effect and need for continued vitamin K 1 tx

hypo coagulable patients at increased risk of internal haemorrhage so monitor condition and minimise physical activity

Dissminated intravascular coagulation

develops 2ry to 1ry disease which in some way damages the vasculature or releases procoagulant tissue factors or other activators into the general circulation

potential causes

neoplasia

infectious disease

shock

heat stroke

envenomation

acute inflammatory processes

categorised as acute or chronic, localised or generalised

clinical signs

signs reflected micro thrombosis of vasculature are harder to recognise than signs associated with extensive failure of the haemostatic mechanism

often recognised well advanced into haemorrhagic phase by this stage the syndrome is increasingly difficult to control or reverse

peracute

(hypercoagulable) stage

may be no overt signs of bleeding or only non-specific signs consistent with organ dysfunction

coagulation screening tests may be normal or decreased and platelet concentration may be normal

acute

excessive bleeding tendency becomes apparant

consumptive phase

bleeding from any/all body orifices

bruise easily

ooze excessively from venipuncture sites or other sites of tissue trauma

platelet count and fibrinogen concentration decrease as these haemostat factors are consumed

all coagulation screening tests (ACT, PTT, PT and TCT) become prolonged as clotting factors are depleted due to excessive consumption +/- degradation

FDPs may accumulate and become detectable in plasma if their rate of production exceeds the liver's ability to clear them from the blood

these contribute to the hypocoagulable state as they exert both anticoagulant and anti platelet effects

chronic

continuous low grade activation of the haemostat mechanism with few if any clinical signs of bleeding

platelet and FDP concentrations and coagulation screening tests may be normal (if replacement balances consumption) or abnormal

treatment

early recognition and intensive therapy

the causal agent or underlying disease must be identified and corrected or removed before any form of therapy likely to be successful

promote capillary blood flow and oxygenation

IV dextran or hydroxyethyl starch solutions (10-15ml/kg) can provide the fluid and colloid properties necessary to improve tissue perfusion and hopefully re-establish organ function

fresh blood/plasma

replace haemostatic components that have been depleted

provide fluid and oncotic components

heparin therapy

potent inhibitor of activated clotting factors

anticoagulant by enhancing the activity of antithrombin III

most likely effective in early stage of DIC

before the plasma antithrombin III concentration decreases

paradoxical syndrome

over activation of a normal body defence mechanism designed to produce a blood clot (haemostatic response) ultimately leads to clinical condition characterised by a tendency to bleed. Patients may die from either thrombotic or haemorrhagic complications before the underlying cause can be identified and eliminated

immune-mediated thrombocytopenia (primary)

one of the most common causes of acquired bleeding in dogs

IMT results from binding of antibodies to the platelet surface + the premature clearance of these stimulated platelets by the mononuclear phagocytic system

secondary IMT occurs in association with neoplasia, viral or bacterial infections, or disease such as systemic lupus erythematous and rheumatoid arthritis. It may also be associated with administration of various drugs

breed predisposition

cocker spaniels

GSDs

old english sheepdogs

poodles

more common in females and middle aged

Diagnosis

exclude other causes of thrombocytopenia

decreased production

bone marrow disease

secondary IM thrombocytopenia

drugs

infection

haemophagocytic syndrome

infection

neonatal alloimmune thrombocytopenia

neoplasia

systemic lupus erythematosus

transfusion reaction

increased utilisation/non-immune destruction

DIC

haemolytic-uraemia syndrome

microangiopathic destruction

septicaemia

snake venom

chronic/severe haemorrhage

coagulopathy

neoplasia

vasculitis

canine adenovirus-1

canine herpes virus

dirofilariasis

ehrlichiosis

FIP

neoplasia

polyarteritis nodosa

rocky mountain spotted fever

septicaemia

systemic lupus erythematosus

sequestration

hepatomegaly

sepsis

splenomegaly

chronic infection

haematoma

IMHA

neoplasia (hemangiosarcoma/oma, mast cell, mets)

portal hypertension

splenic torsion

splenitis

systemic lupus erythematosus

sudden onset of anorexia, lethargy, weakness, pallor, bruising, epistaxis or other forms of mucosal or surface bleeding (esp after stressors e.g. surgery, kennelling, oestrus, parturition) is suggestive of primary IMT

approx 20% of dogs concurrent IMHA

confirmed based on the response to corticosteroid therapy

normalisation of platelet count 7-10 days of initiating therapy

this reduces the rate of sequestration of stimulated platelets. It will not differentiate between primary and secondary forms of IMT

Treatment

cage rest to minimise risk of trauma

glucocorticoids

inhibit macrophage induced sequestration of antibody stimulated platelets, reduce antibody prodcution, increase capillary resistance to haemorrhage and in some patients stimulate platelet production

oral prednisolone (2mg/kg every 12h)

monitor platelets weekly and continue treatment until count returned to normal (1-several weeks) depending on patient

then taper drug over an equal period of time

some must remain on tx to prevent recurrence

dogs with recurrent disease and cases unresponsive to glucocorticoids have been treated with drugs such as vincristine

reduces platelet phagocytosis by macrophages and stimulates thrombopoiesis

also cyclophosphamide and synthetic androgen danazol

or by surgical removal of the spleen

any drug has potential to cause IMT, most common are antibiotics particularly sulphonamides and cephalosporins

neoplasia associated via several mechanisms e.g. increased platelet consumption 2ry to a bleeding tumour or DIC, splenic sequestration, decreased platelet production due to myelophthisis

primary IMT is rarely diagnosed in cats and oral prednisolone not as effective in dogs, consider dexamethasone, cyclosporine and chlorambucil

Von Willebrand disease

hereditary

classification

type 1

low plasma VWF conc

mild to moderate bleeding tendencies

type 2

full array of VWF multimers

variable reduction in plasma VWF concentrations

absence of high molecular weight VWF multimers

moderate to severe bleeding tendencies

type 3

complete absence of plasma VWF

severe bleeding tendency

prompts for investigation

mucosal surface bleeding

excessive bleeding following surgery or trauma in a dog with abnormal platelet count, prothrombin time and activated partial thromboplastin time

diagnosis

buccal mucosal bleeding time

over 4 mins in a dog with a platelet count over 100,000/mcL and PCV >30% is suggestive of VWS , thrombopathia or rarely vasculopathy

quantitative or qualitative VWF assay

DNA testing

treatment

control spontaneous e.g. epistaxis, haematuria or trauma/surgery induced bleeding

prophylactic treatment based off case by case basis

Desmopressin

synthetic analogue to the neurohypophyseal hormone vasopressin

blood component therapy

measurement of plasma VWF:Ag concentration

feline uncommon but still important differential

Hepatic failure

liver responsible for synthesising most pro and anti-coagulant factors and plays a central role in haemostasis

vitamin K deficiency can result from liver disease and it can exacerbate coagulation factor deficiency

aside from 1ry tx for liver disease, supportive care in cases of haemorrhage secondary to liver failure can include vitamin K1 therapy and plasma transfusions